55 replies to this topic

[Happy Gringo]

This is a shot in the dark, but what if women added I3C when they take resveratrol? I THINK the following applies, but I am having a little problem understanding it.

<h2 id="atl">BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells</h2>Indole-3-carbinol (I3C) and genistein are naturally occurring chemicals derived from cruciferous vegetables and soy, respectively, with potential cancer prevention activity for hormone-responsive tumours (e.g., breast and prostate cancers). Previously, we showed that I3C induces BRCA1 expression and that both I3C and BRCA1 inhibit oestrogen (E2)-stimulated oestrogen receptor (ER-) activity in human breast cancer cells. We now report that both I3C and genistein induce the expression of both breast cancer susceptibility genes (BRCA1 and BRCA2) in breast (MCF-7 and T47D) and prostate (DU-145 and LNCaP) cancer cell types, in a time- and dose-dependent fashion. Induction of the BRCA genes occurred at low doses of I3C (20 M) and genistein (0.5–1.0 M), suggesting potential relevance to cancer prevention. A combination of I3C and genistein gave greater than expected induction of BRCA expression. Studies using small interfering RNAs (siRNAs) and BRCA expression vectors suggest that the phytochemical induction of BRCA2 is due, in part, to BRCA1. Functional studies suggest that I3C-mediated cytoxicity is, in part, dependent upon BRCA1 and BRCA2. Inhibition of E2-stimulated ER- activity by I3C and genistein was dependent upon BRCA1; and inhibition of ligand-inducible androgen receptor (AR) activity by I3C and genistein was partially reversed by BRCA1-siRNA. Finally, we provide evidence suggesting that the phytochemical induction of BRCA1 expression is due, in part, to endoplasmic reticulum stress response signalling. These findings suggest that the BRCA genes are molecular targets for some of the activities of I3C and genistein.

I also found this:

Estrogen receptor alpha as a target for indole-3-carbinol.

Wang TT, Milner MJ, Milner JA, Kim YS.

Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA. wangt@ba.ars.usda.gov

A wealth of preclinical evidence supports the antitumorigenic properties of indole-3-carbinol (I3C), which is a major bioactive food component in cruciferous vegetables. However, the underlying molecular mechanism(s) accounting for these effects remain unresolved. In the present study, estrogen receptor alpha (ER-alpha) was identified as a potential molecular target for I3C. Treating MCF-7 cells with 100 microM I3C reduced ER-alpha mRNA expression by approximately 60% compared to controls. This reduction in ER-alpha transcript levels was confirmed using real-time polymerase chain reaction. The I3C dimer, 3,3'-diindolylmethane (DIM), was considerably more effective in depressing ER-alpha mRNA in MCF-7 cells than the monomeric unit. The suppressive effects of 5 microM DIM on ER-alpha mRNA was comparable to that caused by 100 microM I3C. DIM is known to accumulate in the nucleus and is a preferred ligand for aryl hydrocarbon receptor (AhR) to I3C. The addition of other AhR ligands, alpha-naphthoflavone (alpha-NF, 10 microM) and luteolin (10 microM), to the culture media resulted in a similar suppression in ER-alpha mRNA levels to that caused by 5 microM DIM. Thus, it is likely that the binding of ligands to AhR inhibits nuclear ER-alpha transcript. The results from these experiments suggest that the antitumorigenic effects of I3C in MCF-7 human breast cancer cells may arise from its ability to reduce ER-alpha expression through the binding of its metabolite, DIM, to the nuclear AhR. ]

[Crepulance]

Hey Max, couple of things. First, I didn't repost to discuss it, I reposted it so newer members can see the thread. Secondly, and this is very important, it is in your opinion that there is nothing to discuss. You are by far not in any position to say it is not a signifigant threat. As 100 said, (see above) he would not allow women to take Res for the reasons he gave of possible breast cancer related triggers. And regardless of wether or not you deemed the evidence to be enough for you, a reputable paper did deem it enough evidence for them that there is a possibility that it can. Even Anthony himself said if you've had breast cancer you probably shouldn't take it, which follows the same reasoning that if you have it in your history, you probably won't want to take it either.

Please just don't come on here and think you're the ultimate say in the matter, when the results are extremely far from being black and white. And the fact that Anthony resorts to pointing that the study uses the term "may" and "possibly"...ummm, where I have I seen this before. Oh yes...mandatoraly printed on the back of a certain package "Cigarettes "may" cause lung cancer".

In something like resveratrol where every month a study comes out which contradicts the previous months' studies, I'm pretty sure we should be very loud and clear in letting the world know that breast cancer is a possible side effect (increased expression, I mean) based on the study that was done. I don't care if it was done in 2003 or 1984 or 2009. The study was done, and arrived at the results it arrived at. Just because there are contradictory results in future studies, does not negate the past study's results


Again, I didn't repost for discussion, it's been discussed, I reposted for people to be able to read through the discussion and make up their minds for their own.


Crep

Just wanted to resurface this thread so that it's seen every once in a while. I think it's VERY IMPORTANT that this aspect not be glossed over or pushed to the back. Also Anthony, not antagonistically, but don't you think you should put a label on your bottles of RevGen stating that women with a history of breast cancer, or in their family, should be aware of the possible side effect of it increasing the expression of the gene? If not for moral purposes, I would think you'd want to put it on there as a legal disclaimer.


Crep

There's not really much to discuss. There are exactly three studies in Pub Med concerning both resveratrol and BRCA1 or BRCA2. Two of the studies suggest resveratrol inhibits expression of BRCA1 and 2 and so are anti cancer. One older study with low levels of resveratrol found "... expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found." The popular press writeup suggested resveratrol might cause breast cancer, but the actual study suggests no such thing, for though the genes are activated, their proteins were not expressed. Other studies show inhibition of these genes, and many, many studies suggest resveratrol will inhibit breast cancer.

I thought the discussion on this issue has already shown much the same thing. I do not believe that misinterpretation of one anomalous study warrants a specific warning on the label.

Hi 100YTG,

you are correct to ask me about the concentrations required... I pulled the complete paper, and it appears 40uM was used in vitro, while it appears 5 ug or 10 ug was used in vivo.
It appears to be in line with your study regarding a high concentration. I have to say that there is alot of info in this study. Can you take a look 100YTG?

Consistently, we found
resveratrol dramatically reduced the capability of Brca1 mutant
tumor cells to form colonies in soft agar, causing about a 5-fold
decrease in colony size (Figure 3A) and number (Figure 3B) compared
with untreated controls. Such an inhibitory effect was not
obvious for a Brca1 wild-type cell line tested under identical conditions
(Figures 3C and 3D). Our data further indicated that resveratrol
(40 mM) induced a much higher incidence of apoptosis
in Brca1 mutant tumor cells (69) than the Brca1 wild-type cells
(Neu) (data not shown).

In the first set, we pretreated
the nude mice with resveratrol for 10 days before mouse Brca1
mutant tumor cells were implanted. After the implantation, the
treatment continued daily until the tumors were collected. We
demonstrated that the treatment with either 5 ug or 10 ug of resveratrol
significantly delayed tumor initiation and growth

This one was interesting as well:

cells to form tumors in nude mice (Figure 2A).
During the time course, Sirt1-transfected tumor cells had much
more difficulty to initiate tumor formation. At harvest, tumor weight
from the GFP-transfected group (228 mg) was, on average,
4.56-fold of the weight from the Sirt1-overexpressed group

Anthony

After reading the complete 2008 study...ok, ok I skimmed a bit, I find that the studies (2008 vs 2007) don't contradict each other.
There were no low dosage used in the 2008 study. Only high dosage both in vitro and in vivo. The mice
were injected with 5 to 10 ug. So this would easily achieve a concentration much higher than 5 uM mentioned in the 2007 study.

The 2008 study is meant as a demonstration of possible treatment of breast cancer by injecting resv.
It is clear that a high uM concentration is required for that application.

Because the 2007 is an in vitro study one can also not say for sure that supplementing with resv will deliver about 5uM to the breast cells and thus help breast cancer cell proliferate. The only thing that is implied is that there is a risk if you create a concentration of 5uM resv. around these cells in vivo by injection or other means.

Regards,

100YTG

[maxwatt]

Hey Max, couple of things. First, I didn't repost to discuss it, I reposted it so newer members can see the thread. Secondly, and this is very important, it is in your opinion that there is nothing to discuss. You are by far not in any position to say it is not a signifigant threat. As 100 said, (see above) he would not allow women to take Res for the reasons he gave of possible breast cancer related triggers. And regardless of wether or not you deemed the evidence to be enough for you, a reputable paper did deem it enough evidence for them that there is a possibility that it can. Even Anthony himself said if you've had breast cancer you probably shouldn't take it, which follows the same reasoning that if you have it in your history, you probably won't want to take it either.

Please just don't come on here and think you're the ultimate say in the matter, when the results are extremely far from being black and white. And the fact that Anthony resorts to pointing that the study uses the term "may" and "possibly"...ummm, where I have I seen this before. Oh yes...mandatoraly printed on the back of a certain package "Cigarettes "may" cause lung cancer".

In something like resveratrol where every month a study comes out which contradicts the previous months' studies, I'm pretty sure we should be very loud and clear in letting the world know that breast cancer is a possible side effect (increased expression, I mean) based on the study that was done. I don't care if it was done in 2003 or 1984 or 2009. The study was done, and arrived at the results it arrived at. Just because there are contradictory results in future studies, does not negate the past study's results


Again, I didn't repost for discussion, it's been discussed, I reposted for people to be able to read through the discussion and make up their minds for their own.


Crep

...

You do not seem to read or comprehend the responses others -- not just me -- make to your posts. There is STILL not much to discuss on this issue. There are STILL only three studies on resveratrol and BRCA1-2 genes in the scientific literature. Did you post a new study? No. You cherry picked the one study open to misinterpretation, and misinterpreted the results as stated in the abstract. Did you read the entire paper? Did you read the abstract? You only quoted a science newsletter with a misleading write-up of the article.

Did you bump the topic so newbies would read through the issue, or to scare them and create controversy? What you said:

Just wanted to resurface this thread so that it's seen every once in a while. I think it's VERY IMPORTANT that this aspect not be glossed over or pushed to the back. Also Anthony, not antagonistically, but don't you think you should put a label on your bottles of RevGen stating that women with a history of breast cancer, or in their family, should be aware of the possible side effect of it increasing the expression of the gene? If not for moral purposes, I would think you'd want to put it on there as a legal disclaimer.

looks like you want to scare people, and to dig at Anthony despite a disingenuous disclaimer.

What I said still applies:

There's not really much to discuss. There are exactly three studies in Pub Med concerning both resveratrol and BRCA1 or BRCA2. Two of the studies suggest resveratrol inhibits expression of BRCA1 and 2 and so are anti cancer. One older study with low levels of resveratrol found "... expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found." The popular press writeup suggested resveratrol might cause breast cancer, but the actual study suggests no such thing, for though the genes are activated, their proteins were not expressed. Other studies show inhibition of these genes, and many, many studies suggest resveratrol will inhibit breast cancer.

I thought the discussion on this issue has already shown much the same thing. I do not believe that misinterpretation of one anomalous study warrants a specific warning on the label.

If a new study comes out, post a new topic referencing the old one via a link, if the old discussion is relevant.

[Crepulance]

No, I'm good. Just because you have paranoid, delusional thoughts regarding my motives for posting something, won't prevent me from posting it. I'm not on here to assuage your irrational fears. If you're thinking this has anything to do with attacking anthony, then you're so far gone, I can't even really address your absurdities. At no point did I say there were other studies aside from the three. Cherry picked? Ummm, if by Cherry picked, you mean, picked the one that said resveratrol can lead to breast cancer, then, yes, I cherry picked. I'd say a lot of people should see that cherry too. Should I have picked the one that talked about how resveratrol was a white powder, or one that had some other information that wasn't pertinent to the point I was making? Pretty sure when referencing a specific article, I should probably use that particular article in my reference.

You are allowed to say that you believe the study to have misleading results, but again, you are far from being the ultimate say in the matter, and the nebulousness of the situation far outweighs what some random guy (you) says about it on a forum. If there is uncertainty regarding something as sensitive as breast cancer, it should be stayed away from, and people should be aware. That's all there is to it.

You also chose to disregard 100's comment about how he believes people should stay away from it cause it can increase estrogen which can lead to breast cancer. "Resv taken as a supplement will result in low resv serum levels. In the range of 2 to 5 uM.
These low levels mimics estrogen. "These data indicate that estrogen and low concentrations of resveratrol may promote breast cancer metastasis, whereas high concentrations of resveratrol may prevent breast cancer metastasis."
http://www.pubmedcen...i?artid=1813930. I wouldn't take it if I were a female." - 100yearstogo

So yes, if any part of this is true, then yes, I am indeed trying to scare people, they should be.


Crep

Hey Max, couple of things. First, I didn't repost to discuss it, I reposted it so newer members can see the thread. Secondly, and this is very important, it is in your opinion that there is nothing to discuss. You are by far not in any position to say it is not a signifigant threat. As 100 said, (see above) he would not allow women to take Res for the reasons he gave of possible breast cancer related triggers. And regardless of wether or not you deemed the evidence to be enough for you, a reputable paper did deem it enough evidence for them that there is a possibility that it can. Even Anthony himself said if you've had breast cancer you probably shouldn't take it, which follows the same reasoning that if you have it in your history, you probably won't want to take it either.

Please just don't come on here and think you're the ultimate say in the matter, when the results are extremely far from being black and white. And the fact that Anthony resorts to pointing that the study uses the term "may" and "possibly"...ummm, where I have I seen this before. Oh yes...mandatoraly printed on the back of a certain package "Cigarettes "may" cause lung cancer".

In something like resveratrol where every month a study comes out which contradicts the previous months' studies, I'm pretty sure we should be very loud and clear in letting the world know that breast cancer is a possible side effect (increased expression, I mean) based on the study that was done. I don't care if it was done in 2003 or 1984 or 2009. The study was done, and arrived at the results it arrived at. Just because there are contradictory results in future studies, does not negate the past study's results


Again, I didn't repost for discussion, it's been discussed, I reposted for people to be able to read through the discussion and make up their minds for their own.


Crep

...

You do not seem to read or comprehend the responses others -- not just me -- make to your posts. There is STILL not much to discuss on this issue. There are STILL only three studies on resveratrol and BRCA1-2 genes in the scientific literature. Did you post a new study? No. You cherry picked the one study open to misinterpretation, and misinterpreted the results as stated in the abstract. Did you read the entire paper? Did you read the abstract? You only quoted a science newsletter with a misleading write-up of the article.

Did you bump the topic so newbies would read through the issue, or to scare them and create controversy? What you said:

Just wanted to resurface this thread so that it's seen every once in a while. I think it's VERY IMPORTANT that this aspect not be glossed over or pushed to the back. Also Anthony, not antagonistically, but don't you think you should put a label on your bottles of RevGen stating that women with a history of breast cancer, or in their family, should be aware of the possible side effect of it increasing the expression of the gene? If not for moral purposes, I would think you'd want to put it on there as a legal disclaimer.

looks like you want to scare people, and to dig at Anthony despite a disingenuous disclaimer.

What I said still applies:

There's not really much to discuss. There are exactly three studies in Pub Med concerning both resveratrol and BRCA1 or BRCA2. Two of the studies suggest resveratrol inhibits expression of BRCA1 and 2 and so are anti cancer. One older study with low levels of resveratrol found "... expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found." The popular press writeup suggested resveratrol might cause breast cancer, but the actual study suggests no such thing, for though the genes are activated, their proteins were not expressed. Other studies show inhibition of these genes, and many, many studies suggest resveratrol will inhibit breast cancer.

I thought the discussion on this issue has already shown much the same thing. I do not believe that misinterpretation of one anomalous study warrants a specific warning on the label.

If a new study comes out, post a new topic referencing the old one via a link, if the old discussion is relevant.

[Crepulance]

HAHAHAHAHAHAHA how insecure and in the RevGen pocket are you Maxwatt?!? (or whichever navigator did it)! On a topic that's been open for months, you go and make the decision just now to change the subtitle to (The Paper Showed No Cause). HAHAHAHAHAH I CALL ABUSE OF POWER ON YOU!! I was the one who made that title and I did NOT change it. It was however editted originally by you guys to (caused or prevented by) which was fine and fair. But you little sneaky, insecure power hungry boy, you went and used your power to bias the title of the thread. How weak are you? You can't let your words inside here speak for themselves, you have to put suggestions in people's heads before they even open the thread. If it's getting too dangerous for you, why don't you just kill it like you guys do with all the threads that pose opposition. Ooooh, I'd like to have some words with you in free speech if you'd care to indulge. FirstImm, if you're reading, what are your thoughts on the matter. Even if it's not 'illegal' in their handbook, seems to me these guys just caaaaan't help themselves from their little power abuses. Everywhere I turn, I see them doing stuff like this.


Crep

[maxwatt]

HAHAHAHAHAHAHA how insecure and in the RevGen pocket are you Maxwatt?!? (or whichever navigator did it)! On a topic that's been open for months, you go and make the decision just now to change the subtitle to (The Paper Showed No Cause). HAHAHAHAHAH I CALL ABUSE OF POWER ON YOU!! I was the one who made that title and I did NOT change it. It was however editted originally by you guys to (caused or prevented by) which was fine and fair. But you little sneaky, insecure power hungry boy, you went and used your power to bias the title of the thread. How weak are you? You can't let your words inside here speak for themselves, you have to put suggestions in people's heads before they even open the thread. If it's getting too dangerous for you, why don't you just kill it like you guys do with all the threads that pose opposition. Ooooh, I'd like to have some words with you in free speech if you'd care to indulge. FirstImm, if you're reading, what are your thoughts on the matter. Even if it's not 'illegal' in their handbook, seems to me these guys just caaaaan't help themselves from their little power abuses. Everywhere I turn, I see them doing stuff like this.


Crep

I've suspended your posting ability for 10 days while you cool off, and I've put you on indefinite moderation. I am leaving your rant in place for others to see in the hope you one day gain sufficient self-insight to be embarrassed by it. We are not paid to do this, our mission is to keep some rationality in the forums so as not to embarrass the institute or its mission. I am not in business with Revgeneics or Anthony. The reason he looks good is that the others are worse. If I appear to support him, and I don't always, it's because the evidence is on his side. Like Mel Brooks says: "Geh kachen im mer."

[maxwatt]

Hi 100YTG,

you are correct to ask me about the concentrations required... I pulled the complete paper, and it appears 40uM was used in vitro, while it appears 5 ug or 10 ug was used in vivo.
It appears to be in line with your study regarding a high concentration. I have to say that there is alot of info in this study. Can you take a look 100YTG?

Consistently, we found
resveratrol dramatically reduced the capability of Brca1 mutant
tumor cells to form colonies in soft agar, causing about a 5-fold
decrease in colony size (Figure 3A) and number (Figure 3B) compared
with untreated controls. Such an inhibitory effect was not
obvious for a Brca1 wild-type cell line tested under identical conditions
(Figures 3C and 3D). Our data further indicated that resveratrol
(40 mM) induced a much higher incidence of apoptosis
in Brca1 mutant tumor cells (69) than the Brca1 wild-type cells
(Neu) (data not shown).

In the first set, we pretreated
the nude mice with resveratrol for 10 days before mouse Brca1
mutant tumor cells were implanted. After the implantation, the
treatment continued daily until the tumors were collected. We
demonstrated that the treatment with either 5 ug or 10 ug of resveratrol
significantly delayed tumor initiation and growth

This one was interesting as well:

cells to form tumors in nude mice (Figure 2A).
During the time course, Sirt1-transfected tumor cells had much
more difficulty to initiate tumor formation. At harvest, tumor weight
from the GFP-transfected group (228 mg) was, on average,
4.56-fold of the weight from the Sirt1-overexpressed group

Anthony

After reading the complete 2008 study...ok, ok I skimmed a bit, I find that the studies (2008 vs 2007) don't contradict each other.
There were no low dosage used in the 2008 study. Only high dosage both in vitro and in vivo. The mice
were injected with 5 to 10 ug. So this would easily achieve a concentration much higher than 5 uM mentioned in the 2007 study.

The 2008 study is meant as a demonstration of possible treatment of breast cancer by injecting resv.
It is clear that a high uM concentration is required for that application.

Because the 2007 is an in vitro study one can also not say for sure that supplementing with resv will deliver about 5uM to the breast cells and thus help breast cancer cell proliferate. The only thing that is implied is that there is a risk if you create a concentration of 5uM resv. around these cells in vivo by injection or other means.

Regards,

100YTG

The 5uM vs 50uM study was done in vitro with MDA-MB-231 cells; this is a line of breast cancer cells originally harvested from a 53 yr-old patient is 1973. They've lost the expression of estrogen and progesterone receptors, among other things. It's unwarranted to extrapolate to the effect in real breasts, though this is something I'd like to study in greater detail. Cell migration increased with low concentrations of resveratrol in the study, which says little about what might happen in a human body. To conclude that this study implies low concentrations of resveratrol can cause breast cancer is akin to concluding that since birds flap their wings to fly, airplanes must too.

Edited by maxwatt, 22 February 2009 - 05:06 AM.

[VespeneGas]

Thank god.

Crep, I don't know what motivates you to say the things you do. I don't believe this to be an ad hominem attack: you don't understand the science you're interpreting here, and you have disgraced yourself with your alarmism and demeanor towards the moderators, who not only maintain a calm and reasonable attitude, but attempt only to honestly and rationally interpret the evidence for the good of everyone reading the boards.

Personally, between the misinformation and the yelling, it seems charitable that you haven't recieved a permanent ban before.

[maxwatt]

Thank god.

Crep, I don't know what motivates you to say the things you do. I don't believe this to be an ad hominem attack: you don't understand the science you're interpreting here, and you have disgraced yourself with your alarmism and demeanor towards the moderators, who not only maintain a calm and reasonable attitude, but attempt only to honestly and rationally interpret the evidence for the good of everyone reading the boards.

Personally, between the misinformation and the yelling, it seems charitable that you haven't recieved a permanent ban before.

In vivo studies in rodents have consistently shown a protective effect against mammary tumors. Leaving the topic title as an alarmist warning seemed to me to be irresponsible. Discouraging resveratrol supplementation by an unsubstantiated and alarmist warning that it might cause breast cancer could result in the illness in someone who otherwise might have supplemented and remained disease-free. To intentionally or to ignorantly distort facts and misinterpret studies one does not understand could be called unethical in this context. While it is not proven that resveratrol prevents and does not cause breast cancer in humans, it seems to me the evidence is strongly trending in that direction.

J Carcinog. 2006 May 15;5:15.
Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats.

Whitsett T, Carpenter M, Lamartiniere CA.
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA. twhitset@uab.edu
Despite the advent of new and aggressive therapeutics, breast cancer remains a leading killer among women; hence there is a need for the prevention of this disease. Several naturally occurring polyphenols have received much attention for their health benefits, including anti-carcinogenic properties. Two of these are resveratrol, a component of red grapes, and epigallocatechin-3-gallate (EGCG), the major catechin found in green tea. In this study, we tested the hypothesis that these two polyphenols protect against chemically-induced mammary cancer by modulating mammary gland architecture, cell proliferation, and apoptosis. Female Sprague-Dawley CD rats were exposed to either resveratrol (1 g/kg AIN-76A diet), EGCG (0.065% in the drinking water), or control diet (AIN-76A) for the entirety of their life starting at birth. At 50 days postpartum, rats were treated with 60 mg dimethylbenz[a]anthracene (DMBA)/kg body weight to induce mammary cancer. Resveratrol, but not EGCG, suppressed mammary carcinogenesis (fewer tumors per rat and longer tumor latency). Analysis of mammary whole mounts from 50-day-old rats revealed that resveratrol, but not EGCG, treatment resulted in more differentiated lobular structures. Bromodeoxyuridine (BrdU) incorporation studies showed that resveratrol treatment caused a significant reduction in proliferative cells in mammary terminal ductal structures at 50 days postpartum, making them less susceptible to carcinogen insult. The epithelial cells of terminal end buds in the mammary glands of resveratrol-treated rats also showed an increase in apoptotic cells compared to the control or EGCG-treated rats as measured by a DNA fragmentation assay. At the given doses, resveratrol treatment resulted in a serum resveratrol concentration of 2.00 microM, while treatment with EGCG resulted in a serum EGCG concentration of 31.06 nM. 17beta-Estradiol, progesterone, and prolactin concentrations in the serum were not significantly affected by resveratrol or EGCG. Neither polyphenol treatment resulted in toxicity as tested by alterations in body weights, diet and drink consumptions, and day to vaginal opening. We conclude that resveratrol in the diet can reduce susceptibility to mammary cancer, while EGCG in the drinking water at the dose used was not effective.
PMID: 16700914

[FedAce]

Hey gang, okay I don't know how to layman-ize this. Could someone please tell me if this article is saying Res can cause or if it prevents breast cancer.... http://www.nature.co...l/6600983a.html It may be obvious, but it's late, so I can't really tell what I'm reading.


Cheers,
Crep

It says nothing about what happens outside of a test tube. They found some increase in gene expression in genes associated with breast cancer, but the proteins apparently were not affected. Other studies have found resveratrol inhibits nfKappa-B, which would be expected to reduce breast cancer tumors. Until there are actual studies in human patients, we don't know.

Ok if it increases the gene expression in Breast CA genes, that is REALLY bad news. Recent studies have shown much higher incidence or Risk of Breast CA in such people. That was entire idea of doing Gene studies to begin with if you have family history of it. i know there is no human studies with Resveratol to this effect but this is something we have to take seriously,,, Very seriously.

[Crepulance]

I agree completely

Hey gang, okay I don't know how to layman-ize this. Could someone please tell me if this article is saying Res can cause or if it prevents breast cancer.... http://www.nature.co...l/6600983a.html It may be obvious, but it's late, so I can't really tell what I'm reading.


Cheers,
Crep

It says nothing about what happens outside of a test tube. They found some increase in gene expression in genes associated with breast cancer, but the proteins apparently were not affected. Other studies have found resveratrol inhibits nfKappa-B, which would be expected to reduce breast cancer tumors. Until there are actual studies in human patients, we don't know.

Ok if it increases the gene expression in Breast CA genes, that is REALLY bad news. Recent studies have shown much higher incidence or Risk of Breast CA in such people. That was entire idea of doing Gene studies to begin with if you have family history of it. i know there is no human studies with Resveratol to this effect but this is something we have to take seriously,,, Very seriously.

[maxwatt]

Actually, the study below indicates that it is an artifact of the methodology used: studying gene activation profiles in cancer cell lines gives results not seen in normal tissues.

Endocr Relat Cancer. 2008 Mar;15(1):161-73.

Global gene expression profiles induced by phytoestrogens in human breast cancer cells.

Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H.
Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, Zürich, Switzerland.
The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. However, these epidemiological findings remain controversial because low doses of phytoestrogens, achievable through soy-rich diets, stimulate the proliferation of estrogen-sensitive tumor cells. The question of whether such phytochemicals prevent cancer or rather pose additional health hazards prompted us to examine global gene expression programs induced by a typical soy product. After extraction from soymilk, phytoestrogens were deconjugated and processed through reverse- and normal-phase cartridges. The resulting mixture was used to treat human target cells that represent a common model system for mammary tumorigenesis. Analysis of mRNA on high-density microarrays revealed that soy phytoestrogens induce a genomic fingerprint that is indistinguishable from the transcriptional effects of the endogenous hormone 17beta-estradiol. Highly congruent responses were also observed by comparing the physiologic estradiol with daidzein, coumestrol, enterolactone, or resveratrol, each representing distinct phytoestrogen structures. More diverging transcriptional profiles were generated when an inducible promoter was used to reconstitute the expression of estrogen receptor beta (ERbeta). Therefore, phytoestrogens appear to mitigate estrogenic signaling in the presence of both ER subtypes but, in late-stage cancer cells lacking ERbeta, these phytochemicals contribute to a tumor-promoting transcriptional signature.

PMID: 18310284


Some more studies on cancer and resveratrol:

Cancer Prev Res (Phila Pa). 2008 Jul;1(2):135-45.
Resveratrol prevents estrogen-DNA adduct formation and neoplastic transformation in MCF-10F cells.

Lu F, Zahid M, Wang C, Saeed M, Cavalieri EL, Rogan EG.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Exposure to estrogens is a risk factor for breast cancer. Specific estrogen metabolites may initiate breast cancer and other cancers. Genotoxicity may be caused by cytochrome P450 (CYP)-mediated oxidation of catechol estrogens to quinones that react with DNA to form depurinating estrogen-DNA adducts. CYP1B1 favors quinone formation by catalyzing estrogen 4-hydroxylation, whereas NAD(P)H quinone oxidoreductase 1 (NQO1) catalyzes the protective reduction of quinones to catechols. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1B1 expression through the aryl hydrocarbon receptor (AhR). Resveratrol has anticancer effects in diverse in vitro and in vivo systems and is an AhR antagonist that decreases CYP expression but induces NQO1 expression. The chemopreventive effect of resveratrol on breast cancer initiation was investigated in MCF-10F cells. Its effects on estrogen metabolism and formation of estrogen-DNA adducts were analyzed in culture medium by high-performance liquid chromatography, whereas its effects on CYP1B1 and NQO1 were determined by immunoblotting and immunostaining. The antitransformation effects of resveratrol were also examined. TCDD induced expression of CYP1B1 and its redistribution in the nucleus and cytoplasm. Concomitant treatment with resveratrol dose-dependently suppressed TCDD-induced expression of CYP1B1, mainly in the cytoplasm. Resveratrol dose- and time-dependently induced expression of NQO1. NQO1 is mainly in the perinuclear membrane of control cells, but resveratrol induced NQO1 and its intracellular redistribution, which involves nuclear translocation of nuclear factor erythroid 2-related factor 2. Resveratrol decreased estrogen metabolism and blocked formation of DNA adducts in cells treated with TCDD and/or estradiol. Resveratrol also suppressed TCDD and/or estradiol-induced cell transformation. Thus, resveratrol can prevent breast cancer initiation by blocking multiple sites in the estrogen genotoxicity pathway.
PMID: 19138946

Mol Cell. 2008 Oct 10;32(1):11-20.
Comment in:
Mol Cell. 2008 Oct 24;32(2):159-60.
Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis.

Wang RH, Zheng Y, Kim HS, Xu X, Cao L, Luhasen T, Lee MH, Xiao C, Vassilopoulos A, Chen W, Gardner K, Man YG, Hung MC, Finkel T, Deng CX.
Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Germline mutations of BRCA1 predispose women to breast and ovarian cancers. However, the downstream mediators of BRCA1 function in tumor suppression remain elusive. We found that human BRCA1-associated breast cancers have lower levels of SIRT1 than their normal controls. We further demonstrated that mammary tumors from Brca1 mutant mice have low levels of Sirt1 and high levels of Survivin, which is reversed by induced expression of Brca1. BRCA1 binds to the SIRT1 promoter and increases SIRT1 expression, which in turn inhibits Survivin by changing the epigenetic modification of histone H3. Absence of SIRT1 blocks the regulation of Survivin by BRCA1. Furthermore, we demonstrated that activation of Sirt1 and inhibition of Survivin expression by resveratrol elicit a more profound inhibitory effect on Brca1 mutant cancer cells than on Brca1-wild-type cancer cells both in vitro and in vivo. These findings suggest that resveratrol treatment serves as an excellent strategy for targeted therapy for BRCA1-associated breast cancer.
PMID: 18851829

Toxicology. 2008 Jun 27;248(2-3):130-5. Epub 2008 Mar 29.
A positive feedback pathway of estrogen biosynthesis in breast cancer cells is contained by resveratrol.

Wang Y, Ye L, Leung LK.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Cytochrome P450 (CYP) 19 enzyme or aromatase catalyses the rate-determining step of estrogen synthesis. The transcriptional control of CYP19 gene is highly specific in different cell types, for instance, Promoter I.3/II is commonly used for regulation in breast cancer cells. Recently, a positive feedback pathway for estrogen synthesis has been identified in ER alpha expressing SK-BR-3 cells. CYP19 mRNA abundance and activity are increased in this pathway and the promoter usage is switched from Promoter I.3/II to I.1 through a non-genomic process. In the present study, effect of the phytocompound resveratrol on this Promoter I.1-controlled expression of aromatase was investigated. Results indicated that resveratrol reduced the estradiol-induced mRNA abundance in SK-BR-3 cells expressing ER alpha. Luciferase reporter gene assays revealed that resveratrol could also repress the transcriptional control dictated by Promoter I.1. Since the ERE-driven luciferase activity was not repressed by resveratrol, the nuclear events of estrogen were unlikely to be suppressed by resveratrol. Instead the phytochemical reduced the amount of ERK activated by estradiol, which could be the pathway responsible for Promoter I.1 transactivation and the induced CYP19 expression. The present study illustrated that resveratrol impeded the non-genomic induction of estrogen on CYP19.
PMID: 18462857

Mol Nutr Food Res. 2008 Jun;52(6):683-91.
Resveratrol inhibits migration and invasion of human breast-cancer cells.

Tang FY, Su YC, Chen NC, Hsieh HS, Chen KS.
Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan. vincenttang@mail.cmu.edu.tw
Metastasis is the primary cause of death from breast cancer. Cell migration and invasion play important roles in neoplastic metastasis. The insulin-like growth factor (IGF-1) stimulates cell migration through activation of PI-3K/Akt signaling pathway. IGF-1 induces the tumorigenicity of many types of cancer cells and is critical for metastatic cell spread in estrogen receptor (ER)-negative breast-cancer cells. Matrix metalloproteinase-2 (MMP-2) is a key enzyme in the degradation of extracellular matrices and its expression has been dysregulated in breast cancer invasion and metastasis. Resveratrol exhibited potential anticarcinogenic activities in several studies. However, the inhibitory effects of resveratrol on the expression of MMP-2, migration and invasion of breast-cancer cell have not been demonstrated yet. In the present study, we investigated the anti-invasive mechanism of resveratrol in human breast cancer MDA-MB 435cells. Here, we showed that IGF-1 is a potent stimulant of the migration of ER-negative human breast-cancer cells. Resveratrol could inhibit IGF-1-mediated cell migration of MDA-MB 435 in vitro. The inhibitory effect of resveratrol was mediated in part through the suppression of the activation of PI-3K/Akt signaling pathway. Furthermore, IGF-1-mediated expression of MMP-2 was significantly inhibited by resveratrol in concomitance with alteration of cell invasion.
PMID: 18398872

[Crepulance]

I understand there is another side, but that does not negate the findings in the first study showing the increase in expression of the BRCA gene. It should and needs to be known, especially for women so they can make the choice for themselves.


Crep

Actually, the study below indicates that it is an artifact of the methodology used: studying gene activation profiles in cancer cell lines gives results not seen in normal tissues.

Endocr Relat Cancer. 2008 Mar;15(1):161-73.

Global gene expression profiles induced by phytoestrogens in human breast cancer cells.

Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H.
Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, Zürich, Switzerland.
The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. However, these epidemiological findings remain controversial because low doses of phytoestrogens, achievable through soy-rich diets, stimulate the proliferation of estrogen-sensitive tumor cells. The question of whether such phytochemicals prevent cancer or rather pose additional health hazards prompted us to examine global gene expression programs induced by a typical soy product. After extraction from soymilk, phytoestrogens were deconjugated and processed through reverse- and normal-phase cartridges. The resulting mixture was used to treat human target cells that represent a common model system for mammary tumorigenesis. Analysis of mRNA on high-density microarrays revealed that soy phytoestrogens induce a genomic fingerprint that is indistinguishable from the transcriptional effects of the endogenous hormone 17beta-estradiol. Highly congruent responses were also observed by comparing the physiologic estradiol with daidzein, coumestrol, enterolactone, or resveratrol, each representing distinct phytoestrogen structures. More diverging transcriptional profiles were generated when an inducible promoter was used to reconstitute the expression of estrogen receptor beta (ERbeta). Therefore, phytoestrogens appear to mitigate estrogenic signaling in the presence of both ER subtypes but, in late-stage cancer cells lacking ERbeta, these phytochemicals contribute to a tumor-promoting transcriptional signature.

PMID: 18310284


Some more studies on cancer and resveratrol:

Cancer Prev Res (Phila Pa). 2008 Jul;1(2):135-45.
Resveratrol prevents estrogen-DNA adduct formation and neoplastic transformation in MCF-10F cells.

Lu F, Zahid M, Wang C, Saeed M, Cavalieri EL, Rogan EG.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Exposure to estrogens is a risk factor for breast cancer. Specific estrogen metabolites may initiate breast cancer and other cancers. Genotoxicity may be caused by cytochrome P450 (CYP)-mediated oxidation of catechol estrogens to quinones that react with DNA to form depurinating estrogen-DNA adducts. CYP1B1 favors quinone formation by catalyzing estrogen 4-hydroxylation, whereas NAD(P)H quinone oxidoreductase 1 (NQO1) catalyzes the protective reduction of quinones to catechols. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1B1 expression through the aryl hydrocarbon receptor (AhR). Resveratrol has anticancer effects in diverse in vitro and in vivo systems and is an AhR antagonist that decreases CYP expression but induces NQO1 expression. The chemopreventive effect of resveratrol on breast cancer initiation was investigated in MCF-10F cells. Its effects on estrogen metabolism and formation of estrogen-DNA adducts were analyzed in culture medium by high-performance liquid chromatography, whereas its effects on CYP1B1 and NQO1 were determined by immunoblotting and immunostaining. The antitransformation effects of resveratrol were also examined. TCDD induced expression of CYP1B1 and its redistribution in the nucleus and cytoplasm. Concomitant treatment with resveratrol dose-dependently suppressed TCDD-induced expression of CYP1B1, mainly in the cytoplasm. Resveratrol dose- and time-dependently induced expression of NQO1. NQO1 is mainly in the perinuclear membrane of control cells, but resveratrol induced NQO1 and its intracellular redistribution, which involves nuclear translocation of nuclear factor erythroid 2-related factor 2. Resveratrol decreased estrogen metabolism and blocked formation of DNA adducts in cells treated with TCDD and/or estradiol. Resveratrol also suppressed TCDD and/or estradiol-induced cell transformation. Thus, resveratrol can prevent breast cancer initiation by blocking multiple sites in the estrogen genotoxicity pathway.
PMID: 19138946

Mol Cell. 2008 Oct 10;32(1):11-20.
Comment in:
Mol Cell. 2008 Oct 24;32(2):159-60.
Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis.

Wang RH, Zheng Y, Kim HS, Xu X, Cao L, Luhasen T, Lee MH, Xiao C, Vassilopoulos A, Chen W, Gardner K, Man YG, Hung MC, Finkel T, Deng CX.
Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Germline mutations of BRCA1 predispose women to breast and ovarian cancers. However, the downstream mediators of BRCA1 function in tumor suppression remain elusive. We found that human BRCA1-associated breast cancers have lower levels of SIRT1 than their normal controls. We further demonstrated that mammary tumors from Brca1 mutant mice have low levels of Sirt1 and high levels of Survivin, which is reversed by induced expression of Brca1. BRCA1 binds to the SIRT1 promoter and increases SIRT1 expression, which in turn inhibits Survivin by changing the epigenetic modification of histone H3. Absence of SIRT1 blocks the regulation of Survivin by BRCA1. Furthermore, we demonstrated that activation of Sirt1 and inhibition of Survivin expression by resveratrol elicit a more profound inhibitory effect on Brca1 mutant cancer cells than on Brca1-wild-type cancer cells both in vitro and in vivo. These findings suggest that resveratrol treatment serves as an excellent strategy for targeted therapy for BRCA1-associated breast cancer.
PMID: 18851829

Toxicology. 2008 Jun 27;248(2-3):130-5. Epub 2008 Mar 29.
A positive feedback pathway of estrogen biosynthesis in breast cancer cells is contained by resveratrol.

Wang Y, Ye L, Leung LK.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Cytochrome P450 (CYP) 19 enzyme or aromatase catalyses the rate-determining step of estrogen synthesis. The transcriptional control of CYP19 gene is highly specific in different cell types, for instance, Promoter I.3/II is commonly used for regulation in breast cancer cells. Recently, a positive feedback pathway for estrogen synthesis has been identified in ER alpha expressing SK-BR-3 cells. CYP19 mRNA abundance and activity are increased in this pathway and the promoter usage is switched from Promoter I.3/II to I.1 through a non-genomic process. In the present study, effect of the phytocompound resveratrol on this Promoter I.1-controlled expression of aromatase was investigated. Results indicated that resveratrol reduced the estradiol-induced mRNA abundance in SK-BR-3 cells expressing ER alpha. Luciferase reporter gene assays revealed that resveratrol could also repress the transcriptional control dictated by Promoter I.1. Since the ERE-driven luciferase activity was not repressed by resveratrol, the nuclear events of estrogen were unlikely to be suppressed by resveratrol. Instead the phytochemical reduced the amount of ERK activated by estradiol, which could be the pathway responsible for Promoter I.1 transactivation and the induced CYP19 expression. The present study illustrated that resveratrol impeded the non-genomic induction of estrogen on CYP19.
PMID: 18462857

Mol Nutr Food Res. 2008 Jun;52(6):683-91.
Resveratrol inhibits migration and invasion of human breast-cancer cells.

Tang FY, Su YC, Chen NC, Hsieh HS, Chen KS.
Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan. vincenttang@mail.cmu.edu.tw
Metastasis is the primary cause of death from breast cancer. Cell migration and invasion play important roles in neoplastic metastasis. The insulin-like growth factor (IGF-1) stimulates cell migration through activation of PI-3K/Akt signaling pathway. IGF-1 induces the tumorigenicity of many types of cancer cells and is critical for metastatic cell spread in estrogen receptor (ER)-negative breast-cancer cells. Matrix metalloproteinase-2 (MMP-2) is a key enzyme in the degradation of extracellular matrices and its expression has been dysregulated in breast cancer invasion and metastasis. Resveratrol exhibited potential anticarcinogenic activities in several studies. However, the inhibitory effects of resveratrol on the expression of MMP-2, migration and invasion of breast-cancer cell have not been demonstrated yet. In the present study, we investigated the anti-invasive mechanism of resveratrol in human breast cancer MDA-MB 435cells. Here, we showed that IGF-1 is a potent stimulant of the migration of ER-negative human breast-cancer cells. Resveratrol could inhibit IGF-1-mediated cell migration of MDA-MB 435 in vitro. The inhibitory effect of resveratrol was mediated in part through the suppression of the activation of PI-3K/Akt signaling pathway. Furthermore, IGF-1-mediated expression of MMP-2 was significantly inhibited by resveratrol in concomitance with alteration of cell invasion.
PMID: 18398872

[maxwatt]

I understand there is another side, but that does not negate the findings in the first study showing the increase in expression of the BRCA gene. It should and needs to be known, especially for women so they can make the choice for themselves.


Crep

Actually, the study below indicates that it is an artifact of the methodology used: studying gene activation profiles in cancer cell lines gives results not seen in normal tissues.

Endocr Relat Cancer. 2008 Mar;15(1):161-73.

Global gene expression profiles induced by phytoestrogens in human breast cancer cells.

Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H.
Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, Zürich, Switzerland.
The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. However, these epidemiological findings remain controversial because low doses of phytoestrogens, achievable through soy-rich diets, stimulate the proliferation of estrogen-sensitive tumor cells. The question of whether such phytochemicals prevent cancer or rather pose additional health hazards prompted us to examine global gene expression programs induced by a typical soy product. After extraction from soymilk, phytoestrogens were deconjugated and processed through reverse- and normal-phase cartridges. The resulting mixture was used to treat human target cells that represent a common model system for mammary tumorigenesis. Analysis of mRNA on high-density microarrays revealed that soy phytoestrogens induce a genomic fingerprint that is indistinguishable from the transcriptional effects of the endogenous hormone 17beta-estradiol. Highly congruent responses were also observed by comparing the physiologic estradiol with daidzein, coumestrol, enterolactone, or resveratrol, each representing distinct phytoestrogen structures. More diverging transcriptional profiles were generated when an inducible promoter was used to reconstitute the expression of estrogen receptor beta (ERbeta). Therefore, phytoestrogens appear to mitigate estrogenic signaling in the presence of both ER subtypes but, in late-stage cancer cells lacking ERbeta, these phytochemicals contribute to a tumor-promoting transcriptional signature.

PMID: 18310284
....

The study I cited above demonstrated that phytoestrogens including resveratrol mitigate estrogenic signaling in the presence of both ER alpha and ER beta. In cells lacking ER beta "phytochemicals contribute to a tumor-promoting transcriptional profile." The paper you cited to begin this thread used a line of human breast cancer cells that have an abnormally high ER alpha to ER beta ratio. This means only that the BRCA1 and BRCA2 genes are expressed in a human cancer cell line with an abnormal ERalpha to ERbeta ratio in the presence of resveratrol. The study also used a concentration of 30 uM, which is much higher than serum levels that can be obtained from oral resveratrol.

But even in abnormal breast cancer cells lacking in ER beta, resveratrol induces apoptosis (kills cancer cells.) There are many papers demonstrating this.

Cancer Lett. 2006 Jan 8;231(1):113-22. Links
Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo.

Garvin S, Ollinger K, Dabrosin C.
Division of Gynecologic Oncology, Faculty of Health Sciences, University Hospital, SE-581 85 Linköping, Sweden.
Resveratrol, a polyphenol found in grapes and wine, is considered a potential cancer chemopreventive agent. Resveratrol has been shown to induce transcription via both ERalpha and ERbeta. We observed significantly lower tumor growth, decreased angiogenesis, and increased apoptotic index in ERalpha- ERbeta+ MDA-MB-231 tumors in resveratrol-treated nude mice compared with controls. In vitro we found a significant increase in apoptosis in resveratrol-treated MDA-MB-231 cells in addition to significantly reduced extracellular levels of VEGF. This study supports the potential use of resveratrol as a chemotherapeutic agent in breast cancers.
PMID: 16356836

Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo
Cancer Letters, Volume 231, Issue 1, Pages 113-122
S. Garvin, K. Öllinger, C. Dabrosin

Abstract

Resveratrol, a polyphenol found in grapes and wine, is considered a potential cancer chemopreventive agent. Resveratrol has been shown to induce transcription via both ERα and ERβ. We observed significantly lower tumor growth, decreased angiogenesis, and increased apoptotic index in ERα− ERβ+ MDA-MB-231 tumors in resveratrol-treated nude mice compared with controls. In vitro we found a significant increase in apoptosis in resveratrol-treated MDA-MB-231 cells in addition to significantly reduced extracellular levels of VEGF. This study supports the potential use of resveratrol as a chemotherapeutic agent in breast cancers.

So even in cells whre BRCA expression is induced, resveratrol still kills them.

It is not that there is another side, it is that you cannot draw conclusions from an isolated, anomalous and incomplete study. one that is contradicted on several levels by many other, better studies.

[Crepulance]

I didn't say I drew a conclusion or that anything was conclusive. I am saying that women need to know of it and make an informed decision on their own. There have been a handful of scientific minds on here that have said if you're a woman you may want to stay away from Res especially if you have a history of breast cancer based on what they've read in the research and articles.


Crep

I understand there is another side, but that does not negate the findings in the first study showing the increase in expression of the BRCA gene. It should and needs to be known, especially for women so they can make the choice for themselves.


Crep

Actually, the study below indicates that it is an artifact of the methodology used: studying gene activation profiles in cancer cell lines gives results not seen in normal tissues.

Endocr Relat Cancer. 2008 Mar;15(1):161-73.

Global gene expression profiles induced by phytoestrogens in human breast cancer cells.

Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H.
Institute of Pharmacology and Toxicology, University of Zürich-Vetsuisse, Winterthurerstrasse 260, Zürich, Switzerland.
The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. However, these epidemiological findings remain controversial because low doses of phytoestrogens, achievable through soy-rich diets, stimulate the proliferation of estrogen-sensitive tumor cells. The question of whether such phytochemicals prevent cancer or rather pose additional health hazards prompted us to examine global gene expression programs induced by a typical soy product. After extraction from soymilk, phytoestrogens were deconjugated and processed through reverse- and normal-phase cartridges. The resulting mixture was used to treat human target cells that represent a common model system for mammary tumorigenesis. Analysis of mRNA on high-density microarrays revealed that soy phytoestrogens induce a genomic fingerprint that is indistinguishable from the transcriptional effects of the endogenous hormone 17beta-estradiol. Highly congruent responses were also observed by comparing the physiologic estradiol with daidzein, coumestrol, enterolactone, or resveratrol, each representing distinct phytoestrogen structures. More diverging transcriptional profiles were generated when an inducible promoter was used to reconstitute the expression of estrogen receptor beta (ERbeta). Therefore, phytoestrogens appear to mitigate estrogenic signaling in the presence of both ER subtypes but, in late-stage cancer cells lacking ERbeta, these phytochemicals contribute to a tumor-promoting transcriptional signature.

PMID: 18310284
....

The study I cited above demonstrated that phytoestrogens including resveratrol mitigate estrogenic signaling in the presence of both ER alpha and ER beta. In cells lacking ER beta "phytochemicals contribute to a tumor-promoting transcriptional profile." The paper you cited to begin this thread used a line of human breast cancer cells that have an abnormally high ER alpha to ER beta ratio. This means only that the BRCA1 and BRCA2 genes are expressed in a human cancer cell line with an abnormal ERalpha to ERbeta ratio in the presence of resveratrol. The study also used a concentration of 30 uM, which is much higher than serum levels that can be obtained from oral resveratrol.

But even in abnormal breast cancer cells lacking in ER beta, resveratrol induces apoptosis (kills cancer cells.) There are many papers demonstrating this.

Cancer Lett. 2006 Jan 8;231(1):113-22. Links
Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo.

Garvin S, Ollinger K, Dabrosin C.
Division of Gynecologic Oncology, Faculty of Health Sciences, University Hospital, SE-581 85 Linköping, Sweden.
Resveratrol, a polyphenol found in grapes and wine, is considered a potential cancer chemopreventive agent. Resveratrol has been shown to induce transcription via both ERalpha and ERbeta. We observed significantly lower tumor growth, decreased angiogenesis, and increased apoptotic index in ERalpha- ERbeta+ MDA-MB-231 tumors in resveratrol-treated nude mice compared with controls. In vitro we found a significant increase in apoptosis in resveratrol-treated MDA-MB-231 cells in addition to significantly reduced extracellular levels of VEGF. This study supports the potential use of resveratrol as a chemotherapeutic agent in breast cancers.
PMID: 16356836

Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo
Cancer Letters, Volume 231, Issue 1, Pages 113-122
S. Garvin, K. Öllinger, C. Dabrosin

Abstract

Resveratrol, a polyphenol found in grapes and wine, is considered a potential cancer chemopreventive agent. Resveratrol has been shown to induce transcription via both ERα and ERβ. We observed significantly lower tumor growth, decreased angiogenesis, and increased apoptotic index in ERα− ERβ+ MDA-MB-231 tumors in resveratrol-treated nude mice compared with controls. In vitro we found a significant increase in apoptosis in resveratrol-treated MDA-MB-231 cells in addition to significantly reduced extracellular levels of VEGF. This study supports the potential use of resveratrol as a chemotherapeutic agent in breast cancers.

So even in cells whre BRCA expression is induced, resveratrol still kills them.

It is not that there is another side, it is that you cannot draw conclusions from an isolated, anomalous and incomplete study. one that is contradicted on several levels by many other, better studies.

[Anthony_Loera]

This comes from a March 2009 study, which is a bit more recent than the 2003 study that started this thread, and a bit different :

From the 2009 study below, we can see that resveratrol and quercetin in (taken in equal amounts), inhibit breast cancer in animals (both in vitro and in vivo results are shown).
The earlier study is limited to a test tube, and did not test animals. It appears that overall, Res and Q taken in equal amounts, should be someting women should consider taking.

The Study:

http://www.springerl...34781x38545w31/

Linette Castillo-Pichardo1, Michelle M. Martínez-Montemayor2, Joel E. Martínez2, Kristin M. Wall2, Luis A. Cubano2 and Suranganie Dharmawardhane1, 2 Contact Information
(1) Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA
(2) Department of Anatomy and Cell Biology, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR 00960-6032, USA

Received: 13 October 2008 Accepted: 4 March 2009 Published online: 18 March 2009
Abstract The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERα(−), ERβ(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19–27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (−) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IκBα), thus activating apoptosis and potentially inhibiting NfκB (nuclear factor κB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.

Keywords Breast cancer - Catechin - Metastasis - Quercetin - Resveratrol

Edited by Mind, 21 June 2009 - 03:09 PM.

[Crepulance]

Hi Anthony, I understand about the 2009 study, but that doesn't mean the 2003 study didn't happen. It still occurred with the results it produced. And the fact that you are changing your formula considering this, lends further credibility to the concern women should have for res in general. Since there is no conclusive data either way. If there was truly no concern about women in the first place, then there would be no need to change the formula. Yet earlier in the year, or last year, you among others were on here defending against any such possibilities that it could be bad for women in regards to breast cancer, and yet now you've gone out of your way to formulate a specific blend for women to address such issues. Meaning in the window between then and now you were essentially ignoring or covering up some potentially dangerous information.



Crep

This comes from a March 2009 study, which is a bit more recent than the 2003 study that started this thread, and a bit different :

From the 2009 study below, we can see that resveratrol and quercetin in (taken in equal amounts), inhibit breast cancer in animals (both in vitro and in vivo results are shown).
The earlier study is limited to a test tube, and did not test animals. It appears that overall, Res and Q taken in equal amounts, should be someting women should consider taking.

That is why, we are adding Quercetin as a separate item, per this thread here:
http://www.imminst.o...rol-t30115.html

The Study:

http://www.springerl...34781x38545w31/

Linette Castillo-Pichardo1, Michelle M. Martínez-Montemayor2, Joel E. Martínez2, Kristin M. Wall2, Luis A. Cubano2 and Suranganie Dharmawardhane1, 2 Contact Information
(1) Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR, USA
(2) Department of Anatomy and Cell Biology, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR 00960-6032, USA

Received: 13 October 2008 Accepted: 4 March 2009 Published online: 18 March 2009
Abstract The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERα(−), ERβ(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19–27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (−) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IκBα), thus activating apoptosis and potentially inhibiting NfκB (nuclear factor κB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.

Keywords Breast cancer - Catechin - Metastasis - Quercetin - Resveratrol

[Anthony_Loera]

From November 2008

Jennifer,

the words "May", "suggest", "doesn't appear", "may even" in the posts are there for a purpose. The fact is that (just like the common cold) there is no scientifically verified 100% cure for cancer. Even our best medical doctors give us survival rates based on statistics, not based on any cure they may know about or have developed.

From a medical standpoint. A cure simply does not exist for cancer, or for a typical cold. However treatments do exist, and treatments may increase survival rates. Again I said the word "May" in that last sentence simply because treatments will not work for 100% of folks. You need to get yourself mammograms routinely and consult your doctor if you feel this is an issue.

Let's think about the time line regarding studies:

The one Crep brings up is a 2003 study.

The recent velopismo mentioned is from October 2008 (last month!) and it is from Dr. Deng of the Genetics of Development and Diseases Branch at the National Institutes of Health. In it he finds that the compound resveratrol strongly inhibited BRCA1-mutant tumor growth in cultured cells and animal models.

Why is the time line important? I believe it shows a confirmation that resveratrol can be developed by drug makers to be helpful for this issue, while in 2003 it was uncertain. Again, I do not make any claims that resveratrol in any dietary or herbal supplement are intended to diagnose, treat, cure or prevent any disease. FDA rules prevent any supplement company from making those claims, as doing so would have the FDA classify the supplement as a drug. Thats the simple fact regarding supplements in the United States. I am not sure how the rules differ in other parts of the world, but I wanted to clear this up regarding the language used by everyone.

The simple fact is that until human trials are done by a drug company, or research university, Resveratrol remains a molecule that may or may not have benefits people are looking for.


Sorry if is not the concrete answer you are looking for, but if the decision to take resveratrol makes you anxious, do yourself a simple favor.... do not take it until you are 100% sure. Simply wait for better research, it's just that easy.

A

After the New Study this year (2009) shows both in vitro and in vivo info on Resveratrol fighting breast cancer:
http://www.springerl...34781x38545w31/

The Time line again is important. Now we see that studies done using equal amounts of resveratrol and Quercetin inhibit breast cancer in animals.

What does this mean?

Again, there is not cure for humans, but it confirms that resveratrol can be used to fight breast cancer in animals.
So if you have a dog, a cat, a horse... there maybe new life given to them by use of resveratrol.

Jennifer if you still are reading this thread, this is positive news.


Cheers Jennifer, and everyone else,

A

[Crepulance]

Again, just because it shows this fights it, does not negate the study in 2003 showing it can also increase the expression of the brac1 gene


Crep

From November 2008

Jennifer,

the words "May", "suggest", "doesn't appear", "may even" in the posts are there for a purpose. The fact is that (just like the common cold) there is no scientifically verified 100% cure for cancer. Even our best medical doctors give us survival rates based on statistics, not based on any cure they may know about or have developed.

From a medical standpoint. A cure simply does not exist for cancer, or for a typical cold. However treatments do exist, and treatments may increase survival rates. Again I said the word "May" in that last sentence simply because treatments will not work for 100% of folks. You need to get yourself mammograms routinely and consult your doctor if you feel this is an issue.

Let's think about the time line regarding studies:

The one Crep brings up is a 2003 study.

The recent velopismo mentioned is from October 2008 (last month!) and it is from Dr. Deng of the Genetics of Development and Diseases Branch at the National Institutes of Health. In it he finds that the compound resveratrol strongly inhibited BRCA1-mutant tumor growth in cultured cells and animal models.

Why is the time line important? I believe it shows a confirmation that resveratrol can be developed by drug makers to be helpful for this issue, while in 2003 it was uncertain. Again, I do not make any claims that resveratrol in any dietary or herbal supplement are intended to diagnose, treat, cure or prevent any disease. FDA rules prevent any supplement company from making those claims, as doing so would have the FDA classify the supplement as a drug. Thats the simple fact regarding supplements in the United States. I am not sure how the rules differ in other parts of the world, but I wanted to clear this up regarding the language used by everyone.

The simple fact is that until human trials are done by a drug company, or research university, Resveratrol remains a molecule that may or may not have benefits people are looking for.


Sorry if is not the concrete answer you are looking for, but if the decision to take resveratrol makes you anxious, do yourself a simple favor.... do not take it until you are 100% sure. Simply wait for better research, it's just that easy.

A

After the New Study this year (2009) shows both in vitro and in vivo info on Resveratrol fighting breast cancer:
http://www.springerl...34781x38545w31/

The Time line again is important. Now we see that studies done using equal amounts of resveratrol and Quercetin inhibit breast cancer in animals.

What does this mean?

Again, there is not cure for humans, but it confirms that resveratrol can be used to fight breast cancer in animals.
So if you have a dog, a cat, a horse... there maybe new life given to them by use of resveratrol.

Jennifer if you still are reading this thread, this is positive news.


Cheers Jennifer, and everyone else,

A

[tunt01]

Again, just because it shows this fights it, does not negate the study in 2003 showing it can also increase the expression of the brac1 gene


Crep

isn't deactivating the BRCA1 gene also widely associated with tumorogenesis? isn't dealing with the downstream effects of a defective BRCA1 gene the real issue and goal of therapy?



http://www.ncbi.nlm....pubmed/16849561

Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members.

Shukla V, Coumoul X, Cao L, Wang RH, Xiao C, Xu X, Andò S, Yakar S, Leroith D, Deng C.
Genetics of Development and Disease Branch and Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA. shuklav@mail.nih.gov
The breast cancer-associated gene-1 (BRCA1) plays many important functions in multiple biological processes/pathways. Mice homozygous for a targeted deletion of full-length BRCA1 (Brca1Delta11/Delta11) display both increased tumorigenesis and premature aging, yet molecular mechanisms underlying these defects remain elusive. Here, we show that Brca1 deficiency leads to increased expression of several insulin-like growth factor (IGF) signaling axis members in multiple experimental systems, including BRCA1-deficient mice, primary mammary tumors, and cultured human cells. Furthermore, we provide evidence that activation of IGF signaling by BRCA1 deficiency can also occur in a p53-independent fashion. Our data indicate that BRCA1 interacts with the IRS-1 promoter and inhibits its activity that is associated with epigenetic modification of histone H3 and histone H4 to a transcriptional repression chromatin configuration. We further show that BRCA1-deficient mammary tumor cells exhibit high levels of IRS-1, and acute suppression of Irs-1 using RNA interference significantly inhibits growth of these cells. Those observations provide a molecular insight in understanding both fundamental and therapeutic BRCA1-associated tumorigenesis and aging.

PMID: 16849561 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....pubmed/11585672

BRCA1-associated tumorigenesis: what have we learned from knockout mice?

Brodie SG, Deng CX.
Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
A series of allelic mutations in the tumor suppressor Brca1 have been created to study mechanisms underlying BRCA1-associated tumorigenesis. Brca1 is essential in maintaining genome integrity through its involvement in DNA damage repair, G(2)-M cell-cycle checkpoint and centrosome duplication. The loss of Brca1 is not sufficient for malignant transformation, rather, it triggers multiple genetic alterations, including the inactivation of p53 and activation of a number of oncogenes, that ultimately result in mammary tumorigenesis.



Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation.

Deng CX, Scott F.
Genetics of Development and Disease Branch, 10/9N105, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892, USA.
Germline mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. Current evidence demonstrates that mutations in BRCA1 do not directly result in tumor formation, but instead cause genetic instability, subjecting cells to high risks of malignant transformation. In an animal model in which Brca1 is mutated specifically in mammary epithelium, tumorigenesis occurs in mutant glands at low frequency after a long latency. Notably, introduction of a p53-null allele significantly enhanced mammary gland tumor formation in Brca1 conditional mutant mice. These results are consistent with a model that Brca1 is a caretaker gene, whose absence causes genetic instability and triggers further alterations, including inactivation of tumor suppressor genes and/or activation of oncogenes, leading to tumor formation.

[tham]

Metabolic profile of breast cancer patients.

http://www.pubmedcen...bmedid=18665244



Selenium and BRCA1.

http://cebp.aacrjour.../full/14/5/1302

http://www.ncbi.nlm....l=pubmed_docsum

http://www.ncbi.nlm....l=pubmed_docsum



Malaysian study on selenium and breast cancer.

http://www.ncbi.nlm....5003/5003a4.pdf


Gerard Schrauzer has been one of the principal
researchers on selenium and cancer for decades.

http://www.ncbi.nlm....l=pubmed_docsum

http://www.ncbi.nlm....l=pubmed_docsum


Interview with Gerard Schrauzer.

http://sira.ucsd.edu...hwise/Mar05.pdf

[tham]

" Statistically significant increases in risks were observed for
prostate cancer (estimated RR = 4.65), pancreatic cancer
(RR = 3.51), gallbladder and bile duct cancer (RR = 4.97),
stomach cancer (RR = 2.59), and malignant melanoma
(RR = 2.58). The RR for prostate cancer for men below the
age of 65 years was 7.33. "

http://www.ncbi.nlm....t_uids=10433620


" Significant excesses were observed for colon cancer
(estimated relative risk [RR] to gene carriers 4.11) and
prostate cancer (3.33).

http://www.ncbi.nlm....st_uids=7907678


BRCA1 mutation carriers were at a statistically significantly
increased risk for several cancers, including pancreatic
cancer (RR = 2.26) and cancer of the uterine body and
cervix (uterine body RR = 2.65, cervix RR = 3.72).

http://www.ncbi.nlm....t_uids=12237281

[Anthony_Loera]

tham,

BRCA1 mutation carriers are normally predisposed statistically for cancer.

I understand that your are proponent for selenium as part of a regimen for selenium, is that correct?
If we go by the recent studies, it appears that taking resveratrol and quercetin in equal amounts is not bad either.
http://www.springerl...34781x38545w31/

What are your thoughts on taking all 3?

Cheers
A

[porthose]

hello everyone,

i wasn't sure whether to post on this thread or to make a new thread - apologies if i stuffed up. the title after all was Breast Cancer.

i would like to report on my mother's case who is 70yrs of age and the importance of taking control to improve a persons or loved ones life. its a long post and i do apologise for that and thank you for taking the time to read.

in 1977 she was diagnosed with breast cancer (i was 10 yrs old) and subsequently underwent a whole right breast mastectomy. the surgery went well and she was on tamoxifan for years.

in the intervening years, she also underwent a historectamy, apendicitis and gall bladder removal along with a full set of dentures and oh, she is 50% deaf one ear and about 80% deaf in the other. an old letter from a surgeon to another surgeon clearly states that her body was ravaged by disease and that she didn't have long to live. but she is still alive and is a remarkably strong woman who can still drive her car and go and do the shopping.

about a year ago, she began to experience symptoms in her left arm which she would describe to her oncologist of 10 years and GP as 'water travelling up and down her arm'. a number of tests (scans) by her GP and Oncologist were conducted but failed to show anything. her arm symptoms continued until at around late December 2008 she awoke one morning in severe pain. the pain so severe in fact that i had to carry her and rush her to emergency. whole body bone scans were then conducted which clearly showed metastitic cancer at a couple of sites in her spine and hip.

i then began intense research at LEF's site and here at the forums plus a lot of reading on breast and metastitic cancer. i then began to ask myself a couple of questions:

- why didn't the GP and Oncologist educate us that cancer can metastise to the bone and organs, especially breast and prostate cancer?

- why didn't the GP and the Oncologist educate us to the fact that good preventative measures be taken to halt metastasis or at least provide good defense against it?

On top of the research, I spoke to an Oncologist from the US (from LEF actually Dr Stephen Nemeroff - fantastic fellow) who called me here in Canberra, Australia and suggested several things i could do.

I then put my mother on several high dose supps like CoQ10, Melatonin, Selenium, high dose antiox scavengers, Pyridoxal 5 Phosphate, Vit D3, sodium ascorbate and Modified Citrus Pectin. we cleaned up her diet - no sugar or carbs and no milk. her food is now now quality protein and super fresh vegetables. interesting tidbit: its a fact that nearly 50% of older Australians do not consume enough protein and as a result do not prevent the loss of lean body mass. Anyway: almost IMMEDIATELY her condition improved in that there was no more nausia, vomiting and no more pain. this was terrific.

After the diagnosis of the metastitic cancer (her GP read the results to us all the while eating an apple and simply saying "you have a battle on your hands"), we had an appointment with her Oncologist who confirmed the bone disease and prescribed Femara. i gave the list of supps to the oncologist but he neither endorsed nor critised this apart from his comment: "that we must go via the route of text book science and that animal model tests do not necessarily translate to the improvement of the human condition". this upset me and i did all i could to prevent myself from throttling the egotistical f*ck not because of his statement but because of any possible contra indications with the supps against the femara! however, we had still not received an explanation as to my mothers arm symptoms that she was experiencing. in fact the oncologist went so far as to suggest her arm sypmtoms were all just a figment of her imagination! and this bloke teaches at the Australian National University.

okay, we had confirmed my mother's bone disease, the femara would go a long way to help and despite what the oncologist thought, i firmly believed the supps would at least boost the femara's anti cancer properties, this from clinical studies published.

as several days went by and i continued to research and ask questions, i could see my mother's condition steadily improve but with the occasional bouts of nausea and vomiting (my mother by the way has never been on chemo or radiation therapy) i chanced upon an aquantance who suggested i see a GP in town who is also an expert on cancer and nutrition. we were able to get into his clinic almost immediately (usually a 5 month waiting period) and what he did was refreshing: we filled out probably one of the most comprehensive health questionares i have ever seen and he also asked my mother a lot of questions. finally he did basic investigative front line medicine ie to physically examine her and something to my mind her original GP and Oncologist failed to do.

as a result of his investigation, he found a small lump underneath my mothers left armpit. finally we had a possible explanation as to my mums arm symptoms. and this also amazed me - he immediately tracked down and telephoned my mother's oncologist, spoke to him and both agreed as to what further tests should be conducted. tests were conducted and a cancerous tumour was confirmed under her arm pit close to her lymph nodes.

surgery was then scheduled (refered to a quality surgeon by this new GP) and the tumour was taken out along with a couple of lymph nodes. her left breast was clear thank goodness.

as a result of the above, i sacked my mothers old Oncologist and old GP.

as the months have passed, mums condition continues to improve and just several days ago, we had an appointment with her new oncologist a certain proffessor. blood indicators have revealed she has small spots of cancer in her lungs and possibly in her spleen. The good news is that these spots are reducing and the metastitic cancer has NOT spread but has in fact stabilised.

he also wanted to prescribe a bisphosphonate Bondronat calling it a new cutting edge wonder drug but upon researching this, its actually been in existence since 2004 developed in Canada. However, the Canadian review board on new and patented drugs have categorised it as a category 3 medication meaning that it offers little to no therapeutic benefits to other similar medication and with all the friggin' side effects! sigh...

when i pointed this out to him, his response: "what side effects? we have to control the cancer, this is the most important thing that has to be done". my response "yes, i agree but the protocol required just to take it... not to mention the chance of osteonecrosis of the jaw bone. forget it". we refused.

he then tried to reinstate his autority by stating he was the expert here and of course that is true, but when he checked the numbers again, he said, we have done well to control her numbers and here i am thinking: what the hell have you actually done but simply to report and interpret these numbers for me?!

and because her numbers are falling/stabilizing, he changed his tune in that after all, the bisphosphonate need to be taken after all. can you believe this sh*t?

i am thinking of writing a strongly worded letter to the Australian Medical Association reporting this case. i feel that had mum's original GP and Oncologist provided front line investigative medicine by physically examining her, the arm symptoms could have been discovered at least a year ago.

in conclusion: take independent, scientific investigation, ask a lot of questions because while most medical doctors have their hearts in the right place, they are loath to go against what they have been trained to do.

thank you for reading, i feel better in that I have vented!

[tunt01]

it's an unfortunate part of medicine. doctors are doctors, they are not medical scientists. most doctors just regurgitate whatever crap they are told by pharma reps or at medical seminars. they don't spend the time to obsessively analyze all the studies in their field and still treat all their patients. they have families and lives too.

very few doctors in the world are both treating patients while also leading authorities in their disciplines.

you have to be your own doctor or have enough money to be able to get the best treatment from world reknown experts.

Edited by prophets, 24 June 2009 - 03:50 AM.

[tham]

tham,



BRCA1 mutation carriers are normally predisposed
statistically for cancer.

I understand that your are proponent for selenium as
part of a regimen for selenium, is that correct?
If we go by the recent studies, it appears that taking
resveratrol and quercetin in equal amounts is not bad
either.

http://www.springerl...34781x38545w31/

What are your thoughts on taking all 3?

Cheers
A

Thanks, Anthony.

Yes, a combination of selenium, resveratrol and quercetin
would be a good regimen for overall cancer prevention.

However, caution would need to be exercised with resveratrol
and quercetin, if one had a cancer which proliferate vide the
PPAR gamma pathway and its inhibiton, as well as chemotherapy
drugs which act vide the activation of this pathway, as Blutarsky
and Prophet also noted.

This includes small cell lung cancer.


http://www.ncbi.nlm....l=pubmed_docsum

http://www.ncbi.nlm....l=pubmed_docsum

http://www.pubmedcen...bmedid=12069687


http://www.imminst.o...o...st&p=306352

http://www.imminst.o...t...&pid=301030

http://www.imminst.o...t...&pid=300719


https://www.research...available_drugs