Contents

Dedication

Introduction

Who am I?

A History of My Disease

What Did I Do?

Education

Books

Web

MDs

Talking

Radical Prostatectomy

Active Surveillance

PSA

DRE

TRUS

MRSI

The Theory

Vitamins and Herbs

Diet and Exercise

Alternative Practitioners

Secret Weapons

Bottom Lines

Bibliography

Overviews

Standard web sites

Research web sites

Aggressive Monitoring/Active Surveillance

Mothers' Milk

Press Coverage

Other Peoples' Stories

Naturopathy, Homeopathy, etc.

Magnetic Resonance Spectroscopic Imaging

Power Doppler Ultrasound

Diana Schwarzbein on Diet & Nutrition

Dietary Overviews

Nutrition and Herbs Overview

Selenium

Vitamin D

Vitamin E

pau d'arco

pygeum

Green Tea

Alpha-Lipoic Acid

Pomegranate Juice

Pollen Aid

Flax Seed

Conjugated Linoleic Acid

Trans Rectal Ultrasound

Gleason Score

Radical Prostatectomy

Radiation Therapies

Brachytherapy

Hormone Therapy

Cryosurgery

Chemotherapy

PSA Controversy

PSA Variation

Hyperthermia

Angiogenesis & its Inhibition

Clinical Trials

Prostatitis

Other References

Biopsy Readers

Biopsy Dangers

Glossary

Appendix A: The Nature of the Beast - The Course of the Disease

Appendix B: Current Medical Treatment Options

Appendix C: Future Therapies

Appendix D: Change Log (What's New)

Introduction

This is my attempt to flesh in the details and history "once and for all". That is, to write it down in a more complete and narrative style than the slides and also to have a base for keeping my story current, as time and my medical history evolve.

This is a living, evolving document, with continual minor changes, new references, new test results, and ocassional major revisions and additions, although it is based on that talk of hope in November 1999.

The slide show's main page is noted above.
 

Who am I?

Most of the work I have done professionally has involved some sort of scientific or engineering applications (see my web pages for details), including the past several years (since late 1996) in biotechnology and genetics. With this all, I can claim scientific literacy and an analytical approach, a belief that I can master most areas of knowledge, and a sense of numeracy, an appreciation of numbers and statistics. While I have not had much training in biology and none in medicine, I was able to educate myself about prostate cancer and the available treatment modalities in a very intense couple of months immediately after my diagnosis.

I was diagnosed in July 1999, just before my 54'th birthday. I have always been quite healthy, in reasonably good physical condition, slim, and with a good diet.

And I have usually had a take-charge attitude with regard to my own well-being. I view doctors as partners, well trained technicians who should be working for me and with me. I have little regard for those who try to elevate themselves to god-like status or view their patients/clients as slabs of meat to be treated as objects rather than as people with whom they are collaborating. The ultimate responsibility for my health lies with me.

And finally, I have humility in the face of cancer. It is a very serious disease (or set of diseases) with extremely serious consequences and should not be denied, ignored, or trifled with. Being diagnosed was a great shock that was counter to the myth I have lived by, that of Good Health and Immortality (which really translates to a long and healthy life). And it took a little while to hear the diagnosis and its implications and to mobilize myself in the midst of the rest of my life.

A History of My Disease

In about 1993, a friend of mine who was just 50 at the time, was diagnosed with prostate cancer. His PSA was about 142 when diagnosed (normal range is 0.0 to 4.0 ng/ml) and 180 when he received a radical prostatectomy at Stanford University Hospital by the fabled Dr. Freiha, who has since retired and then resumed practice at the Palo Alto Veterans' Administration hospital. Since then, my friend has been on and off hormone therapy and seems to have his cancer under control. (In late 2005, after 12 years of intermittant hormonal blockade [which will be discussed in Appendix B], he seems to have developed hormone refractory prostate cancer and is exploring chemotherapy options. He tried mothers' milk briefly in 2007. He died of prostate cancer in June 2008.)

I thought that his cancer might be correlated with his work and where he has been living for some time. My impression is that the synthetic estrogenergic chemicals used in pesticides and herbicides by agribusiness to increase their yields and profits at the expense of the health of farm workers and the rest of us is correlated with the sharp rise of breast and prostate cancer in the decades since the Second World War. (See reference, below). And my friend was involved in the food processing industry and lived in lovely rural areas where heavy industrial agriculture took place. I thought his exposure was probably higher than normal, hence a likely contributor to the cancer. I don't know if the epidemiology supports this or not, yet we are all, urban and rural, exposed to enormous amounts of toxic and teratogenic chemicals in our air, water and food, things to avoid, yet things impossible to avoid. I have also found out that he has a genetic predisposition, since his father and uncle have had prostate cancer. There have been no cases I know of in my family except an uncle who had a mild case in his mid-80's.

But somehow, I thought I was immune. Even so, in my periodic physicals, I had to insist that my physician do a PSA test in addition to the usual DRE (digital rectal exam, where a gloved finger probes for irregularities on the back wall of the prostate gland).

The PSA's were normal. The last normal one was in December of 1997, when it was 1.9 ng/ml.

In late April 1999, I had another "annual" physical. The PSA came back as 5.4 ng/ml. This was alarming for two reasons. First, the absolute number was above the "normal" range of 0.0-4.0 ng/ml. And second, the rate of increase seemed rather steep. This is also a sign that there is a cancer that is beginning to grow rapidly. In fact, a conservative estimate of the growth rate is to assume that it was linear and started just after the last "normal" reading. In that case, in these 16 months it increased by 3.5 ng/ml, which is a rate of 0.21875 ng/ml/month. If it started increasing (linearly) after that time, its rate of increase must have been even higher.
 

It took until mid-June to get an appointment with a urologist at Stanford, one recommended by my physician, also at Stanford. We chatted and he recommended an ultrasound (TRUS, a trans-rectal ultasound), combined with a biopsy, which was scheduled for early July. With the TRUS, an ultrasound probe is inserted in the anus and moved around. It creates crude images of the interior of your pelvis, especially of the prostate gland. I couldn't see much there, but a trained radiologist (ultra-soundist?) can see abnormalities in the organ and surrounding tissues, if they are bigger than some minimum (and crude) resolution. The prostate volume can also be measured, which helps in determining whether there is enlargement due to BPH or other conditions.

My TRUS showed nothing out of the ordinary.

At the same time, the ultrasound probe can be used for taking biopsy samples. The ultrasound image can guide the doctor to point the tip to particular locations on the gland (for example, left upper, left mid, left lower, etc.). A spring loaded hollow needle can be fired through the rectal wall into the prostate to draw a cell sample about 1 mm in diameter and 10 to 15 mm long. These samples are stained, fixed, and sent to a pathology lab for examination under a microscope. The procedure takes maybe 15 minutes. It is uncomfortable and unpleasant but tolerable. In my case, 10 samples were taken.

A week and a half later, my wife and I went to meet the urologist at Stanford for the results. In my first two visits, he was punctual, pleasant, if drabbly efficient. This time, the bean counters at the hospital, in their increasing quest for milking money from both doctors and patients, had overbooked him, and he was over an hour late getting to see us. This was creating problems since my wife had clients of her own to see that afternoon, and I had business obligations. We were not pleased when he finally had time for us, with a couple of residents hanging out in the back of the room to observe.

The results were kind of ambiguous. The Pathology Department had seen nothing awry in the samples. The Urology Department pathologist (Dr. John McNeal, a world-class master of the art of reading and interpreting slides) had re-examined them and found that in one core from the left midsection, there was a 1 mm square region that seemed as if the cells might be cancerous. I was to come back for some additional sampling in that region.

As soon as he said that, I stopped being able to hear. I was stunned by the news and furious at our mistreatment. He must have talked for a while longer, but I did not remember what he said. I made an appointment for the next week, when 4 more cores were taken from the left-midsection. The results came via a phone call on 27 July: one of these also had a 1 mm square group of cancer cells. The Gleason score was 3+3, a value found in about 2/3 of new diagnoses, meaning a not very aggressive cancer. I had time to think and learn and make some decisions.
 

What Did I Do?

After the initial shock wore off a bit, and I gave myself a week or so to assimilate the bad news, I decided that I had to educate myself about the disease and about my options. My understanding, from a conversation with the Stanford urologist who delivered the news, was that my cancer was still rather small and not very aggressive. This gave me some time to learn, some time to collect my thoughts, some time to explore and find the best practitioners in the Bay Area.

My experience, explorations and evolving program of treatment will be discussed in greater detail in subsequent sections, but the major components should be mentioned here:

• Self-education
• Augmenting the vitamins/nutrients and herbs I was already taking
• Modifying my diet
• Exercise
• Finding a physician I could work with
• Seeing alternative practitioners
• Getting two "secret weapons"
• Deciding that the medical approach that made the most sense to me was a radical prostatectomy, to be done by the physician I had found
• Deciding that aggressive monitoring of the state of my disease was important
• Deciding that if I could avoid surgery or any other medical treatments forever or for as long as I could, that would be even better.

Education

Books

• Prostate Cancer - What Every Man - and His Family - Needs To Know, David D. Bostwick, MD, Gregory T. MacLennan, MD and Thayne Larson, MD, American Cancer Society, Villard (New York), 2nd edition (1999) ISBN 0-375-75319-2
• The Prostate Sourcebook, Steven Morgenstern, MD and Allen Abrahams, PhD, Lowell House (Los Angeles), 3rd edition (1998) ISBN 1-56565-871-X
• The Prostate, A Guide For Men and the Women Who Love Them, Patrick C. Walsh, MD and Janet Farrar Worthington, Warner Books (New York), (1997) ISBN 0-446-60432-1
• Man to Man - Surviving Prostate Cancer, Michael Korda, Vintage Books (New York), (1997) ISBN 0-679-78123-4
• Prostate and Cancer - A Family Guide to Diagnosis, Treatment & Survival, Sheldon Marks, MD, Fisher Books (Tucson, Arizona) 3rd Revision (1997) ISBN 1-55561-078-1
• The ABCs of Prostate Cancer, Joseph E. Oesterling, MD and Mark A. Moyad, MPH, Madison Books (New York), (1997) ISBN 1-56833-085-5 (hardback), ISBN 1-56883-097-9 (paperback)
• A variety of pamphlets from the National Cancer Institute of the national Institutes of Health (call 1-800-4CANCER). Also see their web site, http://www.cancer.gov

Web

Early on in the process I came across Andy Grove's 1996 Fortune Magazine article on his experience with prostate cancer. And, for a while, his choices (high dose seed implants and removal followed by external beam conformal X-radiation) made a lot of sense to me. His is a very well written and important story.
 

MDs

I consulted at first with the Stanford urologist. I knew I did not want him to be my primary physician in treating my cancer, but he could recommend people. Naturally, the several top US institutions came up:

• Memorial Sloan-Kettering Cancer Center in New York City. (See http://www.mskcc.org/mskcc/html/44.cfm)
• Johns Hopkins near Baltimore, where Patrick Walsh, the inventor of the nerve-sparing radical prostatectomy, practices. (See http://urology.jhu.edu/)
• The Swedish Medical Center in Seattle which specializes in radioactive seed implants (brachytherapy), pioneered there by John Blasko and his colleagues. (See http://www.swedish.org/)
• Stanford University Medical Center for external beam conformal X-radiation. (See http://med.stanford.edu/)
• University of Texas M. D. Anderson Cancer Center in Houston. (See http://www.mdanderson.org/)
• Loma Linda University, in southern California, where proton beams have been used for external beam radiation for the last 5 years or so. (See http://www.protons.com/index.html)
• Harbor-UCLA Medical Center (See http://www.humc.edu/)

My wife has a cousin who was a urologist in Southern California. We spoke with her a few times. She was supportive but rather traditional in her approach: being a surgeon, she believed surgery to be the most appropriate thing for me to do. But she was still supportive of my desire to try to avoid both surgery and radiation, if possible. Unfortunately, she was not familiar with Bay Area practitioners.

I called an old college friend who is now a Professor in the Medical School at the University of Virginia. When we had spoken about his research a year or two previous, it seemed as if he were onto something that could be very clinically useful in addressing all kinds of ailments, including cancer. Unfortunately, it still seemed 5 to 10 years out. However, he had a former colleague, an MD/PhD who did post doctoral research with him, who was now a urologist at the University of Chicago. And he was involved with surgery as well as other research. He had been trained at UCLA and did a residency in urology at Stanford, so he was familiar with the players in the Bay Area. And he was open to the possibilities of alternative treatments.

So I called Professor Mitchell Sokoloff in Chicago and he was gracious enough to spend a lot of time on the phone with me, and then kept up an email correspondence. He also recommended Professor Peter Carroll, chairman of the urology deparment at UCSF as a world class surgeon and good person. I felt good getting an independent, knowledgeable person with no axe to grind or self-interest to promote as a foil to my ideas and discoveries.

I spoke with Steven Hancock, MD, at the Stanford Radiological Oncology facility. We spoke of the different forms of radiation, of what they did there, and of survival rates, long term and short term, as well as the side effects of the treatment. When he finally showed up, an hour and a half late for our appointment, he was willing to spend as much time with us as we needed as well as to provide reprints of research he had been involved with on long-term survival rates.

I spoke with Dr. Gill, the Stanford urology surgeon who inherited Dr. Freiha's mantle as the most skillful surgeon there. But he was a rather closed individual, unwilling to even look at some research we had brought for his consideration. He may have been a skilled mechanic, but I wanted to be treated as a person rather than as a slab of meat.

I spoke with Professor Peter Carroll at UCSF, first a long telephone conversation and then in person. He is not only an expert on the nerve sparing forms of radical prostatecomy, but is involved in various kinds of research on prostate cancer, including some studies with colleagues on dietary approaches, including Dr. Dean Ornish's program at the  Preventive Medicine Research Institute in Sausalito, Calif. He was very open to following along with my program, although he also felt that, at best, I'd only be postponing the inevitable. My wife and I felt that we could work with him as a partner, whether I opted for surgery in the end, or if I could avoid it forever.
 

Talking

Radical Prostatectomy

Side effects of incontinence and impotence, however, are significant, even with the best of nerve sparing surgeries and surgeons. (A recent study [Siegel, et al., Journal of Urology, vol 165, no 2, pp 430-435 (Feb 2001)] found that "Erectile dysfunction develops in greater than 80% of the patients treated for prostate cancer" whether by surgery or external beam radiation.)

Radiation therapies (seed implants of various types, external beam Xrays or proton beams) as well as cryotherapies are less invasive, but also lead to similar complications and side effects. They come on a bit more gradually, but in the end roughly 30-50% of men who have undergone either approach are impotent (depending on whose statistics you read) and 10% have some form of incontinence, whether mild and annoying or severe and limiting.

The downside of radiation is the long-term survival statistics relative to surgery. Both are comparable out to about 10 years for "best practice". (Reference) After that, folks who have had radiation do not, on the average, survive as long or have as a high a percentage who remain prostate cancer free. This may not be as great a consideration to, say, an 80 year old with heart problems, but to me, with my intent to live another 40 or more years, it is an important consideration.

Another consideration is that surgeons do not like to operate on someone who has had radiation, if their prostate cancer recurs. This is because the radiation has toughened the tissue of and surrounding the prostate, which makes the surgery a little more difficult. Such "salvage surgery", however, is done by some surgeons.

In the end, physical removal of the organ and the cancer seemed like it would be more effective than trying to kill the cancer cells via some other modality. With improved surgical and post-operative techniques, I had hoped that the negative consequences of the procedure could be minimized, if not eliminated. And having found Dr. Peter Carroll gave me some assurances that I had found a master craftsman with a lot of experience and who I could work with, if or when I chose that route.
 

Aggressive Monitoring/Active Surveillance

The answer is, figure out what techniques and technologies allow one to "see" what is happening with the cancer and sample often enough to follow its course and fluctuations. And do so with a greater frequency than the physicians might recommend. Again, you must be your own best advocate.
 

PSA

Another consideration with PSA is that herbs such as saw palmetto, one of the things I started taking, tend to lower the levels. This is probably a good thing. But is it just masking the cancer or is it really fighting it? I haven't heard any answers to that question.

So, this is one easy step in following how things are going. By and large, since I started my program and PSA monitoring, it has been 2.0 ng/ml +/- 10%, the fluctuation range I was told to expect and within the "normal" reading I had pre-cancer.

It should be noted that as a man ages, his prostate gland starts growing. So a larger normal gland, puuting out a roughly constant amount of PSA protein per unit volume, will, over the years result in higher PSA values overall. That is why the "normal" ranges are larger as men get older. The rise in my PSA with the years, especially after mid-2008 (9 years after diagnosis), is consistent with this and not alarming.
 

DRE

TRUS

MRI Spectroscopy

The spectroscopic part is done simultaneously. Here the returned radiofrequency radiation is analyzed and the energy in various frequency bands calculated. There are particular regions indicative of the amount of activity in the citrate cycle (one path of cellular energy utilization), of choline metabolism, creatine levels, and of some other distinct cellular metabolic processes. Combined, these are very sensitive to the nature of the cells in the voxel (volume element) being sampled. The sampling can distinguish among

• normal prostate cells
• malignant prostate cells
• cells involved in BPH
• prostatitis
• populations of necrotic (dead or dying) cells (say, as a result of previous radiation treatments or brachytherapy)

With the 3 Tesla machine, under development since 2003 (and still in test as of Aug 2004), the spatial and volumetric resolution is much better: voxels are now 0.16 cc, translating to a cube with sides roughly 5.5 mm.
 

September 1999 Imaging

April 2000 Imaging

November 2000 Imaging

And, there is no sign of any disease outside the prostate nor at the capsule (the boundary of the gland).
 

April 2001 Imaging

There was one voxel of borderline cancer metabolism. In previous images, there were several voxels of borderline metabolism, all within the right mid gland. "The spectroscopic abnormalities are much less evident on the present study." And later, "The spectroscopic findings are much less apparent on the present scan, suggestive of positive treatment response."

And again, there was no sign of any disease outside the prostate nor at the capsule (the boundary of the gland). All good news, indeed.
 

January 2002 Imaging

This imaging showed a number of voxels in the right midgland with abnormality, changes in all 3 markers (decreased citrate, elevated choline, ...[?] polyamines). Prostate volume was 33 cc (smaller than previous images). The radiologist's report states "The focus at the right base is more apparent as compared with the prior examination....MR spectroscopy demonstrates interval development of a small focus of tumor metabolism at the right base."

Further discussions, informed by my experience with asymptomatic prostatitis in May 2001, led to my being told that an acute infection could lead to these signals. [Most men with prostatitis have chronic infections, which present differently in the MRIS. The primary researcher said he had seen acute prostatitis only 2 or 3 times out of the several thousand images he had looked over in his career. However, he declined the opportunity to reimage me immediately after my course of antibiotics, foregoing the possibility of developing a before and after to allow better discrimination between acute prostatitis and cancer.] In order to rule that out, or to deal with it, I started on a 2 week course of Cipro, a powerful antibiotic, on 23 January 2002, followed by a second 2-week course. As one can see from the graph and table in the beginning of this paper, my PSA came down to around 2.4 after 3 weeks, stayed there for a couple of months, and then returned to my "normal" levels of about 2.0 ng/ml. I conclude from this that the anomolous readings in this set were another episode of asymptomatic prostatitis.
 

July & September 2002 Imaging

There was no evidence of any metabolic abnormality in the Spectroscopic analysis. That is, no evidence of any cancer. The radiologist concluded that all abnormalities seen in the previous image of 9 Jan 2002 were due to prostatitis rather than cancer, and that all had resolved themselves in the interval. The gland measured 36 cc; using the Stanford PSA of 2.16 ng/ml, my PSA density was 0.060 ng/ml/cc.

My previous images will hopefully be of some help in allowing the research team t come up with a scheme for differentiating prostatitis from cancer. Since they have few unambiguous images of acute infection, all the data they can get will help.

This finding does not necessarily mean all my cancer is eradicated. Rather, it has regressed to the point that this imaging technique is unable to see it amidst the surrounding healthy tissue. As a consequence, I do not plan of changing my regimen.

On 9 September 2002 I had a color doppler TRUS by Dr. Katsuto Shinohara at UCSF. Absolutely no abnormalities or suspect areas were seen. Dr. Shinohara said that "power doppler ultrasounds" that I had heard of were exactly the same as what he was using. It was a relief to have both imaging modalities confirm that any remnant cancer is too small and inactive to be picked up by these techniques. Prostate size was estimated to be about 40 cc; using the previous PSA of 2.08 ng/ml, my PSA density was 0.052 ng/ml/cc. He also noted "about 14 cc of transient hypoplasia", something I need to have clarified.
 

June 2003 Imaging

The MRI images both showed no abnormalities. In the right midgland region, the images were a little darker than normal, but nothing notable. (Recall that previous imaging and the biopsies indicated cancer metabolism in the left midgland, where there is now no evidence of cancer.) The gland volume was estimated to be 38.0 cc; using the PSA value of 2.18 ng/ml, the PSA density was 0.057 ng/ml/cc.

Spectroscopically, in both images, in the right base to midgland, there was an alteration in the expected normal metabolism. Here, however, there was no elevation of the choline signal, there was a loss of some SNR [signal to noise ratio], and there was a loss of citrate levels. These are less a sign of cancer than a possible signal of chronic prostatitis, especially considering how these signatures come and go from image to image over the years.

I had another power doppler TRUS on 04 August 2003 with Dr. Shinohara at UCSF for an independent corroboration of the MRSI results. Again, no signs of cancer were apparent. The gland had grown some (see table below), but showed no signs of malignancy. The left midgland showed a persistant hypervascularity (increase above normal of amount of blood vessels). This is the same area that the June 2003 MRSIs showed signs of lingering possible prostatitis. Recall that the positive biopsies were originally in the right midgland, far from this region.

On 07 June 2004, I had my next power doppler TRUS with Dr. Shinohara at UCSF. The prostate volume was about 48 cc; the year before it was about 46 cc by TRUS. This was essentially the same size. Dr. Shinohara stated that the MRSI underestimates the size by about 20% relative to the TRUS. [The corresponding MRSI volume would thus be about 37 cc.]

He also saw a small protrusion of the prostate into the bladder on one side, indicative of mild BPH. There were a couple of small areas of hypervascularization [that is, increased blood flow], one on each side, but he did not feel that they were large enough or strong enough to be of concern. And he mildly suggested another biopsy, which I resisted and we discussed.
 

August 2004 Imaging

The 3 Tesla images provided a much higher spatial resolution than the 1.5 T images, and both sets were in concordance. The news again was good - no signs of cancer, no changes from the previous imaging, to the limits of the technique's resolution. Recall that my biopsy found some small amounts of cancer in the right midgland in July 1999. None of that has appeared in the images for quite some time, so is not growing, if still present at all.

Again, the radiologist noted "a small focus of decreased T2 signal within the right midgland with equivalent signal on MR spectroscopy." In this region of the gland there is a mix of stromal cells and glandular cells. The glandular cells create the prostatic fluid which flows down the local ducts, eventually accumulating in the seminal vesicles and the ejaculate. This fluid has lots of free water. The T2 imaging measures the morphology or anatomy by looking at water. Lots of free water implies a very long T2 relaxation time.

In prostate cancer, the glandular cells are the ones that become malignant, in general, and the ducts get filled with cancerous growth. This leads to less water being present and a darkening in the T2 weighted image. However, other things can cause this as well, and so spectroscopy is used to try to differentiate what is going on. In my case, this same area has "equivocal metabolism", the same as in previous images, though different from when I was imaged during a bout of prostatitis. So there is no obvious cancer signal and no changes over several years, all good news. Only a biopsy of that region could serve to differentiate histologically what is really going on there, but for me there is currently no incentive to do so -- the potential gain of knowledge would not inform any decision to do anything. If any cancer is still invisible to MRSI and TRUS and my PSA levels are relatively static, I should just keep on doing what I'm doing.
 

March 2006 Imaging

I received a CD-ROM of the non-spectroscopic images, along with WindowsXP software for looking at them, when I left the imaging session, and a more complete CD-ROM with all my images from all MRSIs by mail a week or so later. The CD-ROM now includes a Windows-based image viewing program, with an on disk manual for how to use the software. Still, interpreting the images is another issue altogether, and guidance should be provided there, too. The CD-ROM should also include the spectroscopic images, which take additional processing, but are now also available to the subject.

The radiologist report took about a week to be drafted. It contained very little information -- seemingly, less and less each time -- but the bottom line is that there have been essentially no changes since my previous images, in fact, almost no changes for several years. This is good, as there are also no signs of cancer. On the side opposite where my biopsy found a little cancer, there are some changes again, likely due to inflammation. ("A small band-like area of decreased T2 signal is seen in the left mid gland, which extends towards the apex. This may represent prostatitis.")

The rise in my PSA (at Stanford) to 3.27 ng/ml on the day of the exam is of concern. It may be the beginnings of another round of asymptomatic prostatitis. I doubt that it is an artifact of a URI (upper respiratory infection, a cold) I was just getting over at the time.
 

March 2007 Imaging

The results were the best yet. Essentially, there were still no signs of cancer, a small region of ambiguous signal previously seen in my images was even smaller and more difficult to discern. There were no detectable metabolic abnormalities.

February 2008 Imaging

The written radiology report also noted that the "[p]reviously described focal area of low T2 signal within the right midgland is no longer seen in the current study... MR spectroscopy demonstrates no definite abnormality.... No definite MR or MRS evidence of tumor."

The biopsy I had in 1999 found tumor in the left midgland, which never showed up in the MRSI imaging I have had. However, there have been low level ambiguous signals in the right midgland in all images up until the February 2008 imaging. I take this to indicate some improvement in an undefined irregularity there.

After the imaging, I also was interviewed by a Product Manager from MedRad, a company that makes the transrectal probe used in the MRSI procedure. The videotape is to be used in educational videos on the process and technology from a patient's point of view.

March 2009 Imaging

Again, the radiologist's report stated: "MR imaging and MR spectroscopy demonstrate no convincing evidence of tumor. There is no extracapsular extension or seminal vesicle invasion. No lymphadenopathy is seen in the pelvis.... No suspicious osseous lesions identified."

March 2010 Imaging

Again, the radiologist's report stated: "...no clear cut tumor metabolism is observed. No extracapsular extension, no seminal vesicle invasion, no lymphadenopathy, no suspicious bone lesions.... Compared to the study from 03/2009, no significant change. No tumor focus in either MR or MR spectroscopy."

March 2011 Imaging

Signs of BPH were clear, both spectroscopically and morphologically (the shapes of elements in the regular imaging). Again, there was the "equivocal metabolism" in the right base to mid-gland. This is not a sign of cancer, but not normal cells either. For the most part, it has been present in my images from the beginning, growing and shrinking. It is likely a sign of an underlying inflammation or infection that never quite goes away. There were no significant changes from the last year's MRSI, which is a consistent motif in the radiologist reports over the years.

April 2012 Imaging

Again, "extensive changes related to benign prostatic hypertrophy with associated nodules" were noted. These nodules were "unchanged compared to prior exams, and [do] not demonstrate any other diffusion or spectroscopic abnormality." And, "No change compared to prior exams."

March 2013 Imaging

On 20 March 2013 I had my eighteenth MRSI using the 3 Tesla machine at the UCSF China Basin facility. This time, a gadolinium contrast agent was used for the final set of images, after the spectroscopy.

Again, there were no signs of cancer (or prostatitis), but the radiologist noted "extensive changes related to benign prosthetic hypertrophy [BPH], with associated nodules." As can be seen from the table below, my gland continues to grow.

April 2014 Imaging

On 21 April 2014 I had my nineteenth MRSI using the 3 Tesla machine at the UCSF China Basin facility. This time, a gadolinium contrast agent was used for the final set of images, after the spectroscopy.

The radiology reported noted that my gland continued to grow and that "the central gland (transitional zone) [signal intensity] is related to benign prostatic hyperplasia" or BPH. In addition, there was no evidence of extension beyond the prostate gland , seminal vesical, lymph node or bone involvement.

While there is "no clear abnormal spectroscopy" in the right apex region, a "decreased T2 signal" may be "suspicious for focus of prostate cancer". Again, an ambiguous signal, which may also be an artifact of the prostatitis I had from September to Decemeber of 2013.

In the subsequent imaging, April 2015, this signal from the right apex was absent, an indication that this was inflammation and not cancer.

April 2015 Imaging

On 23 April 2015 I had my twentieth MRSI using the 3 Tesla machine at UCSF's new Bakar Cancer Center in Mission Bay, San Francisco. Gadolinium contrast was again used for the final images in the sequence.

The radiology report discussed a 13 mm focal lesion in the left posterolateral peripheral zone and the midgland/apex, which had not been seen in previous images. On review of the 2014 images, a tiny amount of signal was seen in the diffusion images in this region, but it was unremarkable at the time (i.e., not significant enough to make remarks about). Four of the seven parameters that current imaging technology provides are consistent with cancer -- or inflammation. It is still difficult to differentiate prostatitis from cancer on the images. If cancer, the imaging is consistent with Gleason 3, a slow growing cancer. It was suggested that I continue active surveillance and wait another year for my next imaging.

The change in prostate volume, from 56 cc in 2014 to 75 cc in 2015 is also suspicious. The folks in radiology reexamined the images to derive better volume estimates for both years, which impact the PSA density calculations. Given the current numbers (PSA 8.1 in Feb 2015, volume of 75 cc), my PSA density is 0.108, well within the "safe" range of <0.15.

Note: because the jump in volume as measured by the radiologist from year to year was unreasonably large (56 cc to 75 cc), I asked the researchers to recalculate the 2014 and 2015 volumes more accurately. The 2014 volume was changed to 56.3 cc. The 2015 volume was changed to 60.72 cc. This leads to a PSA density in 2015 of 8.1/60.72 = 0.133.

June 2016 Imaging

On 03 June 2016 I had my twenty-first MRSI using the 3 Tesla machine at UCSF's new Bakar Cancer Center in Mission Bay, San Francisco. Gadolinium contrast was again used for the final images in the sequence.

The radiologist's report noted that the central gland is consistent with benign prostatic hyperplasia (BPH). It also noted again a lesion in the left anterior peripheral zone (1.1 cm x 0.57 cm x 0.8 cm) with a well defined focus of low signal intensity on T2-weighted imaging, marked restricted diffusion and suspicious enhancement (DCE positive). However, on spectroscopy, no suspicious metabolism is seen in the lesion.

On consultation with the researchers, the suspicious area from 2 years ago had vanished (the left peripheral zone), and the new one (left apex peripheral zone) appears with 4 weak signals, but no spectroscopic signal. This can be prostatitis and seems not something to worry about since PSA is steady and PSA density remains steady and within the safe range as well.

The radiology report stated the gland volume was 78.1 cc; on request for a remeasure from the images, a radiologist came up with 82.4 cc and a researcher who had recalculated my PSA volume in the past came up with 73.9 cc. All of these, of course, are estimates.

The next imaging, probably to be done around June 2017, should again be easy to compare with the current images and a progress/regress of the cancer should be discernible.
 

UCSF Protocol

• PSA every 3 months
• free PSA every 6 months
• TRUS every year (power doppler color TRUS)
• MRSI every year
• biopsy every two years

The important point in this is not to remain passive and ignorant, but to keep track of how well life style and other changes are keeping the cancer in check, to buy time for better medical approaches to emerge, and to avoid, as long as possible, the side effects of any medical treatments, noting that many prostate cancers are overtreated and may likely remain indolent for the rest of your life.
 

The Theory

The basic idea is that cells are constantly undergoing division in the body. Statistically, it is likely that some small fraction of these divisions are incorrect, producing malignant cells. This can be due to a variety of factors, including

• random events
• radiation damage (just due to natural background radiation)
• exposure to toxic chemicals (which are more and more around us, in our food, air, water, and environment in general)
• age-related cellular issues
• inflammation
• etc.

In general, the immune system is capable of finding and killing all these cells since cancer is a rather rare disease compared to all the cell divisions that occur in a body over its lifetime. What I was seeking to do was augment and increase the functioning of my cellular immune system, since my malignant load was higher than the "normal" background and additional help was needed. But, if I could succeed at that, I could, at best, eradicate the cancer; at the middle, keep it at bay and treat it like a chronic, non-life threatening disease; and at worst, buy some time for medical techniques and options to improve, as they have been rapidly over the past few years.

Vitamins and Herbs

As a background, this is what I had been taking for years:

• 6 gm vitamin C per day (3 in am, 3 in pm)
• 400 units vitamin E per day (am)
• 16000 units vitamin A per day (am)
• 120 mg gingko biloba per day (60 mg in am, 60 mg in pm)
• "B-100" pill (am)
• Calcium-Magnesium-Zinc tablet (am)
• aspirin (1 in am)

Vitamin C is one vitamin that you cannot overdose on. Any extra amount that your body cannot use is excreted, so it is useful to spread out the dosages over the day. It should also be noted that if you increase the amount you take too rapidly, a possible side effect is diarrhea, so a gradual increase is to be recommended, allowing one's body to adjust.

The vitamin A was suggested to me some years back by my dermatologist to clear up a minor skin problem. It also has good anti-oxidant effects. However, one can overdose on A, and so should be careful about the doses taken.

Gingko is noted as helping increase blood flow. This is why it is often referred to as a memory enhancer (blood flow in the brain). But any improvement in circulation should also help the body function more appropriately.

The "B-100" is a multi-B-vitamin pill with the following ingredients:
 

The Ca/Mg/Zi tablet was for general health. I don't remember when or why I started taking it. I had been taking one aspirin per day as a general prophyllactic for heart and circulatory problems; it is well-known that such a regimen decreases one's risk for heart attacks (combined, of course, with not smoking, eating properly and getting sufficient exercise) as well as colon cancer [studies that came out in 2002].
 

This is what I added to my regimen in the first month or so:

• grape seed extract (proanthocyanodin) - 50 mg am & pm
• CoEnzyme Q10 - 50 mg am & pm
• Selenium - 100 mcg am & pm
• generic prostate health pill (see below)
• lycopenes

The Selenium amd the lycopenes were recommended by Dr. Carroll at UCSF. Lycopenes are a chemical found in cooked tomatoes (as well as some other foods, including strawberries and watermelon) that are thought to be especially helpful in fighting prostate cancer. I get most of mine in one 8 ounce glass per day of a V-8-like juice (Knudsen's Very Veggie is an organic product, Trader Joe's has Garden Patch, and there is always V-8 itself and lots of other variations. I don't know the lycopene content of these, since only Knudsen publishes it on their label.) [Research published in the May 2006 Journal of Nutrition (Vol. 136, pp. 1287-1293) indicates that lycopene is most effective when taken along with viitamin E. (See http://www.biospace.com/news_story.aspx?StoryID=15426.)]

Selenium is noted as helping the anti-oxidant activity of vitamin E and should be taken with it. To quote the Life Extension Foundation,

"As an essential cofactor of glutathione peroxidase, selenium is an important antioxidant. It is also involved with iodine metabolism, pancreatic function, DNA repair, immunity and the detoxification of heavy metals. Studies have shown that selenium can help prevent some cancers and cataracts."

The generic prostate health pill was suggested by my daughter, who is an advocate of alternative medicine. These are its ingredients
 

In March 2001, I added the following items to my regimen:

• Green tea extract (1 capsule = 250 mg ~= 4 cups green tea), one in am and one at night
• NAC (N-acetylcysteine, 600 mg), one in am and one at night

In March 2002 I added this to my regimen:

• Alpha-lipoic acid (one 100 mg capsule in am and one in pm), another potent anti-oxidant.
• Soy isoflavones (one 50 mg capsule in am and one in pm)

In November 2009, I increased my dose of Vitamin D to 2000 IU, twice a day, based on discussions with an MD. My recent blood levels of D3 were 44 ng/ml (Oct 2009), whereas suggested values are in the range 50-65 ng/ml (and many lab tests actually overestimate the blood levels, so perhaps a value of 80 ng/ml may be a reasonble goal).

On 10 March 2007 I started using Peenuts, 2 pills daily, as part of a study at UCSF to investigate whether this herbal supplement can help alleviate prostatitis and its consequent underlying chronic (if asymptomatic) inflammation. Peenuts contains the following ingredients per capsule:
 

Peenuts was created by a Florida Urologist, Dr. Ronald Wheeler (see http://www.peenuts.com/), who claims significant success in reducing prostatic fluid inflammation in men taking this pill. He has at least one peer reviewed paper on these studies and is collaborating with UCSF on another study, where MRSI of both men and their expressed prostatic secretions (EPS) will be used as measuring modalities. That is, microscopic evaluations of the EPS as well as MRSI imaging and analysis of the EPS as well as the men it came from will look for indications of inflammation over time. (See the discussions below for my history of recurrent prostatitis and for current theories of how chronic inflammation may give rise to cancer.)
 

These are the things I stopped taking in September 1999:

• aspirin
• Ca/Mg/Zi pill

Dr. Carroll noted that some cancers feed on Calcium and suggested I stop taking it as a supplement. I haven't changed the amount I do (or do not) get from my food, however. (See http://www.docguide.com/news/content.nsf/news/391BD0B73B4A876C85256ACE00516B45? OpenDocument&id=7ED78FC79E323C75852569CB00019463&c=Prostate%20Cancer&count=10
- "High Calcium Intake May Increase Risk Of Prostate Cancer", for example, which is no longer available as of June 2009.)
 

PollenAid
In late November 2009 I started taking PollenAid (1 capsule in the morning, 1 at night -- although the recommended dose is 3/day) on the suggestion of a urologist. He referred to peer reviewed studies (which I have yet to receive copies of) indicating this may be useful in dealing with my underlying prostatitis. See the references below.
 

statins
In the autumn of 2000, I also started taking Zocor (simvastatin), 10 mg per day, since I had mildly elevated cholesterol (starting about 230). http://www.merck.com/product/usa/pi_circulars/z/zocor.html

In June 2002, my MD switched me to Lipitor (ataorvastatin calcium) http://www.lipitor.com, since my liver enzyme tests had begun to creep up the to high normal boundary. Changing statins is a way to control these, frequently.

I stopped Lipitor after about 9 months, resumed 10 mg of Lipitor in December 2004, and stopped again in February 2005. Blood tests showed good lipid control with the 2 months on Lipitor, and rising levels in the following 2 months off (early April 2005). In mid-April I began taking Niacin (750 mg each evening, increased to 1000 mg per evening after 2 months, and then to 1500 mg each evening 8 months later [Feb 2006]; to 2000 mg each evening as of Feb 2007) to see if that would correct my lipid levels, which it has, for the most part.

These statin drugs, aside from affecting cholesterol and lipid and trigyceride levels, also seem to have some anti-cancer properties. I don't have references available, and I have been on low doses.
 

Naturopath
In October 1999, I saw a Naturopath near Vancouver, British Columbia. I'll discuss him below, in the section on Alternative Practitioners. He also gave me a bunch of stuff to take that I added to my regimen after my PSA test of 27 Oct 1999.
 

Diet and Exercise

My diet has gone through a couple of modifications. At first, the general tendency was to more vegetables and fruit and tofu and less meat. My lunches consist of a smoothie and some salad and sometimes a small amount of leftovers from the previous night's dinner. I cut back my coffee to one cup per day (from 2).

In December 1999, my wife saw Dr. Diana Schwarzbein, a Santa Barbara endocrinologist, for help with her diabetes. Dr. Schwarzbein has a dietary approach to dealing with diabetes that seems applicable to health in general. It is well described in her book, The Schwarzbein Principle. So for our meals at home, we began following this program, where I would eat more carbohydrates than my wife.

It was pretty consistent with our general approach although it involves eating more protein or meat than we were used to. The general principles are

• Stay away from "plastic" foods - anything artificial or processed (junk food, margarine, sodas, etc.) in order to decrease the toxic load on your system
• Eat as much organic and natural food as possible
• Eat food that is in season and fresh and grown locally ("Anything that you could pick, grow, hunt, fish for yourself.")
• Balance what you eat at every meal in terms of proteins, natural oils, vegetables, carbohydrates
• Use only "good" oils, like olive oil and butter and salmon oils in your food and cooking.
• Any carbohydrates consumed should be whole grain, not processed
• Avoid altogether alcohol, tobacco and caffeine as well as over-the-counter medications

By and large, we've always eaten pretty much this way except that we've increased the amount of organic food in our diet.

Alternative Practitioners

However, there are some things lost in its reductionist approach. One is the realization that the patient is a person rather than a bag of symptoms. Another is that the person comes from a complex web of history and social interactions and beliefs. And another is an appreciation of the ability of the body to heal itself given the stimulus and opportunity and help to do so. And another is a dismissal of things that do not fit into its mechanistic picture.

Acupuncture
So I sought to augment my care by seeing three kinds of alternative practitioners. The first is an acupuncturist. The one I chose was trained as an MD and came highly recommended. I see him in order to enhance the functioning of my immune system, to enable it to fight off the cancer. At first I saw him weekly, but after a couple of months, I am down to once a month. I continued with this practitioner until August 2004.

In February 2005 I started seeing a Japanese acupuncturist (a somewhat different style than Chinese acupuncture).

Chiropractic
The second practitioner I saw was a chiropractor. The idea here was that if I had any structural issues, subtle or otherwise, that prevented proper innervation of my organs, that would subtract from my systems' optimum performance and health, including that of my immune system. The chiropractor I initially chose was a friend who had recently graduated Chiropractic College and been licensed. His practice was just starting out so he had a lot of time to work with me and explore various possibilities. I saw him about once a week or so for about 3 months and then stopped when he felt there was nothing more he could do for me structurally.

In July 2000 I started being treated by a Network Chiropractic practice. This is a more subtle form of manipulation, more frequent than standard chiropractic practice, also designed to fully and properly align the spine and permit proper flow of nerve energy, hence better health and healing, including enhanced immune system functioning. In March 2001, the practice moved to another city, which was inconvenient to get to, and I decided to stop going there and focus instead on more active pursuits, such as resuming my yoga practice.

Naturopathy
This is a more interesting story. At the first Prostate Cancer Support Group meeting I went to in September 1999, I replaced another fellow as the youngest in the group. We got to chatting after the meeting and he mentioned that he had a friend in Vancouver who is successfully controlling his prostate cancer through dietary and holistic means.

I contacted the friend via email and then in a long phone conversation. He had also been trained as a physicist and worked as one for some years before drifting into the field of government science and development policies. He was associated with Simon Fraser University in Vancouver and also did work for the Canadian government as well as consulted with other governments on these issues. Obviously a person coming from the same Western analytical approach as I did, at least originally, not one to be easily bamboozled by various forms of mumbo-jumbo. He had decided upon his diagnosis three years earlier (1996) that he too wished to avoid surgery and radiation and their attendant side effects, so sought alternative approaches. Among other things, he increased the amount of organic and healthy food in his diet. And he found a local Naturopath as one of his practitioners, an older Dutch physician who originally trained and practiced as a neurologist for many years. Eventually, Pieter became a psychiatrist and later on retrained again as a naturopath and homeopath.

On this recommendation, we booked a business/pleasure trip to Vancouver, one of our favorite cities, for mid-October 1999. The doctor took some medical history, and then used an interesting device attached to his PC to measure balances and imbalances in my body. There are references in the Bibliography. The technique used is popular in Europe, unknown in the US, and is called ElectroAcupuncture according to Voll (or EAV), after its inventor, a German physician named Voll. He then gave me this list of things noted above. He also gave me an injection of dead and diluted prostate cancer cells to boost my immune response, a homeopathic approach.

We saw him again over Christmas 1999. He said I was better but not cured yet and did more of the same, keeping the medications almost the same.

As I ran out of his supplements during the month of April 2000, I stopped taking them. We had noted that my PSA had gone down for 2 months before I started the naturopathic treatments, and so determined that whatever good they might be doing, they were not crucial to my good health. It was also expensive and inconvenient to travel to Canada, even a few times a year (he would have preferred every 2 months). So the next part of the experiment has been to omit the naturopathic treatments and supplements. I always have the option of resuming them.

Secret Weapons

pau d'arco

My younger daughter spent the 1998-1999 academic year studying in Costa Rica, with an emphasis on alternative medicine techniques. Part of the time was spent doing an internship on a farm where medicinal plants are grown using organic, sustainable agriculture. And pau d'arco is one of the plants grown there. She brought some back to the U.S. and suggested I take it as a tea when I was diagnosed. Since then, we've bought a pound at a time directly from the source. It goes a long way. We've found the tea to be available in some health food stores in California and over the web, but we've also found that it is difficult to vouch for the quality of what you're getting. Since  pau d'arco comes from the inner, living, bark (the phloem) of the tree, often it is adulterated with other barks.

The mixture I get is mixed with some ginger and tumeric, spices also noted for their medicinal qualities as well as interesting tastes. I bring a quart of water with 1 teaspoon of the mix to a boil, them simmer 10 minutes and strain. The suggested dosage is 2 to 3 cups a day, although I seem to average one to two a day.

One can also buy the tea without the ginger and tumeric or use it to make an infusion. I don't mind the taste as it is and haven't experimented with it.

In October 2001 I sent in another order for pau d'arco to my source in Costa Rica. Six weeks later, my letter was returned for having an insufficient address, though it used the same address I had been successful with several times before. Email did not bounce nor did it receive a reply. And a fax also went through, again with no reply. I had no direct phone number to call. As I was running low, I decreased the amount I was drinking to a few cups a week, and gradually stopped taking pau d'arco as the year ended, with no apparent effect on PSA. I can only conclude that this tea is not crucial in my program. It may well have helped, but was not the "Secret Weapon" I originally hoped it might be. In early 2002, my Costa Rican contact resumed communications (new email address, more complete postal address) and I am again able to get an ongoing supply.

I stopped taking pau d'arco in July of 2003. I noticed no change in my condition or numbers without that tea and have come to believe that it was not an essential element of my regimen.
 

Mother's Milk

In brief, about 1994 Anders Håkansson, then a graduate student in Catharina Svanborg's laboratory at Lund University, found by accident that adding human mother's milk to a cell culture of cancer cells caused them to all die. This was true for a wide variety of human cancer cell types. On the other hand, normal cells were unaffected.

So they injected human tumors into rats. When the tumors started growing, they started treating the tumors with mother's milk. In most cases the tumors shrank or died. What seems to be happening is that there is some combination of factors in the milk that causes "programmed cell death" or apoptosis in cancer cells and not in non-malignant cells.

Why would this work? One speculation is that the time of most rapid post-natal cell growth is the months and year just after birth, when the normal infant should be nursing. Since rapid cell growth is fraught with the dangers of bad replication and malignant transformations, a natural mechanism that would kill such new cancer cells is a reasonable thing to have developed evolutionarily. In fact, it should be common in all mammals, one might conjecture.

In fact, it is well known that nursed infants have 1/9 the probability of contracting any kind of childhood cancer as infants who are not nursed, as well as having fewer allergies, less asthma, and fewer childhood diseases.

The Swedes then turned the focus of their research into understanding the cellular and molecular basis of these observations, doing some good science in the process. It seems as if the major factor is something called MAL, multimeric Alpha-Lactalbumin, along with some potentiating factors. They found that pastuerization destroys the multimeric character of this compound and also its cancer-killing abilities. Their focus, however, is to isolate and patent the factors, then to license them to drug companies and live well on the royalties.

My reasoning was quite the opposite. If the potent parts of mother's milk can get into the infant's body via his/her gut, it is very likely that the same is true for an adult who ingests it as well. True, with a much larger body weight and size than an infant, there would be a greater dilution, but any apoptosis than can be induced over as long a period of time as the milk is available would help keep the cancer under control or even, in the best of worlds, eliminate it.

I contacted Dr. Håkansson by email and received copies of three of their research papers (in English).

Shortly after we found the New York Times article, we reconnected with a colleague I had worked with some years previous. His wife was nursing an 8 month old and she herself was a cancer survivor. She agreed to pump her breasts for me. So from late August 1999 for almost a year, I had a supply of mother's milk, which ended when my donor weaned her child. I am endeavoring to continue having a supply from healthy, health-conscious women.

Almost every day (depending on the supply), I took about 2 ounces of mother's milk mixed into a smoothie (orange juice, yogurt, tofu, various fresh and frozen fruits) as part of my lunch. It is a simple, healthy, and palatable way to take this part of my regimen.

I believe that these two items, but mostly the mother's milk, have made the difference for me in keeping my cancer under control and my PSA scores down in the mid-normal range. Everything else has helped, to a greater or lesser degree, but these "secret weapons" have been the crux of it all.

While pau d'arco is mildly difficult to get, it is available. Mother's milk, on the other hand, requires some luck or connections. It is a hypothesis I made that the same positive anti-cancer effects can also be obtained from certain kinds of raw mammal milk, perhaps goat or cow, perhaps some more closely related species. The key word here is "raw", since pastuerization (heat) destroys the effect, and raw milk might come with its own health concerns. It would be interesting and quite useful if some academic, less motivated by greed, would pursue this line of inquiry.

In July 2000, my source of mother's milk told me she was planning on weaning her child, which was a perfectly reasonable thing to do. My wife found a possible source via a Milk Bank, but they needed a prescription from an MD to give me the milk, only because providing milk to adults was not a usual course of action. So, in mid-July I asked my urologist for one.

In the meantime, I had received the April 2000 PNAS paper from the Swedish researchers. In it, they had isolated the essential cofactor in human mother's milk that caused multimeric alpha-lactalbumin to undergo its shape changes into the form that kills cancer cells. This cofactor is oleic acid, which I then discovered was abundant in olive oil. While waiting for the prescription, I experimented using raw cow's milk from a health food store instead of the no longer available mother's milk, adding in about 1 cc or so of olive oil. I also increased the amount of cow's milk to 4 ounces a day, from the 1 to 2 ounces of milk that my donor had been pumping, on the average.

This did not work. After about 1 week of the new regimen, the PSA on 10 August was a consistent 2.2. About 4 weeks later, on 8 September, it had increased to 3.8! This is a doubling time of about 6 weeks.

Again, I requested a prescription from my urologist, but he wrote back

	"...I have no experience with prescribing mother's milk and do not 
	feel comfortable prescribing something I know little about...."

Within one week, my PSA had dropped to 2.5 ng/ml, and I was greatly relieved. Since nothing else had changed in my regimen, it became abundantly clear that the crucial factor in controlling my cancer was the milk. Everything else may help, but nothing else was sufficient unto itself to keep my PSA down and the cancer under control.

(According to their papers and personal communication, the oleic acid, in the warm, acid environment of the human gut, transforms the physical conformation (or shape of the molecule) of the multimeric alpha-lactalbumin molecules into another form they call HAMLET [for Human Alpha-lactalbumin Made LEthal to Tumors], which induces apoptosis in malignant cells.)

This experience leads to some additional questions:

• Was the amount of oleic acid I used too little?
• Are cow and primate alpha-lactalbumin different enough so that the bovine variant is not transformed into HAMLET?
• Are other necessary but so far unidentified cofactors present in primate milk but lacking in bovine milk?

The milk from the Milk Bank is pasteurized. According to Dr. Håkansson, the process they use, required by California state law, will degrade some, but not all, of the apoptotic activity of the milk. For that reason, I was using 7 ounces a day of the Milk Bank's pasteuerized mother's milk.
 
 

Strange PSA values in May 2001

I went back two days later, on 11 May 2001, to repeat the test. It came back as 14.0 ng/ml. Curiouser and curiouser. Is a drop of 5.6 ng/ml in two days reasonable? The numbers were frightening and did not make a lot of sense until I got the MRI report. As noted above, it showed (marginally) less cancer than in previous images, but also noted evidence of prostatitis, something which could account for these PSA values. My urologist suspected prostatitis as the cause of these readings and put me on antibiotics. After one week, the PSA went down to 4.0 ng/ml. We decided, after a week break, to do another week's worth of Cipro (500 mg), which brought the PSA back to 2.5 ng/ml, roughly where it had been before the infection. Apparently, prostatitis may be asymptomatic, though rarely. Reviewing the original biopsy report of July 1999, it stated that there was evidence for my having had prostatitis (apparently it permanently affects some noticeable characteristics of the prostate cells it infects) and I may well be harboring a latent infection which occasionally flares asymptomatically. There is some sense of relief, but also one of mystery.

By the way, the Milk Bank claimed no changes to its processing/pasteurization protocol.
 

Raw Milk Again

The Milk Bank routinely screens all donated samples for bacterial count. The biochemist had started sequestering samples with extremely low counts for me. The bacterial levels in these is equivalent (or almost) to those in pasteurized samples. Naturally, all donors are screened via blood tests, when they sign on, for an array of potentially transmissable diseases. So the milk, raw or processed, is likely quite clean. I have no need to fight off cancer to catch some other disease.

A week and a half later, a PSA test gave the value of 1.9 ng/ml, equivalent to my "normal" value of December 1997 and among the lowest values I have had, even though I halved the quantity of milk I was using (from 7 ounces/day of pasteurized to 3.5 ounces/day of raw milk). This is very encouraging.
 

Strange PSA values in January 2002

It is apparent to me that cancer and BPH do not behave this way, spiking and dropping, as my PSA did in May 2001 and again in January 2002. Certainly, Dr. Carroll also seemed unable to explain this behavior. And Dr. Kurhanewicz pointed out that the increased activity in the MRIS of 9 January 2002 might be attributable to an acute stage of prostatitis rather than increased cancer metabolism. He mentioned that he had only seen this twice in the 4000 or so images he has looked at over the years, since most prostatitis he sees is chronic, and so has less metabolic activity. This seems to be the explanation.
 

Strange PSA values in the winter and spring of 2005

About 10 days after I finished the Cipro, I had the symptoms of a prostatitis attack, including painful and frequent urination. Blood work showed a raging infection. So I started a 2 week course of Floxin, another antibiotic in the same family as Cipro. It took a few days for the symptoms to abate, but they did around mid-February.

On 28 March 2005, I went for another PSA and my first free PSA measurement. The result is expressed as a ratio of free (or unbound PSA) to total PSA (that is, to bound plus unbound PSA). Values below 10% are indicative of cancer (>40% probability of active PCa); values above 25% are indicative of no active cancer (<10% probability), for PSA values in the range of 4-10 ng/mL. Mine was 15%, in the ambiguous range. [A conversation with Nanette Perez, RN at UCSF Urologic Oncology on 3 April 2013 led to the rule of thumb that free PSA > 20% is considered to indicate no cancer present.]

Since Stanford sends the Free PSA to an outside lab to be processed, I figured the PSA value was not comparable to most of the others, so I redid my PSA on 05 April 2005. It was significantly elevated from the value of the previous week, indicating to me that I was still harboring an infection (which was thankfully asymptomatic). Further followup was due with a power doppler TRUS on 11 April and a consultation with my urlogist the following week.

The TRUS showed no changes from the previous year or the year before and no obvious signs of cancer, which was reassuring. My uroligist agreed that I still had prostatitis, that I was lucky to be symptom free, and that chronic infection was problematic for several reasons:

• it masks my "true" PSA levels, making it impossible to track the state of my cancer via blood tests;
• it makes any MRSI invalid since prostatitis signals in the spectroscopic images look too much like prostate cancer to be able to clearly differentiate the two; and
• chronic infection itself can lead to cellular and DNA damage and hence possibly more normal prostate cells making a transition into a malignant state. (See a discussion below on this issue.)

My PSA values continued to jump wildly about, 4.42 in June, 18.3 in July, and then settled back to normal at 2.44 in early August, for reasons that elude me. Somehow, the infection has (hopefully) run its course and is done.
 

Dosage Summary

• August 1999 - July 2000: raw milk from my donor, approximately 2 ounces per day; the amount varied
• August 2000: organic cow's milk mixed with olive oil for the oleic acid, about 4 ounces per day. This did not successfully emulate human mother's milk.
• September 2000 - June 2001: pasteurized milk from the Milk Bank, 7 ounces per day (two 3.5 ounce bottles) during most of this time, one bottle per day during some of this time.
• July 2001 - December 2002: raw milk from the Milk Bank, one 3.5 ounce bottle per day; 2 bottles per day for a few months during this time.
• January 2003 - September 2003: one bottle of raw milk from the Milk Bank every other day.
• October 2003 - April 2013: one bottle of raw milk from the Milk Bank two times a week.
• Approx April 2013 - present: one bottle of pasteurized milk from the Milk Bank two times a week. (The Milk Bank stopped making raw milk available around this time.)

Bottom Lines

PSA Improvement

Instead, it came down to "normal" (1.9 ng/ml) right away and more or less has stayed at 2.0 +/- 10%. This was quick; I was suprised and pleased.

What is the "magic bullet"?

Since I started the Naturopathic remedies relatively late in the game (at the end of October 1999, when I already had 2 or so low PSA's), I know that these were not decisive. They may well have helped sustain the effects of everything else, but were not the crucial elements in controling my PSA levels.

My experience in August and September 2000, when I did not have access to human mother's milk but everything else in my regimen stayed constant, as discussed above, leads me to now believe that the mother's milk is the crucial aspect of my program, the "magic bullet". It seems insufficient, so far, to eliminate the disease, but capable of holding it at bay, as indicated by my monthly PSA results and validated by the semi-annual MRI/MRIS imaging.

I stopped taking the pau d'arco in July 2003, with no noticeable effect on my TRUS (Aug 2003) or subsequent PSAs. I currently don't think this is a "magic bullet", although it may well have some positive medicinal effects.
 

How General is This?

How Long Will it Last?

What should you do?

You need to understand your own health, your own unique personal conditions and values, the stage and aggressiveness of your cancer, and what all the (rapidly changing) medical options that are available to you may be. And you may often have to fight an unresponsive medical bureaucracy or HMO or insurance company that has only its owners' bottom line at heart, not your well-being or even survival. A large and daunting task for anyone, no doubt, but do-able.

Another caveat is that if you have any Gleason 4 or above in your biopsy samples, you will need to do more than only lifestyle changes. According to a paper by Professor Thomas Stamey of Stanford University Hospital [ref needed!], the strongest negative indicator of survival time is the percent of Gleason 4 or higher in one's biopsy samples. In this case, informed medical action is appropriate along with lifestyle and dietary changes. Even in this case, give yourself enough time to get past your shock, to become informed enough about all alternatives, and to find the best practitioner of the approach you decide upon.

In any event, do not try my approaches instead of medical modalities if your cancer is spreading, growing, creating symptoms, or otherwise showing signs of aggressiveness. All of this can be used as an adjunct to more conventional therapies, if necessary. Remember, I am not practicing medicine, I am presenting my own personal story and discoveries and you are, in the end, the only one responsible for your own health, along with those experts you hire to inform and assist you.

Aggressive Monitoring

Other tests are available. These include the DRE (digital rectal examination), the TRUS (trans-rectal ultrasound), biopsies and other blood work. In my case, I don't think these would tell me anything, mostly because they didn't before. That is, my cancer was so small and early stage, it was invisible to the DRE and TRUS I had in July 1999. And the biopsies are like poking into a haystack with a needle, looking for a pingpong ball. Or perhaps a marble. If the target is small enough, one has a very small likelihood of poking into it with a few at random stabs. Finally, the blood work (such as Free PSA and other enzymes) merely serve to indicate the likelihood of cancer; since we know that cancer exists, these also would not yield new information.

I have more confidence in the MRIS, in my case, because it can image everything (bigger than some minimum, of course) and differentiate cancer from non-malignant tissue. I also have a "before" for comparison, a "before" that showed the location and extent of cancer, so we will be able to see its progression or regression.

Simple Conclusion

Bibiography

• Overviews
  • The Dilemmas of Prostate Cancer, Marc B. Garnick, Scientific American, pp 72-81, April 1994
  • Combating Prostate Cancer, Marc B. Garnick and William R. Fair, Scientific American, pp. 75-83, December 1998
  • Prostate Dilemmas, Susan Brink, U S News & World Report, pp. 66-81, 22 May 2000. URL for most of the article is http://www.usnews.com/usnews/culture/articles/000522/archive_016843.htm  
  • Early Detection and Treatment of Prostate Cancer: Case Study and Commentary, Timothy J. Wilt, MD, MPH and Melissa R. Partin, PhD, JCOM, vol 7, No 4, pp 55-68 (April 2000)
    Available on the web until 30 April 2001 at a very long URL. Includes references on 5 and 10 year survival and recurrence rates for various treatments.
  • Localized Prostate Cancer, Patrick C. Walsh, MD, Theodore L. DeWeese, MD, and Mario A. Eisenberger, M.D., New England Journal of Medicine, 357:26, pp. 2696-2705 (27 December 2007). [Available for purchase at http://content.nejm.org/cgi/content/short/357/26/2696 after 27 June 2008 to registered users; registration is free]
    This is a summary of the dilemmas of treating prostate cancer, the side effects and relative effectiveness of the primary medical approaches -- Expectant Management (or watchful waiting), surgery, and radiation. Dr. Walsh invented the nerve sparing surgical techniques.
    Download from ftp://www.cohensw.com/pub/pca/Walsh_NEJM_20071227.pdf
  • Systematic Review: Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer, Timothy J. Wilt, MD, MPH; Roderick MacDonald, MS; Indulis Rutks, BA; Tatyana A. Shamilyan, MD, MS; Brent C. Taylor, PhD; and Robert L. Kane, MD; Annals of Internal Medicine, Vol 0, Issue 2008, pages 000605-200803180-00209-E-209 (18 March 2008). Available at http://www.annals.org/cgi/content/full/0000605-200803180-00209v1
    This is a thorough meta-analysis of all relevant peer reviewed studies of the standard treatments for prostate cancer, their relative effectiveness, and their side effects. The conclusions are that there are few good randomized clinical trials to differentiate between treatments (their "success", survival rates, and side effects, as appropriate for men in general or for specific subpopulations of those diagnosed with PCa).

    An excellent summary of this study may be found in a New York Times Health blog: htpp://well.blogs.nytimes.com/2008/02/05/no-answers-for-men-with-prostate-cancer/

  • http://www.businessweek.com/magazine/content/06_22/b3986001.htm
    "Medical Guesswork -- From heart surgery to prostate care, the health industry knows little about which common treatments really work", John Carey, Business Week, 29 May 2006 cover story.
    An earlier and more accessible discussion of the issues raised in the previous two items, including a short discussion on prostate cancer.
  • http://www.scientificcomputing.com/blogs/2015/05/prostate-cancer-jungle-navigating-diagnosis-and-treatment-options-daunting
    Prostate Cancer Jungle: Navigating Diagnosis and Treatment Options is Daunting
    An accessible overview of PCa, its diagnosis and possible treatments, as well as some controversies in the field (e.g., whether or not to measure PSA). (28 May 2015)
  • http://www.health.harvard.edu/mens-health/2016-annual-report-on-prostate-diseases
    "Most men eventually develop some type of prostate problem, and when they do there are usually no easy solutions. More than a primer on prostate conditions, the Annual Report on Prostate Diseases includes roundtable discussions with experts at the forefront of prostate research, interviews with men about their treatment decisions, and the latest thinking on complementary therapies. This report will provide you with the information you need to understand the current controversies, avoid common pitfalls, and work with your doctor to make informed choices about your prostate health".
  
   
• Standard web sites
  • http://www.cancer.gov/
    The National Cancer Institute of the National Institutes of Health. Call 1-800-4CANCER to speak with knowledgeable and friendly people about your case and concerns, to get their literature and further references.
  • http://www.prostatecancerfoundation.org
    The Prostate Cancer Foundation, formerly CapCure, The Association for the Cure of Cancer of the Prostate
  • Formerly at http://www.submitterassistant.com/Capcure2001/
    Slides and notes from CapCure 8th Scientific Retreat, Lake Tahoe, NV, 6-9 Sept 2001
    Looks like lots of good talks. (No longer available when searched for in June 2009, though some of the talks are if one does a Google search on "CapCure 8th Scientific Retreat".)
  • http://www.prostatecancerfoundation.org/site/c.itIWK2OSG/b.1316899/k.19D/Nutrition_Exercise_and_Prostate_Cancer.htm
    A downloadable copy of the CapCure monograph on Nutrition, Exercise and Prostate Cancer. It may also be ordered as a paperback.
  • https://sites.google.com/site/mylinksfamily/pc
    Combined web site of the San Jose and Silicon Valley Prostate Cancer Support Groups.
  • http://www.prostatepointers.org/
    Another rich source of links and information.
  • http://hypertext.org/
    An excellent guide, with lots of references. To quote, "[This Guide] was created by a patient who spent a lot of time reading, asking questions, searching the internet - and learning some things the hard way. The main page of the Guide is essentially an outline of the entire subject, and it can be read in less than half an hour." Versions are available in English, Spanish amd Portugese.
  • http://rattler.cameron.edu/information.html
    Another copious set of references and links put together by a prostate cancer survivor. This site is inoperative as of or before June 2009.
  • http://www.ustoo.com/
    One of the main prostate cancer advocacy and support organizations
  • http://ustoo.org/Hot_Sheets.asp
    All of the monthly newsletters on prostate cancer can be downloaded from this location as PDF documents. They have interesting and useful summaries of relevant research, among other things.
  • http://www.cancerfacts.com/
    Another source of cancer information for physicians as well as consumers.
  • http://www.bccancer.bc.ca/default.htm
    The British Columbia (Canada) Cancer Agency. Also includes a set of pages about alternative (unconventional) treatments for cancer. (See the link under the pau d'arco references, below.)
  • http://www.prostate-cancer.org/ or
    http://www.prostate-cancer.org
    The Prostate Cancer Research Institute. They also have a telephone helpline (800.641.PCRI or 800.641.7274).
  • http://www.prostate-cancer.org/resource/insights.html
    A location from which the PDF files of all issues of PCRInsights can be downloaded. This is a very useful publication, in my opinion, with lots of in depth yet accessible articles about various aspects of prostate cancer and some appropriate medical treatments at various stages of the disease. The PCRI is an advocate of triple hormone blockade, but all articles are well balanced with no axe to grind.
  • http://www.pslgroup.com/PROSTCANCER.HTM
    The Doctor's Guide Prostate Cancer Information and Resources pages. Lots of references & links, updated with great frequency.
  • http://www.prostate-online.com/
    Virgil's Prostate On-Line, A Guide to Fighting Prostate Cancer
  • http://www.cancer.med.umich.edu/cancertreat/urologiconcology/prostate_cancer_information.shtml
    The University of Michigan Medical School Comprehensive Cancer Care prostate cancer top page.
  • http://www.cancernews.com/male.htm
    Another extensive set of links
  • http://urology.jhu.edu/
    Johns Hopkins University's Brady Urological Clinic home page. JHU is the home of Patrick Walsh, MD, the inventor of nerve sparing radical prostatectomy, and a site of much related research.
  • http://www.oncolink.org/types/article.cfm?c=16&s=57&ss=608&id=8039
    University of Pennsylvania site on Prostate Cancer, frequently updated.
  • http://www.jurology.com
    The Journal of Urology provides a searchable web site for highly technical articles. Titles and references are available. Some few issues have full text available without a paid subscription.
  • http://www.moffitt.org/moffittapps/ccj/index.html
    The Moffitt Cancer Control Journal devotes issues to particular forms of cancer. All articles are downloadable as PDF files. For example, the November/December 2001 issue is devoted to prostate cancer, with review articles on Radical Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Cryosurgery, and Chemotherapy for hormone refractory disease, as well as 2 articles about dealing with side effects of treatment.
  • http://www.prostatecalif.com
    The web site of the California Prostate Cancer Coalition.
  • http://www.paactusa.org/
    The web site for PAACT or Patient Advocates for Advanced Cancer Treatments, Inc.
  • http://www.medsch.wisc.edu/pca/  Prostate Cancer Answers
    This was a service of the University of Wisconsin Comprehensive Cancer Center. It provided accurate and up-to-date information about prostate cancer research, prevention, detection, diagnosis and treatment. However, it was removed sometime before June 2009; the URL is inoperative.
  • http://www.canadian-prostate.com/  The Canadian Prostate Health Council
    An affiliate of the Canadian Urologic Association, whose mission is "to create awareness; stimulate interest; gather, assess, and disseminate knowledge on diseases of the prostate, current and innovative therapies, the consequences of untreated disease and the differential diagnosis of benign prostate hyperplasia, prostate cancer and other diseases of the prostate."
  • http://www.roblesmar.com/Prostate/proslink.htm
    An extensive set of links contributed by Wil de Jong, a prostate cancer survivor in Holland. These pages no longer exist as of or before June 2009,nor does the web site.
  • http://www.fightprostatecancer.org/   National Prostate Cancer Coalition
    The National Prostate Cancer Coalition (NPCC) advocates for research funding and treatment access, provides free screenings, raises awareness, and provides news, information and online services for prostate cancer patients, their families, and men at risk
  • http://www.Cancer411.org/
    The Cancer411.org has a complete and searchable list of new cancer treatments and clinical trials, world-wide, for all kinds of cancers, including Prostate Cancer.
  • http://gday-mate.com/prostate_cancer
    Another site with lots of info, pages on alternative treatments as well. Includes lots of references. As of June 2009, this is now a site on Australian history. Don't know where the PCa info went.
  • http://www.bnpcc.org/
    Buffalo Niagara Prostate Cancer Consortium
    A research and treatment organization with some tutorial material on their web site
  • http://www.hrpca.org/
    Hormone-RefractoryProstate Cancer
    A site created by and for people involved with this stage of the disease. Has references, discussions, roadmaps for making treatment choices.
  • http://www.medscape.com/resource/prostate
    Medcape's Prostate Cancer Resource pages, frequently updated with new reference material. One needs a (free) registration to Medscape to see this site.
  • http://mayoclinic.com/health/prostate-cancer/DS00043
    The Mayo Clinic Health Information web site prostate cancer top page.
    
  • http://www.malecare.com
    "For five years [since 1999], our nonprofit Malecare has been facilitating activism and providing men's prostate cancer support programs to hundreds of men, free and open, in the United States and Canada. Our web site contains two hundred pages of helpful prostate cancer information, including dozen's of pages in English, Spanish, French, Italian and Hebrew. We are a proven critical resource to men and their families... I hope that you will add us to your efforts to help men diagnosed with prostate cancer." -- From an email from Darryl Mitteldorf, LCSW, Director.
  • http://urology.ucsf.edu/patientGuides/uroOncPt_Doc.html
    This site from UCSF's Urologic Oncology Patient Information service contains a number of downloadable PDF documents on various aspects of prostate cancer and related issues (such as BPH and bladder cancer).
  • http://www.prostatecancerfoundation.org
    Prostate Cancer Foundation (formerly CapCure)
    The Prostate Cancer Foundation is the world's largest philanthropic source of support for prostate cancer research. Founded in 1993, the PCF has raised more than $210 million and provided funding for prostate cancer research to more than 1,100 researchers at 100 institutions worldwide. The PCF has a simple, yet urgent goal: to find better treatments and a cure for recurrent prostate cancer.
  • http://www.cancercurecoalition.org/
    The Cancer Cure Coalition
    A web site devoted to conventional, dietary, and alternative approaches to cancer, with an emphasis on prostate cancer and multiple myeloma. It includes a dietary/nutritional protocol that worked for the founder and his wife, as well as critiques of the FDA as a bottleneck to the timely approval of effective drugs.
  • http://www.prostateforum.com/
    Charles E. Myers, Jr. MD ("Snuffy" Myers) web site on prostate cancer. Dr. Myers is a Charlottesville, VA based physician who treats and researches prostate cancer and who was himself diagnosed with PCa in 1999. He seeks to integrate Western medicine with nutritional approaches.
  • http://www.acor.org/
    Association of Cancer Online Resources
    "ACOR is a unique collection of online communities designed to provide timely and accurate information in a asupportive environment." "ACOR offers access to mailing lists that provide support, information, and community to everyone affected by cancer and related disorders."
  • http://www.mycancerplace.com/
    A set of forums on various cancers and approaches, including PCa. Looks new, as of summer 2006.
  • http://www.beatcancer.org/
    Center for Advancement in Cancer Education
    "The Center's goals are two-fold: Our short-term goal is to provide individualized resources and referrals to help patients make informed decisions, participate in the wellness process, and improve the quality and longevity of their lives. Our long-term goal is to change, through professional education, the paradigm of oncologic care from a monolithic approach focusing on tumor destruction to an integrative approach focusing on biological repair."
    A no cost center for education in prevention and treatment of cancers, seeking to integrate Western medical technology and knowledge with nutrition and more holistic approaches.
  • http://www.strivewell.com/groups/home/prostate_cancer
    This site is for PCa patients only, and allows individuals to share, find info, etc. Free membership required to participate in the community, not to read the tutorials, etc. The site was started in 2006.
  • http://www.zerocancer.org/index.html
    ZERO -- The Project to End Prostate Cancer
    "To accomplish our goal, we provide comprehensive treatment information to patients, education to those at risk and we're conducting more free screenings than ever before. We increase research funds from the federal government to find new treatments and we fund research in the pursuit of a better test for the disease."
    [This group was formerly known as the National Prostate Cancer Coalition.]
  • http://conquerprostatecancernow.typepad.com/
    The web site of rabbi and prostate cancer survivor who has written a book about the spiritual and psychological aspects of treatment and recovery. It also contains general information. As he says, "This site is a physical, emotional and spiritual guide for fellow prostate cancer patients and survivors and those who love them. Our goal is to let you know that you're not alone in the struggle to overcome prostate cancer and enhance your daily life."
  • http://prostatecancerinfolink.net/
    The "New" Prostate Cancer Infolink
    Early in 2008, the founders decided to rebuild The "New" Prostate Cancer InfoLink using Web 2.0 tools and capabilities. It first went "live" on March 20, 2008. Hopefully we will be able to attract back a few of our earlier patrons and they will tell their friends.
     
    The "New" Prostate Cancer InfoLink includes two components:
     
    * This site, which combines a news and opinion blog, an extensive and expanding series of articles on specific aspects that address risk for, prevention of, and diagnosis and management of prostate cancer, and a mentoring service through which people can seek answers to their specific questions
    * The "New" Prostate Cancer InfoLink Social Network, where patients, family members, health care professionals, and others can gather on line to learn from and support each other in addressing all the effects of this disorder....
    A valuable list of resources and web sites is available at http://prostatecancerinfolink.net/tips-tools/ustoos-on-line-resources/
  • http://www.auafoundation.org/auafhome.asp
    American Urological Association Foundation
    
  • http://www.menshealthnetwork.org
    "Men's Health Network (MHN) is a national non-profit organization whose mission is to reach men and their families where they live, work, play, and pray with health prevention messages and tools, screening programs, educational materials, advocacy opportunities, and patient navigation."
  • http://www.naspcc.org/
    NASPCC - National Alliance of State Prostate Cancer Coalitions
    Their mission is "To provide support to existing state prostate cancer organizations; to facilitate the development of new state prostate cancer organizations; and to serve as a collective and collaborative voice to make prostate cancer a national health care priority."
  • http://pcainternational.org/
    Prostate Cancer International
    Prostate Cancer International, Inc. currently manages a series of five interconnected, informational prostate cancer web sites for the global community:
    • http://prostatecancerinfolink.net/
      The 'New' Prostate Cancer InfoLink (See above)
    • http://pcafrica.wordpress.com/
      Prostate Cancer Africa
      "Prostate Cancer Africa is being developed as a web site to carry basic information about prostate cancer for people of the African continent."
    • http://pccaribbean.wordpress.com/
      Prostate Cancer Caribbean
      "Prostate Cancer Caribbean is being developed as a web site to carry basic information about prostate cancer for the varied groups of people who populate the Caribbean islands."
    • http://cplatinoamerica.wordpress.com/
      El Cáncer de Próstata en Latinoamérica
      A Spanish-language site on prostate cancer for a Latin American audience.
  • http://www.prostateconditions.org/
    Prostate Conditions Education Council (PCEC)
    "Our mission is to save lives through awareness and the education of men, the women in their lives as well as the medical community about the prevalence of prostate cancer, the importance of early detection, available treatment options and other men's health issues. To conduct nation wide screenings for men and perform research that will help the detection and treatment of prostate cancer and other mens health issues."
  • http://www.prostatehealthed.org/
    Prostate Health Education Network (PHEN)
    "PHEN's primary mission is to increase prostate health education and awareness among the men at highest risk for prostate cancer in the United States, African Americans. Saving lives through early detection and eliminating the African American prostate cancer disparity is PHEN's education and awareness goal. PHEN's mission also includes efforts to increase the overall support and resources to wage a war on prostate cancer that will eventually lead to a cure for the disease."
  • http://pcmission.org/
    A Florida based organization.
  • http://www.prostatenet.org/
    The Prostate Net
    "Virgil H. Simons founded the Prostate Net in 1996 as a result of his encounter with prostate cancer. When he was diagnosed, there was little to no readily accessible information to help prostate cancer patients and their families make informed treatment decisions. Moreover, Mr. Simons learned that black men bear a much greater risk for prostate cancer, both in regard to incidence and mortality, but found that there was no vehicle for educating that population about their situation. In response to these two crucial needs, The Prostate Net came into existence."
  • http://www.vapcacoalition.org/
    Virginia Prostate Cancer Coalition
    "The mission of the Virginia Prostate Cancer Coalition is to make prostate cancer an urgent priority for the medical, patient and legislative communities. "
  • http://www.womenagainstprostatecancer.org/
    "Women Against Prostate Cancer (WAPC) is a national organization working to unite the voices and provide support for the millions of women affected by prostate cancer, and their families. WAPC advocates prostate cancer education, public awareness, screenings, legislation, and treatment options."
  • http://www.hopelink.com/
    Suggested by UsToo. Site has lots of useful links, as well as links to folks peddling their wares. Use with care.
  • http://www.yananow.net/
    You Are Not Alone Now
    This site has an overview of PCa and available treatments, with a strong disussion of Active Surveillance. It also contains many first person accounts.
  • http://www.nccn.com/
    National Comprehensive Cancer Network
    "NCCN.com is the new consumer website of the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world's leading cancer centers.
    The goal of this website is to educate patients with cancer to engage in more informed conversations with health care providers so they can live longer and better quality lives...."
    See also http://www.nccn.org/index.asp
    Their Guidelines for [Prostate Cancer] Patients can be downloaded from http://www.nccn.org/patients/guidelines/prostate/
  • http://www.admetech.org/
    "The AdMeTech Foundation is a 501(c)(3) nonprofit organization based in Boston, MA. Our mission is to end the prostate cancer crisis [via] ground-breaking programs in research and education for facilitated development of accurate diagnostic tools for early detection and minimally-invasive treatment of prostate cancer...."
  • http://ipcsg.org
    Informed Prostate Cancer Support Group, in San Diego, California
  • http://www.scprostate.org/
    Santa Cruz County Prostate Cancer Support Group
    Contains a rich set of resources for further research; an archive of newsletters can be accessed at http://www.scprostate.org/news_archive.htm
  • http://www.ustoowichita.org/
    The Wichita, Kansas USToo web site has a great deal of useful information and a set of links to other sites.
  • http://www.MyProstateCancerRoadmap.com
    "My Prostate Cancer Roadmap offers resources and information specific to advanced prostate cancer patients and those who love them, as well as a wide range of information and features relevant to daily living with advanced prostate cancer. The resource was developed by Janssen Biotech, Inc. in partnership with the non-profit organization Us TOO International Prostate Cancer Education & Support Network (www.ustoo.org)."

  • Or use the standard search engines (Netscape, Alta Vista, Yahoo, Google, scholar.google.com, Excite, Lycos, dogpile, etc.) on "Prostate Cancer" to get an enormous number of links.
  
   
• Research Sites
  • http://www.medscape.com/
  • http://www.medscape.com/urology
    "Medscape offers specialists, primary care physicians, and other health professionals the Web's most robust and integrated medical information and educational tools. After a simple, 1-time, free registration, Medscape automatically delivers you the specialty site that best fits your profile. You can also change your Medscape homepage to any of our other specialty and profession sites at any time."
  • http://www.nlm.nih.gov/medlineplus/
    "MedlinePlus will direct you to information to help answer health questions. MedlinePlus brings together authoritative information from NLM, the National Institutes of Health (NIH), and other government agencies and health-related organizations. Preformulated MEDLINE searches are included in MedlinePlus and give easy access to medical journal articles. MedlinePlus also has extensive information about drugs, an illustrated medical encyclopedia, interactive patient tutorials, and latest health news."
  • http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?CMD=&DB=PubMed
    "PubMed comprises more than 19 million citations for biomedical articles from MEDLINE and life science journals. Citations may include links to full-text articles from PubMed Central or publisher web sites."
  • http://www.BioMedSearch.com
    "BioMedSearch is an enhanced version of the NIH PubMed search that combines MedLine/PubMed data with data from other sources to make the most comprehensive biomedical literature search available. BioMedSearch also provides advanced account features that allow saved searches, alerts, saving documents to portfolios, commenting on documents and portfolios, and sharing documents with other registered users. Registering for BioMedSearch is free."
  • http://www.quertle.info/
    Quertle is the brainchild of two researchers/scientists who envisioned a better way to do literature searching. They have been dedicated to making it happen and maintaining it as a free resource for active researchers. They did it and they're continually improving it with upgrades. It seems to be new in 2011.

    From their FAQ page: "Quertle goes beyond simple term matching to identify the most salient information in the literature. Using a combination of linguistic methods, Quertle finds facts defined within documents, creating its own database of about 250 million relationships, and is able to report the ones that are relevant to your query. Quertle's approach is based on a thorough understanding of biology and chemistry and was built from the ground up to address the unique needs of this technical literature."

  • http://oedb.org/open/subjects/health-medical/
    The Open Education Database is a comprehensive OpenCourseWare (OCW) portal featuring almost 800 courses (as of August 2013) from leading universities in an array of topics, all freely accessible. In particular, this link within the site is to their health and medical courseware.
  
   
• Aggressive Monitoring/Active Surveillance
  • http://www.prias-project.org/modules/news/ (22 Dec 2007)
    The PRIAS Project is a Dutch-based research poject with a focus on following men with non-aggressive prostate cancer with active surveillance, using frequent PSA measures, twice yearly M.D. visits with DREs, and biopsies at years 1, 4, 7, 10, 15, etc. If the cancer is obviously progressing, "standard" medical treatments are then pursued. They have collaborating doctors in Europe and Canada.
  • http://www.medscape.com/viewarticle/715129?src=mp&spon=15&uac=24203PX
    Active Surveillance Now Prominent in NCCN Prostate Cancer Guidelines
    "January 14, 2010 — For the first time, the National Comprehensive Cancer Network's (NCCN) practice guidelines for prostate cancer recommend the use of active surveillance as the sole initial treatment — not just an option — for many men with prostate cancer...." (From Medscape Medical News)
    (See also http://www.sciencedaily.com/releases/2010/01/100105112113.htm)
  • http://www.ustoowichita.org/pdf/ACTIVE%20SURVEILLANCE.pdf
    A collection of thoughts on active surveillance, along with suggestions from Stephen Strum, MD, on various tests to monitor PCa, related health factors, and its probability of spreading (or not).
  • http://consensus.nih.gov/2011/prostate.htm
    Role of Active Surveillance in the Management of Men With Localized Prostate Cancer, NIH Conference, Bethesda, MD, 5-7 December 2011, Conference Proceedings and Webcast available here.
  • http://www.renalandurologynews.com/prostate-cancer-active-surveillance-safe-long-term/article/342267/
    Prostate Cancer Active Surveillance Safe Long Term
    "Active surveillance (AS) for patients with favorable risk prostate cancer (PCa) is safe long-term, with patients much more likely to die from causes other than PCa, according to study findings presented at the European Association of Urology 29th annual congress...." (13 April 2014)
  • http://www.nytimes.com/2016/05/25/health/prostate-cancer-active-surveillance-surgery-radiation.html
    More Men With Early Prostate Cancer Are Choosing to Avoid Treatment, By Gina Kolata, (24 May 2016)
    "Seemingly overnight, treatment of men with early-stage prostate cancer has undergone a sea change. Five years ago, nearly all opted for surgery or radiation; now, nearly half are choosing no treatment at all.
    The approach is called active surveillance. It means their cancers are left alone but regularly monitored to be sure they are not growing. Just 10 percent to 15 percent of early-stage prostate cancer patients were being treated by active surveillance several years ago. Now, national data from three independent sources consistently finds that 40 percent to 50 percent of them are making that choice...."
  
   
• Mother's Milk and Cancer Cell Apoptosis
  • http://www.milkbanks.org or http://www.hmbana.com/  Human Milk Banking Association of North America
    The umbrella organization for all 9 milk banks in North America plus three that are under development (as of May 2005). Contains information on donating and purchasing mother's milk.
    
  • http://www.milkbanksj.org/ or The Mothers' Milk Bank of San Jose
    The web site for the Mothers' Milk Bank of San Jose, California.
  • http://community.lsoft.com/SCRIPTS/WA-LSOFTDONATIONS.EXE?A2=ind9905b&L=lactnet&T=0&F=&S=&P=26566
    A posting from 9 May 1999 in lactation discussion group about the use of breast milk in treating cancer, referring to the Lund work.
  • Peter Radetsky, Got Cancer Killers?, Discover Magazine, June 1999, pp 68-75
    http://discovermagazine.com/1999/jun/featcancer
  • New York Times, Monday 19 July 1999 Human Breast Milk Kills Cancer Cells
    This article from the New York Times Syndicate had been on the Cancer Facts web site in the summer of 1999. In March 2000, I was not able to find it there or on the NYTimes web site archives. It is a summary of the Discover article. A copy of the artcle had been available at http://www.bcexperience.org/hamlet.html (with the wrong date attributed to it), but is no longer there as of June 2009.
  • http://ublib.buffalo.edu/libraries/projects/cases/milk/milk.html
    Mother's Milk Cures Cancer? Researchers Deliberate Over Whether to Publish, Linda Tichenor, Department of Biological Science University of Arkansas, Fayetteville (18 Jan 2002)
    A brief summary of the discovery of HAMLET in the format of a case study of scientific process and politics.
  • http://www.ehponline.org/realfiles/docs/1995/103-12/forum.html#milk
    A summary of the original work on mothers' milk killing cancer cells, from Environmental Health Perspectives (Dec 1995)
  • http://bcaction.org/index.php?page=newsletter-58j
    New Research Links Breast Milk to Cancer Cell Death, from Breast Cancer Action newsletter (Mar/Apr 2000). Discusses early work on HAMLET as well as positive benefits of breastfeeding for mothers and infants. Also discusses accumulation of toxins in breast milk and the need to clean up our environment and food supply.
  • http://www.sciencenews.org/articles/20061209/bob8.asp
    Milk Therapy: Breast-milk compounds could be a tonic for adult ills , Julie J. Rehmeyer, Science News Online, Week of Dec. 9, 2006; Vol. 170, No. 24 , p. 376
    A discussion of health effects of human mothers' milk, including anti-cancer activity. Available to paid subscribers only.
  • http://jhl.sagepub.com/cgi/content/abstract/25/2/211
    Qualitative Analysis of Cancer Patients' Experiences Using Donated Human Milk, Susanne M. Rough, Pauline Sakamoto, Caroline H. Fee, Clarie B. Hollenbeck, Journal of Human Lactation, Vol. 25, No. 2, 211-219 (2009) DOI: 10.1177/0890334409333422
    Ten cancer patients (diverse ages, cancers, and stages) who had used human breast milk as part of their therapy, or their caregivers, were interviewed for an investigation of quality of life issues. (I am "Patient C".)
    The Abstract is available at the above URL. The article may be downloaded from ftp://www.cohensw.com/pub/pca/Rough_2009_human_milk_Rx_impr_QOL.pdf

  • http://hamletpharma.com/hamlet/vetenskapliga-publikationer/
    A HAMLET bibliography with many downloadable PDF papers, at the Hamlet Pharmaceuticals web site, a Swedish company founded by Catharina Svanborg.

  • Apoptosis Induced by a Human Milk Protein, Anders Håkansson, Boris Zhivotovsky, Sten Orrenius, Hemant Sabharwal, and Catharina Svanborg, Proceedings of the National Academy of Sciences, USA, 92: 8064-8068 (1995)
  • Multimeric Alpha-Lactalbumin from Human Milk Induces Apoptosis through a Direct Effect on Cell Nuclei, Anders Håkansson, Jesper Andréasson, Boris Zhivotovsky, Diana Karpman, Sten Orrenius, and Catharina Svanborg, Experimental Cell Research, 246: 451-460 (1999) (**)
    Download from ftp://www.cohensw.com/pub/pca/AH_ECR.pdf
  • Molecular Characterization of Alpha-Lactalbumin Folding Variants That Induce Apoptosis in Tumor Cells, Malin Svensson, Hemant Sabharwal, Anders Håkansson, Ann-Kristin Mossberg, Peter Lipniunas, Hakon Leffler, Catharina Svanborg, and Sara Linse, Journal of Biological Chemistry, vol 275, no 10, pp 6388-6396 (5 March 1999) (**)
    Download from ftp://www.cohensw.com/pub/pca/Malin_JBC.pdf
  • Protease Activation in Apoptosis Induced by MAL, Camilla Köhler, Anders Håkansson, Catharina Svanborg, Sten Orrenius, and Boris Zhivotovsky, Experimental Cell Research, 249: 260-268 (1999) (**)
    Download from ftp://www.cohensw.com/pub/pca/MAL-caspases.pdf
  • Conversion of Alpha-Lactalbumin to a Protein Inducing Apoptosis, M. Svensson, A. Håkansson, A.-K. Mossberg, S. Linse, C. Svanborg, Proceedings of the National Academy of Sciences, USA, 97: 4221-4226 (2000) (**)
    Download from ftp://www.cohensw.com/pub/pca/PNAS_2000-97-4221.pdf
  • A Folding Variant of alpha-lactalbumin With Bactericidal Activity Against Streptococcus pneumoniae, Anders Håkansson, Malin Svensson, Ann-Kristin Mossberg, Hemant Sabharwal, Sara Linse, Irene Lazou, Bo Lönnerdal, and Catharina Svanborg, Molecular Microbiology (2000), 35(3), 589-600 (**)
    This paper also discusses the cancer-killing aspect of the molecule.
    Download from ftp://www.cohensw.com/pub/pca/MolMicro2000-35-589.pdf
  • A Folding Variant of Human Alpha-Lactalbumin Induces Mitochondrial Permeability Transition in Isolated Mitochondria, Camilla Köhler, Vladimir Gogvadze, Anders Håkansson, Catharina Svanborg, Sten Orrenius, Boris Zhivotovsky, European Journal of Biochemistry, 268, 186-191 (Feb 2001) (**)
    Download from ftp://www.cohensw.com/pub/pca/EurJBiochem2001-268-186.pdf
  • Hamlet -- A Complex From Human Milk That Induces Apoptosis in Tumor Cells But Spares Healthy Cells, Malin Svensson, Caroline Düringer, Oskar Hallgren, Ann-Kristin Mossberg, Anders Håkansson, Sara Linse, Catharina Svanborg, Advances in Experimental and Medical Biology (US), 503, 125-132 (2002) (***)
    Download from ftp://www.cohensw.com/pub/pca/ISRHML_review.doc
  • Alpha-lactalbumin Unfolding is not Sufficient to Cause Apoptosis, but is Required for the Conversion to HAMLET (Human Alpha-lactalbumin Made Lethal to Tumor cells), Malin Svensson, Jonas Fast, Ann-Kristin Mossberg, Caroline Dürringer, Lotta Gustafsson, Oskar Hallgren, Charles L. Brooks, Lawrence Berliner, Sara Linse, and Catharina Svanborg, Protein Science (2003), 12:2794-2804.
    Full text is avaliable at http://www3.interscience.wiley.com/cgi-bin/fulltext/121602046/HTMLSTART
    One interesting aspect of this study was the conversion of bovine alpha-lactalbumin to a cancer killing form (BAMLET) with a C18:1 fatty acid (which is not present in cow's milk but is abundant in human milk). BAMLET was not as effective as HAMLET in inducing tumor cell death.
  • BAMLET activates a lysosomal cell death program in cancer cells, Rammer P, Groth-Pedersen L, Kirkegaard T, Daugaard M, Rytter A, Szyniarowski P, Høyer-Hansen M, Povlsen LK, Nylandsted J, Larsen JE, Jäättelä M., 2010 Jan;9(1):24-32. Epub 2010 Jan 6
    From the Abstract: A complex of human alpha-lactalbumin and oleic acid (HAMLET) was originally isolated from human milk as a potent anticancer agent. It kills a wide range of transformed cells of various origins while leaving nontransformed healthy cells largely unaffected both in vitro and in vivo. Importantly, purified alpha-lactalbumins from other mammals form complexes with oleic acid that show biological activities similar to that of HAMLET...
  • Lipids as Cofactors in Protein Folding: Stereo-Specific Lipid-Protein Interactions are Required to Form HAMLET (Human Alpha-lactalbumin Made Lethal to Tumor cells), Malin Svensson, Ann-Kristin Mossberg, Jenny Pettersson, Sara Linse, and Catharina Svanborg, Protein Science (2003), 12:2805-2814.
    Full text is avaliable at http://www3.interscience.wiley.com/cgi-bin/fulltext/121602048/HTMLSTART
  • HAMLET Kills Tumor Cells by Apoptosis - Cellular, Molecular and Therapeutic Aspects, Catharina Svanborg, Helena Ågerstam, Caroline Dürringer, Walter Fischer, Lotta Gustafsson, Oskar Hallgren, Irene Leijonhuvud, Sara Linse, Ann-Kristin Mossberg, Hanna Nilsson, Jenny Peterson, Malin Svensson, Annika Aronson, Rolf Bjerkvig, Advances in Cancer Research 88:1-29 (2003) (**)
    Download from ftp://www.cohensw.com/pub/pca/Svanborg_apoptosis_AdvCancRes_2003.pdf
  • Human Alpha-lactalbumin Made Lethal to Tumor Cells (HAMLET) Kills Human Glioblastoma Cells in Brain Xenografts by an Apoptosis-Like Mechanism and Prolongs Survival, Walter Fischer, Lotta Gustafsson, Ann-Kristin Mossberg, Janne Gronli, Sverre Mork, Rolf Bjerkvig, and Catharina Svanborg, Cancer Research 64, 2105-2112, March 15, 2004 (**)
    This research was partially funded by the American Cancer Society.
    Download from ftp://www.cohensw.com/pub/pca/Fischer-braintumor-HAMLET.pdf
  • Treatment of Skin Papillomas with Topical Alpha-Lactalbumin-Oleic Acid, Lotta Gustafsson, Irene Leijonhufvud, Annika Aronsson, Ann-Kristin Mossberg, and Catharina Svanborg, New England Journal of Medicine 2004; 350:2663-72 (June 24, 2004) (**)
    Download from ftp://www.cohensw.com/pub/pca/Gustafsson-papilloma-HAMLET.pdf
  • Apoptotic Cell Death in the Lactating Mammary Gland is Enhanced by a Folding Variant of Alpha-Lactalbumin, A. Baltzer, C. Svanborg and R. Jaggi, Cellular and Molecular Life Sciences, 61 (2004) 1221-1228 (**)
    Download from ftp://www.cohensw.com/pub/pca/Baltzer-lactation-HAMLET.pdf
  • HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53, O. Hallgren, L. Gustafsson, H. Irjala, G. Selivanova, S. Orrenius and C. Svanborg, Apoptosis, vol 11, No 2, 2006. pp 221-233. (**)
    Download from ftp://www.cohensw.com/pub/pca/Hallgren-bcl2-p53-HAMLET.pdf
    Indicates that HAMLET may have several pathways to induce tumor cell death (apoptosis), including avoiding pathways that tumor cells often block.
  • Bladder Cancers Respond to Intravesical instillation of HAMLET (Human α-Lactalbumin Made Lethal to Tumor Cells), Ann-Kristin Mossberg, Björn Wullt, Lotta Gustafsson, Wiking Månsson, Eva Ljunggren, and Catharina Svanborg, Int. J. Cancer: Vol. 121, pp 1352-1359 (2007) [15 September 2007]
    Download from ftp://www.cohensw.com/pub/pca/Mossberg-bladder-cancer-HAMLET.pdf
    Nine bladder cancer patients received 5 daily instillations of HAMLET during the week before surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily. Most of the shed cells were dead and 6 of 9 patients showed an apoptotic response. At surgery 8 of 9 patients showed a reduction in tumor size or change of tumor character. Adjacent healthy tissue showed no negative changes.
  • http://luur.lub.lu.se/luur?func=downloadFile&fileOId=605650
    Structure-function analysis of HAMLET, Jenny Pettersson's Ph.D. thesis at Lund University, Institute of Laboratory Medicine, Department of Microbiology, Immunology, and Glycobiology (MIG), 13 December 2007. Also, downloadable from ftp://www.cohensw.com/pub/pca/jenny_pettersson_HAMLET.pdf
  • Mini review: HAMLET, protein folding, and tumor cell death, K. Hun Mok, Jenny Pettersson, Sten Orrenius and Catharina Svanborg, Biochemical and Biophysical Research Communications, Volume 354, Issue 1, 2 March 2007, Pages 1-7. Downloadable from ftp://www.cohensw.com/pub/pca/Mok_BiochemBiophysResComm_2007.pdf
  • Heat-treatment method for producing fatty acid-bound alpha-lactalbumin that induces tumor cell death, Kamijima T, Ohmura A, Sato T, Akimoto K, Itabashi M, Mizuguchi M, Kamiya M, Kikukawa T, Aizawa T, Takahashi M, Kawano K, and Demura M, Biochemical and Biophysical Research Communications, Volume 376, 5 September 2008 (online), Pages 211-214. Downloadable from ftp://www.cohensw.com/pub/pca/Kamijima_BiochemBiophysResComm_2008_18774773.pdf
  • Can misfolded proteins be beneficial? The HAMLET case, Pettersson-Kastberg J, Aits S, Gustafsson L, Mossberg A, Storm P, Trulsson M, Persson F, Hun Mok K, and Svanborg C, Annals of Medicine, (2008), Pages 1-15. Downloadable from ftp://www.cohensw.com/pub/pca/Pettersson-Kastberg_AnnMed_2008.pdf
  • HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death, Aits S, Gustafsson L, Hallgren O, Brest P, Gustafsson M, Trulsson M, Mossberg AK, Simon HU, Mograbi B, and Svanborg C, Int. J. Cancer, 124, Pages 1008-1019 (2009). Downloadable from ftp://www.cohensw.com/pub/pca/Aits_IntJCancer_2009_19048621.pdf
  • Who Is Mr. HAMLET? Interaction of Human α-Lactalbumin with Monomeric Oleic Acid, Ekaterina L. Knyazeva, Valery M. Grishchenko, Roman S. Fadeev, Vladimir S. Akatov, Sergei E. Permyakov and Eugene A. Permyako, Biochemistry, 2008, 47 (49), pp 13127-13137 (online publication 12 Nov 2008). Downloadable from ftp://www.cohensw.com/pub/pca/Knyazeva_Biochem_20081112.pdf
  • Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells, Lotta Gustafsson, Sonja Aits, Patrik Önnerfjord, Maria Trulsson, Petter Storm, Catharina Svanborg, PLoS ONE 4(4): e5229. doi:10.1371/journal.pone.0005229 (April 14, 2009). Access or download from
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005229
  • HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity, Ann-Kristin Mossberg, Maja Puchades, Øyvind Halskau, Anne Baumann, Ingela Lanekoff, Yinxia Chao, Aurora Martinez, Catharina Svanborg, Roger Karlsson, PLoS ONE, Volume 5, Issue 2: e9384. oi:10.1371/journal.pone.0009384. Access or download from
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009384
  • HAMLET Treatment Delays Bladder Cancer Development, Ann-Kristin Mossberg, Yuchuan Hou, Majlis Svensson, Bo Holmqvist and Catharina Svanborg, Journal of Urology, Vol. 183, 1590-1597, April 2010, DOI:10.1016/j.juro.2009.12.008. Abstract available at http://www.jurology.com/article/S0022-5347%2809%2903152-8/abstract. Full text available from ftp://www.cohensw.com/pub/pca/Mossberg_et_al_HAMLET_BladderCa_JUrol_201004.pdf
  • HAMLET Binding to α-Actinin Facilitates Tumor Cell Detachment, Maria Trulsson, Hao Yu, Lennart Gisselsson, Yinxia Chao, Alexander Urbano, Sonja Aits, Ann-Kristin Mossberg, Catharina Svanborg, PLoS ONE 6(3): e17179. doi:10.1371/journal.pone.0017179. (8 March 2011) Access or download from
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017179
  • Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes, Ann-Kristin Mossberg, Kenneth Hun Mok, Ludmilla A. Morozova-Roche and Catharina Svanborg, FEBS Journal 277 (2010) 4614–4625. Full text available at ftp://www.cohensw.com/pub/pca/Mossberg_et_al_Structure_Function_HAMLET_FEBSJournal_2010.pdf
  • Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex, Anders P. Hakansson, Hazeline Roche-Hakansson, Ann-Kristin Mossberg, Catharina Svanborg, PLoS ONE 6(3): e17717. doi:10.1371/journal.pone.0017717. (10 March 2011) Access or download from
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017717
  • Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells), Manoj Puthia, Petter Storm, Aftab Nadeem, Sabrina Hsiung, Catharina Svanborg, Gut 2014;63;131-142 (24 January 2013)
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888589/pdf/gutjnl-2012-303715.pdf
    Peroral HAMLET administration reduced tumour progression and mortality in Apc^Min/+ mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly pevented tumour development.
  • Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components, Emma M. Rath, Anthony P. Duff, Anders P. Håkansson, Catherine S. Vacher, Guo Jun Liu, Robert B. Knott, W. Bret Church, J Pharm Pharm Sci (www.cspsCanada.org) 18(4) 773 - 824, 2015. (21 November 2015) Access or download from
    http://ejournals.library.ualberta.ca/index.php/JPPS/issue/view/1714
    From the Abstract: "...This review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified."

  • http://www.hakanssonlab.com
    Professor Anders Hakansson's research web site, which includes a discussion of the HAMLET research he initiated in 1995 as a graduate student.
     
  • http://www.mig.lu.se/svanborg.hamlet.html
    is a bibliography of HAMLET related papers by Catharina Svanborg and her group at Lund University's Section on Microbiology, Imunology and Glycobiology. No texts or links are available here, but the titles may be of some help in further searches. Links to PubMed abstracts for each paper cited are available on this page.

  • http://www.bmj.com/cgi/content/full/322/7301/1536 What is Apoptosis and Why is it Important?, Andrew G. Renehan, Catherine Booth, Christopher S. Potten, British Medical Journal, vol 322, pp 1536-1538 (23 June 2001)
    A simple overview of apoptosis, with reference.
    (Note that the BMJ requires a free registration to view its archives.)
     
  • https://www.roche-applied-science.com/sis/apoptosis/index.jsp
    is a good general reference on cell proliferation and apoptosis, especially the first chapter. From this web page, one or more PDF files may be downloaded from the text Apoptosis and Cell Proliferation, 2nd edition, published by Boehringer Mannheim, 1988.
     
  • http://www.portfolio.mvm.ed.ac.uk/studentwebs/session2/group28/apoptosis.html
    Another simple introduction to apoptosis, with pictures.
     
  • http://www.medscape.com/viewarticle/408813
    "Breastfeeding: Unraveling the Mysteries of Mother's Milk", Margit Hamosh, PhD, Georgetown University Medical Center, Medscape Women's Health eJournal 1(5), 1996.
    An overview of the composition and characteristics of human mother's milk. This article no longer is available as of or before June 2009. The next listing has similar information.
     
  • http://emedicine.medscape.com/article/976504-overview
    "Human Milk and Lactation", Carol L Wagner, MD, (last updated 9 June 2009).
     
  • http://www.aap.org/advocacy/releases/feb05breastfeeding.htm
    (This link is no longer operative as of Feb 2013. See the next list item for a more current policy statement.)
    A Press Release frm the American Academy of Pediatrics announcing their revised breast feeding recommendations. This speaks briefly of many of the benefits of breast feeding infants.
     
  • http://pediatrics.aappublications.org/content/129/3/e827.full
    Policy Statement: Breastfeeding and the Use of Human Milk, Pediatrics, vol 129, No. 3, pp. e827-e841, (1 March 2012)
    An updated policy statement.
  • http://aappolicy.aappublications.org/cgi/content/full/pediatrics;115/2/496
    The American Academy of Pediatrics Policy Statement on Breastfeeding and the Use of Human Milk (from Pediatrics, Vol. 115, No. 2, 2 Feb 2005, pp 496-406). Contains extended statements on benefits of nursing for infants (as well as mothers and society in general).

  • http://pediatrics.aappublications.org/cgi/content/full/123/3/e406
    Does Breastfeeding Reduce the Risk of Sudden Infant Death Syndrome?, M.M. Vennemann, MD, MPH, PD, T. Bajanowski, MD, PD, B. Brinkmann, MD, PD, G. Jorch, MD, PD, K. Yücesan, MD, C. Sauerland, MScd, E.A. Mitchell, FRACP, DSc and the GeSID Study Group, Pediatrics Vol. 123 No. 3 March 2009, pp. e406-e410
    "This study shows that breastfeeding reduced the risk of sudden infant death syndrome by ~50% at all ages throughout infancy. We recommend including the advice to breastfeed through 6 months of age in sudden infant death syndrome risk-reduction messages."

  • http://www.nytimes.com/2009/04/22/health/research/22breast.html
    Breast-Feeding Benefits Mothers, Study Finds (see next reference)
    "Most doctors agree that breast-feeding is best for babies' health. Now a large study suggests that the practice benefits mothers as well: women who have breast-fed, it says, are at lower risk than mothers who have not for developing high blood pressure, diabetes and cardiovascular disease decades later, when they are in menopause."
  • http://journals.lww.com/greenjournal/Abstract/2009/05000/Duration_of_Lactation_and_Risk_Factors_for.5.aspx Duration of Lactation and Risk Factors for Maternal Cardiovascular Disease, Schwarz, Eleanor Bimla MD, MS; Ray, Roberta M. MS; Stuebe, Alison M. MD, MSc; Allison, Matthew A. MD, MPH; Ness, Roberta B. MD, MPH; Freiberg, Matthew S. MD, MSc; Cauley, Jane A. DrPH, Obstetrics & Gynecology: May 2009 - Volume 113 - Issue 5 - pp 974-982
    Abstract is free, full text available for purchase.

  • http://www.lifescript.com/Health/News/Reuters/2009/12/08/Breastfeeding may curb heart diabetes risk factors.aspx
    Breastfeeding may curb heart, diabetes risk factors
    A lay summary of the following reference, discussing long term health benefits for women who nurse.
  • http://diabetes.diabetesjournals.org/content/early/2009/11/12/db09-1197.abstract
    Duration of Lactation and Incidence of the Metabolic Syndrome in Women of Reproductive Age According to Gestational Diabetes Mellitus Status: A 20-Year Prospective Study in CARDIA—The Coronary Artery Risk Development in Young Adults Study, Erica P. Gunderson, David R. Jacobs, Jr., Vicky Chiang, Cora E. Lewis, Juanran Feng, Charles P. Quesenberry, Jr., and Stephen Sidney, Diabetes; published ahead of print December 3, 2009, doi:10.2337/db09-1197 (Free abstract at this URL; full article available for purchase)

  • http://www.jacn.org/cgi/content/abstract/26/6/704S (free abstract)
    Emerging Health Properties of Whey Proteins and Their Clinical Implications, Geoffrey W. Krissansen, Journal of the American College of Nutrition, Vol 26., No. 6, 713S-723S (December 2007)
    A review of the various classes of molecules found in milk (both human and bovine), and their actual or potential therapeutic effects. The article includes a brief discussion of HAMLET and a longer discussion of Lactoferrin. The artcle may be downloaded from ftp://www.cohensw.com/pub/pca/Emerging_Health_Properties_of_Whey_Proteins_and_Their_Clinical_Implications_JAmCollNutr_2007.pdf
    

  • http://onctalk.com/2008/01/26/tlf-for-nsclc/
    Talactoferrin Alfa (TLF): Mother's Milk Becomes Cancer Treatment is a related article, discussing Agennix' recombinant version of human lactoferrin and its use in treating non-small cell lung cancer. (See also http://www.agennix.com/ and http://www.rediff.com/news/2008/feb/26breast.htm)

  • http://babychangingstation.com/breastfeeding/
    A guide to breast feeding by a new mother and RN.

  • ftp://www.cohensw.com/pub/pca/obama_letter_v4_20090512.pdf
    A letter sent to President Obama and other government figures suggesting increasing support for nursing mothers and the vigorous investigations needed to bring mothers' milk into the clinic in fighting cancer. Includes a Bibliography.

  • http://jrs.sagepub.com/content/108/6/208.full.pdf
    Journal of the Royal Society of Medicine; 2015, Vol. 108(6) 208–209, Doi: 10.1177/0141076815588539
    More than a lucrative liquid: the risks for adult consumers of human breast milk bought from the online market, Sarah Steele, Jens Foell, Jeanine Martyn and Andreas Freitag
    An article about the dangers of purchasing mothers' milk on-line. Their caveats are true (e.g., contamination, adulteration, etc.), but they ignore or denigrate the positive (and anti-cancer) effects of milk. (Published 2015)

  • http://www.israel21c.org/breastfeeding-reduces-childhood-cancer/
    Breastfeeding reduces childhood cancer, University of Haifa research shows nursing for at least six months reduces rate of childhood leukemia and lymphoma by 19%, Viva Sarah Press (2 August 2015). This is an overview of the article
    http://archpedi.jamanetwork.com/article.aspx?articleid=2299705
    Breastfeeding and Childhood Leukemia Incidence, A Meta-analysis and Systematic Review, Efrat L. Amitay; Lital Keinan-Boker, JAMA Pediatrics, June 2015, Vol 169, No. 6.

  • http://apps.who.int/iris/bitstream/10665/79198/1/9789241505307_eng.pdf
    Long-term effects of breastfeeding, A Systematic Review, Bernardo L. Horta, MD, PhD, Cesar G. Victora, MD, PhD, World Health Organization (2013)

  • (**) These articles are available in PDF format if you email me requesting them.
  • (***) This article is available in RTF format if you email me requesting it.
  
   
• Press Coverage
  • http://www.mercurynews.com/mld/mercurynews/living/health/10512576.htm
    [The original URL does not work any more; a local copy is here: ( sjmerc_20041228_10512576.html )]
    "Mothers' milk may hold promise for ill adults -- SOME FIND BENEFITS FOR CANCER, OTHER SERIOUS DISEASES", San Jose Mercury News, 28 December 2004, page B1. This article briefly mentions me and my program.

  • http://www.telegraph.co.uk/news/main.jhtml;sessionid=G2AONU0000DPHQFIQMGCNAGAVCBQUJVC?xml=/news/2005/01/16/nteat16.xml&secureRefresh=true&_requestid=20958
    This URL no longer works, nor does searching for '"breast milk" cancer' on their web site, which is http://www.telegraph.co.uk/ (free registration required).
    [A local copy is here: (telegraphuk_20050116.html]
    "Adults turn to breast milk to ease effects of chemotherapy
    By Michael Day, Health Correspondent", published 16 January 2005

  • http://news.bbc.co.uk/2/hi/health/4187697.stm
    [If the original does not work, a local copy is here: ( bbc_20050123_4187697.stm.html )]
    "The man who swears by breast milk. A 59-year-old American has been drinking breast milk for the past four years in a bid to fight cancer." From the BBC news Health page, 23 Jan 2005. More focused on me, they got much of the information right but have a fairly skeptical tone, ignoring the scientific literature.
    bbc_comments_24Jan2005.html
    My letter to the BBC on their news story. They have not had the courtesy to respond to my critique of their unbalanced and distorted reporting.
     
  • http://cbs5.com/health/local_story_131150105.html
    A slightly different version was moved to http://cbs5.com/watercooler/Health.mothers.breast.2.284289.html
    [If the original does not work, a local copy of the text is cbs5_20070511_story.html]
    "Breast Milk as a Cancer Treatment?
    (CBS 5) SAN JOSE Making smoothies is routine for Howard Cohen. His concoctions contain yogurt, fruit and milk. But not any kind of milk. Cohen uses breast milk. ..." Another mostly contentless article, with some baseless "anti" opinions thrown in. This story ran on the 11 p.m. local news on the San Francisco CBS affiliate on Friday 11 May 2007. It originated with a news story syndication bureau, so it likely appeared on other CBS affiliates this same week. (I received feedback that it aired in various markets areound the U.S. through at least July 2007.)
     
  • http://www.myfoxchicago.com/dpp/news/Is_Human_Breast_Milk_a_Cure_for_Cancer
    Fox News from Chicago did a story on me which aired on 6 Nov 2007, titled "Is Human Breast Milk a Cure for Cancer?" and which was likely picked up and rebroadcast by other Fox affiliates in the U.S. (This web page contains a Flash copy of the short piece.) [A transcript I created may be found at http://www.cohensw.com/fox_transcript_20071106.html ]
     
  • http://www.ktvu.com/station/14619281/detail.html
    [If the original does not work, a local copy of the text is KTVU_20071116_14619281.html
    A story done by KTVU-TV, Oakland, California and aired on the 5:00 pm news, Friday 16 November 2007, titled "Palo Alto Man Fights Cancer With Unusual Treatment."
     
  • http://www.medicalhub.com.au/index.php?option=com_content&task=view&id=3188&Itemid=228
    Mother's milk: the pleasant panacea, Dr Fiona Giles, Sydney University 01 Apr 2009, MedicalHub.com.au, a web site for medical professionals in Western Australia.
     
  • http://jellytheory.blogspot.com/2009/06/june-interview-howard-cohen-on-fighting.html
    Jessica Lee's blog, Jelly Theory Interviews, Monthly interviews about the sweet, the opaque, the colorful, and all mixtures in between.
  
   
• Other People's Stories
  • http://money.cnn.com/magazines/fortune/fortune_archive/1996/05/13/212394/index.htm
    Taking on Prostate Cancer, Andy Grove's story, in the 13 May 1996 Fortune Magazine, well worth reading.
  • Reflections of a Prostate Cancer Patient, Ed DeHart, Urology, 48 (2), pp 171-177, (1996)
  • Man to Man - Surviving Prostate Cancer, Michael Korda, Vintage Books (New York), (1997) ISBN 0-679-78123-4
    A well written but harrowing account of Korda's radical prostatectomy and recovery from it.
  • http://www.prostate-help.org/
    (Formerly http://www.cooleyville.com/cancer)
    Don Cooley's extensive site with references, his story, and an email prostate cancer help site.
    Don underwent a combination of brachytherapy and EBRT at the Radiotherapy Clinics of Georgia (RCOG) ( http://www.prostrcision.com), which, he claims, is the best location in the U.S. for this type of treatment. .
  • http://www.roblesmar.com/
    (This site is no longer active as of June 2009.) Doug Thornton's story. Doug received proton beam therapy at Loma Linda and EBRT at UCSF. He is presently undergoing Dendritic Cell therapy at UCSF. Doug is an engineer and is well read on prostate cancer as he made his treatment decisions. He has been a Team Member of PHML (prostate help mailing list) assisting in its growth and development. Lots of additional references.
  • http://www.protons.com/
    The Loma Linda University Medical Center site used to host Nick DeWolf's experience with proton beam therapy, but no longer does. Nick died on 12 April 2006 of prostate cancer and a stroke, about 10 years after his initial cancer diagnosis. Memorials and obituaries may be found at http://www.psa-rising.com/blog/2006/05/nickdewolfe-obit/
    http://www.aspentimes.com/article/20060417/NEWS/104170023/0/FRONTPAGE
    
  • http://www.prostate90.com/
    Larry Clapp's web site. He is the Author of Prostate Health in 90 Days Without Drugs or Surgery (referenced below), and advocates a combination of alternative treatments which he says cured his prostate cancer.
  • http://www.phoenix5.org/essaysry/menuryessays.html
    Robert Vaughn Young's site. He was diagnosed in Nov 1999 with metastatic prostate cancer and a PSA over 1000. This link is to a powerful and honest set of essays, his emotional and treatment journal. The top level URL for his site is http://www.phoenix5.org, which also contains much useful information. Because of the stage of his disease, Mr. Vaughn used androgen deprivation therapy (ADT).
  • http://www.affirming.com/
    Affirming the Darkness, An Extended Conversation About Living With Prostate Cancer, Chuck & Martha Wheeler's site. Chuck died in 1994 of PCa, age 73. A book by this name exists, but the web site is no longer available (June 2009).
  • http://pcafamily.org/index.htm
    The entrance to two related web sites and organizations:
    • Family to Family (Americans for Prostate Cancer Awareness & Support)
    • Women's Suffrage for Prostate Cancer Awareness & Support
    The first offers advice and support to men, the second to the women involved with prostate cancer.
  • http://www.squarf.com/cancer.htm
    "Lorenzo Q. Scarf's" Prostate Cancer site, only slightly tongue in cheek and rather brilliant. Lorenzo was diagnosed in 1997, but opted to stay healthy by not breaking what seemed to be working very well, thank you. His story and philosophy, advocating, for most men, that we'd be better off without medical intervention and all of the likely nasty side effects. A refreshing contrarian viewpoint. As of 2003, he's alive and symptom free, enjoying life.
    As of June 2009, this web site is not operable. A small but significant subset may be found at http://www.prostatelab.com/squarf.htm
    
  • http://www.cancercurecoalition.org/articles/powertwo.html
    The story of a couple with multiple myeloma (the wife) and prostate cancer (the husband) and the nutritional/dietary/alternative approaches they took to controlling their disease.
  • http://dittany.googlepages.com/
    A wife's prostate cancer voyage.
    In the form of a BLOG (web log) or diary, with lots of embedded references and useful information from some newsgroup discussions.
  • http://home.earthlink.net/~dectiri/TheCure.htm The Cure
    A fable about mothers' milk and curing cancer, and a plea for help.
    http://home.earthlink.net/~dectiri/TheCure1.htm
    Comments on this web site, circa 2002.
  • http://www.cohensw.com/As_story.html
    A's husband had stage 4 colorectal cancer which had metastasized to his liver and was found in September 2007. Along with chemotherapy, he received milk from his wife who was nursing their child. After 9 months, the liver tumors were dead and the rectal and colon tumors had disappeared. This is a set of emails between us with the story unfolding. He is still cancer free as of May 2012 and has resumed drinking his wife's breast milk, after a second child was born.
  • http://humanmilktherapyforcancer.weebly.com/
    The story of a throat cancer patient who used mothers' milk to fight his metastatic and recurrent cancer and mitigate the side effects of chemotherapy and radiation therapy.
  • Walt D'Ardenne is a member of my support group. He was diagnosed in January 2002 with Gleason 4+4 PCa. This is his story and wisdom, including the guidelines he arrived at for dietary and medical interventions, as well as a set of external references he found useful: ftp://www.cohensw.com/pub/pca/WaltDs_PCa_Experience.pdf
    More recently (April 2010), he has created a web site with his ongoing experience and lessons learned: http://www.caringbridge.org/visit/whdpca (Free registration is required.)
  • Bob Whitesel was diagnosed with aggressive metastatic PCa in 2004. This blog is his story:
    http://pcaexperience.info/welcome/
  • Dana Jennings, a reporter for the New York Times, was diagnosed with prostate cancer in the spring of 2008 and opted for a radical prostatectomy. He has been writing a(n almost) weekly series of blogs on living with prostate cancer, which may be found at http://well.blogs.nytimes.com (go to the site and search on "prostate cancer" to get his posts, which are ongoing. Or try this page: http://well.blogs.nytimes.com/tag/jennings/. Some of them are, to date,
    
    • http://well.blogs.nytimes.com/2008/11/11/the-good-cancer/
    • http://well.blogs.nytimes.com/2008/11/18/real-men-get-prostate-cancer/
    • http://well.blogs.nytimes.com/2008/11/25/10-things-i-learned-from-prostate-cancer
      
    • http://well.blogs.nytimes.com/2008/12/02/after-cancer-the-echo-of-desire/
      
    • http://well.blogs.nytimes.com/2008/12/08/getting-angry-about-prostate-cancer/
      
    • http://well.blogs.nytimes.com/2008/12/15/prostate-cancer-in-the-flesh/
      
    • http://well.blogs.nytimes.com/2008/12/23/talking-about-prostate-cancer/
      
    • http://well.blogs.nytimes.com/2008/12/30/life-as-a-cancer-blogger/
      
    • http://well.blogs.nytimes.com/2009/01/06/the-song-of-my-prostate/
      
    • http://www.nytimes.com/2009/01/11/weekinreview/11jennings.html
      Notes to Soothe the Savage Cells, on music and cancer
      
    • http://well.blogs.nytimes.com/2009/01/20/the-glow-of-cancer/
      
    • http://well.blogs.nytimes.com/2009/01/29/a-conversation-about-prostate-cancer/
      A podcast of an interview on radio WNYC with Dana Jennings
    • http://www.nytimes.com/2009/01/27/health/views/27case.html
      Post-Op Strategies: Painkillers, to Start
      
    • http://well.blogs.nytimes.com/2009/02/03/after-prostate-cancer-treatment-uncertainty/
      
    • http://well.blogs.nytimes.com/2009/02/09/love-in-the-time-of-prostate-cancer/
      
    • http://well.blogs.nytimes.com/2009/02/17/the-many-shades-of-cancer-fatigue/
      
    • http://well.blogs.nytimes.com/2009/02/24/ask-your-questions-about-prostate-cancer/
      
    • http://well.blogs.nytimes.com/2009/03/03/living-with-incontinence-after-prostate-cancer/
      
    • http://www.nytimes.com/2009/03/10/health/10case.html
      Time Is a Trickster When Cancer Runs the Clock
      
    • http://well.blogs.nytimes.com/2009/03/23/the-impossible-calculus-of-psa-testing/
      
    • http://www.nytimes.com/2009/03/26/fashion/26skin.html
      With a Buzz Cut, I Can Take On Anything (also linked to from the next entry)
    • http://well.blogs.nytimes.com/2009/03/27/when-cancer-requires-a-new-hairstyle/
      
    • http://well.blogs.nytimes.com/2009/03/31/life-lessons-from-the-family-dog/
      
    • http://well.blogs.nytimes.com/2009/04/07/in-cancer-a-deeper-faith/
      
    • http://www.nytimes.com/2009/04/21/health/21case.html
      A Bond Shaped by Illness, but Not Defined by It (an article on the way prostate cancer altered his relationship with his son).
    • http://well.blogs.nytimes.com/2009/04/28/did-my-hometown-cause-my-cancer/
      
    • http://well.blogs.nytimes.com/2009/05/05/after-a-winter-of-cancer-the-optimism-of-spring/
    • http://www.nytimes.com/2009/05/19/health/19case.html
      Willing to Be Vulnerable: The Patient Grows Up
    • http://well.blogs.nytimes.com/2009/05/26/running-to-reclaim-your-body-from-cancer/
    • http://well.blogs.nytimes.com/2009/06/02/my-brief-life-as-a-woman/
    • http://well.blogs.nytimes.com/2009/06/16/a-wifes-view-of-prostate-cancer/
      
    • http://well.blogs.nytimes.com/2009/06/23/radiation-fears-poisoned-to-be-cured/
      
    • http://www.nytimes.com/2009/06/30/health/30case.html
      Losing a Comforting Ritual: Treatment
      
    • http://well.blogs.nytimes.com/2009/07/07/cancers-recovery-longer-than-you-think/
      
    • http://www.nytimes.com/2009/07/21/health/21case.htm
      Our Scars Tell the Stories of Our Lives
      
    • http://well.blogs.nytimes.com/2009/08/04/after-cancer-gratitude-for-simple-pleasures/
      
    • http://www.nytimes.com/2009/08/18/health/views/18cases.html
      Whispers From the Cancer Foxhole (When the Waiting Room is Quiet)
      
    • http://well.blogs.nytimes.com/2009/09/08/when-the-family-gets-cancer/
      
    • http://well.blogs.nytimes.com/2009/09/15/finding-my-inner-dog-through-cancer/
      
    • http://www.nytimes.com/2009/09/22/health/22case.html
      Pain Beyond Words, and an Impulse Just to Endure
      
    • http://well.blogs.nytimes.com/2009/09/29/after-cancer-treatment-waiting-for-the-sadness-to-lift/
    • http://www.nytimes.com/2009/10/20/health/20case.html
      At Home in Solitude as a Spirit Recovers
      
    • http://well.blogs.nytimes.com/2010/01/12/feeling-like-myself-again-after-cancer/
    • http://www.nytimes.com/2010/01/19/health/19case.html
      Healing Physically, Yet Still Not Whole
    • http://well.blogs.nytimes.com/2010/02/02/living-in-the-post-cancer-moment/
    • http://well.blogs.nytimes.com/2010/02/15/after-surviving-cancer-a-focus-on-true-manhood/
      Reflections on post treatment erectile dysfunction.
    • http://well.blogs.nytimes.com/2010/03/02/life-with-a-pouch-on-the-side/
      
    • http://well.blogs.nytimes.com/2010/03/15/with-cancer-lets-face-it-words-are-inadequate/
      
    • http://well.blogs.nytimes.com/2010/04/06/after-cancer-everyday-miracles/
      
    • http://well.blogs.nytimes.com/2010/04/19/in-blood-lifes-ebb-and-flow/
      
    • http://well.blogs.nytimes.com/2010/05/11/the-friendship-of-cancer/
      
    • http://well.blogs.nytimes.com/2010/05/24/a-return-to-normalcy-for-all-to-admire/
      
    • http://well.blogs.nytimes.com/2010/06/21/bidding-farewell-to-ghosts-of-pain/
      
    • http://well.blogs.nytimes.com/2010/08/10/an-old-dogs-new-tricks/
      
    • http://well.blogs.nytimes.com/2010/08/30/a-rush-to-operating-rooms-that-alters-mens-lives/
      
    • http://well.blogs.nytimes.com/2010/09/14/still-walking-in-my-cancer-shoes/
      
      
  • Mark Lichty, a practitioner of Active Surveillance for prostate cancer has three connected YouTube videos on his approach, which is mostly dietary. It was recorded 27 May 2007. They are
    • http://www.youtube.com/watch?amp;v=1wtNdvvzMsE
    • http://www.youtube.com/watch?amp;v=dGvugnkMqBY&feature=related
    • http://www.youtube.com/watch?amp;v=7ZuoigW0fYc&feature=related
  • Rabbi Ed Weinsberg has written a book about his experience with robotic surgery and its aftermath. His book is "[a]n inspiring physical, spiritual and emotional guide for boomer and senior prostate cancer patients, survivors and their loved ones." Published on October 2008, it is CONQUER PROSTATE CANCER, How Medicine, Faith, Love and Sex Can Renew Your Life, by Rabbi Ed Weinsberg, with Dr. Robert Carey. See http://conquerprostatecancernow.typepad.com/lp/
  • http://www.minofreund.org/
    Mino Freund was diagnosed with a grade-4 glioblastoma multiflori (gbm) (a particularly nasty and lethal brain cancer) in August 2009. He is director of research in nanotech and advanced things like satellite constellations, and the brain-nanotech interface, working at NASA. This blog is a moving journey (still on-going two years later) as he mixes Eastern and Western medicine, nutrition and psychology. Prostate cancer -- and all cancer -- warriors can learn much from him. He died on 17 January 2012 and his web site is no longer available. However, the latest capture of his site by the Internet Archive (27 April 2012) may be found at https://web.archive.org/web/20120427135848/http://www.minofreund.org/
  • Michael Slater (an obituary is at http://www.eetimes.com/document.asp?doc_id=1329955) did not have prostate cancer, nor did he use mothers' milk. In November 2015 he was diagnosed with terminal duodenal cancer and began a blog http://www.partingthoughts.net/category/my-cancer-story/ discussing his physical and emotional journey through treatments and living what remained of his life to the fullest. He died 18 June 2016. I found his writing honest and touching.
  • http://humanmilktherapyforcancer.weebly.com/index.html
    Cheryl Scott, RN, Ph.D., IBCLC, writes (2009-2013) about her "Sweetheart Bill"'s experience with metastatic throat cancer and the benefits of using mother's milk to treat it. These included
    • Protected and supported his immune system
    • Natural Tranquilizer: Assisted him to sleep soundly after his doses
    • Healed his bed sore (secondary to severe malnutrition) within 4 hours
    • Destroyed his cancer cells
    • Minimized mucositis (sores in throat and oral region from radiation)
    • Supported his T cell count and leukocyte count during chemo & radiation safeguarding Bill during his hospitalizations from nosicomial infections
    • As of April 2013: He is cancer free for over 2.5 years! His doctors are amazed and happy at how strong and lively he is!
  
   
• References on Naturopathy, Homeopathy, EAV and related topics, passed on from my Canadian contact
  • http://www.eav.org/
    (Select the English flag for an English language version of the site.)
  • http://www.oirf.com
  • http://www.vegatest.com/default_e.asp
  • http://www.med-tronik.de/home.html?&L=1
  • http://www.besthealth.com.au/Avatar.htm
  • http://www.startechhealth.com/
     
  • http://www.onlinehealthresources.com/Alternative/Holistic-and-Integrated-Medicine.html
    OnLine Health Resources Guide to Alternative and Integrative Medicine. This is essentially an organized list of web sites. There seems to be a lot of New Age quackery here, but also a lot of useful alternative approaches. The site is not specifically cancer oriented but deals with health and wellness in general.
  
   
• Magnetic Resonance Imaging and Spectroscopy (MRIS) References
  • Penelope Wood BS, John Kurhanewicz PhD, Daniel Vigneron PhD, Mark Swanson PhD, Saying Li MD, The Combined Role of MRI & MRSI in Treating Prostate Cancer, PCRInsights, Vol 3, No 2, August 2000, pp 1 - 10
    A good introduction and review article. Also available on the web as a downloadable PDF file, along with all previous issues, at http://www.prostate-cancer.org/resource/insights.html.
  • The UCSF Comprehensive Cancer Center Report, vol 8.3, Fall 2006, has a short summary article on "Harnessing the Power of Magnetic Resonance to Interrogate Tumors". The PDF is downloadable from http://cancer.ucsf.edu/ccr/index.php (Scroll down to the appropriate issue.)
  • John Kurhanewicz PhD, Daniel B. Vigneron PhD, Sarah J. Nelson PhD, Hedvig Hricak MD PhD, Jerrrey M. McDonald PhD, Badrinath Konety MD, Perinchery Narayan MD, Citrate as an in vivo Marker to Discriminate Prostate Cancer From Benign Prostatic Hyperplasia and Normal Prostate Peripheral Zone: Detection via Localized Proton Spectroscopy, Urology, Vol 45, No 3, March 1995, pp 459-466
  • Yasushi Kaji MD, John Kurhanewicz PhD, Hedvig Hricak MD PhD, Dahlia L. Sokolov BS, L. Royal Huang PhD, Sarah J. Nelson PhD, Daniel B. Vigneron PhD, Localizing Prostate Cancer in the Presence of Postbiopsy Changes on MR Images: Role of Proton MR Spectroscopic Imaging, Radiology, Vol 206, No 3, March 1998, pp 785-790
  • John Kurhanewicz PhD, Daniel B. Vigneron PhD, Ryan G. Males PhD, Mark G. Swanson PhD, Kyle K. Yu MD, and Hedvig Hricak MD PhD, The Prostate: MR Imaging and Spectroscopy - Present and Future, Radiologic Clinics of North America, Vol 38, Num 1, January 2000, pp 115-138 (with 104 references)
  • John Kurhanewicz, Daniel B. Vigneron and Sarah J. Nelson, Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer, Neoplasia, Vol 2, Nos 1-2, Jan-Apr 2000, pp 166-189 (with 200 references)
  • A. E. Wefer, H. Hricak, D. B. Vigneron, F. V. Coakley. Y. Lu, J. Wefer, U. Mueller-Lisse, P. R. Carroll, J. Kurhanewicz, Sextant Localization of Prostate Cancer: Comparison of Sextant Biopsy, Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging With Step Section Histology, The Journal of Urology, Vol 164, August 2000, pp 400-404 (with 15 references)
  • http://www.gehealthcare.com/usen/mr/applications/products/prose.html
    "Magnetic Resonance Imaging - Sigma Infinity 1.5T - Prostate Spectroscopy/Imaging Exam", John Kurhanewicz
    Some case studies and sample images from prostate MRSI studies. This page is a blurb for the commercial package GE has put together based on the research of the UCSF Radiology group over the past decade or so.
  • http://defeatosteosarcoma.org/2010/11/new-prostate-cancer-imaging-shows-real-time-tumor-metabolism/
    New prostate cancer imaging shows real-time tumor metabolism (Posted 30 Nov 2010)
    "A UCSF research collaboration with GE Healthcare has produced the first results in humans of a new technology that promises to rapidly assess the presence and aggressiveness of prostate tumors in real time, by imaging the tumor’s metabolism...." This is an extension of the MRSI technology discussed above. A special magnetized preparation of pyruvate is infused, and its real-time transformation into lactate is followed in the MRI. Results are prognostic of tumor aggressiveness and extent. The article notes the resolution is 50,000 times greater than previous techology allowed. This is still, however, in an early research phase.
  • http://prostate-cancer.org/PDFs/QualityMRICenters.pdf
    A list of sites where 3T MRSI is available, from the PCRI web site (added 20 Nov 2014)
  • http://paactusa.org/blog/adding-multiparametric-mri-to-prostate-cancer-screening-will-save-lives-and-money/
    Adding Multiparametric MRI to Prostate Cancer Screening Will Save Lives and Money by PAACT Inc. (14 July 2015), Robert Princenthal, MD, Rolling Oaks Radiology, Ventura County, California
    An overview of PCA diagnostics with an emphasis on the utility of Multiparametric MRI.

    The following references are provided (as of March 2006) in an MRSI Radiology Report:
     

  • A. V. D'Amico, R. Whittington, B. Malkowicz, et al, Endorectal magnetic resonance imaging as a predictor of biochemical outcome after radical prostatectomy in men with clinically localized prostate cancer, Journal of Urology 2000; 164: 759-763.
  • F.V. Coakley, J. Kurhanewicz, Y Lu, et al, Prostate cancer tumor volume: Measurement with endorectal MR and MR spectroscopic imaging, Radiology 2002; 223: 91-97
  • F.V. Coakley, S. Eberhardt, D.C. Wei, et al, Blood loss during radical retropubic prostatectomy: relationship to morphologic features on preoperative endorectal magnetic resonance imaging, Urology 2002; 59: 884-888
  • F.V. Coakley, S. Eberhardt, M.W. Kattam, et al, Urinary continence after radical retropubic prostatectomy: relationship with membranous urethral length on preoperative endorectal magnetic resonance imaging, Journal of Urology 2002; 168: 1032-1035
  • D.H. Clarke, S.J. Banks, A.R. Wiederhorn, et al, The role of endorectal coil MRI in patient selection and treatment planning for prostate seed implants, International Journal of Radiation Oncology Biology Physics 2003; 52: 903-910
  • B. Pickett, J. Kurhanewicz, B. Fein, et al, Use of magnetic resonance imaging and spectroscopy in the evaluation of external beam radiation therapy for prostate cancer, International Journal of Radiation Oncology Biology Physics 203; 57: S163-164
  • A. Qayyum, F.V. Coakley, Y. Lu, et al, Organ-confined prostate cancer: effect of prior transrectal biopsy on endorectal MRI and MR spectroscopic imaging, American Journal of Roentgenology 2004; 183: 1079-1083
  • H. Hricak, L. Wang, D.C. Wei, et al, The role of preoperative endorectal magnetic resonce imaging in the decision regarding whether to preserve or resect neurovascular bundles during radical retropubic prostatectomy, Cancer 2004; 100: 2655-63
  • L. Wang, M. Mullerad, H.N. Chen, et al, Prostate cancer: incremental value of endorectal MR imaging findingd for prediction of extracapsular extension, Radiology 2004; 232: 133-139
  • F.V. Coakley, H.S. Teh, A. Qayyam, et al, Endorectal MR imaging and MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: Preliminary experience , Radiology 2004; 233: 441-44
  
   
• Power Doppler Ultrasound
  • http://www.prostate-cancer.org/education/staging/Bahn_ColorDopplerUltrasound.html
    Color Doppler and Tissue Harmonic Ultrasound in the Early Detection and Staging of Prostate Cancer, Duke K. Bahn, M.D., Prostate Institute of America, Reprinted from PCRI Insights November 2002 v5.2
    An overview of the technique by one of the renowned practitioners.
  
   
• Diana Schwarzbein's books on Diet & Nutrition
  • The Schwarzbein Principle, Diana Schwarzbein MD and Nancy Deville, Health Communications, Inc. (Deerfield Beach, FL) (1999) ISBN 1-55874-680-1
  • The Schwarzbein Principle Cookbook, Diana Schwarzbein MD, Nancy Deville, and Evelyn Jacob Jaffe, Health Communications, Inc. (Deerfield Beach, FL) (1999) ISBN 1-55874-681-1
  • The Schwarzbein Principle Vegetarian Cookbook, Diana Schwarzbein MD, Nancy Deville and Evelyn Jacob Jaffe, Health Comunications, Inc. (Deerfield Beach, FL) (1999) ISBN 1-55874-682-X
  
   
• Dietary Overviews
  • The ABC's of Nutrition and Supplements for Prostate Cancer, Mark A. Moyad, Sleeping Bear Press (Chelsea, MI) (2000) ISBN 1-88694769-4
    A level headed summary of peer-reviewed literature on the subject.
  • The Moyad Medical Journal
    A quarterly journal on nutrition, summarizing peer-reviewed literature. One of its emphases is on prostate cancer.
    As of 8 August 2001, it is no longer being published. The letter I received states that "In the future, Mark Moyad hopes to make the Moyad Health Journal available on-line at no charge. We will notify you when this becomes available."
  • http://www.pmri.org Dean Ornish's Preventive Medicine Research Institute
    They have run some successful studies in both prostate cancer and heart disease treatment using dietary modifications, exercise, stress reduction and social support. They are always looking for qualified volunteers for their program.
  • http://www.ucsfhealth.org/adult/medical_services/cancer/urologic/nutrition.html
    A good, commonsensical overview of diet and prostate cancer from the UCSF Urologic Oncology Department.
  • http:/www.islandnet.com/~hoffer/homepage.htm Abram Hoffer's home page
    Dr. Hoffer has a Ph.D. in Biochemistry and is an M.D. and a psychiatrist. He is one of the founders of orthomolecular medicine, co-author of a number of papers with Linus Pauling. Dr. Pauling followed Hoffer's dietary program (as well as conventional medical approaches) when treating the prostate cancer he contracted at age 92. An interesting summary of approaches to preventing and treating cancer.
     
  • http://urology.medscape.com/reuters/prof/2002/01/01.02/20020101clin004.html
    (This URL is no longer available.) A short 10 person study at UCSD showed that in some cases a vegetarian diet combined with stress management could slow or reverse PSA growth. The population had already had radical prostatectomies and rising PSAs. See J Urol 2001;166:2202-2207. (Dec 2001). This seems similar to Dean Ornish's program.
     
  • T. Colin Campbell and his colleagues did a long term multi-cultural study correlating diet and incidence of disease, published in 2005 as The China Study. They found that the greater the dietary intake of meat based protein and of dairy, the higher the incidence of "Western" diseases, such as cancers, diabetes, macular degeneration and coronary conditions. See, for example,
    • http://www.thechinastudy.com/about.html
    • http://en.wikipedia.org/wiki/The_China_Study
    • http://www.mcspotlight.org/media/reports/campbell_china2.html
    
     
  • http://www.ucsf.edu/news/2005/08/6319/lifestyle-and-diet-may-stop-or-reverse-prostate-cancer-progression
    A UCSF article (12 August 2005) about the positive effects of a Dean Ornish style program (vegan diet, moderate exercise, meditation, social support) on men using active surveillance. PCa progression was moderated or reversed in this cohort; a control group showed no such positive effects.
     
  • http://www3.interscience.wiley.com/cgi-bin/fulltext/122296322/HTMLSTART
    A systematic review of the effect of diet in prostate cancer prevention and treatment, R. W.-L. Ma & K. Chapman, Journal of Human Nutrition and Dietetics, Volume 22, Issue 3, Pages 187-199, Published Online: 1 Apr 2009
    "[T]he current data are indicative that a diet low in fat, high in vegetables and fruits, and avoiding high energy intake, excessive meat, excessive dairy products and calcium intake, is possibly effective in preventing PC. However, caution must be taken to ensure that members of the public do not take excessive amounts of dietary supplements because there may be adverse affects associated with their over consumption. The dietary recommendations for patients diagnosed with PC are similar to those aiming to reduce their risk of PC." The review also found there is evidence that eating healthier may help slow tumor progression in men who have prostate cancer.
     
  • http://urology.ucsf.edu/patientguides/pdf/uroOnc/Nutrition_Prostate.pdf
    A 44 page guide on Nutrition and Prostate Cancer (December 2009) from UCSF. It explains the theory, includes meal plans and some recipes, as well as references and a glossary. Authored by Natalie Ledesma, MS, RD, DSO.
     
  • http://www.huffingtonpost.com/david-katz-md/nature-nurture-fate_b_681732.html
    How You Nurture Your Health Could Change Your Genetic Nature, David Katz, M.D. (Dr. Katz is the Director of Yale University's Prevention Research Center) (August 20, 2010)
    In this post, Dr. Katz discusses research by Dr. Dean Ornish and UCSF showing how diet and lifestyle affect gene expression in tumor cells -- following the Ornish program for 3 months had post-program prostate cancer biopsy samples compared to pre-program prostate cancer biopsy samples. "Roughly 50 genes associated with cancer suppression became more active in generating RNA, and nearly 500 genes associated with cancer progression became less active. The pattern of change observed in gene activity was consistently, and decisively associated with lower risk of cancer development and progression."
  
   
• Nutrition and Herbs Overviews
  • http://www.nutrasanus.com
    NutraSanus - A non-commercial natural health, nutrition and herbal supplements directory. "Review a comprehensive directory providing current information on natural healthcare, alternative medicine, herbal remedies and health nutrition."
  
   
• Selenium

  Selenium helps prevent prostate cancer
  

  • http://www.jurology.com/article/S0022-5347(05)65500-0/abstract
    PLASMA SELENIUM LEVEL BEFORE DIAGNOSIS AND THE RISK OF PROSTATE CANCER DEVELOPMENT (Abstract of J. Urology 2001, vol 166, pp 2034-2038)
    
  • http://tigger.uic.edu/htbin/cgiwrap/bin/newsbureau/cgi-bin/index.cgi?from=Releases&to=Release&id=1501
    Press release from U Illinois Chicago (23 May 2006) on a study published in the Proceedings of the National Academy of Science: Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model, PNAS 2006 103: 8179-8184; (23 May 2006) 10.1073/pnas.0508218103. Full text available at http://www.pnas.org/content/103/21/8179.full
  
   
• Vitamin D
  • Higher Vitamin D levels are associated with less risk of cancer and less aggressive cancers, including prostate, breast and colon cancers.
  • http://www.nature.com/bjc/journal/v100/n3/abs/6604865a.html
    Association between serum 25(OH)D and death from prostate cancer, S Tretli, E Hernes, J P Berg, U E Hestvik and T E Robsahm, British Journal of Cancer (2009) 100, 450-454 (Published online 20 January 2009) This is the abstract only; full text is available for purchase.
  • http://articles.mercola.com/sites/articles/archive/2009/03/19/Slash-Your-Prostate-Cancer-Risk-With-Sunlight.aspx
    A summary of the BJC article with further information about Vitamin D.
  • http://www.johnshopkinshealthalerts.com/reports/prostate_disorders/3115-1.html
    "Vitamin D may turn out to be a ray of hope for men with prostate cancer. Laboratory and population-based research suggest that adequate levels of vitamin D reduce the risk of developing prostate cancer and may help suppress the growth and spread of prostate cancer cells in men who already have it. A significant proportion of older men have suboptimal levels of vitamin D, especially during the winter and spring months. But boosting your vitamin D levels isn't difficult.... When choosing a supplement, look for one that contains vitamin D3, which is more effective than vitamin D2."
  • http://www.foodconsumer.org/newsite/Nutrition/Vitamins/070920090906_vitamin_d_what_you_need_to_know.html
    Vitamin D: What you need to know -- A brief summary article
  • http://articles.mercola.com/sites/articles/archive/2009/11/26/Want-to-live-longer-Try-Vitamin-D.aspx
    A discussion of several journal articles correlating Vitamin D levels with disease risk (overall, cardiovascular, cancer) and suggesting optimal blood levels.
  • http://www.medscape.com/viewarticle/712529
    Vitamin D Supplementation and Cancer Prevention, Thomas L. Lenz, Posted: 12/08/2009; Am J Lifestyle Med. 2009;3(5):365-368
    "The purpose of this article is to briefly review the physiology behind vitamin D, provide an overview of key research linking vitamin D intake with decreased cancer risk, and present the current recommendations for vitamin D intake."
  • http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2bTumors&d_id=148&i=September+2012&i_id=887&a_id=21704
    Prostate Cancer: Low-Cost Interventions, a summary of some results from the 2012 American Association for Cancer Research meeting. Discusses Vitamin D, Metformin, treating obesity, and some new drugs for Castration Resistent Prostate Cancer. In particular, those men on higher doses (3 groups, 400 IU/day, 10,000 IU/day and 40,000 IU/day) had better markers for less metastasis and slower cancer growth, with no adverse effects at any dose. (There were only about 20 men with Gleason 6 or 7 in each group, and they used the Vitamin D for 4 to 8 weeks before radical prostatectomy. At higher doses, blood levels should be checked periodically and should remain less than 100.) A study cited found higher blood levels decrease the risk of aggressive PCa.
  
   
• Vitamin E
  • Vitamin E Suppresses Androgen Receptor and PSA Expression in PCa
    http://www.pnas.org/content/99/11/7408.full
    Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells, Yu Zhang, Jing Ni, Edward M. Messing, Eugene Chang, Chin-Rang Yang, and Shuyuan Yeh, Proceedings of the National Academy of Sciences, May 28, 2002, vol. 99, no. 11, pp. 7408-7413
  • Researchers Make Vitamin E Offshoot A Potent Cancer Killer
    http://researchnews.osu.edu/archive/vitesuccin.htm
    A press release from Ohio State University, 19 May 2006. A modified form of alpha-tocopherol was found to have anti-oxidant as well as anti-cancer effects. This describes the article
    Chung-Wai Shiau, Jui-Wen Huang, Da-Sheng Wang, Jing-Ru Weng, Chih-Cheng Yang, Chia-Hui Lin, Chenglong Li, and Ching-Shih Chen {alpha}-Tocopheryl Succinate Induces Apoptosis in Prostate Cancer Cells in Part through Inhibition of Bcl-xL/Bcl-2 Function J. Biol. Chem., Apr 2006; 281: 11819 - 11825 ; doi:10.1074/jbc.M511015200, which is available at http://www.jbc.org/cgi/content/full/281/17/11819/
    The study to this point was strictly in vitro.
  
   
• pau d'arco refs
  • http://www.rain-tree.com/paudarco.htm
    A good summary of pau d'arco's uses and background, with references.
  • http://www.rain-tree.com/clinic/clinicp.htm
    A more extensive bibliography, with some abstracts from the refereed medical and ethnobotanical literature
  • http://healthfree.com/herb_lapacho.html
    A pamphlet also discussing the history and clinical uses of pau d'arco, which is also known as lapacho.
  • < http://home.global.co.za/~mikemat/plants10.html
    Web page no longer available. Contains a picture of the tree's flowers, a botanical summary, and a set of references
  • http://www.asktom-naturally.com/naturally/lapacho.html
    A short article from the June-July 1997 Health Store News
  • http://www.asktom-naturally.com/naturally/lapacho3.html
    A longer article from the Feb-Mar 1996 Health Store News
  • http://www.quackwatch.com/01QuackeryRelatedTopics/OTA/ota04.html
    Contains a discussion of the positive effects of pau d'arco on some cancers, critiques of the nature of some of the studies done. Also contains a discussion of Essiac, the Hoxsey Treatment, and several other herbal-based approaches to cancer treatment.
  • http://biotech.icmb.utexas.edu/botany/laphist.html
    A short skeptical blurb containing a nice color picture of the Tabebuia flower.
  • http://www.bccancer.bc.ca/HPI/UnconventionalTherapies/PauDArco.htm
    The British Columbia (Canada) Cancer Agency has a host of information. This particular page contains some quotes and skepticism about pau d'arco, and a few additional references. This is part of a set of references on Unconventional Cancer Therapies. Their top-level page is noted above.
     
  • http://urology.medscape.com/ASHP/AJHP/2000/v57.n12/ajhp5712.01.gran/ajhp5712.01.gran.html
    A brief reference (no longer available as of June 2009) about the medicinal properties of tumeric. One needs a (free) registration to Medscape to see this paper. (Full reference is American Journal of Health-System Pharmacy, 57(12), pp 1121-1122, 15 July 2000
  • http://www.lef.org/magazine/mag2001/aug2001_itn.html
    A short article about the anti-cancer aspects of curcumin, a major active ingredient in tumeric (with literature references).
  
   
• pygeum refs
  • http://urology.medscape.com/ASHP/AJHP/2001/v58.n02/ajhp5802.01.mcqu/ajhp5802.01.mcqu.html
    An overview of pygeum from the American Journal of Health-System Pharmacy. This web page is no longer available as of June 2009.
  
   
• Green Tea refs
  • http://www.pnas.org/content/98/18/10350.full
    Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols, Sanjay Gupta, Kedar Hastak, Nihal Ahmad, Jonathan S. Lewin, and Hasan Mukhtar, Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 18, 10350-10355, August 28, 2001
    The abstract is available at http://www.pnas.org/content/98/18/10350.abstract]
    The equivalent of 6 cups of green tea a day decreased the incidence and extent of prostate cancer in mice bred to have 100% incidence. Onset was delayed or eliminated, life expectancy increased 70%.
  • http://www.lef.org/magazine/mag2004/dec2004_supp_green_01.htm
    http://www.lef.org/magazine/mag99/june99-report2.html
    http://www.lef.org/magazine/mag98/may98_tea.html
    Some LEF articles on green tea. Again, interesting info is available here, mixed in with the sales spiel.
  • http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/1940-6207.CAPR-08-0167v1
    Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In vitro, Jerry McLarty, Rebecca L.H. Bigelow, Mylinh Smith, Don Elmajian, Murali Ankem and James A. Cardell, Published Online First on June 19, 2009 [Cancer Prevention Research, 10.1158/1940-6207.CAPR-08-0167]. This is a link to the abstract; full article available for purchase.
    Active compounds in green tea may slow the progression of prostate cancer. The study also showed that green tea might lower the incidence of prostate cancer in the first place. The study is one of the few green tea trials that evaluated biomarkers in order to predict prostate cancer’s progression,
  
   
• Alpha-lipoic Acid refs
  • http://en.wikipedia.org/wiki/Lipoic_acid
  • http://www.berkeleywellness.com/html/ds/dsAlphaLipoicAcid.php
  • http://www.wholehealthmd.com/ME2/dirmod.asp?sid=17E09E7CFFF640448FFB0B4FC1B7FEF0&nm=Reference+Library&type=AWHN_Supplements&mod=Supplements&mid=&id=37ED2328B8FB4A6EB021C382E2452530&tier=2
  • (These are but 3 of the 1,300,000 hits returned on a Google search in June 2009)

   

• Pomegranate Juice
  • An article in Clinical Cancer Research of 1 July 2006 discussed a Phase II study in which men who had been treated either with radiation or radical prostatectomy and had rising PSAs were given 8 ounces of pomegranate juice a day. On the average, their PSA doubling times changed from 15 months before treatment to 54 months after treatment. Some men had significant decreases in PSA. The reference is Phase II Study of Pomegranate Juice for Men with Rising Prostate-Specific Antigen following Surgery or Radiation for Prostate Cancer, Allan J. Pantuck, John T. Leppert, Nancy Zomorodian, William Aronson, Jenny Hong, R. James Barnard, Navindra Seeram, Harley Liker, Heijing Wang, Robert Elashoff, David Heber, Michael Aviram, Louis Ignarro, Arie Belldegrun, Clinical Cancer Research 2006; 12(13), July 1 2006, pp 4018-4026.
    A web link is http://clincancerres.aacrjournals.org/content/vol12/issue13/
    which requires payment or a subscription. It may also be downloaded from ftp://www.cohensw.com/pub/pca/PomegranatesProstateCa_ClinCancRes_2006_12_13_4018.pdf

    The article also contains a good, though short, description of the relationship between inflammation and oncogenesis. (See below)

   

• PollenAid
  • http://www.graminex.com/products/pollenaid.php
    They claim this product
    • Reduces the size and the congestion of the prostate cells.
    • Urinary flow, rate and clearance is improved via the action on the smooth muscle tissue that lines the urinary system.
    • Flower Pollen effects the metabolism of DHT (dihydrotestosterone) and prohibits the production.

   

• Flax Seed
  • http://www.sciencedaily.com/releases/2001/07/010712080024.htm
    New Pilot Study Suggests Flaxseed And Low-Fat Diet Can Be Protective Against Prostate Cancer, ScienceDaily (Jul. 12, 2001)
  
   
• Conjugated Linoleic Acid (Cla)
  • http://www.ustoo.org/Hot_Sheets_2002.asp
    (Download the June 2002 issue as a PDF and see page 2, top of middle column.)
    The 28 March 2002 issue of Cancer Letters (vol 177, pp 163-172) had an article by Harvard Medical School researchers, indicating that CLA, an omega-6 fatty acid, can inhibit tumor growth and proliferation of human cancer cells. CLA also helps maintain a healthy heart and veins, maintain healthy cholesterol and triglyceride levels, act as an anti-oxidant and possesses anti-atherogenic properties. Recent human studies appear to indicate positive effects in helping to control plasma lipids, blood glucose and body weight when used in conjunction with diet and exercise.
     
  • http://www.health-n-energy.com/cla.htm
    More about CLA from a company selling it.

   

• Trans Rectal Ultrasound
  • http://www.moffitt.org/moffittapps/ccj/v8n2/toc.htm
    Transrectal Ultrasound and Biopsy in the Early Diagnosis of Prostate Cancer, Jefferey C. Applewhite, MD, Brian R. Matlaga, MD, MPH, David L. McCullough, MD, and M. Craig Hall, MD, in Cancer Control, JMCC 8(2) 141-150 (2001)
    A good review of the history of TRUS as well as a thorough discussion of biopsy strategy for most efficient detection of prostate cancer. The standard 6-core approach is noted to be significantly inferior to 10-core and related strategies. The full text is downloadable as a PDF from this URL.

   

• Gleason Score
  • The Gleason Score: A Significant Biologic Manifestation of Prostate Cancer Aggressiveness on Biopsy, Gerry J. Dowd, Robert W. Veltri, M. Craig Miller, and Stephen B. Strum, PCRInsights, Vol 4, No 1, January 2001, pp 1 - 5
    A good introduction and review article. Also available on the web as a downloadable PDF file, along with all previous issues, at http://www.prostatepointers.org/a27dsk329.html.
  • http://www.scprostate.org/news_archive/2010_03.html
    The article AN UPDATE OF THE GLEASON GRADING SYSTEM contains information (as of December 2009) on modifications to the Gleason scoring system, based on J Urol. 2010 Feb;183(2):433-40. Epub 2009 Dec 14. ( http://www.jurology.com/article/S0022-5347(09)02704-9/abstract -- full article is available for purchase.)
  
   
• Radical Prostatectomy
  • http://urology.jhu.edu/prostate/RRPdraw.php
    A very visual description of the surgery by its inventor, Dr. Patrick Walsh and his colleagues Arthur L. Brunett, MD and Alan W. Partin, MD, PhD. The presentation was originally written in 1993.
    See also additional resources at http://urology.jhu.edu/prostate/cancer.php
  • http://www.medscape.com/viewarticle/426777
    Radical Prostatectomy in the Management of Clinically Localized Prostate Cancer, Raviender Bukkapatnam, MD, and Julio M. Pow-Sang, MD, Cancer Control 8(6):496-502, 2001.
    A more modern summary of the procedure, including a discussion of laparoscopic techniques.
  • http://pqasb.pqarchiver.com/washingtonpost/access/209592671.html?dids=209592671:209592671&FMT=ABS&FMTS=ABS:FT&fmac=&date=Oct+15%2C+2002&author=Sandra+G.+Boodman&desc=Less+Invasive%2C+More+Questions%3B+Experts+Debate+the+Benefits+of+Laparoscopic+Prostate+Surgery
    Had been at http://www.washingtonpost.com/wp-dyn/articles/A25443-2002Oct14.html
    A Washington Post article from 15 October 2002 on laparoscopic prostate surgery, with pros, cons and a graphic. Abstract is available for free, full article is now for sale.
  • http://nyp.org/news/hospital/robotic-prostatectomy-technique.html
    New Catheter-less Technique May Ease the Pain and Discomfort of Prostate Cancer Recovery when used with robotic laparoscopic surgery. This is a press release from NewYork-Presbyterian/Weill Cornell Medical Center (2 Oct 2008)
  • http://www.nytimes.com/2010/02/14/health/14robot.html
    Results Unproven, Robotic Surgery Wins Converts, Gina Kolata (13 February 2010) -- A status report on robotic radical prostatectomies versus laparoscopic and open surgeries.
  
   
• Radiation Therapies
  • http://caonline.amcancersoc.org/cgi/reprint/50/6/349 External Beam Radiation Therapy for Prostate Cancer, Eric M. Horowitz MD, Gerald E. Hanks MD, CA: A Cancer Journal for Clinicians, Vol 50, No 6, November/December 2000, pp 349-375
    An overview of the history, technology and statistics of various approaches to external beam radiation therapies.
    This link allows the free download of a PDF of the article.
  • http://www.docguide.com/news/content.nsf/news/852576140048867C852577B6005CCDA1?Open&id=48DDE4A73E09A969852568880078C249&count=10
    Cancer Associated With a Greater Risk of Local Second Malignancy: Presented at ACS (8 October 2010). "Patients who receive radiation therapy for prostate cancer have a 3.5-times greater risk of developing a second malignancy, according to a study presented here at the 96th Annual Clinical Congress of the American College of Surgeons (ACS)...."
  
   
• Brachytherapy
  • http://www.americanbrachytherapy.org/
    The American Brachytherapy Society web site
  • http://www.nocancer.com/
    Stephen W. Doggett MD's site. Dr. Doggett practices in southern California an advanced approach to brachytherapy, involving real-time imaging and plan modification. His site contains a good tutorial on his techniques, with images.
  
   
• Hormone Therapy Discussions
  • http://www.lef.org/protocols/prtcl-138.shtml
    Life Extension Foundation's overview on Prostate Cancer
  • http://www.lef.org/protocols/prtcl-093.shtml
    Their overview on Early Stage Prostate Cancer
    They are selling products, but have an interesting and accessible discussion of nutritionally oriented information.
     
  • http://cme.medscape.com/viewarticle/416543
    Current Issues in the Management of Prostate Cancer: Charles Huggins Symposium. This CME (Continuing Medical Education) activity is based on transcripts and slides of presentations as delivered by the faculty at "Current Issues in the Management of Prostate Cancer: Charles Huggins Symposium" held just prior to AUA's 96th Annual Meeting at the Hilton Anaheim, Anaheim, California, on June 1, 2001, published 28 September 2001.
  • http://compassionateoncology.org/
    The web site of Doctor Bob Liebowitz and Steven Tucker's Compassionate Oncology Medical Group in Los Angeles. They have been on the forefront of the application of triple hormonal blockade therapies in prostate cancer.
     
  • http://www.prostate-cancer.org/education/andeprv/Myers_HormonalTherapyDiet.html
    Beating Prostate Cancer with Hormonal Therapy, Charles E. (Snuffy) Myers, M.D, Reprinted from PCRI Insights May, 2007 v 10.2
    Dr. Myers, a urologic oncologist, was himself diagnosed with aggressive prostate cancer at age 55 in 1999. In this article he talks about myths about hormonal blockade, about the positive effects of attitude, and how hormonal blockade can be an effective therapy, even for many advanced cases of PCa.
     
  • http://www.cancernetwork.com/display/article/10165/1646741
    Androgen Deprivation Therapy: A Survival Benefit or Detriment in Men With High-Risk Prostate Cancer?, L. Christine Fang, MD, Gregory S. Merrick, MD, Kent E. Wallner, MD, ONCOLOGY. Vol. 24 No. 9 (August 24, 2010)
    An overview of the positive and negative aspects of ADT, both as a mono-therapy and as an adjuvant therapy.
  • http://www.medpagetoday.com/Urology/ProstateCancer/22887
    "The FDA has asked manufacturers of gonadotropin-releasing hormone (GnRH) agonists -- a class of drugs used primarily to treat prostate cancer -- to add new warnings about the potential risk for heart disease and diabetes....Earlier this year, the American Heart Association, the American Urological Association, and the American Cancer Society issued a joint advisory warning of the increased risks of diabetes, myocardial infarction, stroke, and sudden death among men who use androgen deprivation therapy (ADT) to treat prostate cancer. GnRH is the most common form of ADT..." (20 Oct 2010)
  
   
• Cryosurgery
  • http://www.medinfosource.com/gt/g010537.html
    Prostate Cancer Management and Cryosurgery in Older Adults, Ronald M. Benoit, M.D., Jeffrey K. Cohen, M.D., and Ralph J. Miller Jr., M.D., Geriatric Times, May/June 2001, Vol. II, Issue 3
    An overview of treatment options for older men with an emphasis on cryosurgery.
    Not available as of June 2009.
  • http://www.hopeforprostatecancer.com/
    The website of Dr. Gary Onik and Florida Hospital/Celebration Health. Dr. Onik is the inventor and pioneer of ultrasound guided cryosurgery for both the prostate and the liver, and an advocate of prostate lumpectomy as well as 3D Prostate Mapping Biopsy. These are discussed on this site.
  
   
• Chemotherapy
  • http://www.medscape.com/viewarticle/424627
    The Treatment Challenge of Hormone-Refractory Prostate Cancer, Julie A. Kish, MD, Raviender Bukkapatnam, MD, and Felipe Palazzo, MD, Cancer Care 8(6):487-495, 2001.
    A summary of current and experimental chemotherapy approaches, with an emphasis on HPRC.
     
  • http://www.vancouversun.com/health/cancer+drug+will+prolong+lives+Vancouver+scientists/3452755/story.html
    New cancer drug will prolong lives, Vancouver scientists say, Tiffany Crawford, Vancouver Sun August 27, 2010
    OncoGenex Technologies, a University of British Columbia spinoff company, has licensed the drug OGX-011. In Phase 2 clinical trials, scientists discovered that the drug OGX-011 will extend a patient's life by about seven months, roughly double the life expectancy of chemotherapy alone in hormone resistant prostate cancer. The drug is given in conjunction with docetaxel and prednisone, and serves to inhibit the production of a gene protein called clusterin that protects cancer cells from cancer treatments, such as radiation and chemotherapy.

   

• PSA Controversy

  There has been an on going controversy on the overall utility of PSA testing and whether too many men with indolent cancer have their prostate cancers detected with this test, are treated when it is unnecessary to do so, and suffer the expense and side effects of treatment; or whether enough lives are saved by earlier detection for the PSA test to be promoted. Certainly, better tests which could indicate which cancers were aggressive and which indolent are to be desired.

  • http://www.nytimes.com/2009/03/19/health/19cancer.html
    Prostate Cancer Test Found to Save Few Lives
    An article summarizing two large studies on this subject (the next two references)
  • http://content.nejm.org/cgi/content/full/NEJMoa0810696
    Mortality Results from a Randomized Prostate-Cancer Screening Trial , Gerald L. Andriole, M.D., et alia, New England Journal of Medicine (18 March 2009)
  • http://content.nejm.org/cgi/content/full/NEJMoa0810084
    Screening and Prostate-Cancer Mortality in a Randomized European Study, Fritz H. Schröder, M.D., et alia, New England Journal of Medicine (18 March 2009)
  • http://www.nytimes.com/2009/03/24/health/24well.html
    Screen or Not? What Those Prostate Studies Mean -- A discussion of the ambiguities of the two previous studies.
  • http://www.ustoo.org/UsTOOAdvocacyAlertV7.asp
    Us TOO and 13 of America's prostate cancer organizations issue reaction to the PSA screening studies (23 March 2009)
  • http://health.usnews.com/blogs/heart-to-heart/2009/03/23/what-to-make-of-the-prostate-cancer-screening-studies.html
    What to Make of the Prostate Cancer Screening Studies, Bernadine Healy, M.D (March 23, 2009)
    Commentary by the former head of the National Institutes of Health, the American Red Cross, and the College of Medicine and Public Health at Ohio State University.
  • http://cancerres.aacrjournals.org/cgi/content/full/68/3/645
    A First-Generation Multiplex Biomarker Analysis of Urine for the Early Detection of Prostate Cancer, Bharathi Laxman, David S. Morris, Jianjun Yu, Javed Siddiqui, Jie Cao1, Rohit Mehra, Robert J. Lonigro, Alex Tsodikov, John T. Wei, Scott A. Tomlins, and Arul M. Chinnaiyan, Cancer Research 68, 645, February 1, 2008. doi: 10.1158/0008-5472.CAN-07-3224
    A study of a set of proteins found in men's urine has identified a suite of 4 that together seem to have a greater selectivity and specificity for identifying the presence or absence of prostate cancer than the PSA test.
  • http://www.usnews.com/health/managing-your-healthcare/cancer/articles/2010/03/29/can-this-test-be-saved-improving-on-psa-for-prostate-cancer-screening.html
    Can This Test Be Saved? Improving on PSA for Prostate Cancer Screening, Katherine Hobson, US News and World Report, Posted: March 29, 2010
    Discussion of the PSA testing controversy and some additional related tests that may help differentiate indolent from aggressive cancers. One of these tests is noted in the next reference.
  • http://www.medscape.com/viewarticle/719161?src=mp&spon=15&uac=24203PX
    New PSA Test Improves Detection of Prostate Cancer, from Reuters Health Information, 24 Mar 2010 (See also J Urol 2010;183:1355-1359)
    "Testing for the (-2)-isoform of proenzyme prostate specific antigen (p2PSA) is more accurate than PSA testing in differentiating prostate cancer from benign disease, according to a report in the April issue of The Journal of Urology...."
  • http://www.bloomberg.com/news/2011-05-05/prostate-exam-deaths-tied-to-superbug-ills-spur-cancer-test-inquiries.html
    An article (5 May 2011) discussing infection and sepsis risk from PSA testing, adding to the controversy of whether the test may pose more harm than risk. (Further information may be gleaned from an abstract from the 2010 American Urological Association Meeting, May 29–June 3, 2010, San Francisco, CA -- see the first abstract at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931291/, Infectious Complications of Prostate Biopsies, and the references therein).

   

• PSA Variation References
  • These references are courtesy of Professor Gary Grossfeld, MD, of the UCSF Urologic Oncology Department who was kind enough to do a literature search for me in the summer of 2000.
     
  • Mark H. Wener, Phyllis R. Daum, Michael K. Brawer, Variation in Measurement of Prostate-Specific Antigen: Importance of Method and Lot Variation, Clinical Chemistry, Vol 41, No. 12, 1995, pp 1730-1737
    Two major PSA test kits were used to evaluate samples from over 200 men. Significant differences were found in the results of the kits versus each other and within each manufacturer's assay, depending on the lot of test chemicals used. The variations were in the 10% range overall.
  • Anthony F. Prestigiacomo and Thomas A. Stamey, Physiological Variation of Serum Prostate Specific Antigen in the 4.0 to 10.0 ng/ml Range in Male Volunteers, The Journal of Urology, Vol 155, June 1996, pp 1977-1980
    Men without prostate cancer who had initial PSA in the 4.0-10.0 range were tested twice within 2 to 3 weeks. The variation from first to second sample was 23.5%; when the first sample was retested at the time of the second test, the variation found was 10.5%.
  • Glenn S. Gerber, Heather L. Gornick, Evan R. Goldfischer, Gerald W. Chodak, Daniel B. Rukstalis, Evaluation of Changes in Prostate Specific Antigen in Clinically Localized Prostate Cancer Managed Without Initial Therapy, The Journal of Urology, Vol 159, April 1998, pp 1243-1246
    PSA was followed in 49 men with prostate cancer who used "watchful waiting". PSA was measured roughly every 6 months. No correlation was found with rate of increase and any other factor (age, stage, etc.). Significant variability was found in the rate of change. The most interesting result, of which there was no followup or further investigation, was that in 22% of the men in the study, the PSA levels decreased during the study with no medical intervention.
  • Marcos Lujan, Alvaro Paez, Ernesto Sanchez, Alberto Herrero, Eduardo Martin, Antonio Berenguer, Prostate Specific Antigen Variation in Patients Without Clinically Evident Prostate Cancer, The Journal of Urology, Vol 162, October 1999, pp 1311-1313
    A sample of 949 men from a prostate cancer screening program who had no signs of cancer were studied with 2 or 3 PSA measurements taken 2 to 3 years apart. They found significant variation within individuals over time, but all within normal ranges. Overall, the values were fairly constant (PSA velocity approximately 0.0 ng/ml/year).

  • http://www.prostatecancerwatchfulwaiting.co.za/PersonalPSA.html
    An interesting one man study of PSA variations as well as a discussion of his history and treatment decisions. As an experiment, for one month, he had his PSA measured at the same time every day, trying to keep his diet and routines fairly constant. Significant variation was seen.

  • Several additional references of interest on PSA follow. (Thanks to Terry Herbert of Melbourne, Australia, for pointing them out.) Aside from providing some additional background on PSA, they indicate that non-prostate tissue can generate the protein, but in much smaller quantities than the prostate gland does and some may be found in human breast milk.
    • http://www.clinchem.org/cgi/content/abstract/41/1/54
    • http://www.cancerindex.org/geneweb/KLK3.htm
    • http://en.wikipedia.org/wiki/Prostate_specific_antigen
  
   
• Hyperthermia
  • North American Hyperthermia Society (telephone: +1 630 571-2904)
    http://www.thermaltherapy.org
  • European Society for Hyperthermic Oncology (ESHO)
    http://www.esho.info/
  
   
• Angiogenesis & its Inhibition
  • http://www.nature.com/nrm/journal/v1/n1/full/nrm1000_076a.html
    Cancer: looking outside the genome, Judah Folkman, Philip Hahnfeldt & Lynn Hlatky, Nature Reviews Molecular Cell Biology 1, 76-79 (2000)
    An overview of why taking a non-genomic point of view can be useful in synthesizing an approach to all cancers.
    The full text is for sale; the abstract is available for free at http://www.nature.com/nrm/journal/v1/n1/abs/nrm1000_076a.html
  • http://groups.yahoo.com/group/angiogenesis/files/CaPAngiogenesis.html
    A bibliography of research articles; free group membership required for access.
  • COX-2 inhibitors such as Vioxx and Celebrex may also be anti-angiogenesis factors
    http://www.sciencedaily.com/releases/2001/11/011108064331.htm

• Clinical Trials References
  • http://centerwatch.com/
    Center Watch Clinical Trials Listing Service
  • http://www.centerwatch.com/clinical-trials/listings/studylist.aspx?CatID=36
    State by state listing of current clinic trials for prostate cancer.
  • http://www.cybermedtrials.com/
    Clinical trials site, etc
  • http://cancernet.nci.nih.gov/trialsrch.shtml
    NCI pages
  • http://www.centerwatch.com/clinical-trials/listings/
    Clinical trials search engine
  • http://www.cancertrialshelp.org/ The Coalition of Cancer Cooperative Groups is a nonprofit organization whose mission is to improve the quality of life and survival of cancer patients by increasing participation in cancer clinical trials.
  • http://www.usoncology.com/portal/page/portal/PubWeb/
    U.S. Oncology organizes & finds patients for trials
  • http://www.clinicaltrials.gov/
    National Institutes of Health / National Library of Medicine pages on clinical trials - what they are and search capabilities. As of June 2001, over 5000 current trials were listed. As of June 2010, this search
    ( http://www.clinicaltrials.gov/ct2/results?cond="Prostate+Cancer") led to 1655 listed trials.
  • http://www.nccn.org/index.asp
    The National Comprehensive Cancer Network Also suggested by UsToo
  • http://www.ustoo.org/clinical_trials.asp
    The UsToo clinical trials page
  • http://www.nih.gov/news/health/nov2009/ncrr-10.htm
    NIH Announces First National Research Study Recruitment Registry
    Nationwide Registry to "Match" Volunteers with Researchers
    Individuals who want to participate in research studies now can connect online with researchers nationwide through the first disease-neutral, volunteer recruitment registry....
  • http://www.demandcurestoday.org/
    The Gateway for Cancer Research
    An independent organization that funds cancer clinical trials. As of June 2012, they have 9 PCa trials ongoing (see http://www.demandcurestoday.org/cancer-research/cancer-type?cancertype=Prostate+Cancer)
  
   
• Prostatitis
  • http://cme.medscape.com/viewarticle/550342
    Prostatitis -- Old Questions, New Answers: An Update for Clinicians CME/CE
    Author: J. Curtis Nickel (Free registration required)
    An overview of the current state (9 Jan 2007) of diagnosis and treatment of the several kinds of prostatitis.
  • http://en.wikipedia.org/wiki/Prostatitis
    The Wikipedia entry, with diagrams & references.
  • http://www.prostatitis.org
    The Prostatitis Foundation, A patient oriented site dedicated to information on the cure and treatment of this disease.
  • http://www.prostate-usa.com/
    Prostatitis Center, Tucson, Arizona
    A medical practice centering around the treatment of prostatitis using a combination of prostatic massage and appropriate antibiotics (based on a pathologist's examination of expressed prostatic secretions). The approach of using deep prostate massage to empty the sacs and make them accessible to antibiotics or other medications seems to be more used in Europe and Asia than in North America.
  • http://www.prostatitisclinic.com
    The Prostatitis Clinic at the MacLeod Laboratory, New York City
    Attila Toth, MD, Director
    Their approach is a detailed examination of urine and seminal fluid for Chlamydia trachomatis (from the urethral swab), Mycoplasma group, complete screening for aerobic and anaerobic bacteria and yeast. This is followed by direct ultrasound guided transrectal injection of antibiotics and/or anti-fungals into the prostate.
  • http://www.cleanprostate.com
    Lou Surette's site on how to cheaply and easiy "clean out the plumbing" of your prostate using Sitz baths, an intriguing idea. He argues that this simple procedure can decrease the chances of prostatitis, BPH symptoms, and the possibility of prostate cancer. He's also an advocate of appropriate diet and supplementation. He seems to have created this site in early 2003. In May 2003, he was diagnosed with Chronic Lymphatic Leukemia (CLL) and began a separate web site to blog his experiences (http://radio.weblogs.com/0135129/ ). His last entry there is 12 May 2006 where he talks of palliative care.
  • Google returns 1,910,000 entries for "prostatitis".

  It is interesting to note that the embryonic tissue that gives rise to the prostate gland in male children gives rise to two small glands that surround the female urethra -- the Skene glands and the paraurethral glands. These glands also stain positive for PSA. It is thought that their inflammation, a kind of female prostatitis, is one of the causes of female urethral syndrome. Females with these disorders suffer the same symptoms of urinary frequency, pain with urination, and pelvic pain, that men with prostatitis have. See

  • http://www.prostatitis.org/femalep.html
  • http://www.prostatitis.org/99workshop/Abstracts/abstract1/abstract1.html
  • http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1303542
  
   
   
• Environmental Insults and Prostate Cancer
  • http://www.truthout.org/article/chemical-plastics-is-tied-prostate-cancer
    Chemical in Plastics Is Tied to Prostate Cancer
    (Originally published in the Los Angeles Times, 01 June 2006). "Bisphenol A, found in baby bottles and microwave cookware, permanently altered genes in newborn lab rats, a study finds."
  • This was an exemplary study I came across. Searching will provide the reader access to an enormous literature in the scientific and lay press.
  
   
• Other References
  • Spontaneous Healing, Andrew Weil, MD, Alfred Knopf, (New York) (1995) ISBN 0-679-43607-3

    These are books that I have not yet read but that came highly recommended.

  • Choices in Healing: Integrating the Best of Conventional and Complementary Approaches to Cancer, Michael Lerner, MIT Press (April 1996) ISBN 0262621045
  • The Journey Through Cancer: An Oncologist's Seven Level Program for Healing and Transforming the Whole Person, Jeremy Geffen, MD, Crown Publishers (February 2000) ISBN 0609604503
  • Second Opinion: Stories of Intuition and Choice in a Changing World of Medicine, Jerome E. Groopman, MD, Viking Press (February 2000) ISBN 067088801X
  • A Primer on Prostate Cancer - Empowered Patient's Guide, Dr. Stephen Strum, MD and Donna Pogliano, Life Extension Media, Hollywood, FL (Second edition, February 2005) ISBN 0-9658777-7-9
  • Dr. Patrick Walsh's Guide to Surviving Prostate Cancer, Patrick C. Walsh, MD and Janet Farrar Worthington, Warner Books (August 2002) ISBN 0446679143
  • Dr. Katz's Guide to Prostate Health: From Conventional to Holistic Therapies, Aaron Katz, M.D., Freedom Press (CA) (September 2005) ISBN 1893910377
  • Beating Prostate Cancer: Hormonal Therapy & Diet, by Dr. Charles "Snuffy" Myers, MD, Oct 2006, Rivanna Health Publications, LLC.
    An enthusiastic review and more information is at http://www.mycancerplace.com/forum/?action=view_topic&id=53&fid=15
    The book is available from http://www.prostateforum.com

    These books were referred to me by a leader of The Prostate Forum of Fullerton, California, the last of which is used in their classes for the "newly diagnosed". Again, I have not read them.

  • Prostate Health in 90 Days Without Drugs or Surgery, Larry Clapp, Ph.D., J.D., Hay House; (January 1998) ISBN 1561704601
    Reveiews on Amazon are either very positive or very negative.
  • The Prostate Miracle, Jesse Stoff, M.D., Kensington Pub Corp (September 2000) ISBN: 1575665441
  • I Survived Prostate Cancer and So Can You, James Lewis, Health Education Literary Pub, (April 1994) ISBN 1883257069
  • New Guidelines for Surviving Prostate Cancer, James Lewis and E. Roy Berger, M.D., Health Education Literary Pub (1997) ASIN 1883257131

  • Prostate Cancer Breakthroughs 2014: New Tests, New Treatments, Better Options: A Step-by-Step Guide to Cutting-Edge Diagnostic Tests and 12 Medically-Proven Treatments, Jay S Cohen, M.D., Oceansong Publishing (March 2013) ISBN-10: 0988710501
    An M.D. diagnosed with prostate cancer, Cohen researched the current and forthcoming diagnostics and treatments to avoid overtreatment and its side effects. Said to be pithy and highly readable.
  
   
• Biopsy Readers
  There are several world-class experts in reading prostate cancer biospsy slides in addition to Dr. John McNeal, mentioned above. It might be prudent to have your slides sent to one of these folks to get their readings. A correct Gleason score, number of positive cores, and percentage of the cores that are positive are important factors in helping to decide the extent and aggressiveness of one's cancer and hence the appropriate course of action.
   
  • David Bostwick
    Bostwick Laboratories
    2807 N. Parham Road, Suite 114
    Richmond, VA 23294, USA
    Phone: 800 214-6628, Fax: 804 288-6568
    Email: bostwick@bostwicklaboratories.com
    Web Site: http://www.bostwicklaboratories.com
     
  • Jonathan Y. Epstein, M.D.
    Surgical Pathology
    Johns Hopkins Hospital
    401 North Broadway
    Baltimore, MD. 21231-2410
    Phone: 410-955-3580
     
  • John McNeal, MD
    Stanford University Hospital, Department of Urology
    300 Pasteur Drive
    Stanford, CA 94305
    Phone: 650-723-6024 (Urology Dept.)
     
  • Jon Oppenheimer, MD
    OUR Lab
    1854 Bearlane Drive Suite 17a Nashville, TN 37210
    Phone: 615-847-0410 or 1-888-8OURLAB
    Email: dro@ourlab.net
    Web Site: http://www.prostatelab.com
     
  • http://www.scprostate.org/news_archive/2010_03.html has another (current as of March 2010) list of recommended practitioners in the article There Is Too Much Valuable Information In The Pathology, by Stephen Strum, MD.
     
  
   
• Biopsy Dangers
  One danger of not having a biopsy, when called for, is not knowing the histology of one's prostate cancer, if present. However, there are dangers as well, which one should be aware of.
  • http://www.veteransresources.org/2011/10/rao-bulletin-update-01-october-2011/
    This is the October 2011 Veterans' Resources newsletter. Go to the bottom of the page and click on "Download Bulletin 111001". The article of note starts on page 12 of the Word file you'll get.
    Men who underwent prostate biopsy were more than twice as likely to be hospitalized within 30 days compared with men who did not undergo the procedure, a study of Medicare beneficiaries showed. Procedural complications, such as infection and bleeding, as well as exacerbations of comorbid conditions contributed to a hospitalization rate of 6.9% following prostate biopsy versus a 2.9% hospitalization rate for controls....
  • The original popularized article this is based on comes from http://www.medpagetoday.com/Urology/ProstateCancer/28679,
    the 22 September 2011 issue of MedPage Today.
  • The journal article with the original research is
    http://www.jurology.com/article/S0022-5347%2811%2904336-9/abstract
    Complications After Prostate Biopsy: Data From SEER-Medicare Presented at annual meeting of American Urological Association, San Francisco, California, May 29–June 3, 2010, Stacy Loeb, H. Ballentine Carter, Sonja I. Berndt, Winnie Ricker, Edward M. Schaeffer, The Journal of Urology, Volume 186, Issue 5 , Pages 1830-1834, November 2011.

Glossary

[A more extensive prostate cancer glossary is available at http://www.phoenix5.org/glossary/glossary.html, part of Robert Young's Phoenix5 site, referenced above.]
 

• apoptosis
  Programmed cell death. The biological process where a cell can "commit suicide". This is a normal part of the cell cycle at all stages of development, for some cells, and may be part of the aging process. Research has shown that human mother's milk can induce cancer cells to undergo apoptosis while leaving non-malignant cells unaffected.

  It should be noted that other chemicals and drugs may also induce tumor cell apoptosis. To my (limited) knowledge, some of these are in various experimental or pre-clinical stages, but all have side effects of one sort or another. I do not believe that mother's milk has known side effects and it is currently available, whereas alternatives are not.

  Necrosis is non-programmed cell death, usually due to outside factors, such as radiation or attack by toxins. In the case of necrosis the cell does not have time to orderly shut down. It appears differently than an apoptotic cell.
   

• BPH
  Benign Prostate Hyperplasia. A benign disease of the prostate, usually occurring in older men, which causes the gland to grow or swell beyond its normal size. This often squeezes the urethra, which passes through the middle of the prostate, causing urinary difficulties. Prostate cancer, too, can squeeze the urethra, and so it is important to differentiate these two conditions.
   
• DRE
  The Digital Rectal Exam. The physician puts on a latex glove and lubricates it, then inserts his finger into the patient's rectum, probing the prostate gland. In general, he is looking for hardness, lumps and other abnormalities on the back wall of the prostate, which is right next to the rectal cavity. Most early stage prostate cancers that are palpable (that is, can be felt in this exam) occur in this region of the prostate. Until the PSA test was invented in the mid-1980's, this was the only way to detect prostate cancer.
   
• Free PSA
  (See PSA.) Prostate Specific Antigen may be found either bound or free in the blood. The standard PSA value is the total PSA found, in nanograms per milliliter. The greater the percentage of unbound, or free, PSA, the less likely one is to have prostate cancer. The rule of thumb is that free PSA greater than 20% or so means one is unlikely to have prostate cancer and so may be spared a biopsy, for moderate ranges of total PSA. Once a biopsy proves cancer is present, the free PSA test no longer provides information of value.
   
• HAMLET
  Human Alpha-lactabumin Made Lethal to Tumors
  The shape modified form of human alpha-lactalbumin that causes cancer cells to undergo apoptosis.
   
• MAL
  Multimeric Alpha-Lactalbumin. Lactalbumin is a protein found in milk. In raw milk, it exists in both its monomeric form and in multimeric forms. Pastuerization breaks the multimeric forms down so that pastuerized milk only contains the monomeric form.

  A monomer in chemistry is a single unit. When a number of these single units are bound together, this is called a multimer. Just noting that something is multimeric does not say what the fraction is that is 2-meric, 3-meric, etc.

  MAL in human mother's milk has been found to cause cancer cell death (apoptosis) in vitro (in the test tube). The researchers at Lund University also found that certain cofactors in the mother's milk (oleic acid) are also required for MAL to be effective as a cancer killer.
   

• MRIS
  Magnetic Resonance Imaging and Spectroscopy. Also called MRSI, for Magnetic Resonance Spectroscopic Imaging. MRIS is an imaging technique which uses strong and rapidly oscillating magnetic fields to image noninvasively soft body tissues in three dimensions at fairly high resolution. For current prostate magnetic resonance imaging, the resolution of a pixel is 0.5 x 0.5 mm, with virtual slices every 3 mm.

  The spectroscopy component, done at the same time as the imaging, has a coarser resolution, roughly cubes about 6mm on a side. The spectral results can be overlaid on the image to correlate cancer, BPH, necrotic (dead) cells, and normal cells with the image.
   

• PSA
  Prostate Specific Antigen. A chemical produced only by prostate cells and prostate cancer cells. Its level increases gradually with age and prostate volume, but is expected to be between 0.0 and 4.0 ng/ml. Higher values and/or rapid increases can indicate prostate cancer. Higher values might also indicate BPH or prostatitis. Cancer can exist at low PSA levels. In general, however, it is thought of as a good proxy for cancer levels.

  Healthy prostate cells also produce PSA. A rule of thumb for what one's "background" PSA should be if all cells are healthy is to multiply the gland volume in cc by 0.066. For example, my gland's volume on 22 July 2002 was 36 cc, as measured in an MRI. The background PSA level should have been about 2.38 ng/ml; my measured PSA was 2.16. [This value of 0.066 ng/ml/cc comes from the PCRI ( http://www.prostate-cancer.org/) newsletter PCRInsights, vol 5, no 1, July 2002, page 7. All isues may be downloaded in PDF format from http://www.prostate-cancer.org/resource/insights.html
   

• TRUS
  Trans-Rectal UltraSound. An imaging technique involving an ultrasound probe inserted into the patient's rectum, enabling imaging of the prostate and surrounding regions. The resolution (at least to me) seemed fairly crude and the images blurry and distorted, but the radiologist doing the exam seemed to be able to read them easily.

  TRUS is often done in conjunction with a prostate biopsy and is used to guide the biopsy sampling. It can also measure the prostate volume, that is the size of the gland.

  A good review of TRUS, both historically and in guiding biopsies, can be found in the Bibliography.

APPENDIX A: The Nature of the Beast - The Course of the Disease

• Scope of the issue
• Pre-detection
• The Possible Role of Infection
• Early Stage
• Post-treatment recurrence
• Metastasis

Scope of the Issue

The corresponding 2003 figures are "more than 220,000" men being diagnosed with prostate cancer in the U.S, "nearly 30,000" dying from it. (From a Seatle Times story.) A New York Times article ( http://www.nytimes.com/2003/12/23/health/23CANC.htm) notes that the U.S. 2003 incidence will be 220,900 cases with 28,900 deaths and 1.8 million men living with the disease.

The American Cancer Society's 2004 estimates are 230,000 men diagnosed, almost 30,000 deaths (from http://www.hon.ch/News/HSN/518884.html, but this site seems to have removed all archives before 2008).

The American Cancer Society's 2005 estimates are 232,000 men diagnosed, and 30,000 deaths (from http://www.nytimes.com/aponline/AP-FIT-Prostate-Cancer-Obesity.html, 9 Jan 2006).

"The National Cancer Institute of Canada estimates that 17,800 Canadian men will be diagnosed with prostate cancer in 2001, making prostate cancer the leading cancer diagnosed in Canadian men." (From http://www.isip.com/press/press01/112601-Oncogenex.htm, a press release, 26 Nov 2001, no longer available on the www.isippharm.com web site as of June 2009.)

"Prostate cancer is on course to become the most common men's cancer in Britain in the next 3 years, health experts said on Monday. Cases of the disease have doubled in the past 20 years and scientists predict the numbers will continue to rise as the population ages and more men are tested for the illness. ... Around 22,000 cases of prostate cancer are diagnosed in Britain each year and 9,500 men die of the disease annually." (Originally from http://www.medscape.com/viewarticle/434192, which is no longer available. It was a summary of a press release from Reuters, 27 May 2002. -- June 2009.)

"As the Baby Boomers approach 60, there is an increased need to assist newly diagnosed and advanced disease patients and their families. The number of men diagnosed with prostate cancer is expected to increase by 40% from approximately 230,000 to more than 300,000 a year. Over the next 10 years, the number of prostate cancer deaths could rise from 30,000 to 50,000." (From an USToo email, 30 May 2006)

"Prostate cancer is one of the most common cancers in men. Each year 543,000 new cases are reported worldwide and the disease kills 200,000 mostly older men in developed countries." (From a Reuters news story, 5 Dec 2006, that had been located at
http://www.prostatecancerfoundation.org/site/c.itIWK2OSG/b.2280299/k.2DC5/Baldness_Drug_Can_Mask_Prostate_Cancer_Marker.htm?msource=dec06np&auid=2210147
but is no longer there as of June 2009.)

"Among men, prostate cancer is the most common cancer (next to skin) and the second leading cause of cancer-related deaths in men in the United State. According to the American Cancer Society more than 218,890 men will be diagnosed with prostate cancer in 2007." (From an email from the National Prostate Cancer Coalition, 12 March 2007.)

"In 2007, approximately 1 of 6 men in the United States received a diagnosis of prostate cancer, and 1 in 34 died from it." (From Walsh, et al., NEJM, 357:26, p 2696, referring to A. Jemal , R. Siegel, E. Ward, T. Murray, J. Xu, M.J. Thun, Cancer Statistics, 2007, CA Cancer J Clin 2007;57:43-66.)

"In 2007, prostate cancer was diagnosed in an estimated 218,900 men in the United States, and approximately 27,050 men died of the disease." (From , Wilt, et al., Annals of Internal Medicine, Vol 0, Issue 2008, pages 000605-200803180-00209-E-209 (18 March 2008))

"More than 186,000 U.S. men will be diagnosed with prostate cancer [in 2009], and nearly 29,000 will die, according to cancer society estimates." (From http://www.nytimes.com/aponline/2009/03/10/health/AP-MED-ProstateCancer.html, a New York Times article on over diagnosis of prostate cancer.)

"It is estimated [by the American Cancer Society that] 192,280 men will be diagnosed with prostate cancer in 2009 and 27,360 men will die from the disease." (From a Reuters press release, reproduced at http://www.zerocancer.org/site/News2?page=NewsArticle&id=10772, 27 May 2009.)

The American Cancer Society estimated that in 2009 192,280 men were diagnosed with prostate cancer and 27,360 died from prostate cancer. Alarmingly, their 2010 estimates (issued 15 June 2010) were of a significant increase: 217,730 men diagnosed and 32,050 deaths. (From http://www.zerocancer.org/site/News2?page=NewsArticle&id=11611&news_iv_ctrl=1001 )

In 2010, it was estimated that 217,730 men were diagnosed with prostate cancer and 32,050 men died of the disease in the U.S. U.S. medical costs linked to prostate cancer care were estimated at $9.9 billion in 2006. (From http://www.bloomberg.com/news/2011-05-05/prostate-exam-deaths-tied-to-superbug-ills-spur-cancer-test-inquiries.html )

It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. (From http://www.nih.gov/news/health/dec2011/od-07.htm)

According to ASCO [the American Society of Clinical Oncology], more than 241,000 men in the United States will be diagnosed with prostate cancer in 2012, and 28,000 men will die from the disease. (From http://health.msn.com/health-topics/cancer/experimental-drugs-do-battle-against-advanced-prostate-cancer>)
 

Pre-Detection

Thus, it is more and more likely, as one ages, that there is a small but real burden of prostate cancer cells that could become active. The relative frequency of this being the case seems to vary from society to society, which informs some of the thinking about the relationship between diet and nutrition and prostate cancer. For example, the death rates at all ages of prostate cancer in Japan is much lower than in the United States. However, it is likely not a genetic difference that is in play here, since second and subsequent generation Japanese-Americans have substantially similar incidence rates to Caucasian Americans. That is, acculturation to the typical U.S. diet or lifestyle (versus the typical traditional Japanese diet) increases the incidence of active prostate cancer and its resulting death rate.

The questions one must ask are, What causes the cancer to become activated? How can we reasonably alter lifestyle to decrease our probability of getting or activating our latent prostate cancer? How can we reasonably alter our lifestyle to deal with prostate cancer that has already become active? These issues were discussed briefly in the body of this paper from the point of view of my personal experience.

In the pre-detection phase, life is normal -- PSA remains in the normal range, the gland stays a normal size and does not cause urinary problems. The cancer cells, if any, remain microscopic or as very small inclusions within the gland. (It should be noted that unlike many other cancers which seem to arise from a single cell gone awry, prostate cancer, even in its pre-detection phase, seems to be multi-focal. That is, it arises in a number of locations within the gland. In that sense, too, it may be thought of as a systemic disease.)
 

The Possible Role of Infection and Inflammation

BALTIMORE, Sept. 15 (AScribe Newswire) -- Researchers at Johns Hopkins, Wake Forest, and The National Human Genome Research Institute have implicated mutations in a "heart disease gene" in hereditary prostate cancer. The findings, which offer new evidence that at least some cases of prostate cancer may begin with an infection and inflammatory response, will be published online September 16, 2002, in Nature Genetics.

The gene, called macrophage scavenger receptor-1 (MSR1), was identified more than 20 years ago as a factor in plaque formation in arteries, a process that contributes to coronary artery disease, or so-called hardening of the arteries. MSR1 helps immune system cells called macrophages clean up cellular debris from bacterial infections and damaged fats or lipids. Macrophage activity has been known to increase in the early stages of prostate cancer, and the Hopkins investigators suspected that some MSR1 mutations might inhibit the ability of macrophages to clean up properly after prostate infections, producing inflammatory lesions that are often markers of prostate cancer.

This is the first time that MSR1 has been linked to cancer, and it may tie infections and similar environmental exposures to cancer of the prostate in a way that we haven't thought about before, says William B. Isaacs, Ph.D., professor of urology and oncology at the Brady Urological Institute and Kimmel Cancer Center at Johns Hopkins.

Hunting for gene mutations that increase one's risk for prostate cancer, researchers screened 159 families with hereditary prostate cancer and found seven different mutations in the MSR1 gene in 13 families or about eight percent of the hereditary prostate cancer families studied.

To compare the impact of this gene in men with non-hereditary sporadic prostate cancer, the researchers screened another 731 men, 365 with prostate cancer and 366 without. Overall, the research team found that MSR1 mutations were about seven times more common in men with prostate cancer than in those without. Mutations were found in 12.5 percent of African American men with prostate cancer as compared to 1.8 percent without the disease. In men of European descent, 4.4 percent of men with prostate cancer and less than one percent without prostate cancer had MSR1 mutations. "This genetic evidence suggests that MSR1 may play an important role in prostate cancer susceptibility in both African American men and men of European descent," says Jianfeng Xu, M.D., Dr. PH, of the Center for Human Genomics at Wake Forest.

Isaacs and colleagues will conduct additional studies to uncover the pathway that the MSR1 gene controls and confirm the prevalence of MSR1 mutations in larger studies.

The research was funded by the National Cancer Institute, the Department of Defense, CaPCURE, Fund for Research and Progress in Urology, and the William Thomas Gerrard, Mario Anthony Duhon, Jennifer and John Chalsty Professorship in Urology.

Participants in this research include Jianfeng Xu and S. Lilly Zheng of Wake Forest University, Akira Komiya of Johns Hopkins, Josyf Mychaleckyj of Wake Forest, Sarah Isaacs of Johns Hopkins, Jennifer Hu of Wake Forest, David Sterling of St. Louis University, Ethan Lange, Gregory Hawkins, and Aubrey Turner of Wake Forest, Charles Ewing, Dennis Faith, Jill Johnson, Hiroyoshi Suzuki, Piroska Bujnovszky, Kathleen Wiley, Angelo DeMarzo, and G. Steven Bova of Johns Hopkins, Baoli Chang, M. Craig Hall, and David McCullough of Wake Forest, Alan Partin of Johns Hopkins, Vahan Kassabian of Georgia Urology P.A., John Carpten, Joan Bailey-Wilson, and Jeffrey Trent of the National Human Genome Research Institute (NHGRI), NIH, Jill Ohar of St. Louis University, Eugene Bleecker of Wake Forest, Patrick C. Walsh of Johns Hopkins, and Deborah Meyers of Wake Forest.

Related Web Sites: Johns Hopkins Brady Urological Institute:
http://urology.jhu.edu

Johns Hopkins Kimmel Cancer Center: http://www.hopkinskimmelcancercenter.org/

AScribe - The Public Interest Newswire / 510-653-9400
(c)2002 AScribe News, Inc.

Most cancers develop at the site of a chronic inflammation. During an inflammatory response, damaged cells and invading white blood cells release a large amount of highly damaging free radicals into the tissues spaces. These free radicals serve many different functions, including the destruction of microorganisms. Phagocytic white blood cells, such as neutrophils and macrophages, are not all that intelligent. They do not know if they are eating a microorganism or cleaning up debris, such as cigarette tar in the lungs. The free radicals they release can kill microorganisms in the tissues, as well as induce substantial tissue damage. If this inflammation becomes chronic, the free radicals can damage the DNA and repair proteins of cells resulting in the formation of cancer cells. [1 September 2005]

In March 2006, the possible involvement of a virus in the development of some prostate cancers was published (Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant, Urusman, et al., Public Library of Science, Volume 2, Issue 3, MARCH 2006 http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020025)

The study on pomegranate juice (noted above) from 1 July 2006 Clinical Cancer Research has an interesting discussion of the role of inflammation on oncogenesis. To quote at length again

Chief, however, among the potentially explanatory hypotheses is the role of inflamation in cancer and the antioxidant and anti-inflammatory effects of pomegranate polyphenols. Chronic inflammation has been linked to the incidence of many cancers, including that of prostate (37). Studies investigating samples of human tissues have shown that epithelial cell proliferation is increased by inflammation (38). An increased risk of cancer is associated with inflammatory mechanisms, as ~15% of all cancers can be related to chronic inflammation (38). Epidemiologic studies have found an increased risk for prostate cancer in men who have a prior history of sexually transmitted disease or prostatitis (39). Inflammation in the microenvironment of the prostate cancer cell may stimulate the multistep process of carcinogenesis by up-regulating the production of pro-inflammatory cytokines and their signaling pathways. In fact, proliferative inflammatory atrophy has recently been proposed as a precursor to prostatic intraepithelial neoplasia and prostate cancer (40).

Inflammation can result in persistent oxidative stress in cancer cells and the reactive oxygen species may lend cancer cells a survival advantage (41-43). Mild levels of oxidative stress stimulate cancer cell proliferation (42) and increase mutation rates through DNA damage and/or epigenetic changes (44). De Marzo et al. (40) have shown the loss of glutathione S-transferase P1 as an early event in prostate tumors that sets the stage for stimulation of growth by oxygen radicals. Oxidative stress has also been shown to increase cancer cell proliferation by increasing the sensitivity of growth factor receptors and by altering transcription factor activity. Inflammatory cells, such as macrophages and mast cells, release angiogenic factors and cytokines like tumor necrosis factor-α, interleukin-1, and vascular endothelial growth factor, which signal cell growth and proliferation. Additionally, cytokines regulate signaling pathways that control proliferation, apoptosis, differentiation, and metastasis....

The role of antioxidants derived from the diet in protection against oxidative stress and the development or progression of cancer remains a topic of significant controversy.

• (37) Weitzman SA, Gordon LI, Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood 1990;76: 655-63.
• (38) Kuper H, Adam HO, Trichopoulos D. Infections as a major preventable cause of human cancer. J Intern Med 2000;248:171-83.
• (39) Palapattu GS, Sutcliffe S, Bastian PJ, et al. Prostate carcinogenesis and inflammation: emerging insights. Carconogenesis 2005;26:1170-81.

• NF-κB: Linking Inflammation and Immunity to Cancer Development and Progression, Michael Karin and Florian R. Greten, Nature Reviews, Immunology, Vol 5, pp 749-759 (October 2005), available at http://www.nature.com/nri/journal/v5/n10/pdf/nri1703.pdf
• Nuclear Factor - κB: A Holy Grail in Cancer Prevention and Therapy, Bharat B. Aggarwal, Gautham Sethi, Asha Nair, and Haruyo Ichikawa, Current Signal Transduction Therapy, 2006, 1, pp 25-52, available from http://www.bentham.org/cstt/samples/cst1-1/Aggarwal.pdf
  This contains an extensive list of NF-κB inhibitors, including human breast milk.

• The Role of Inflammation in the Pathogenesis of Prostate Cancer, William G. Nelson, Angelo M. de Marzo, Theodore L. DeWeese, William B. Isaacs, The Journal of Urology, Volume 172, Issue 5 (Supplement), Pages S6-S12 (November 2004) (abstract available at http://www.jurology.com/article/PIIS0022534705613006/pdf ) This may be downloaded from ftp://www.cohensw.com/pub/pca/inflammation/WmNelson_jurol_proof_8-9-04.pdf.

• Mechanisms of Disease: Prostate Cancer, William G. Nelson, Angelo M. De Marzo, William B. Isaacs, The New England Journal of Medicine 2003:349-366-81 (24 July 2003). This may be downloaded from ftp://www.cohensw.com/pub/pca/inflammation/WmNelson_nejm_mechanisms_of_disease_2003.pdf.

• Prostate Carcinogenesis and Inflammation: Emerging Insights, Ganesh S. Palapattu, Siobhan Sutcliffe, Patrick J. Bastian, Elizabeth A. Platz, Angelo M. De Marzo, William B. Isaacs, William B. Nelson, Carcinogenesis, vol 26, no 7, pp 1170-1181 (21 Oct 2004). This article may be downloaded from ftp://www.cohensw.com/pub/pca/inflammation/palapattu_etal_carcinogenesis_2004.pdf .

• What is the Role of Inflammation in the Pathogenesis of Prostate Cancer?, Miles A. Goldstraw, John M. Fitzpatrick and Roger S. Kirby, British Journal of Urology International, Volume 99, Issue 5, Pages 966-968 (Published Online: 8 Apr 2007), available at http://www3.interscience.wiley.com/cgi-bin/fulltext/118508477/HTMLSTART

A Malignant Flame
Understanding chronic inflammation, which contributes to heart disease, Alzheimer's and a variety of other ailments, may be a key to unlocking the mysteries of cancer
By Gary Stix
 
More than 500 million years ago a set of specialized enzymes and proteins evolved to defend our primitive ancestors against assaults from the outside world. If a microbe breached the shell of some Cambrian-era fauna, the members of this early vintage immune system would stage a savage but coordinated attack on these interlopers -- punching holes in cell walls, spitting out chemical toxins or simply swallowing and digesting the enemy whole. Once the invaders were dispatched, the immune battalion would start to heal damaged cells, or if the attacked cells were too badly damaged it would put them to rest....

...Conclusion: Inflammation, most of which was chronic, was common in benign prostate tissue, and was positively associated with prostate cancer, especially high grade. The association did not seem to be due to detection bias.
 
Impact: This study supports an etiologic link between inflammation and prostate carcinogenesis, and suggests an avenue for prevention by mitigating intraprostatic inflammation.

Pesticide Links

(From Pesticide Action Network Updates Service 10 May 2007-- See http://www.panna.org/resources/panups )
 

Early Stage

In general, at this time, the cancer is still completely contained in the prostate gland (within the capsule, which is a membrane surrounding the gland) and is likely not to be too aggressive (say, Gleason score 3+3, which is what 2/3 of initial diagnoses are, according to my original urologist). The cancer is still relatively slow growing. One has time to become educated and make an informed decision about the appropriate course of action. Do not let anyone (including doctors) push you into doing anything irreversible before you understand what you are dealing with and what your options truly are.

Treatment options are discussed in Appendix B.
 

Post-Treatment Recurrence

But that does not happen all the time. Or sometimes, the cancer is detected after it has escaped the gland. There are second line treatments, also discussed in Appendix B. These often help for a significant period of time. (I have met men in my support group who have been on hormone blockades of one sort or another for over 20 years.)

The likelihood of recurrence is a function of how soon the cancer was detected, what treatment modality was used, the skill of the practitioner, and luck. Also is age -- older men (70% of those first diagnosed are over 65 years old) may well die of something else before their prostate cancer recurs, which is considered a "cure".

Usually recurrence is detected via periodic PSA blood tests. Less frequently, PSA stays low but other symptoms indicate the cancer has come back. [Is this true??] Some of the originally available treatments may be used for recurrence - radiation and hormone blockade, primarily. Surgery is possible after radiation (called "salvage surgery"), though many surgeons do not want to put in the extra effort required, as noted above.

In general, the population of prostate cancer cells needs a form of testosterone, the male hormone produced 95% in the testes and 5% in the adrenal glands, in order to live and thrive and grow. This form is dihydrotestosterone, or DHT, and is produced in the prostate by an interaction with another hormone, 5-alpha-reductase. What hormone blockade therapies do is to deprive these cells of DHT and starve them. There are a number of different ways of doing this.

However, there is often a subpopulation of prostate cancer cells that are not dependent on DHT for survival. The longer DHT is missing, the more the sensitive cells will die and a subpopulation that "doesn't care" will be left and will grow to be the majority population. And there are no standard and effective treatments for dealing with them that are available yet. This is one of the reasons for using an intermittant hormone blockade regimen -- when the cancer has been knocked back "enough", it is given a rest (along with the rest of your system) so that the androgen-independent cells remain a minority population. If/when the cancer again recurs, the hormone blockade approach may well work again.
 

Metastasis

There is no commonly effective treatment for metastatic prostate cancer except for hormonal blockade although other chemotherapies are used as well, especially for hormone refractory prostate cancer. Various new therapies are in development and in clinical trials now, so the situation may improve in the not too distant future. However, any new drug or treatment must undergo a significant gauntlet in terms of efficacy and safety testing in order to achieve FDA approval, so this process of staged trials can go on for years. One can search for clinical trials to participate in, if you and your cancer meet certain criteria.

Unfortunately, prostate cancer that has metastasized to the bone is often quite painful. Combine this with the fact that hormonal blockade often leads to decalcification of the bones (osteoporosis), which makes them irreversibly weaker and more subject to fracture, and the situation of end game is not very pleasant, even with good pain management techniques.
 

APPENDIX B: Medical Treatment Options

Current Therapies

• "Watchful Waiting"
• Radical Prostatectomy
• External Beam Conformal Radiation (X-Rays)
• Brachytherapy (Seed Implants)
• Proton Beams
• Cryotherapy
• Ultrasound/thermal therapy (?)
• Hormonal Blockade
• Chemotherapy
• Diet, Nutrition, Holistic modalities

Caveat

Nomograms

Watchful Waiting/Active Surveillance

Watchful waiting should always be combined with frequent monitoring of the cancer, usually via PSA testing (most MDs would say every 3-4 months or so) or some other modality (DRE, TRUS or MRI/MRIS, for example). It should probably be combined with some of the lifestyle changes also recommended, an increase in exercise, improvement in nutrition and diet.

With watchful waiting, it is not likely that the cancer will go away. It can be a time of self-education, a breather between the shock of diagnosis and the point at which intelligent, informed decisions can be made about the next steps to be taken in dealing with the condition.
 

Radical Prostatectomy

A relatively new technique is nerve replacement in those cases where the original nerves need to be removed. Nerves are taken from the ankle and microsurgically attached after the prostate and the erectile nerves are excised. This adds about 2 hours to the surgery time and has had some success.

A second approach to removing the prostate is to go in through the perineum, the area between the scrotum and anus. The incision is smaller, but the ability of the physician to see is more limited and I do not think that a nerve sparing approach is taken here.

A third approach is being pioneered at one hospital in Virginia. (I read about it on the web in Jan 2001, but lost the reference.) They are doing laparoscopic prostatectomies, going in through a small incision in the abdomen. They claim some successes, though I do not know much about this. It is also being done by James Karol, MD at the San Ramon Regional Medical Center in northern California. Here they use a da Vinci Surgical System, a computer enhanced surgical system approved by the FDA in July 2000. (Reference was Associated Press Newswires, 11 May 2001, as paraphrased in the California Prostate Cancer Coalition News, vol 3, issue 4, July 2001).

The positive things to say about radical prostatectomies are that they often can remove the entire cancer burden, if caught early enough. The survival rates of best practice after 10 years is highest for RP. The operation also makes sense, in my personal opinion, even if the cancer has spread from the gland, although further treatments are necessary for follow on. The purpose in this case would be to physically remove as much of the cancer burden as possible, allowing the subsequent therapies to have a greater chance of success. My friend, spoken of above, is a case where this approach saved his life. However, most surgeons will not do this. The protocol is to open you up and remove the lymph glands and seminal vesicles and send them to a pathology lab. If the immediate biopsies of these organs indicates that the cancer has spread from the prostate gland, the surgery is aborted and the patient sewn back up with his prostate and his cancer.

If you want something different to occur with you in this case, you must be very clear and very firm with your physician before an operation, perhaps insist on a written agreement.

The downside of RP is the high rates of impotence and non-trivial rates of incontinence. Impotence results from nerve removal or nerve damage (as well as often having a psychological component). Incontinence results from the nature of the surgery. The urethra is a tube which starts at the bladder, passes through the prostate and out through the penis. There are two sphincter muscles controlling the flow of urine - one at the attachment to the bladder, and one at the place where the urethra passes out of the prostate. In the surgery, the upper sphincter is removed with the prostate and the lower surgically reattached to the bladder. So, one has half the muscles stopping the flow that one had pre-surgery; and the reattachment might not have the integrity that the original sphincter had.

Walsh and his colleagues note that "other estimates from studies in the United States have been less promising, with rates of incontinence as high as 74% and rates of impotence as high as 90%. Thus, patients considering surgery should be referred to surgeons with considerable experience in order to optimize the likelihood of effective cancer control and to minimize the likelihood of complications." (See Walsh article and references therein.)

Even if potency returns, one has no ejaculate. (The bulk of the ejaculatory fluid is created by the prostate gland and seminal vesicles; when these are removed, the fluid is no longer present.) However, even if one has erectile disfunction, the nerves controlling sexual pleasure and arousal are not affected, so orgasm is possible with an openness to sexual exploration.
 

External Beam Conformal Radiation

Often, a man will be put on 3 months of hormone blockade therapy before undergoing X radiation. This is done in order to shrink the size of the prostate and weaken the cancer, both of which allow this technique to be more effective. (This is known as neo-adjuvant hormonal blockade.)

X-Rays (basically very high energy photons or light waves) start depositing their energy as soon as they encounter matter. In this case, the matter is the patient's flesh. If too much energy is deposited outside the prostate there will be severe side effects. So the technology uses a number of external beams conformed to the patient's physiology. Each beam alone is too weak to do much damage to the tissue it goes through. But when they all meet at the prostate, their combined energy in the gland is supposed to be high enough to be effective there in causing cellular damage and death.

The software and hardware for designing and shaping the beams is constantly improving, as are the imaging techniques used to inform this software.

Survival rates for best practice out to about 10 years are comparable with best practice radical prostatectomy, but after 10 years fall off in comparison. (These are age-adjusted survival rates; that is, all other things being equal.) Other positives are that this technique is not as traumatic as surgery and can be done again if cancer recurs.

The X radiation damages the tissue it passes through. It makes it tougher, among other things. Most surgeons will refuse to do a radical prostatectomy on a patient who has had external beam radiation because the job of cutting through the tissues and removing the prostate is a little more difficult and time consuming than if radiation had not been used. There are, however, surgeons willing to do such "salvage surgery" if indicated (that is, if, after radiation, localized prostate cancer returns).

The side effects during radiation treatment are usually fatigue and often bowel problems. The lower bowel passes right behind the prostate and is naturally subject to significant radiation. Also, since intestinal cells are naturally very rapidly dividing, the radiation will do more damage to their DNA than to that of more quiescent cells.

Longer term side effects do include damage to the rectal wall, incontinence and impotence. These latter two effects often come on slowly, say over the course of a year after treatment. In best practice they are comparable to the rates quoted for radical prostatectomy. (These rates of side effects seem to be somehat higher if patients are asked rather than their doctors. Also, the answers do depend quite sensitively on how the questions are posed and the degrees of effect that can be described. But this is true for all side effects of all the treatments discussed here, and, I would venture, all other medical interventions.)

Walsh and his colleagues note that "Dose-escalated radiation with the use of conformal techniques causes intermittent rectal bleeding of grade 2 or higher (requiring transfusions, interventional radiology, or endoscopic or operative intervention) in 1.5 to 18% of patients and causes impotence in 40 to 60% of patients." (See Walsh article and references therein.)
 

Brachytherapy (Seed Implants)

There are two flavors of this treatment. In one, the radioactive substance is put into the prostate gland in carefully controlled locations for carefully controlled amounts of time. This uses high powered radioactive materials (I don't recall which isotopes) and was the form that Andy Grove had done (see the article in the references, above).

In the other approach, the radioactive material is permanently emplanted in the prostate. One substance used has a half-life of about 3 months; the other has a half-life of about 18 months.

In all cases, the radioactive material is encased in rice-grain sized metal (titanium) pellets. The emplantation is done using trans-rectal ultrasound imaging to guide the placement of the pellets; and the planning is done beforehand using the various available imaging techniques. The idea is to spread the placement of the seeds throughout the gland, but not too close to the urethra, its sphincters, the nerve bundles running along the back side of the prostate which control erections, or the rectal wall, to minimize damage to those structures. The point of entry is again the perineal region between the anus and the scrotum, with long hollow tubes used to guide the placement.

Iodine-125 is one isotope used. It has a half-life of 59.4 days, with predominant decay energies at 27 and 35 kev. In a titanium seed, there is also a peak about 22 kev. These energies imply that the radiation is most intensive within millimeters.

Another isotope used is Palladium-103, with a half-life of 17 days. It has predominant peaks at 20 and 22 kev, so also deposit energy within millimeters of the seed.

Other isotopes are also used.

Both types of brachytherapy can be done with local anesthetic on an outpatient basis, so are far less traumatic than surgery and far less time consuming than Three-D Conformal Radiation. Survival rates for best practice are probably comparable to external X-Rays out to 5 years (but I do not have any of the statistics and that last statement is just a guess for now).

Brachytherapy may be done in conjunction with hormonal blockade (beforehand, to shrink the gland and kill off some of the cancer), or with external beam X-radiation (afterward, to enhance the effects).

Side effects also include impotence and incontinence as well as bowel upset and sometimes bowel damage.

In my opinion, follow on imaging with MRI/MRIS after, say 1 year, would allow the effectiveness of the treatment to be assessed. Any remaining cancer metabolism would indicate that additional seeds are needed and that the original placement did not fully cover the appropriate parts of the gland.

Another approach to brachytherapy is to do real-time planning. This involves pre-operative MRI, perhaps CT scans and prostascint scans which are combined (via software and hardware) with high resolution ulltrasound images minutes before and during the seed implantation procedures. The software determines the best location for each seed, based on the gland location and geometry and based on image analysis of the cancer's locations. Each seed is monitored and deviations from a planned location lead to immediate modifications in the planned locations of seeds not yet implanted. This prevents both cold spots and hot spots, locations which would receive too little or too much radiation. Such dyanmic adjustment can decrease the incidence of side effects, such as impotence, incontinence and rectal wall damage. Not all practitioners follow this approach yet.
 

Proton Beams

Particle beams behave differently than X-Rays, which is the attractive feature of this technique. The goal of both is to deposit enough energy in the target cells that their DNA is broken and their metabolic processes are interfered with, leading to cell death. X-Rays, as noted above, start depositing their energy as soon as they encounter matter, such as the patient's flesh and organs outside the prostate, on their way to the prostate. That is why using many simultaneous low power beams from many directions, and shaping each quite precisely is important in trying to minimize collateral damage.

Protons go right through matter until a certain depth, at which they deposit all their energy. This depth can be tuned by carefully calculating the matter the beam will go through (by imaging and computer modelling) and then precisely tuning the beam's energy. In this way, much less collateral damage may be done. The process is designed to be more efficient than X-Rays in that regard.

Still, one needs to undergo a series of treatments for some weeks, meaning that one needs to be able to spend that time at Loma Linda. In addition, Three-Dimensional Conformal X-Radiation is often used in conjunction with proton beam therapy, though obviously less than when it is used alone.

Because the technique is relatively new, I don't believe the survival statistics go out beyond 5 years or so.

A web site for men who have undergone proton beam therapy, and with a great deal of information about that technology, is the Brotherhood of the Balloon, http://www.protonbob.com/proton-treatment-homepage.asp

A summary of the state of proton beam therapy as of 26 March 2012 may be found at http://www.businessweek.com/news/2012-03-26/prostate-cancer-therapy-too-good-to-be-true-explodes-health-cost.
There are around 10 centers providing this therapy in the U.S., with more being built. The cost is greater than that of standard X-ray treatments, but the article questions whether or not the side effects of treatment are less than those of other medical therapies.
 

Cryotherapy

Liquid nitrogen is introduced into the cooling tubes for enough time to freeze the areas that are desired to be killed. I believe this can be done on an outpatient basis, much like brachytherapy.

The positives of this technique are its ease (vis-a-vis surgery and radiation therapies). Best practice is said to give comparable survival rates out to 5 years [I think - check this out later]. Side effects include damage to areas not intended for treatment, and include impotence, incontinence and bowel damage, with the resulting infections.

I don't think that cryotherapy has been around long enough for 10 year survival statistics to be available.
 

Ultrasound/thermal therapy/Hyperthermia

Side effects would come about from damage to surrounding tissue - incontinence, impotence, bowel damage are the possibilities.
 

Hormonal Blockade

In order to starve the prostate cancer cells, one wishes to deprive them of the DHT they need. This can be done in a number of ways, since there are a variety of pathways in the body to the production of DHT.

• Block the production of lutinizing hormone releasing hormone (LHRH) in the pituitary. This is the initial hormone in the cascade that leads to testicular production of testosterone.
• Block the production of testosterone by the adrenal glands.
• Block the conversion of testosterone into DHT.
• Block the action of the testosterone with an estrogenergic compound such as diethylstilbesterol (spelling?) (DES).
• what else??

Common side effects of hormonal therapy are

• breast swelling and tenderness
• hot flashes
• loss of libido
• bone loss/osteoporosis

If hormonal blockade is used too long, the prostate cancer cells that are sensitive to the lack of DHT die off sometimes leaving behind a small subpopulation that can live and grow independent of the presence or absence of DHT. These are called hormone refractory cells and a recurrence of the cancer due to these cells is known as hormone refractory prostate cancer. It is a form of the disease for which hormonal blockade, in any of its manifestations, does not work.

Thus, a standard protocol for hormonal blockade therapy is to be on it for about a year (or until the PSA falls below some standard value, nominally 0.01 ng/ml) and then to go off of treatment until it rises to some nominal value (say 1.0 or 2.0 ng/ml), cycling through on and off periods. The logic of the off period is to both allow your body to recuperate from the effects of the hormonal blockade and to allow any hormone-dependent prostate cancer cells to become the dominant population. Too long on blockade and any refractory cells may become the dominant population.

Hormonal blockade may also be used as a preliminary therapy, before surgery or radiation, to weaken and shrink the cancer and make it more amenable to the other treatments. It is also a therapy of last resort, after surgery and/or radiation have been ineffective in eradicating the cancer and it has metastasized. In this case, it buys time and some quality of life, but generally does not "cure" the cancer or keep it in check forever.

Further, for men with large glands, whether due to BPH or normal aging, a course of hormonal blockade is usually required before other treatments in order to shrink the physical size of the gland and allow subsequent treatments to be more effective. This is known as neo-adjuvant hormonal therapy.

The standard agents of hormonal blockade are

• Lupron (leuprolide acetate) - LHRH inhibitor, acts on pituitary gland to block production of hormones that eventually lead to testosterone production by testes. Available as an injection, either every 1, 3, or 4 months.
• Eulexin (flutamide) - an anti-androgen (two capsules orally every 8 hours)
• Proscar (finasteride) - a 5-alpha reductase inhibitor; blocks transformation of testosterone to dihydrotestosterone (DHT) - oral administration (what frequency?)
• Zolodex (goserelin acetate) - another LHRH inhibitor - one injection every 4 or 12 weeks
• Casodex (bicalutamide) - blocks testosterone production in the adrenal gland - one pill a day
• Nilandron
  Nilandron(R) (nilutamide)is a hormonal therapy that blocks the production of testosterone and is used to increase survival time and promote disease regression in men with advanced prostate cancer.
  ...
  Nilandron(R) is a nonsteroidal anti-androgen indicated for use in combination with surgical castration for the treatment of men with metastatic prostate cancer. Nilandron(R) binds strongly with androgen receptors and prevents the normal androgenic response, resulting in complete peripheral anti-androgenic activity when combined with surgical castration. Results of well-controlled clinical trials have demonstrated that Nilandron(R) in combination with surgical castration increases survival time and relieves metastatic bone pain.
  (From a Cell Pathways press release, 5 July 2000)
• Pamidronate
  http://www.medscape.com/reuters/prof/2001/09/09.28/20010927clin002.html
  had described these studies, but the press release is no longer available. The full article and an extract of a commentary are available at http://content.nejm.org/cgi/content/full/345/13/948 (article) and http://content.nejm.org/cgi/content/extract/345/13/989 (commentary)
  Pamidronate Protects Men From Bone Loss During Androgen-Deprivation Therapy, Matthew R. Smith, M.D., Ph.D., Francis J. McGovern, M.D., Anthony L. Zietman, M.D., Mary Anne Fallon, L.P.N., Douglas L. Hayden, M.A., David A. Schoenfeld, Ph.D., Philip W. Kantoff, M.D., and Joel S. Finkelstein, M.D., New England Journal of Medicine, vol 345, pp 948-955, 989-991 (27 September 2001). The drug is given intravenously every 12 weeks to men taking Lupron.
• Nizoral
• what else??

Bob Leibowitz, MD, in Los Angeles, is an advocate of triple hormone blockade. His web pages may be found at http://www.compassionateoncology.org/

A recent paper of his on triple hormone blockade is Treatment of Localized Prostate Cancer With Intermittent Triple Androgen Blockade: Preliminary Results in 110 Consecutive Patients, Robert L. Leibowitz and Steven J. Tucker, The Oncologist, Vol. 6, No. 2, 177-182, April 2001 and is currently available on line at http://theoncologist.alphamedpress.org/cgi/content/full/6/2/177
(Free registration is required for access.)

If Lupron is given with no other treatments, a situation known as PSA flare occurs which can be quite dangerous. For the first week or so after the injection, one's PSA levels rise dramatically and the prostate cancer cells seem to have greater activity. In some men, this has led to the formation of metastases where there were none previously or to a sudden exacerbation of symptoms. Flare may be avoided by simply preceding the administration of the Lupron by a week or so of Casodex.

Recent research at Johns Hopkins (published 1 Oct 2007) indicates that ADT may, however, promote the production of a molecule, Nestin, which promotes metastasis. A summary may be found at http://www.hopkinsmedicine.org/Press_releases/2007/10_01_07.html ("STANDARD TREATMENT FOR PROSTATE CANCER MAY ENCOURAGE SPREAD OF DISEASE"). The full article is Roles for the Stem Cell-Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis, Wolfram Kleeberger, G. Steven Bova, Matthew E. Nielsen, Mehsati Herawi, Ai-Ying Chuang, Jonathan I. Epstein and David M. Berman, Cancer Res 2007; 67 (19): 9199-206 (1 October 2007). The abstract is available at http://cancerres.aacrjournals.org/cgi/content/abstract/67/19/9199; they charge for access to the full article.

Research presented at the 2009 ASCO (American Society of Clinical Oncology) meeting presented newer findings about the androgen dependence of prostate cancers -- rather than being totally dependent on the androgens produced by the testes and adrenal glands, some prostate cancers can produce their own testosterone and drive their own growth. This has implications for ADT. A summary of the meeting's news for prostate cancer may be found at http://www.medscape.com/viewarticle/704968?src=mp&spon=15&uac=24203PX, by Christopher J. Logothetis, MD (Published: 06/29/2009), which includes a video tutorial. The research paper is Increased expression of androgen receptor (AR) and enzymes involved in androgen synthesis in metastatic prostate cancer: Targets for novel personalized therapies, N. Mitsiades, N. Schultz, B. S. Taylor, H. Hieronymus, J. Satagopan, P. T. Scardino, V. E. Reuter, C. Sander, C. Sawyers, H. I. Scher and Prostate Cancer Genome Project Group, http://meeting.ascopubs.org/cgi/gca?SEARCHID=1&FULLTEXT=mitsiades&VOLUME=27&ISSUE=15S&FIRSTINDEX=0&hits=10&RESULTFORMAT=&gca=ascomtg%3B27%2F15S%2F5002&sendit=Get+All+Checked+Abstract(s)

One caveat about hormonal blockade appeared in a study published in the 26 August 2009 issue of the Journal of the American Medical Association: Hormonal Therapy Use for Prostate Cancer and Mortality in Men With Coronary Artery Disease–Induced Congestive Heart Failure or Myocardial Infarction, Akash Nanda, MD, PhD; Ming-Hui Chen, PhD; Michelle H. Braccioforte, BS; Brian J. Moran, MD; Anthony V. D’Amico, MD, PhD, JAMA. 2009;302(8):866-873 (See http://jama.ama-assn.org/cgi/content/short/302/8/866 for the abstract; full text may be purchased). Hormonal blockade in conjunction with radiation therapy led to increased mortality for men with a history of Coronary Artery Disease (CAD) induced Congestive Heart Failure or Myocardial Infarction but not among men with no comorbidity or a single CAD risk factor.
 

Chemotherapy

Diet, Nutrition, Holistic modalities

• PC-SPES
  • http://www.vivacity.com/pcspes.html
    They sold PC-SPES and had a bibliography and further info. As of June 2009, this site does not seem to be available at all. PC-SPES was removed from the U.S. market.
  • http://www.cancer.gov/cancertopics/pdq/cam/pc-spes/patient
    The National Cancer Insitute patient information page on PC-SPES.
  • http://www.cancer.org/docroot/ETO/content/ETO_5_3X_PC-SPES.asp
    The American Cancer Society page on PC-SPES.
  • http://nccam.nih.gov/news/alerts/spes/
    The consumer advisory (5 September 2002) from the National Center for Complementary and Alternative Medicine of teh NIH on the removal of PC-SPES from the marketplace becuase of contamination.

ProstRcision practiced by Radiotherapy Clinics of Georgia (RCOG)

APPENDIX C: Future Therapies

The simple message here is that there are many avenues under investigation for controling or curing prostate cancer, many more than I've listed below. Not all will be effective, in the end of clinical trials, but there is no doubt that some will be. In two years or five years or ten years.

If one can control one's cancer by mean of some non-irreversible treatment for however long it takes for these future therapies to come to market, then cancer will be a chronic disease or one that is indeed eradicable. My dietary approach, with mother's milk, has been quite successful for me. It is up to each man, in consultation with his trusted and knowledgeable advisors, to decide which approach is most appropriate for him, given what he knows about his particular disease, his health in general, and a whole panoply of philosophical and quality of life issues.

But here there lies even more hope for the future, if we can get from here to there.

• Expensive Professional Overviews

  The BioSeeker Group had three interesting but prohibitively expensive publications which are no longer available on their web site as of June 2009. They would be out of date at this point. These are examples of other research reports available there:

  • http:www.bioseeker.com/view/Product.do?productID=804
    Analysis of Prostate Cancer R&D: The Complete Guide
    Released 2 Feb 2004, $2750.00
     
  • http://www.bioseeker.com/view/Product.do?productID=722
    The Prostate Cancer R&D Database
    Released 18 Sep 2003, $2950.00
     
  • http://www.bioseeker.com/view/Product.do?productID=721
    The Global Structure of Prosate Cancer R&D
    Released 18 Sep 2003, $1950.00
     
  • http://www.bioseeker.com/component/page,shop.product_details/flypage,shop.flypage/product_id,472/category_id,72/manufacturer_id,0/option,com_virtuemart/Itemid,1/
    Is an overview page of their prostate cancer offerings.
     
  If any reader purchases any of these and wishes to share on-line access with me, I would be infinitely grateful.
   
• A Summary of the State of the Art

  http://www.newsweek.com/id/157548/
  "We Fought Cancer...And Cancer Won", from Newsweek, 6 September 2008.
  "After billions spent on research and decades of hit-or-miss treatments, it's time to rethink the war on cancer." Not specifically about prostate cancer, but cancers in general.
   

• One man's overview

  http://ragingbull.quote.com/mboard/boards.cgi?board=AVN&read=29271
  (No longer available as of June 2009) A review of 4 emerging technologies in oncology: antibodies, anti-angiogenesis, signal transduction inhibition, and epidermal growth factor receptors (EGFR). (Dated 2 Jan 2002)

  http://www.the-scientist.com/yr2002/may/bahls_p16_020527.html
  The 27 May 2002 issue of The Scientist had a cover story ("Reining in a Killer Disease") on work to control cancer, turning it into a chronic disease.
   

• From an emailed newsletter (May 2005):

  The five major targets in apoptosis, p53, Bcl-2, TRAIL, IAP and Caspases, are the corner stones for further analysis in study to address whether they are successful cancer therapeutic targets or not and what level of competition is present. Only p53 and Bcl-2 are apoptotic targets with drug candidates that have reached Phase III clinical testing, although death receptors "TRAIL" are closing the gap. ... [There are currently] 5 drug candidates targeting the cell death pathway, apoptosis. Additionally, more early stage candidates are also under investigation, which brings the total number of companies interested in this field to around 40.
   

• Better Diagnostics
   
  • http://news-service.stanford.edu/news/medical/2004/february4/prostate.html
    This press release discusses work published in the 20 Jan 2004 issue of The Proceedings of the National Academy of Sciences. Researchers at Stanford, using microarray technology ("gene chips") have found several genes that are strongly correlated with whether a man's prostate cancer will be aggressive or not. They analyzed samples from men whose histories were known for 8 or more years post treatment (surgery). As the technology is developed, perhaps simple and inexpensive tests can be run on biopsy samples to look for the presence of a few particularly significant marker genes. Knowing which cancers are more aggressive can help in treatment decisions. Conversely, knowing that one has a non-aggressive cancer may lead to a less radical treatment, with its expense and side effects.
     
  • http://tmlr.net/testing/jump/?c=18976&tf=2796,2797,2798,2799,2800,2802,2807,2808,2809,2827,2855,2856&uf=&a=754&m=3673&p=1882682&t=2203
    Target Discovery of Palo Alto, CA ( http://www.targetdiscovery.com) and Virginia Prostate Center are collaborating to develop clinical assays that will provide information on tumor aggressiveness and guide treatement. These tests will detect different protein isoforms and use them as biomarkers for potential aggressiveness or indolence of the cancer, in order to help guide treatment choices. (Press release from 21 March 2006).
     
  • http://www.bloomberg.com/apps/news?pid=email_en&refer=&sid=acCwbLsSivVQ
    Summary from Bloomberg news
    http://jnci.oxfordjournals.org/cgi/content/full/98/19/1420
    ftp://www.cohensw.com/pub/pca/JNCI_HenshallOct406.pdf
    Full article
    A study published in the 4 Oct 2006 Journal of the National Cancer Institute (Vol 98, No 19, pp 1420-1424) by a group of Australian researchers looked at gene expression of the AZPG1 (Zinc-alpha-2-glycoprotein) gene in prostate tissues removed in radical prostatectomies. They found lower levels of gene expression correlated with a more aggressive cancer and a higher probablility of recurrence and metastasis. If this test can be applied to biopsy samples with a simple microarray (gene chip) implementation, perhaps it would be useful in helping men choose an appropriate treatment course, neither overtreating nor undertreating their cancer.
     
  • http://tmlr.net/testing/jump/?c=19409&tf=2796,2797,2798,2799,2800,2802,2807,2808,2809,2827,2855&uf=&a=754&m=3721&p=1882682&t=2203
    A PharmaWeek item from 5 April 2006 discusses two genetic tests for probablility of prostate cancer recurrance. Both are currently done on tissues removed after RP. One, from Illumina, Inc. (San Diego) (http://www.illumina.com/) analyzes a set of 16 genes. The other, from Epigenomics AG (Berlin), (http://www.epigenomics.com/) detects the PITX2 gene and its methylation, which is correlated with hormone regulation. The issue, again, is both the predictability of the tests and their extension to biopsy material to better help inform the newly diagnosed man's choices.
     
  • http://www.webmd.com/prostate-cancer/news/20090211/key-piece-to-prostate-cancer-puzzle-found
    In an article published in the 12 Feb 2009 issue of Nature, a group led by Arul M. Chinnaiyan, MD, PhD of the University of Michigan discusses metabolomics research which led to the identification of a marker in urine (sarcosine) which may distinguish between indolent and aggressive forms of prostate cancer. Further work may find ways to interfere with the pathways involved, making prostate cancer a manageable disease, and may also find additional such biomarkers for diagnostics and treatment. See a summary and discussion at http://www.nature.com/news/2009/090211/full/news.2009.94.html. The reference is Sreekumar, A. et al. Nature 457, 910-914 (2009).

    Additional commentary may be found at

    • The San Jose Mercury News Archive site (payment required) -- search for "sarcosine" on 19 Feb 2009. The URL had been http://www.mercurynews.com/nationworld/ci_11733242?nclick_check=1
      
    • http://blog.newsweek.com/blogs/labnotes/archive/2009/02/11/for-prostate-cancer-just-pee-not-so-fast.aspx
     
  • http://online.wsj.com/article/SB10001424052748703279704575334982806405218.html
    The Prostate Cancer Quandary, Melinda Beck (29 June 2010)
    "Scientists may soon be able to answer the agonizing question facing men with prostate cancer: Does their cancer need immediate treatment or can it be left alone?..."
    Article about new genetic tests, and biomarker tests to predict vurulence of individual cancers, as a guide to treatment.
     
  • http://scienceinsociety.northwestern.edu/content/articles/2009/smaller-probes-earlier-detection
    An overview of an ultra-sensitive PSA test, based on nanoparticle technology and developed at Northwestern University. This test seems to offer a better prognostication of post-operative recurrence that other tests currently available. This article is from 4 December 2009. Updates on this work were presented at the American Urological Association meeting in June 2010 and summarized in the PCAI Digest (vol 5, Issue 261).
     
  • http://www.zerocancer.org/site/News2?page=NewsArticle&id=11696&news_iv_ctrl=1001
    Nanosensors Detect Cancer From Exhaled Breath, Mark Lyall | KnowAboutHealth.com | 08.16.2010
    "Could you have imagined that the cancer can be detected by analysis of your breath? Researchers at Technion – Israel Institute of Technology have developed nanosensors that can detect lung, breast, bowel and prostate cancer via exhaled breath...."
    The original research article is http://www.nature.com/bjc/journal/v103/n4/full/6605810a.html
    Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors, G Peng, M Hakim, Y Y Broza, S Billan, R Abdah-Bortnyak, A Kuten, U Tisch and H Haick, British Journal of Cancer (2010) 103, 542–551. doi:10.1038/sj.bjc.6605810, www.bjcancer.com, Published online 20 July 2010 (article available for free)
     
  • http://www.zerocancer.org/site/News2?page=NewsArticle&id=11754
    Urine Test for Prostate Cancer Hopeful, by Catharine Paddock, MedicalNewsToday.com | 10.15.2010
    This article is a lay level summary of http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013363
    (The rs10993994 Risk Allele for Prostate Cancer Results in Clinically Relevant Changes in Microseminoprotein-Beta Expression in Tissue and Urine, Hayley C. Whitaker, et al., published online 13 October 2010)
    "New research led by UK scientists has shown that a protein in urine could be a reliable marker for prostate cancer risk, and although there is still a lot of work to be done to move it from the laboratory to the clinic, the finding is raising hopes that an easy and reliable clinical test for prostate cancer is now much closer...."
     
  • http://www.newswiretoday.com/news/94428/Prostate_Mapping_Biopsy_Impacting_Treatment_Decisions_Says_A_Recent_Study/
    Prostate Mapping Biopsy Impacting Treatment Decisions Says A Recent Study
    This article (18 July 2011) discusses an approach to more thorough mapping of the prostate than the standard 6-12 core TRUS guided approach. Under general anesthesia, multiple cores are taken trans-perineally into to map the entire gland in 3D and plan treatment.
     
  • http://www.doctorslounge.com/index.php/news/pb/22395
    Five SNPs Validated As Linked to Lethal Prostate Cancer
    Summary of a report from the 16 August 2011 Cancer Epidemiology, Biomarkers & Prevention. (Abstract is available at http://cebp.aacrjournals.org/content/early/2011/08/12/1055-9965.EPI-11-0236.abstract) When the appropriate microarrays are available to find the presence or absence of these SNPs (single nucleotide polymorphisms) in a biopsy sample, there will be much more knowledge than the Gleason score for informing a man's decision on what to do, if anything, once diagnosed.
     
  • http://m.prnewswire.com/news-releases/new-prostate-cancer-blood-test-now-available-in-the-us-256509831.html
    In April 2014, Beckman Coulter announced the availability of a new test, phi (for Prostate Health Index), that they claim is significantly more specific for PCa that a plain PSA test. It combines PSA, free PSA and p2PSA tests. See also http://prostatehealthindex.us/ for the company web site.
     
  • http://www.washingtonpost.com/news/to-your-health/wp/2015/07/30/five-subtypes-of-prostate-cancer-identified-paving-way-for-more-personalized-treatments/
    Five subtypes of prostate cancer identified, paving way for more personalized treatments (30 July 2015)
    Washington Post article summarizing a study of 259 men with prostate cancer and 482 tumor samples. Genomic analysis identified a number of new gene markers for predicting the course of the disease. The full article is http://www.ebiomedicine.com/article/S2352-3964%2815%2930071-2/fulltext Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study, H. Ross-Adams, et al., EBioMedicine (29 July 2015) http://dx.doi.org/10.1016/j.ebiom.2015.07.017
  
   
• Viral therapies
   
  • http://ragingbull.quote.com/mboard/boards.cgi?board=CLPA&read=110035
    http://www.oncolyticsbiotech.com/ Oncoyltics Biotech, a Canadian company, is beginning a Phase I study of a reovirus (Reolysin) after successful in vitro and animal studies.

    Cancer cells are often able to 'hide' from the immune system. However, certain type of cancers have a weakness in their cellular armor: an 'activated' Ras pathway, a sort of genetic soft spot found in perhaps more than two-thirds of all latent and actual tumors. Happily, healthy cells don't have this 'oncogene' or 'cancer gene' in their makeup. However, the Ras-activated cells are unable to manufacture the cellular protein PKR. In healthy normal cells, PKR prevents reoviruses from replicating. In Ras cells, this protection doesn't exist. Which means the reovirus can slip aboard, multiply and burst the infected cancer cell from within. Kill the killer.

    "The big bonus is that the 'infection' is a true one; the reovirus spreads from cancer cell to cancer cell, clearing away the invader but leaving normal cells alone. This cycle of infection, replication and cell death is believed to roll on until there are no more 'victims' - cancer cells unwittingly burdened with an activated Ras pathway - left to kill." (From the press release quoted. 8 Mar 2002)

    A more recent (29 April 2003) stock newsletter talking up Reolysin may be found at http://ragingbull.quote.com/mboard/boards.cgi?amp;board=CLPA&read=121973
     

  • http://www.ustoo.org/screamoutput/2002/07/22/eng-ascribe/eng-ascribe_100814_38_979810308665.html
    A press release on the AScribe newswire (no longer available on the UsToo web site as of June 2009) discusses how researchers at UCLA's Jonsson Cancer Center, led by Prof. Lily Wu, have engineered a virus that binds selectively to prostate cancer cells, based on the PSA protein presented by these cells. (Original article is in Nature Medicine, 1 Aug 2002 issue -- see http://www.nature.com/nm/journal/v8/n8/abs/nm743.html for the abstract; full article may be purchased.)
    Original experiments attached luciferase, the firefly luminescence chemical, to the virus for imaging. Future experiments will bind toxic chemicals to the virus with the intent of killing the main tumor and distant, although perhaps microscopic, metastases. These experiments were done on mice in which human prostate cancer had been implanted. See also http://www.cancer.ucla.edu.
     
  • http://www.nci.nih.gov/ncicancerbulletin/NCI_Cancer_Bulletin_070505/page2
    Virus Selectively Kills Cancer Cells, Study Indicates (5 July 2005)
    "A common, benign virus may be a more powerful foe of some cancer cells than previously thought. Research has indicated that the virus, adeno-associated virus type 2 (AAV2), can inhibit the growth of some cancer cells and, in some cases, cause cell death (apoptosis)." This research is being done at Pennsylvania State University Medical College with Dr. Craig Meyers as the lead researcher. So far, it has only been done in vitro, but they are working on animal studies.
     
  • 'Tame' Virus Could Prove Prostate Cancer Weapon
    http://www.zerocancer.org/site/News2?page=NewsArticle&id=11409
    A copy of a story in the Telegraph (9 March 2010) at a lay level. A harmless reovirus kills prostate cancer cells in vitro. When injected into the prostates of 6 men with PCa three weeks before prostatectomies, histology showed death of cancer cells in the tumors but no effect in healthy tissue.
    http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-09-2408v1
    Oncolytic Viral Therapy for Prostate Cancer: Efficacy of Reovirus as a Biological Therapeutic, Chandini M. Thirukkumaran, Michael J. Nodwell, Kensuke Hirasawa, Zhong-Qiao Shi, Roman Diaz, Joanne Luider, Randal N. Johnston, Peter A. Forsyth, Anthony M. Magliocco, Patrick Lee, Sandra Nishikawa, Bryan Donnelly, Matt Coffey, Kiril Trpkov, Kevin Fonseca, Jason Spurrell and Don G. Morris, Published online first on March 9, 2010 [Cancer Research, 10.1158/0008-5472.CAN-09-2408], Cancer Res; 70(6); 2435–44
    This is the article's abstract; full text is available for purchase.

• Generic Vaccines
  • http://www.bayarea.com/mld/bayarea/business/3438203.htm
    The San Jose Mercury News, 11 June 2002, p. E1 (article ID 0206120082) has an article about a variety of approaches to cancer vaccines, a number of which are targeted at prostate cancer. (The article is available for purchase, but no longer at the URL shown; to find it, go to Help pulldown menu, choose Past Articles, and then search on 'Cancer' and the date.)

  • Biomira (now Oncothyreon) (see http://www.oncothyreon.com/) is developing vaccines to enhance immune response to particular cancer antigens. In September 2001 they announced a phase II clinical trial of BLP25 in a small group of post-prostatectomy patients with rising PSAs will soon start.

  • Genzyme Oncology (see http://www.genzymeoncology.com/) is pursuing immunotherapy as well as antiangiogenesis approaches.

  • Use of glucopeptides to prime T cells to kill cancer (see http://health.ucsd.edu/news/2009/1-8-vaccine-sweet-spot.htm), a UCSD Medical Center press release (8 Jan 2009)

  • http://health.usnews.com/blogs/on-men/2009/12/04/coming-vaccine-that-fights-prostate-cancer.html
    Coming: Vaccine That Fights Prostate Cancer, Ford Vox, M.D., U.S. News & World Report (4 December 2009)
    A summary of the current state of two vaccines, Provenge from Dendreon, and an anti-PSA vaccine.

  • http://www.news-medical.net/news/20100127/Study-PROSTVAC-VF-vaccine-effective-in-treating-patients-with-metastatic-prostate-cancer.aspx
    Study: PROSTVAC-VF vaccine effective in treating patients with metastatic prostate cancer (27 January 2010). Based on a cowpox virus, this anti-PSA vaccine has extended life in metastatic hormone-blockade resistant men in a Phase II clinical trial. It is produced by produced by BN ImmunoTherapeutics, Inc., of Mountain View, California.

• Custom Vaccines

  See, for example, https://www.stanfordalumni.org/news/magazine/2001/julaug/features/cancer.html
  or http://www.genitope.com/
   

• Generic apoptosis inducing medications
  • Aptosyn (exisulind) from Cell Pathways (now merged with OSI Pharmaceuticals). See http://www.osip.com,
    The following URLs no longer work as of June 2009:
    http://www.cellpathways.com/
    http://ragingbull.quote.com/mboard/boards.cgi?board=CLPA&read=98102
    which quotes a discussion relative to hormone refractory prostate cancer.

  • CP-461, a second generation compound from Cell Pathways
    A brief overview of Aptosyn and CP-461 in hormone refractory prostate cancer, given by Dr. Petrylak of Columbia University at the Nov 2002 MSSM Chemotherapy Symposium can be found at http://www.mssmtv.org/conferences/template/frameset_demo.html?folder=chemo_2002&doctor=111502cp_petrylak
     
  • Irofulven (MGI 114, hydroxymethylacylfulvene, or HMAF) from MGI PHARMA. See http://www.mgipharma.com
    http://biz.yahoo.com/bw/011107/72546_1.html - no longer available
    Initial clinical trials have been in pancreatic cancer, but in vitro effects have also been seen in prostate and other solid tumors.
     
  • http://www.the-scientist.com/yr2001/jun/research1_010625.html A brief overview of companies looking at drugs to initiate programmed cell death (apoptosis) from The Scientist, 15[13]:18, Jun. 25, 2001
     
  • http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=MAXM&script=410&layout=9&item_id=258460
    Maxim Phramaceuticals press release (13 Feb 2002) on high throughput screening technology focused on finding pro-apoptotic drug candidates.
     
  • http://www.medicalnewstoday.com/articles/60085.php
    Hybrid Molecule Causes Cancer Cells To Self-Destruct (5 Jan 2007)
    Johns Hopkins researchers, led by Kevin Yarema, have combined butyrate with a sugar, N-acetyl-D-mannosamine (ManNAc), to enhance the anti-cancer properties of each molecule. Once inside the cancer cell, the molecules separate. The ManNAc is processed into sialic acid, which "plays key roles in cancer biology, while butyrate orchestrates the expression of genes responsible for halting the uncontrolled growth of cancer cells." The two molecules seem to have a synergistic effect on apoptosis of cancer cells, better than either alone or the two administered separately. The researchers believe this compound has minimal effect on healthy cells. This work has all been done in vitro and has so far focussed on the molecular mechanisms of the apoptotic effects.

    Published in the Elsevier journal Chemistry & Biology (Targeting Glycosylation Pathways and the Cell Cycle: Sugar-Dependent Activity of Butyrate-Carbohydrate Cancer Prodrugs, Srinivasa-Gopalan Sampathkumar, Mark B. Jones, M. Adam Meledeo, Christopher T. Campbell, Sean S. Choi, Kaoru Hida, Prasra Gomutputra, Anthony Sheh, Tim Gilmartin, Steven R. Head and Kevin J. Yarema, Chemistry & Biology 13, 1265-1275, December 2006). PDF is available for download from http://download.cell.com/chemistry-biology/pdf/PIIS1074552106003760.pdf

• Novogen's Phenoxodiol (inhibits the enzyme sphingosine kinase) - Phase I & II trials. See http://www.novogen.com and newsreleases under there.
   
• Myriad Genetics' MPI-176716 and related compounds. See http://biz.yahoo.com/prnews/011009/latu027_1.html (no longer available on Yahoo!) for a press release; http://www.myriad.com/ for the company's web site.
   
• Angiogenesis inhibitors
  
  • See, for example, combrestatin (via a web search or (no longer available) at http://cancer.med.upenn.edu/upcc/pr_combrestatin.html or the OXiGENE web site at http://www.oxigene.com. They bill this an a "vascular targeting" drug rather than as an anti-angiogenesis drug (attacks old vessels as well as inhibiting formation of new ones).
     
  • AVE8062, an experimental drug from Aventis, "represents a new strategy for the treatment of solid tumors. AVE8062 works by targeting existing tumor blood vessels that supply critical nutrients and oxygen to tumor cells." See http://biz.yahoo.com/prnews/010712/nyth047b.html (no longer available on Yahoo!)
     
  • Search also on Angiostatin and endostatin.
     
  • "Icon" is an engineered molecule which destroys tumor blood vessels by binding to tissue factor and activating a cytolytic immune response. This approach has been tested in mice and found to completely eradicate prostate cancer. (See Proc Natl Acad Sci USA 9 Oct 2001, vol 98, pp 12180-12185). It is still in very early stage investigation.
    http://www.medscape.com/reuters/prof/2001/10/10.02/20011001scie004.html (is no longer available)
     
  • PCK3145 is an experimental drug currently in Phase I/II clinical trials (summer 2008) at Memorial Sloan Kettering in New York for treatment of hormone refractory prostate cancer. It is both an angiogenessis inhibitor and has anti-metastatic effects. It is produced by Ambrilia Biopharma, or Verdun, Quebec, Canada. See http://www.ambrilia.com/en/products/prostate-cancer-pck3145.php
     
• Antivascular Therapies
  http://www.technologyreview.com/biomedicine/12882/
  The Technology Review, July/August 2002, has a brief article on antivascular therapies. Whereas antiangiogenic therapies deal with stopping the growth of new blood vessels to feed a cancer, antivascular therapies temporarily close off existing blood vessels that feed tumors for a long enough time to damage the tumors, but not so long as to damage healthy tissue. Companies working in this area are Oxigene, Aventis and AstraZeneca.
   
• COX-2 inhibitors (e.g., Celebrex -- cf http://www.celebrex.com, and Vioxx)

  http://ragingbull.quote.com/mboard/boards.cgi?board=CLPA&read=113424
  Two research abstracts on COX-2 inhibition and the suppression of prostate cancer. Quoted from the American Urological Association annual meeting, May 2002.
   

• Dendritic cell therapy:
  • http://www.dendreon.com  Dendreon Corp.
     
  • http://urology.medscape.com/reuters/prof/2001/12/12.31/20011228drgd002.html
    (Article no longer available on Medscape.) Research at Stanford on use of dendritic cells potentiated against mouse prostatic acid phosphatase proves promising in a Phase I trial. See J Immunol 2001;167:7150-7156. (15 Dec 2001)
     
  • Phase 3 trial results announced 12 Jan 2004 (see Dendreon's web site). A study involving men with Gleason scores of 7 or less and advanced prostate cancer had a prolongation in their median survival times of 8.4 months (30.7 months versus 22.3 for those on placebo). Provenge has an FDA Fast Track status. The pivotal phase 3 trial is ongoing (as of 12 Jan 2004).

    In March 2007, the FDA overruled its own scientific panel which had recommended approval of the drug, and sent it back for another clinical trial, with results due in 2009. This story may be found at http://caretolive.com/. This is of interest and concern since Provenge seemed effective with many fewer side effects than other medical treatments for prostate cancer.

  • http://www.nytimes.com/2009/04/15/business/15cancer.html
    Promising Test for Dendreon's Prostate Cancer Drug
    "A prostate cancer drug developed by the Seattle biotechnology company Dendreon prolonged the lives of men in a decisive clinical trial, the company announced Tuesday morning...." Full results to be presented in May 2009.

  • http://seattletimes.nwsource.com/html/localnews/2011695773_dendreon25m.html
    Seattle biotech firm on verge of a groundbreaking cancer vaccine -- A prostate-cancer treatment, if approved this week, could launch a whole new way to battle tumors — by firing up the body's natural defenses. (24 April 2010)

  • http://www.nytimes.com/2010/04/30/health/30drug.html
    F.D.A. Approves 'Vaccine' to Fight Prostate Cancer, By Andew Pollack, Published: April 29, 2010
    Provenge was approved after showing it added about 4 months to the lives of men with metastatic hormone refractory prostate cancer. The drug will cost about $93,000.00 for a course of treatment.

• Gene therapy --
  • http://www.usnews.com/usnews/nycu/health/articles/020624/24cancer.htm
    U.S. News and Worlds Reports, 24 June 2002, article (no longer available on their site) discussing genetic issues in cancer as an overview to possible detection, differentiation, and treatment futures. There's no such thing as "prostate cancer"; rather there are various genetic defects that can occur in prostate (and other) cells, each responding best to different treatments, some perhaps needing no treatment at all.
     
  • cf Cell Genesys http://www.cellgenesys.com/view.cfm/1/Cell-Genesys---Changing-the-Future-of-Oncology

    http://www.ustoo.org/screamoutput/2002/05/19/pr/0000-0270-fl-cell-genesys-report.html
    (no longer available) discusses Phase II trial results of Cell Genesys' GVAX prostate cancer vaccine, with encouraging long term survival data. (19 May 2002)
      http://www.cellgenesys.com/view.cfm/20/GVAX-Immunotherapy-for-Prostate-Cancer
    notes that on 16 October 2008 the GVAX prostate cancer vaccine program was terminated during its phase 3 trials. A discussion of the program can be found in this article.

  • Also, http://urology.medscape.com/reuters/prof/2001/06/06.27/20010626drgd002.html
    (This page is no longer available.) Cobra Therapeutics (Keele, Staffordshire, England) launched a Phase I/II clinical trial using a pro-drug converting enzyme. A pro-drug is a chemical that is transformed into a drug when it or its carrier is bound to an appropriate target cell. (27 June 2001)
     
  • http://www.medscape.com/reuters/prof/2001/10/10.18/20011017scie004.html
    (No longer available on the medscape web site) "Prostate-Specific Gene Therapy Induces Apoptosis in Prostate Cancer Cells" -- Summary of Gene Therapy 2001;8:1363-1371. Researchers at the Medical University of South Carolina in Charleston inserted into an adenovirus both a gene to cause apoptosis and a promoter specific to prostate cells. Tests have only been done in vitro to date. (17 Oct 2001)
     
  • http://my.aol.com/news/news_story.psp?type=1&cat=0200&id=0203011327590490
    (No longer available on AOL's web site.) Work in Sweden on a drug to fix mutated p53 genes via a drug called Prime-1. p53 helps repair DNA damage and is mutated in about 1/2 all cancers. The drug restores the functionality of the gene product and works in vitro and in rats. Full article in March 2002 issue of Nature Medicine.
  
   
• http://urology.medscape.com/33819.rhtml?srcmp=urol-021601
  (Article no longer available, June 2009)
  PROSTATE TUMOR ABLATION TECHNIQUE USES IMPLANTED MAGNETIC RODS
  Implanting magnetic rods that heat up in a magnetic field, shows promise in treating prostate cancer without causing the side effects commonly seen with radiation therapy or surgery, according to Dr. Robert D. Tucker of the University of Iowa in Iowa City.
   
• Telomerase inhibitors
  (See http://www.geron.com - Geron Corp)

  Also http://www.reuters.com/news_article.jhtml?type=sciencenews&StoryID=98742
  (Article no longer available at Reuter web site.) Research at UCSF by Prof Elizabeth Blackburn (2 July 2001)

  http://www.reuters.com/news_article.jhtml?type=sciencenews&StoryID=251913
  (Article no longer available on the Reuters web site.) Work by British Scientists to block telomerase and restore mortality to cancer cells (28 September 2001)

  http://dailynews.yahoo.com/h/nm/20011121/sc/health_cancer_dc_3.html
  (Article no longer available.) Scottish scientists turn cancer cell's signal to turn on telomerase gene into one to turn on nitroreductase gene, which activates a cell-killing drug. (21 November 2001)
   

• High Intensity Focused Ultrasound (HIFU)
  http://www.medscape.com/viewarticle/430760
  Discusses Urology 2002; 59(3):394-399 on the use of this technique. (Summary from 28 March 2002)

  http://en.wikipedia.org/wiki/High_intensity_focused_ultrasound
  Another summary, last updated 28 May 2007 (but may be newer when you read it)
   

• Thermotherapy
  (See, for example, http://www.Celsion.com)

  http://urology.medscape.com/reuters/prof/2001/11/11.16/20011115drgd001.html
  (Page no longer available on Medscape.) Microwave Therapy Shows Promise as Treatment for Prostate Cancer
  Press releases discusses J Urol 2001;166:1707-1714, a report on Phase I/II clinical trials using heat generated via microwaves from 5 antennas implanted in the prostate, with no major and few short term minor side effects. (16 Nov 2001)
   

• IL-4 bound with a cytotoxin, binds preferentially to tumor cells; in phase I for brain tumors, with some possible applications to prostate cancer. See http://www.neurocrine.com/clinical/clinical_malbraintum.html
    As of June 2009, there is no mention of this project on the Neurocrine web site. Early trials likely did not pan out.
• New anti-androgren compounds (in Phase III trials - June 2001) work faster than Lupron (Plenaxis/abarelix from Amgen & Praecis) with similar side effects and no PSA flare. See http://urology.medscape.com/reuters/prof/2001/06/06.05/20010604drgd006.html (5 June 2001) (This article is no longer available.)
   
• Antisense drugs
  For example, http://www.genta.com/pipeline/genasense.php?v=5, Genta.

  http://ir.isispharm.com/releasedetail.cfm?ReleaseID=386855 Isis Pharmaceuticals and Oncogenex Technologies are developing antisense drugs for prostate cancer, OGX-011. (Original article was dated 26 Nov 2001, but is no longer available. This is a press release from 1 June 2009.)

  http://www.avibio.com/ AVI BioPharma
  From a press release (14 May 2002): "...announced the publication of two studies in Current Opinion in Molecular Therapeutics (2002) 4(2). These preclinical studies demonstrated potential for use of AVI's third-generation antisense drug platform, NEUGENE(R), in treating prostate cancer and viral infections caused by the Caliciviridae, a family of RNA viruses. 'AVI continues to build strong scientific support for its antisense technology,' said Patrick L. Iversen, Ph.D., AVI's senior vice president of research and development. 'These studies confirm our belief that NEUGENE compounds are capable of addressing a broad range of health problems for which there are no known cures.' Antisense as a Treatment for Prostate Cancer[:] Prostate cancer is the most frequently diagnosed malignancy and is the most common cause of mortality among men. In 'Prostate cancer: Status of current treatments and emerging antisense-based therapies,' Gayathri Devi, Ph.D., senior scientist at AVI, compared current prostate cancer treatment strategies with preclinical and clinical prostate cancer antisense studies conducted in the past year. Dr. Devi reviewed stages and treatment options for prostate cancer, which were linked to the antisense approach. Her research showed that AVI's antisense technology is an attractive alternative to traditional cancer therapies."
   

• RNA Interference
  http://www.inpharm.com/intelligence/esp_news0441002.html
  (Article no longer available on teh web site.) (11 Oct 2002) Reports on a paper in Nature (2002;419:624-629) on 10 Oct 2002 on the biomarker EZH2 for metastatic prostate cancer. The researchers at the University of Michigan Comprehensive Cancer Center also discuss RNA interference in the paper, a new technique used to inhibit this biomarker. The RNAi technique was discovered in 2001 and uses short sequences of RNA to shut down the activity of specific genes. It has only been used in in vitro studies to date.
   
• Immunotherapy vs hormones
  
  • http://www.aphton.com/technology.html
    Aphton was conducting clinical trials against hormone refractory prostate cancer. It filed for bankruptcy in May 2006. Its medical assets were purchased by Receptor BioLogix Inc. (See http://www.biospace.com/news_story.aspx?NewsEntityId=25806;
    Receptor's web site is http://www.rblx.com/ )
     
  • https://www.ohsu.edu/xd/about/news_events/news/2016/07-13-Study-finds-first-evidence-that-PD-1-antibody-could-help-men-with-metastatic-prostate-cancer.cfm
    A pilot study at Oregon Health Sciences University on 10 men with castration resistant metastatic PCa had encouraging results. Three participants who responded to PD-1 blockade started with serum PSA levels of 46, 71 and 2,503 ng/ml. These PSA levels plummeted to less than 0.1 ng/ml after treatment. Three others had stable disease, and four had no response.
  
   
• Monoclonal Antibodies
  
  • For example, http://www.peregrineinc.com/, Peregrine Pharmaceuticals. Among other things in trials, they have a radiolabeled monoclonal antibody that binds to the necrotic core of tumors and uses beta-radiation to kill the tumors from the inside out. Since necrotic tissue is common to all tumors, TNT (Tumor Necrosis Therapy) may have broad application across all tumor types. It is currently (Oct 2001) in phase I studies on a variety of tumor types, including prostate cancer.
     
  • http://www.medscape.com/reuters/prof/2001/10/10.22/20011019drgd006.html
    (Article no longer available on Medscape.) Millenium Pharmaceuticals has an Mab called J591 in phase I clinical trials. It combines a target of the prostate specific membrane antigen (PSMA) protein on the surface of prostate cancer cells with a radioisotope, designed to kill the cancer cells. [Oct 2001]
     
  • http://urology.medscape.com/reuters/prof/2001/11/11.16/20011115scie003.html
    (Article no longer available.)
    Alpha Particle 'Nanogenerator' Targets and Destroys Tumor Cells
    Press release discussing Science 2001;294:1537-1540 [16 Nov 2001]. Research in vitro and in mice involves attaching a radioactive atom to a monoclonal antibody to cancer cells. Given such a target-specific antibody, any number of lethal substances could be bound to it in order to kill tumors.
    Other discussions of this work may be found at http://www.cnn.com/2001/HEALTH/11/15/cancer.smart.bomb.ap/index.html (article is no longer available), at
    http://www.cephas-library.com/health/health_microscopic_smar_bomb_kills_cancer.html
    (article originally from http://www.foxnews.com/story/0,2933,38873,00.html), and at
    http://www.sciencedaily.com/releases/2001/11/011116065322.htm
     
  • http://www.biospace.com/news_story.aspx?StoryID=14674
    Cytogen Corporation (CYTO) Announces Submission Of IND For CYT-500 For The Treatment Of Metastatic Hormone-Refractory Prostate Cancer (6 April 2006)
    "... CYT-500 incorporates the same monoclonal antibody utilized in Cytogen's PROSTASCINT(R) (capromab pendetide) molecular imaging agent, but is linked to a therapeutic as opposed to an imaging payload. This novel product candidate is designed to enable targeted delivery of a cytotoxic agent to PSMA- expressing cells. Cytogen retains full and exclusive development rights to CYT-500...."
     
• EGFR Inhibitors (Epidermal Growth Factor Receptor)
  http://ragingbull.quote.com/mboard/boards.cgi?board=CLPA&read=104260
  is a reprint of a Reuters news article (1 Nov 2001) discussing Iressa from AstraZeneca (http://www.astrazeneca.com/) and C225 from ImClone. (http://www.imclone.com/)
   
• Other Chemotherapies
  • kahalalide F
    http://www.docguide.com/news/content.nsf/NewsPrint/8525697700573E1885256AF6005BEEC5
    Undergoing Phase I clinical trials in hormone refractory PCa by Pharmamar S.A. of Madrid, Spain (http://www.pharmamar.com/ ). The chemical is derived from a mollusk found in Hawaii and has shown some promise.
     
  • Artemisinin and Iron
    http://www.msnbc.com/news/667259.asp?0dm=H11NH
    (Article no longer available.)
    Artemisinin (or wormwood), when in cells with high iron concentrations, generates free radicals that kill the cells. Cancer cells have high iron concentrations, necessary for rapid cell division. The studies, so far only in vitro and in some animals, show that giving iron to a patient followed by artemisinin, kills cancer cells and leaves almost all normal cells unaffected. Work so far has been on breast and bone cancers and leukemia. It would seem to be most effective on more aggressive or rapidly growing cancers because of the mechanism involved. Article published in Life Sciences, November 2001 (70 (2001): 49-56, by Drs Narenda Singh and Henry Lai of U of Washington).

    http://en.wikipedia.org/wiki/Artemisinin
    An up-to-date summary with references. Artemisinin is still primarily used as an anti-malarial agent, but work on cancer is continuing.

    http://depts.washington.edu/bioe/about/news/artemisinin.html
    A bibliography of some scientific journal publications relating to research on using artemisinin to treat cancer. Also contains a link to a more extensive biobliography (> 350 articles as of Feb 2005).

    http://www.artemisinin101.com/Artemisinin-Anti-Cancer.html
    Summarizes some of this information in more lay terms.

    http://www.mskcc.org/mskcc/html/69126.cfm
    A summary from Memorial Sloan Kettering with a short bibliography.

    http://www.mnwelldir.org/docs/cancer1/altthrpy.htm
    A reasonable sounding alternative medicine site with more information about artemisinin.
     

  • Satraplatin for HRPC
    See http://www.spectrumpharm.com/satraplatin.html
    (Formerly NeoTherapeutics, name was changed to Spectrum Pharmaceuticals in 2002. The URL above is to a more recent web page than the quotes below were taken from.)
    In Phase 1 for HRPC, phase 2 for PCa (July 2002 web page); by 2009, had been in a Phase 3 HRPC study.

    "Satraplatin (BMS-182751 or JM-216) or bis (acetato) ammine dichloro (cyclohexylamine) platinum is a member of a novel class of platinum (IV) compounds developed by Johnson Matthey which are absorbed by the oral route. In preclinical studies, Satraplatin had shown cytotoxic and antitumor activities that are comparable to that of cisplatin or carboplatin."

    "Clinical studies were conducted and had shown activity on platinum sensitive tumors, small cell lung cancer, and ovarian cancer. It has also shown activity in hormone-refractory prostate cancer. Dose-limiting toxicities are myelosuppression (neutropenia and thrombocytopenia) and gastrointestinal toxicity (diarrhea)."

    "NeoOncoRx will explore this drug for prostate cancer. Prostate cancer is now the second leading cause of cancer death in men. It is estimated that in 2001, approximately 198,100 new cases and 31,500 prostate cancer-related deaths will occur in the United States. Treatment in prostate cancer provides prolonged disease-free survival for many with localized disease, but is rarely curative on patients with locally extensive tumor. Metastatic tumor is currently not curable. A continuing unmet medical need for new effective drugs still exist."

    "The advantages expected from this novel oral platinum compound rely upon its oral route of administration. These include patient convenience and health cost containment, meaning outpatient therapy."

  
   
• Bacterial Therapy
  • Anaerobic Bacteria combined with Chemotherapy to destroy tumors
    http://www.sunspot.net/news/health/bal-te.md.cancer27nov27.story?coll=bal%2Dhome%2Dheadlines (Press release) -- Page no longer available at the Baltimore Sun web site.
    http://www.pnas.org/content/98/26/15155.full (article)
    http://www.pnas.org/content/98/26/15155.abstract (abstract)
    Proc. Natl. Acad. Sci. USA, vol 98, Issue 26, 15155-15160, 18 Dec 2001
    Still in mouse study phase, with promising results.

  • Sequential use of targeted minicells to kill cancer
    • http://www.nytimes.com/2009/06/29/health/research/29drug.html New Treatment for Cancer Shows Promise in Testing, Nicholas Wade, June 28, 2009
      "A new method of attacking cancer cells, developed by researchers in Australia, has proved surprisingly effective in animal tests.
      The method is designed to sidestep two major drawbacks of standard chemotherapy — the treatment’s lack of specificity and the fact that cancer cells often develop resistance..."
    • http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1547.html
      Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug, Jennifer A MacDiarmid, Nancy B Amaro-Mugridge, Jocelyn Madrid-Weiss, Ilya Sedliarou, Stefanie Wetzel, Kartini Kochar, Vatsala N Brahmbhatt, Leo Phillips, Scott T Pattison, Carlotta Petti, Bruce Stillman, Robert M Graham & Himanshu Brahmbhatt, Nature Biotechnology, Published online: 28 June 2009 | doi:10.1038/nbt.1547
      The dose-limiting toxicity of chemotherapeutics, heterogeneity and drug resistance of cancer cells, and difficulties of targeted delivery to tumors all pose daunting challenges to effective cancer therapy. We report that small interfering RNA (siRNA) duplexes readily penetrate intact bacterially derived minicells previously shown to cause tumor stabilization and regression when packaged with chemotherapeutics. When targeted via antibodies to tumor-cell-surface receptors, minicells can specifically and sequentially deliver to tumor xenografts first siRNAs or short hairpin RNA (shRNA)–encoding plasmids to compromise drug resistance by knocking down a multidrug resistance protein. Subsequent administration of targeted minicells containing cytotoxic drugs eliminate formerly drug-resistant tumors. The two waves of treatment, involving minicells loaded with both types of payload, enable complete survival without toxicity in mice with tumor xenografts, while involving several thousandfold less drug, siRNA and antibody than needed for conventional systemic administration of cancer therapies.
      Abstract is free; full text is for sale.

• Photodynamic Therapy
  http://www.americanvoiceinstitute.org/PHHealth13.htm
  (Scroll down past the Table of Contents to the sixth article.) A discussion of Journal of Urology 2002;168:1427-1432 (Oct 2002), by Timothy R. Nathan & colleagues at University College Hospital, London, UK.
  This was a pilot study of 14 men whose PCa returned after radiation therapy. Each received a drug that tends to collect in tumors and makes the containuing tissue abnormally sensitive to light. Then laser light of an appropriate wavelength is shined on the cancer [the summary does not indicate how this is done] with generally good results.
   
• Targeting Prostate Specific Membrane Antigen -- Immunotherapy
  (From a news release 4/24/2006): Progenics Pharmaceuticals has acquired complete control of PSMA Development by buying Cytogen's 50 percent interest.... The venture has been developing in vivo cancer immunotherapies based on prostate-specific membrane antigen. PSMA is a protein primarily found on the surface of prostate cancer cells and new blood vessels associated with other solid tumors. Targeting PSMA offers the potential for highly specific cancer therapy.
   
  "Having acquired all rights to in vivo PSMA immunotherapies, we now plan to develop them fully," said Paul J. Maddon, Progenics' founder and CEO. "Prostate cancer patients with metastatic disease have the greatest unmet medical need, and we intend to initiate phase 1 clinical studies in this setting in 2007 with our PSMA ADC. Progenics has core research and development, manufacturing, clinical, and regulatory teams in place and plans to leverage them to expedite PSMA-based drug development."
  See http://www.progenics.com/ and documents under a search for "PSMA".
   
• Electroporation
  http://www.eetimes.com/showArticle.jhtml?articleID=201000258
  "An Electronic Cure for Cancer?", EETimes, 9 July 2007. Discusses a research program at the University of California, Berkeley and Virginia Tech using short localized electrical pulses to selectively open the pores in cancer cells' membranes to kill them, leaving healthy cells unaffected. Experiments have worked in vitro and in rat, mouse , and dog models, with human tests to begin in 2008. Questions I have are (1) how to know where all the cancer cells are in order to kill them; (2) how to get the probes and electrodes in to the tumor locations with minimal invasiveness.
  http://www.vtnews.vt.edu/story.php?relyear=2007&itemno=379
  A Virginia Tech press release on this technology (3 July 2007)
  See also the August 2007 issue of Technology in Cancer Research and Treatment ( http://www.tcrt.org/index.cfm?d=3029&c=4236&do=list), where a suite of articles describe this technology, including one on prostate cancer. These articles are openly available.
   
• Nanotechnology
  
  • http://kanziuscancerresearch.com The John Kanzius Cancer Research Foundation
    By attaching nanoparticles of gold or carbon nanotubes to molecules which are specifically bound to or absorbed into cancer cells, low power radio waves may be used to selectively heat these cells until they die, with no effect on normal cells. Mr. Kanzius is a radio engineer who is working on the electronics aspect of this approach in conjunction with doctors at M.D. Anderson Cancer Center in Houston, Texas and at the University of Pittsburgh Medical Center. The trick, as in all these targeted therapies, is to find a molecule that will specifically bind only to cancer cells and not to any non-cancer cells.
     

    Additional work reported on in December 2008 in the Journal of Experimental and Therapeutic Oncology ( http://www.oldcitypublishing.com/JETO/JETO.html) has been summarized in several news articles

    • http://www.news-press.com/article/20081219/HEALTH/81219037/1013/LIFESTYLES
    • http://www.winknews.com/news/local/36462509.html
    • http://www.goerie.com/apps/pbcs.dll/article?AID=/20081219/NEWS02/312199956
    • http://www.naplesnews.com/news/2008/dec/19/researchers-target-cancer-cells-note-treatment-sw-/

  • http://www.israel21c.org/bin/en.jsp?enDispWho=Articles^l2466&enPage=BlankPage&enDisplay=view&enDispWhat=object
    Israeli researchers have developed a nanotechnology based method of delivering chemotherapy drugs to targeted cancer cells, to avoid many of the side effects of traditional chemotherapy. It sounds like the bubble surface is coated with monoclonal antibodies to make it cancer-cell specific. (News release 24 Feb 2009; articles published in Nature Nanotechnology and Journal of Controlled Release (2008).)

  • http://www.dddmag.com/news-Nanoscopic-Probes-Attack-Cancer-Cells-031609.aspx
    Nanoscopic Probes Can Track Down and Attack Cancer Cells (Drug Discovery & Development - March 16, 2009)
    A press release reporting on work done by Joseph Irudayaraj of Purdue University. His team created probes that use both gold nanorods and magnetic particles, making them easier to track with different imaging devices as they move toward cancer cells (MRI for the magnetic particles, gold microrod luminescence via microscopy). These particles also have antibodies that bind to the target cancer cells. For now, only Herceptin for finding a major class of breast cancer cells is used. So far the work is only in vitro.

• Androgen Receptor Blockade
  
  • http://investors.medivation.com/ReleaseDetail.cfm?ReleaseID=375932
  • http://www.sciencemag.org/cgi/content/full/sci;324/5924/165a (subscription required)
    DRUG DEVELOPMENT: New Way to Target Hormone Receptor Thwarts Prostate Cancer, Jocelyn Kaiser, Science 10 April 2009: Vol. 324. no. 5924, p. 165
  • http://www.sciencemag.org/cgi/content/abstract/sci;1168175v1
    (link is to paper's abstract) Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer, Chris Tran, Samedy Ouk, Nicola J. Clegg, Yu Chen, Philip A. Watson, Vivek Arora, John Wongvipat, Peter M. Smith-Jones, Dongwon Yoo, Andrew Kwon, Teresa Wasielewska, Derek Welsbie, Charlie Chen, Celestia S. Higano, Tomasz M. Beer, David T. Hung, Howard I. Scher, Michael Jung, and Charles L. Sawyers, Published online 9 April 2009 [DOI: 10.1126/science.1168175] (in Science Express Reports)
  This is a press release from Medivation (7 April 2009) and the Science news coverage and on-line prepublication article.

  A new drug by Medivation, Inc. offers a radically different way of attacking prostate cancer, showing promising results in an initial trial and is set for larger-scale testing. A study report in the journal Science looked at this drug, MDV3100, and its ability to block the receptors for androgens which drive tumor growth on cells. After treatment with the drug, there were "sustained declines" in PSA levels in 43 percent of the participants, which the report called a "promising" result. The researchers now have data on 114 men given the drug.

  "It showed not only declines in PSA but also regression of the tumor on scans and also that circulating tumor cell counts, another measure of treatment, converted from unfavorable to favorable in a considerable percentage of patients," said Dr. Howard I. Scher, chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer Center in New York City and co-author of the study.

  Based on those results, an application for a large-scale trial has been submitted to the U.S. Food and Drug Administration.

• PARP Inhibitors
  "Most cancer treatments work by blasting DNA with chemotherapy or radiation. Cancer can fight back by using PARP enzymes to fix damaged strands of DNA. The new medicines are designed to block the enzymes and kill the cancer." (From a Bloomberg news article, 31 May 2009, URL not available)

  "A parp also known as a Poly (ADP-ribose) polymerase is an enzyme which repairs damage done to our DNA. In basic terms a parp enzyme regulates our body repairing damaged DNA. In normal cells this is useful and stops cell death however Doctor de Bono and his colleagues have suggested that cancer cells may used the PARP repair method to their advantage. A parp-1 inhibitor is a new drug which causes inhibition of parp function. Studies recently conducted have shown that this new parp drug is an inhibitor of cancer as it disrupts the chemotherapy resistance in cancer cells." (From http://www.parp-inhibitors.com/

  • http://www.medscape.com/viewarticle/704990
    PARP Inhibitors Represent New Direction in Cancer Treatment (25 June 2009)
  • http://www.biparsciences.com/000010.html
    Science of PARP
  • http://www.fiercepharma.com/story/asco-hightlights-herceptin-parp-inhibitors/2009-06-01
    ASCO hightlights Herceptin, PARP inhibitors (June 1, 2009)
   
  
• ...
   
• Access to Unapproved Drugs (FDA regulations)
  http://www.fda.gov/Drugs/default.htm
  From this page, contact info is available or one can do a search. The previous set of regulations is now difficult (impossible?) to find, as of June 2009.

Outlook

...more to come...

Top

APPENDIX D: Change Log

© Copyright 2000-2016, Howard J. Cohen, Ph.D., All Rights Reserved