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

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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

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ron wrote:
> 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

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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

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ron wrote:
> 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

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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

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ron wrote:
> 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

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"Ed Friedman" <ed@math.uchicago.edu> wrote in message
news:y2V6e.14$45.2630@news.uchicago.edu..
> ron wrote: 
>
> 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
>
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.

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