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Cancer Preventive Properties Identified In Resveratrol


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#1 VP.

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Posted 08 July 2008 - 05:20 AM


The good news keeps coming. I wish Sirtris didn't sell out so early.

Cancer Preventive Properties Identified In Resveratrol, Found In Red Wine, Red Grapes
ScienceDaily (July 7, 2008) — Early laboratory research has shown that resveratrol, a common dietary supplement, suppresses the abnormal cell formation that leads to most types of breast cancer, suggesting a potential role for the agent in breast cancer prevention. Resveratrol is a natural substance found in red wine and red grapes. It is sold in extract form as a dietary supplement at most major drug stores.

"Resveratrol has the ability to prevent the first step that occurs when estrogen starts the process that leads to cancer by blocking the formation of the estrogen DNA adducts. We believe that this could stop the whole progression that leads to breast cancer down the road," said Eleanor G. Rogan, Ph.D., a professor in the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center.

Rogan was the lead author of the report that was published in the July 2008 issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.

For the current study, Rogan and colleagues measured the effect of resveratrol on cellular functions known to contribute to breast cancer.

The formation of breast cancer is a multi-step process which differs depending on type of disease, a patient's genetic makeup and other factors. However, scientists know that many breast cancers are fueled by increased estrogen, which collects and reacts with DNA molecules to form adducts. Rogan and colleagues found that resveratrol was able to suppress the formation of these DNA adducts.

"This is dramatic because it was able to be done with fairly low concentrations of resveratrol to stop the formation of these DNA adducts in the cells we studied," said Rogan. Although researchers experimented with up to 100 µmol/L of resveratrol, the suppression of DNA adducts was seen with 10 µmol/L. A glass of red wine contains between 9 and 28 µmol/L of resveratrol.
The researchers also found that resveratrol suppressed the expression of CYP1B1 and the formation of 2,3,7,8-Tetrachlorodibenzo-p-dioxin, two known risk factors for breast cancer.

Rogan said resveratrol works by inducing an enzyme called quinone reductase, which reduces the estrogen metabolite back to inactive form. By making estrogen inactive, resveratrol decreases the associated risk.

The current study was conducted in laboratory cultures, and will need to be confirmed in larger human trials, Rogan said.

http://www.scienceda...80707081848.htm

#2 niner

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Posted 08 July 2008 - 06:20 AM

"This is dramatic because it was able to be done with fairly low concentrations of resveratrol to stop the formation of these DNA adducts in the cells we studied," said Rogan. Although researchers experimented with up to 100 µmol/L of resveratrol, the suppression of DNA adducts was seen with 10 µmol/L.

[b]The current study was conducted in laboratory cultures, and will need to be confirmed in larger human trials, Rogan said
.


And if they try to confirm it in human trials, I wish them luck. The "fairly low" concentrations they looked at in cell culture are going to be very hard to attain in humans. As a point of reference, a five gram oral bolus dose of resveratrol resulted in a plasma Cmax of 2.4 µmol/L. This could be improved with formulating agents, as has been done in SRT501, but 10 uM would still be hard to hit.

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#3 missminni

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Posted 20 July 2008 - 12:07 AM

"This is dramatic because it was able to be done with fairly low concentrations of resveratrol to stop the formation of these DNA adducts in the cells we studied," said Rogan. Although researchers experimented with up to 100 µmol/L of resveratrol, the suppression of DNA adducts was seen with 10 µmol/L.

[b]The current study was conducted in laboratory cultures, and will need to be confirmed in larger human trials, Rogan said
.


And if they try to confirm it in human trials, I wish them luck. The "fairly low" concentrations they looked at in cell culture are going to be very hard to attain in humans. As a point of reference, a five gram oral bolus dose of resveratrol resulted in a plasma Cmax of 2.4 µmol/L. This could be improved with formulating agents, as has been done in SRT501, but 10 uM would still be hard to hit.

Minni had breast cancer. Res cured it. I gave her 7 gms a day for a few months. Then 5 g, and now 3g. She's doing great. I've been told that dogs metabolize res better than people, so I would imagine a person would need a higher dose. Although, quite honestly, it might have been just as effective if I had given her 3g. I'll never know. I just started off high because I wanted to be aggressive about it.

#4 maxwatt

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Posted 20 July 2008 - 11:11 AM

The problem with comparing dogs to humans is this: humans have very efficient conjugation mechanism, and break down resveratrol before it reaches high blood serum levels. Dogs do not, and attain much higher levels with equivalent doses. So while I am hopeful resveratrol wil prove effective with cancer, I am by no means certain.

#5 missminni

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Posted 20 July 2008 - 12:00 PM

The problem with comparing dogs to humans is this: humans have very efficient conjugation mechanism, and break down resveratrol before it reaches high blood serum levels. Dogs do not, and attain much higher levels with equivalent doses. So while I am hopeful resveratrol wil prove effective with cancer, I am by no means certain.

Wouldn't that indicate that humans need higher doses to get the same results as dogs? Would the micronized version of resveratrol provide that edge? The wonderful thing about res, afaic, is how safe it is. It makes experimenting possible.

#6 steelheader

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Posted 20 July 2008 - 02:58 PM

The problem with comparing dogs to humans is this: humans have very efficient conjugation mechanism, and break down resveratrol before it reaches high blood serum levels. Dogs do not, and attain much higher levels with equivalent doses. So while I am hopeful resveratrol wil prove effective with cancer, I am by no means certain.


Dogs have a good deal on the diarrhea front as well, if my pup is typical. On a regimen of one gram per day for a 50 pound dog there has been no change in her stool.

#7 missminni

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Posted 20 July 2008 - 04:02 PM

The problem with comparing dogs to humans is this: humans have very efficient conjugation mechanism, and break down resveratrol before it reaches high blood serum levels. Dogs do not, and attain much higher levels with equivalent doses. So while I am hopeful resveratrol wil prove effective with cancer, I am by no means certain.


Dogs have a good deal on the diarrhea front as well, if my pup is typical. On a regimen of one gram per day for a 50 pound dog there has been no change in her stool.

so true. minni never got diahhrea either....even with 7 g. Her stool was looser however.

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#8 Hedgehog

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Posted 31 August 2008 - 04:21 PM

I think resveratrol can be beneficial for some cancers. At least this first article can be read two ways. It's an indicator that might be associated with shorter survival. Or maybe the cells are trying to use this enzyme to correct itself and is the reason for the + expression?

http://www.ncbi.nlm.nih.gov/pubmed/18724249?dopt=AbstractPlus

Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. <b>Positive expression of SIRT1 was seen in 74% (77/104) of patients.</b> In total DLBCL patients, <b>SIRT1 and p53 expression were significantly associated with shorter overall surviva</b>l (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.


Very interesting....

http://www.ncbi.nlm.nih.gov/pubmed/18723829?dopt=AbstractPlus

Tumors frequently develop resistance to cisplatin, a platinum drug used as a cornerstone of present-day chemotherapy regimens, significantly decreasing its usefulness in the clinic. Although it is known that<b> cisplatin</b>-<b>resistant </b>(CP-r) cancer cells commonly grow more slowly and exhibit reduced uptake of various compounds, including nutrients, the effect of tumor metabolism on cisplatin resistance is unclear. It was found that in CP-r cells, uptake of 2-deoxyglucose was reduced due to dysfunction and altered morphology of mitochondria compared with cisplatin-sensitive parental cancer cells. The CP-r cells overexpressed SIRT1, a histone deacetylase that plays a central role in DNA damage response and transcriptional silencing. Incubation of drug-sensitive cells in low glucose medium induced the expression of SIRT1 and increased cellular resistance to cisplatin. Reduced SIRT1 expression by a SIRT1 SMART small interfering RNA duplex sensitized the >20-fold resistant CP-r cells to cisplatin treatment 1.5- to 2-fold, and SIRT1 overexpression by SIRT1 cDNA transfection increased cisplatin resistance in cisplatin-sensitive cells by 2- to 3-fold. Our findings therefore suggest that reduced glucose use and altered mitochondrial metabolism mediated by <b>SIRT1 is one of several alterations that contribute to cellular resistance to cisplatin.</b> (Mol Cancer Res 2008;6(9):OF1


SIRT1 is one of several alterations that contribute to cellular resistance to cisplatin.






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