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Medical Forum / Diseases and Disorders / Prostate Cancer / April 2005The definitive model of prostate cancer
I want to thank Leonard for encouraging me to submit my model to a peer reviewed journal. My model of prostate cancer is the only one to date that is totally consistent with all known experimental findings. For those who want to read it, the full text is available for free online viewing at: http://www.tbiomed.com/content/2/1/10 Ed Friedman Ed...I have read your article, but can't say that I have digested it yet. So at this point I just want to say thanks. Anyone who makes an effort, as you have done, to sort things out helps us all...Best wishes and good health, Ron > Ed...I have read your article, but can't say that I have digested it > yet. So at this point I just want to say thanks. Anyone who makes an > effort, as you have done, to sort things out helps us all...Best wishes > and good health, Ron Ron, Thank you for your kind words. If you have any questions about my model, feel free to ask. My model explains complex experimental results with surprising ease. Take the following facts, which appear to represent a paradox: 1. Consumption of soy has been shown to prevent prostate cancer. 2. Dr. Leibowitz reports that the PSA goes up for any of his patients who consume soy products. 3. Other doctors report no correlation between soy consumption and PSA. Before completing my model, I assumed that Dr. Leibowitz must be mistaken. After finishing my model, however, I realized that: 1. Soy protein binds specifically to ER-beta. Since both ER-alpha and ER-beta are needed to form telomeres in prostate cells, soy would prevent telomere formation and thus prevent prostate cancer. 2. Since bcl-2 prevents apoptosis, you want to have as little bcl-2 as possible in your prostate cancer cells. Bcl-2 production is inhibited by DHT+iAR and by E2+ER-beta. Since all of Dr. Leibowitz's patients are on 5AR2 inhibitors, they are dependent on E2+ER-beta to keep bcl-2 levels low. Soy binds to ER-beta preventing E2 from binding to ER-beta, resulting in increased bcl-2 production. Therefore, Dr. Leibowitz's patients have an increased PSA when eating soy, not because the prostate cancer is growing faster, but because apoptosis is occuring at a much lower rate. 3. Since other doctors do not use 5AR2 inhibitors on their patients, bcl-2 levels are kept low by DHT+iAR even when the soy binds to the ER-beta. Therefore, no major change in PSA is observered. The take home lesson from the above is that everyone on 5AR2 inhibitors should be avoiding soy, flaxseed, and any other foods which bind specifically to ER-beta. Ed Friedman Ed Friedman wrote:...snip... Therefore, Dr. Leibowitz's patients have an increased PSA when eating soy, not because the prostate cancer is growing faster, but because apoptosis is occuring at a much lower rate. Ed...I thought prostate cell infarction, or apoptosis, released PSA into the bloodstream (e.g. infections such as prostatitis result in prostate cell death and lead to a PSA spike). Yet you state above that a lower apoptosis rate leads to a rising PSA? Am I just plain wrong?..Ron > Ed...I thought prostate cell infarction, or apoptosis, released PSA > into the bloodstream (e.g. infections such as prostatitis result in > prostate cell death and lead to a PSA spike). Yet you state above that > a lower apoptosis rate leads to a rising PSA? Am I just plain > wrong?..Ron Ron, I've never heard that prostatitis causes apoptosis. Do you have any references on that? As far as I know, PSA is released by normal prostate cells as a response to pressure, and by prostate cancer(PCa) cells as they grow. Normal cells will produce an average increase of 0.4 in PSA as a response to DRE. Also, infections, inflammation, even bicycle riding have all been shown to raise normal PSA scores. When someone undergoes RP, however, whatever PSA shows up in the following years is a direct measure of the amount of PCa cells present. Men in that situation are definitely not celebrating if they see a rise in their PSA scores. In the case of soy for Dr. Leibowitz's patients, we are talking about continual increase in PSA until the soy is discontinued. This is definitely not a sign of increased apoptosis, but of increased number of PCa cells. Keep in mind that the average growth rate for individual prostate cancer cells is 56 days, but the average doubling time for the overall population of PCa cells in 475 days. The difference is due to the fact that the rate of apoptosis is almost the same as the rate of growth. So lots of apoptosis is going on all of the time for PCa. My model predicts that the lower the level of T, the lower the level of apoptosis, until you get to castrate level of T, at which point the cessation of calreticulin production leaves the PCa vulnerable to calcium overload and you see a huge spike in the amount of apoptosis. Basically, castrati and teenagers don't have to worry about getting PCa, but the rest of us do. Ed > > Ed...I thought prostate cell infarction, or apoptosis, released PSA > > into the bloodstream (e.g. infections such as prostatitis result in [quoted text clipped - 37 lines] > > Ed By 80, we all have it Ed. So? Mere detection is not the goal. Life is. For most men, it is not an issue., except if the PSA, which has never been proven to save actual lives, makes it one. George Conklin wrote...snip... PSA, which has never been proven to save actual lives ---------------------------------------------------------------------------- Between 1990-92 and 2000-02, the prostate cancer death rate in Iowa declined around 30 percent in men in the age groups less than 85 years of age, but de-clined only 10 percent in those 85 years and older. "This correlates with the stage shift information and supports the hypothesis that prostate cancer screening is saving lives," Lynch said. A recently published study from researchers at the Mayo Clinic has provided further evidence that screening for levels of prostate specific antigen (PSA) leads to earlier diagnosis and increased survival from prostate cancer. The researchers found a 22% decline in prostate cancer deaths from a period when the PSA test did not exist (1980-'84) compared with when it was utilized (1993-'97). The cases were in Olmstead County in Minnesota, where the clinic is located. In the United States, following several decades of gradually increasing death rates that reached their peak in 1993, the prostate cancer mortality rate began to decline steadily in the late 1990s. Since 1993, the prostate cancer mortality rate has decreased by 17.6%, at an annual mean rate of 4.4% between 1994 and 1997 Evidence for a possible beneficial effect of prostate cancer screening came from the urology department of the University of Innsbruck, Austria, where, in contrast to other parts of Austria, the PSA test had been made freely available to the population in 1993 and acceptance of testing was high.17 The investigators reported 33% fewer prostate cancer deaths than expected in the Innsbruck area between 1996 and 1999 in men aged 40-79 years. The authors concluded that the policy of making the PSA assay universally available to the population (and at no cost) might have reduced the prostate cancer mortality rate in that population.17 > George Conklin wrote...snip... > PSA, which has never been proven to save actual lives [quoted text clipped - 6 lines] > "This correlates with the stage shift information and supports the > hypothesis that prostate cancer screening is saving lives," Lynch said. Still, the studies have not been done. If you want to cite demography, as life expectancy goes UP in general, there will be declines in specific diseases. History shows that of the 35 year life expectany increase since 1900, 30 years came from social improvemnts and 5 years from medicine. Your logic would impute the entire improvemnt to some medical change. So why have not the real studies been done? Why interrupt the money train? Further, knowing you have a disease longer does mean you live longer. The high-dose chemotherapy for breast cancer is good example. It failed. > A recently published study from researchers at the Mayo Clinic has > provided further evidence that screening for levels of prostate [quoted text clipped - 21 lines] > cost) might have reduced the prostate cancer mortality rate in that > population.17 But was life expectany higher? That was the original point. Those studies in the USA have run for about 10 years now with NO announcements. >>George Conklin wrote...snip... >>PSA, which has never been proven to save actual lives [quoted text clipped - 10 lines] > > Still, the studies have not been done. It seems to me he has cited several studies. > If you want to cite demography, > as life expectancy goes UP in general, there will be declines in specific > diseases. History shows that of the 35 year life expectany increase since > 1900, 30 years came from social improvemnts and 5 years from medicine. It is hard to see how "social improvements" could lead to a decrease in prostate cancer specific death rates. Also, it would help if you quoted specific studies which made such estimates, so we could evaluate the validity of the claims. > Your > logic would impute the entire improvemnt to some medical change. No. His logic doesn't lead to any such conclusion. There are significant differences between general increases in life expectancy over a 100 year period and differences in prostate cancer death rates over a 10-15 year period. > So why > have not the real studies been done? As you know there is one large scale study, PLCO, under way. It may or may not be more scientifically valid than those that ron quoted. > Why interrupt the money train? Statements about money trains are scientifically irrelevant and show your bias. > Further, knowing you have a disease longer does mean you live longer. The > high-dose chemotherapy for breast cancer is good example. It failed. Agreed. One problem with the PLCO study is that followup treatment is not a standard part of the protocol. >>A recently published study from researchers at the Mayo Clinic has >>provided further evidence that screening for levels of prostate [quoted text clipped - 23 lines] > > But was life expectany higher? > That was the original point. Those > studies in the USA have run for about 10 years now with NO announcements. Actually they have published some results on the how often PSA testing might be warranted. > >>George Conklin wrote...snip... > >>PSA, which has never been proven to save actual lives [quoted text clipped - 12 lines] > > It seems to me he has cited several studies. And you the man who trashes correlational analysis!!!! > > If you want to cite demography, > > as life expectancy goes UP in general, there will be declines in specific [quoted text clipped - 5 lines] > specific studies which made such estimates, so we could evaluate the > validity of the claims. That is because you are back trashing correlations once again. Can't be consistent even for one post can you? As death rates decline, most diseases decline too. > > Your > > logic would impute the entire improvemnt to some medical change. [quoted text clipped - 3 lines] > over a 100 year period and differences in prostate cancer death rates > over a 10-15 year period. Any special interest group could say the same thing about any specific disease. Like YOU. > > So why > > have not the real studies been done? [quoted text clipped - 6 lines] > Statements about money trains are scientifically irrelevant and show > your bias. The reason why surgical and other treatments go unevaluated (and in this case for 100 years) is that the MONEY is in the procedure, and NEVER in the evaluation, which is not desired in any case by those who are making the money. > ... > Still, the studies have not been done. If you want to cite demography, [quoted text clipped - 6 lines] > high-dose chemotherapy for breast cancer is good example. It failed. > ... On the one point about "social improvements", I think that actually counts against the argument you're making. If by "social improvements", you mean increased sanitation, reduced auto accidents, improved diet, and things like that, those improvements reduce the death rate from preventable diseases and accidents, but increase the death rate from diseases of old age like cancer and heart disease. It's true that "as life expectancy goes UP in general, there will be declines in specific diseases". But I would expect that prostate cancer wouldn't be one of those specific diseases. Alan |
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