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Old 07-06-2006, 01:50 PM   #41
R.B.
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NSAIDS plus DHA better than NSAIDS in melanoma

More straws in the wind.

Melanoma this time.

Another wild thought on the edge - As a short term measure? - Boost threes, NSAIDS to block six and force body to use up six reserves and at the same time cut down omega six intake ???

All significant changes to diet should be discussed with your medical advisor.

RB


Department of Biology, The Chinese University of Hong Kong, Shatin, China. chimingchiu@graduate.hku.hk

Recent studies have suggested the inhibition of cyclooxygenase-2 (COX-2) as strategy to prevent colorectal cancer. In this study, the cytostatic and cytotoxic effects of different non-steroidal anti-inflammatory drugs (NSAIDs), all of them are reported COX inhibitors, were investigated in human skin melanoma A-375 cells. Using BrdU-cell proliferation assay, we showed that 50 and 100 microM of celecoxib (CEL) reduced proliferation of the melanoma cells at 72-h incubations by 34.0% and 82.7%, respectively. As determined by Toxilight-cytotoxicity assay, the drug was only toxic to the cancer cells at 100 microM. Indomethacin (IND) also inhibited the cell proliferation by about 40% at 240 and 480 pM and was only slightly toxic to the melanoma. Neither aspirin (ASP) nor piroxicam (PIR) exhibited cytostatic or cytotoxic effect on the cancer cells. Combinatory effects of the above NSAIDs with dietary docosahexaenoic acid (DHA) on inhibiting growth of the melanoma cells were further elucidated. Each of the NSAIDs, at doses 10-480 pM, was incubated simultaneously with the melanoma cells and 160 pM of DHA for 72 h. Results from MTT assay showed that both CEL and IND, starting from 20 microM. exhibited additive effects on the DHA-induced growth inhibition. ASP also enhanced the DHA-induced growth inhibition by 42.8% at 480 microM. To our surprise, although PRX did not suppress the melanoma growth, the drug at 40-240 microM enhanced the DHA-induced growth inhibition by 15.9-66.4%, respectively. Results from these studies suggest that the anticancer effects of NSAIDs may not be explained solely by their COX-inhibitory activities. Further studies are therefore required to understand their modes of action, before they could be used alone or in combinations with other agents for cancer chemoprevention.

PMID: 16507396 [PubMed - indexed for MEDLINE]

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Old 07-06-2006, 01:57 PM   #42
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NSAIDS DHA and PROSTATE CANCER

The same principle DHA plus NSAID shows possibility in Prostate Cancer.

RB


http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15703837

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA. nnarayan@env.med.nyu.edu

Epidemiological studies have provided evidence that high intake of saturated fat and/or animal fat increases the risk of prostate cancer, but on the other hand, diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), present in fish oils were found to reduce the risk. There are indications of an increased expression of immunoreactive PPARgamma in prostatic intraepithelial neoplasia (PIN) and prostate cancer, suggesting that PPARgamma ligands may exert their own potent anti-proliferative effect against prostate cancer. The experimental evidence for the role of cyclooxygenase-2 (COX-2) in prostate carcinogenesis is well established through several investigations. It clearly suggests the need for development of strategies to inhibit COX-2 mediated prostate carcinogenesis. However, administration of high doses of COX-2 inhibitors, such as celecoxib, over longer periods may not be devoid of side effects. We assessed the efficacy of DHA and celecoxib individually and in combination at low doses in three prostate cancer cell lines (LNCaP, DU145 and PC-3) measuring cell growth inhibition and apoptosis, and on the levels of expression of COX-2, nuclear factor-kappaB (NF-kappaBp65), and nuclear receptors, such as PPARgamma and retinoid X receptors (RXR), all of which presumably participate in prostate carcinogenesis. A 48-h incubation of prostate cancer cells with 5 microM each of DHA or celecoxib induced cell growth inhibition and apoptosis, and altered the expression of the above molecular parameters. Interestingly, the modulation of these cellular and molecular parameters was more pronounced in cells treated with low doses of DHA and celecoxib (2.5 microM each) in combination than in cells treated with the higher doses of individual agents. In conclusion, the present study demonstrates for the first time that a combination of lower doses of the n-3 PUFA, and DHA with the selective COX-2 inhibitor celecoxib effectively modulates the above cellular and molecular parameters that are relevant to prostate cancer. This raises the intriguing prospect that the use of low doses of a COX-2 inhibitor in combination with an n-3 PUFA could be a highly promising strategy for prostate cancer chemoprevention while minimizing undesired side effects.

PMID: 15703837 [PubMed - indexed for MEDLINE]
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Old 07-06-2006, 02:04 PM   #43
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NSAIDS OMEGA 3's and COLON CANCER

And Colon Cancer...

A subject for for your oncs?

RB


Chemoprevention and Nutritional Carcinogenesis Program, Institute for Cancer Prevention, American Health Foundation-Cancer Center, Valhalla, NY, USA.

To develop efficient synergistic or additive combinations of chemopreventive and nutritional agents to reduce the risk of colon cancer, experiments were designed to test the application of a selective cyclooxygenase-2 (COX-2) inhibitor together with dietary omega-3 polyunsaturated fatty acids (PUFAs), such as decosahexaenoic acid (DHA). Thus, individual application of celecoxib, a COX-2 inhibitor, DHA, a omega-3 PUFA, and combinations of both were tested for their effectiveness using cell proliferation, apoptosis, and COX-2 expression as markers in the human colon cancer HCA-7 cell line. HCA-7 cells exposed to various subtoxic doses of celecoxib, DHA, or combinations of both were analyzed for inhibition of cell proliferation by trypan blue exclusion and proliferating cell nuclear antigen methods, induction of apoptosis by 4',6-diamidino-2-phenylindole method, and COX-2 by reverse transcription-PCR and Western blot analysis. In addition, we examined the inhibitory potential of celecoxib and DHA on (14)C-arachidonic acid metabolism mediated by COX-2 in the HCA-7 cell line. We found that treatment with celecoxib (50-150 micro M) or DHA (150-225 micro M) individually induces apoptosis and inhibits cell proliferation only at high concentrations in HCA-7 cell lines. A synergistic effect was observed on induction of apoptosis and inhibition of proliferation when cells were exposed to low doses of celecoxib (50-100 micro M) together with DHA (75 micro M). At high concentrations, celecoxib and DHA blocked the increase in COX-2 protein and mRNA expression in HCA-7 cells. Importantly, the inhibition of COX-2 expression was more pronounced in cells treated with low-dose combinations than with individual agents at high concentrations. In addition, celecoxib and DHA at low-dose levels inhibited (14)C-arachidonic acid metabolism (50-85%, P < 0.0001) leading to very low levels of type 2 series prostaglandin formation. These findings provide the basis for the development of combinations of low-dose regimens of a COX-2 inhibitor and omega-3 PUFAs such as DHA for the prevention and treatment of colon cancer. We are currently testing this concept in preclinical models.

PMID: 14985462 [PubMed - indexed for MEDLINE]
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Old 07-06-2006, 02:14 PM   #44
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Smile omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

Combined with the above I think this might even merit a smiley.


Would omega three plus low dose COX blocker yield even better result.


Maybe deliver as intravenous lipid feed plus cox blocker ?


As ever changes to diet should be discussed with your medical advisor.

RB


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. ydenkins@vetmed.lsu.edu

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel invasion. Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

PMID: 15772428 [PubMed - indexed for MEDLINE]

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Old 07-06-2006, 02:32 PM   #45
R.B.
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n-3 Polyunsaturated fatty acids (PUFAs) inhibit microvessels in mammary tumours

Busy little things these n-3s ?

RB




http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15358633

Institute of General Pathology, Catholic University, L.go F. Vito, 1, 00168 Rome, Italy. g.calviello@rm.unicatt.it

n-3 Polyunsaturated fatty acids (PUFAs) inhibit the development of microvessels in mammary tumors growing in mice. Human colorectal tumors produce vascular endothelial growth factor (VEGF) whose expression is up-regulated in tumor cells by both cyclooxygenase-2 (COX-2) and PGE(2) and directly correlated to neoangiogenesis and clinical outcome. The goal of this study was to examine the capability of n-3 PUFAs to regulate VEGF expression in HT-29 human colorectal cells in vitro and in vivo. Constitutive VEGF expression was augmented in cultured HT-29 cells by serum starvation and the effects of eicosapentaenoic (EPA) or docosahexaenoic acid (DHA) on VEGF, COX-2, phosphorylated extracellular signal-regulated kinase (ERK)-1 and -2 and hypoxia-inducible-factor 1-alpha (HIF-1alpha) expression and PGE(2) levels were assessed. Tumor growth, VEGF, COX and PGE(2) analysis were carried out in tumors derived from HT-29 cells transplanted in nude mice fed with either EPA or DHA. Both EPA and DHA reduced VEGF and COX-2 expression and PGE(2) levels in HT-29 cells cultured in vitro. Moreover, they inhibited ERK-1 and -2 phosphorylation and HIF-1alpha protein over-expression, critical steps in the PGE(2)-induced signaling pathway leading to the augmented expression of VEGF in colon cancer cells. EPA always showed higher efficacy than DHA in vitro. Both fatty acids decreased the growth of the tumors obtained by inoculating HT-29 cells in nude mice, microvessel formation and the levels of VEGF, COX-2 and PGE(2) in tumors. The data provide evidence that these n-3 PUFAs are able to inhibit VEGF expression in colon cancer cells and suggest that one possible mechanism involved may be the negative regulation of the COX-2/PGE(2) pathway. Their potential clinical application as anti-angiogenic compounds in colon cancer therapy is proposed.

PMID: 15358633 [PubMed - indexed for MEDLINE]
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Old 07-08-2006, 10:44 AM   #46
R.B.
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65% of pregnant canadian women below minimum omega three recommendation

Thought provoking.

Particularly when considered in light of Canadian trial on trans fats in breast milk etc above - implications for wider community - etc.

RB

Directly Quantitated Dietary (n-3) Fatty Acid Intakes of Pregnant Canadian Women Are Lower than Current Dietary Recommendations1

http://jn.nutrition.org/cgi/content/full/135/2/206

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Old 07-08-2006, 03:08 PM   #47
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Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian

This is interesting in that it gives an idea as to dietary fat profiles, and underlines the low levels of DHA EPA.

From the previous post some of this will be trans.

There are suggestions that the preference given to the omega three pathway drops after the 3 6 ratio gets lower than 1:7.

IF women are getting insufficient DHA EPA to provide for their infants, and the pathway for fabrication are restricted by trans fats, poor three six ratios, cox blockers in some instances aspirin, any inherent deficiency etc they can only provide by drawing on their own reserves.

Trials suggests sources include the brain. (A factor in post natal depression?).

Other trials suggest that in the absence of replenishment this reduction in the mothers stores becomes a trend.

The table below is helpful in that it gives an indication of the long chain three six balance in meat eggs fish etc.

RB


Intakes of essential n-6 and n-3 polyunsaturated fatty acids among pregnant Canadian women1,2,3

http://www.ajcn.org/cgi/content/full/77/2/473

http://www.ajcn.org/cgi/content/full/77/2/473/T3

AA EPA DHA
mg/d
Fatty fish 3.5 0.6 (0.0–16.0) 9.1 3.3 (0.0–88.1) 83.5 14.4 (0.0–384.4)
Lean fish 3.1 0.3 (0.0–10.7) 14.9 1.6 (0.0–51.6) 27.4 3.0 (0.09–5.3)
Shellfish and crustaceans 7.6 1.2 (0.0–38.8) 16.9 2.7 (0.0–86.2) 14.7 2.4 (0.0–75.0)
Total fish and seafood 14.2 1.8 (0.0–50.8) 50.4 6.1 (0.0–58.7) 125.7 17.0 (0.0–426.5)
Chicken 34.6 3.8 (0.0–120.1) 3.8 0.4 (0.0–13.3) 6.7 0.7 (0.0–23.2)
Turkey 24.3 5.7 (0.0–188.9) 1.1 0.2 (0.0–8.2) 3.8 0.9 (0.0–29.1)
Total poultry 58.8 6.5 (0.0–202.9) 4.9 0.5 (0.0–13.3) 10.4 1.1 (0.0–31.8)
Beef and beef products 20.5 0.2 (0.0–63.1) 15.7 1.6 (0.0–4.8) 2.7 0.3 (0.0–8.5)
Pork and pork products 14.4 1.8 (0.0–49.1) 1.4 0.1 (0.0–4.9) 1.4 0.1 (0.0–4.9)
Lamb and lamb products 1.5 0.3 (0.0–8.7) 1.2 0.3 (0.0–6.7) 0.4 0.1 (0.0–2.2)
Total meat 36.4 3.3 (0.0–97.4) 18.4 1.8 (0.0–43.5) 4.6 0.4 (0.0–11.9)
Eggs 32.7 3.6 (0.0–82.7) 0.31 0.04 (0.0–0.9) 14.6 1.6 (0.0–37.0)
Total 112.0 7.8 (0.5–275.8) 73.5 6.3 (0.4–186.8) 153.6 17.9 (17.7–518.6)

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Old 07-08-2006, 05:13 PM   #48
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I don't mean to be a bad girl here, but I hope to provoke thought on this issue of diet. Diet plagues me... I have had a very good diet for a long time, and still managed to get breast cancer at age 28 because of my genetics. Is it possible that people in other countries have better genetics because they are in a different gene pool - per say? Over time, I have heard that if you take a chinese woman to the US and feed her american foods, that she will develop the same risk for breast cancer, so I feel compelled that there may be genetic factors that supercede dietary factors. Meaning, if you have bad genetics, no matter what you do, you will get cancer. If you have good genetics, you may be able to sway your risk if you eat better. But do you have any way of knowing what your risk are if you could potentially get a bad genetic combination at conception? I think it's always a good idea to eat right, but I wouldn't hold out my hopes on it preventing cancer or curing our cancer.
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Old 07-09-2006, 04:27 AM   #49
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From the little I have read on genetics there are clearly those who carry higher risks of particular diseases.

Dietary change is not going to eliminate disease but can be a significant modifier of risk. For example I have previously posted this tale but I have read that vascular / heart disease was so rare at the turn of the 1900s that students would rush to see a case as they did not want to miss the opportunity.

Around 70 % is the figure most generally quoted for the increase of western diseases over those with more culturally traditional diets, and lack of access to refined western food.

Diet can and does manipulate expression of genes by significant amounts. ("Expression" Our gene pool is largely similar but we use or expression different amounts according to environmental factors - Most have the same basic ingredients in the kitchen cupboard but they "express" it in their cooking in different quantities according to cultural factors. )

I have previously tried to formulate a scenario where those who considered themselves on a very healthy diet high in polyunsaturates low in fat etc in fact had high omega six compared to omega three. As I keep reiterating it is not about absolute quantities it is about balance.

All of the evidence is that diet does pay a large part in the overall risk factor when looking at issues on a population wide basis.

BC is a dreadful disease. I cannot begin to understand how you feel having contracted it so young. If you have been healthy it must feel like a double whammy.

I too have read lots of health books etc, juiced, etc for many years and it was only about a year ago that I realised that my avid pursuit of polyunsaturates was actually very bad news as it was pushing my omega three six balance way out from the ideal of somewhere around one to one ( or may be even 2:1). I suspect I was not the only one falling into this trap.


My limited field of knowledge relates to what I have read on fats. I would urge all to look VERY closely at their dietary intake in terms of balancing the omega threes and sixes. This can only be done by knowing or looking up the approximate fat contents of the foods you eat until you get to have an reasonable idea of what you are likely to be consuming. For most on a western diet omega three supplementation will be needed. Sources are limited so this is likely to include flax seed and oily fish or fish oil, or algae based products for vegetarians.


RB

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Old 07-09-2006, 05:57 AM   #50
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Here is a link where change expression of genes in the brain for rate fed high fish oil or high perilla diets is shown by reference to a standard diet.

The trials are looking at the impact of fats on the brain ageing alzheimer's etc. This is one of many in the general subject area.

I have no idea as to the significance of various genes.

I just post the chart to try and illustrate the point that changes in diet and particularly fats can alter the ways our bodies work even in the way we use the genetic ingredients available to us.

Significantly

In numerous subtle ways

At very fundamental levels

Different recipe for different cakes some of which will work and some which will not. I suspect nature is no different from cookery - go beyond certain parameters and your cake mix will not work.


http://www.pnas.org/cgi/content/full/99/5/2619/T5


and the link to the trial


http://www.pnas.org/cgi/content/full...7faf8fdb716645

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Old 07-09-2006, 03:21 PM   #51
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I guess my point was that I watched my mother "juice" herself to her grave - thinking it would extend her life. She got 4 months, and the doctors thought she would have had 6. She was a healthy 33 year old woman with a good BMI and on a healthy food kick like you wouldn't believe... Then her son died at age 12 from Stage 4 Rhabdomyosarcoma, that was originally Stage 2 when he was 5. Then I got cancer at 28, early stage 2a and I was healthy... Then my daughter got cancer at age 5, stage 2 Adrenal Cortical Carcinoma... then she had a local recurrance. She was our healthiest eater, and of course at a normal BMI. Then I had a recurrance, and BOOM stage 4 for me. Then we found out that we had Li-Fraumeni syndrome. Back in 1991, they told us our p53 gene was normal. Now they told us our p53 gene was mutated. The far end of the gene was where the mutation was, which they didn't know about in 1991. So I just hesitate to hear so many hold out hope that diets were the cause of their cancers. For years I tried to "do the right thing" to prevent cancer. I asked the doctor in tears, why I couldn't have prevented it when I was doing so many things to prevent it. He said "Your risk was 80% of developing cancer before the age of 50. In your family, I would guess that it would be more like 80% before the age of 30. With odds like that, diet wouldn't prevent your cancer. I've seen hundreds people try to prevent cancer with diet, knowing they had the 'cancer gene', and failure was almost 100%." His field of study was Brazilian children with adrenal cortical carcinoma with a p53 mutation called Arg337Cys. He also studies genetic retinal cancer that almost 100% get before the age of 5 with the gene. You can probably see now why I am on the other side of the fence. It failed for me, my mother, my brother, my daughter, and probably will fail for my other 2 children, and hundreds of patients of my daughter's doctor. We have all tried to eat the "right diet" and it has failed us all. I think the only case I know of is an author with stage 4 breast cancer, named Jane Plant, who has been cancer free for a while now after practically eliminating cow and dairy products. And then I guess I know about Lance Armstrong, but he ate like 5 apple fritters every day...
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Old 07-09-2006, 04:14 PM   #52
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Who Knows???

My husband has made vast improvements in his "heart health" after a heart attack 10 years ago. I have watched him exercise, eat "amazing things", and take a handful of supplements.

Now, I am working hard to eat right, exercise everyday, and take some vitamins and fish oil.

But I must confess that I don't have a clue whether it will help with my cancer. I just know when I eat those veggies and fruit and drink my tons of water, I feel better to fight the next fight!

I'm so glad that I have access to so many who are learning so much and are willing to share. Thanks a million!
ma
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Old 07-09-2006, 04:24 PM   #53
R.B.
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Thank you for your post.

Life has certainly dealt you all a desperately difficult hand, and you appear to be dealing with it very bravely.

I very clearly understand your point and position.

I have never claimed diet will cure cancer. I have just suggested that on a population wide basis it will reduce risks for some, and that specifically that there are a significant number of trials implicating fat intake in cancer risk and inflammatory pathways etc.

I have also always said there that the commonly quoted figure of differential in "western" disease from non "western" populations is about 70%. This leaves a very large 30% for whom it would be reasonable to assume that diet if that is the factor has no effect.

I still hold to a position that there is evidence that balancing the omega threes and sixes will moderate the inflammatory pathways, and assist in maintaining the immune system, general health, and moderate risks based on the trials I have read.

Based on the trials being conducted research organisations are sufficiently interested to explore the impacts of lipids on health, and some products developed in consequence, some products being legislated against in some countries eg trans fats etc.

Again I understand your position, and can only begin to imagine your frustration. Please do not associate me with those that are holding diet as the only way to go, or who does not appreciate the huge advances in medicine.

There is room for both and it is important we do not lose sight that the body is immensely complex and has developed this complexity in relation to its environment and the limiting factors in that environment, and so much is simply not understood.

I wish I had the knowledge and expertise to relate what I have read over the last year to your very specific circumstances but I don't.

I have not begun to walk in your shoes and experience the see-saw of hurt and anguish that you must have been through and continue to face.

Thank you for your post. It is important for all of us to know and try and understand if that is ever possible the impossible difficulties in life that many have to face.

RB


PS please find below the results of a search on the ncbi site for "p53 gene and fats" which might suggest fats have a bearing on P53 activity which may or may not be relevant in your circumstances just in case of any interest to you or your doctor.


http://www.ncbi.nlm.nih.gov/entrez/q...arch&DB=pubmed

1: Wu B, Iwakiri R, Ootani A, Tsunada S, Fujise T, Sakata Y, Sakata H, Toda S, Fujimoto K. Related Articles, Links
Free Full Text Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.
Exp Biol Med (Maywood). 2004 Nov;229(10):1017-25.
PMID: 15522837 [PubMed - indexed for MEDLINE]

2: Chi TY, Chen GG, Lai PB. Related Articles, Links
Abstract Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells.
Cancer J. 2004 May-Jun;10(3):190-200.
PMID: 15285929 [PubMed - indexed for MEDLINE]

3: Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS. Related Articles, Links
Abstract Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.
Mutat Res. 2003 Oct 29;531(1-2):25-36. Review.
PMID: 14637245 [PubMed - indexed for MEDLINE]

4: Hanibuchi M, Sone S. Related Articles, Links
No abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2002 May;60 Suppl 5:63-6. Review. Japanese. No abstract available.
PMID: 12101751 [PubMed - indexed for MEDLINE]

5: Shabany K, Chiu PC, Raghian A, Chang KW, Solt DB. Related Articles, Links
Abstract Rapid in vivo assay for topical oral cancer chemopreventive agents.
Int J Oncol. 2002 Jul;21(1):159-64.
PMID: 12063563 [PubMed - indexed for MEDLINE]

6: Perjesi P, Pinter Z, Gyongyi Z, Ember I. Related Articles, Links
Abstract Effect of rancid corn oil on some onco/suppressor gene expressions in vivo. A short-term study.
Anticancer Res. 2002 Jan-Feb;22(1A):225-30.
PMID: 12017293 [PubMed - indexed for MEDLINE]

7: Diggle CP, Pitt E, Roberts P, Trejdosiewicz LK, Southgate J. Related Articles, Links
Free Full Text N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function.
J Lipid Res. 2000 Sep;41(9):1509-15.
PMID: 10974058 [PubMed - indexed for MEDLINE]

8: Yano S, Sone S. Related Articles, Links
Abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2000 May;58(5):1017-22. Review. Japanese.
PMID: 10824542 [PubMed - indexed for MEDLINE]

9: Taylor DD, Gercel-Taylor C, Weese JL. Related Articles, Links
Abstract Modulation of colon tumor oncogene expression by cancer patient-derived lipids.
J Surg Oncol. 1996 Sep;63(1):46-51.
PMID: 8841466 [PubMed - indexed for MEDLINE]

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Old 07-09-2006, 05:38 PM   #54
mamacze
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Lightbulb Thanks Rhonda, great nutritional links!

A bit late Rhonda, but thank you for your nutritional links...teamed up with RB's data, it was extremely helpful. My sis in law has scleroderma and this information will be helpful to her as well. You and RB are sharing a real wealth of information and "food" for thought!
Love Kim from CT

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Old 07-10-2006, 03:05 AM   #55
R.B.
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Julierene.

Re P53 gene mutation and fats.

The technicalities are beyond me but the generality seems to be that oxidised fats and particularly omega 6 (AA archidonic acid is a product of omega six.) can induce gene mutation, AND it seems to suggest the body may have some ability to repair them...? (thanks I had not seen anything about this subject before)

"HNE-dG adducts were detected exclusively in incubations with AA."

"It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers,"

"Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation."





One for your doctor if of interest?


RB







http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Biochemistry. 2003 Jul 1;42(25):7848-54. Related Articles, Links
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Mutational spectrum and genotoxicity of the major lipid peroxidation product, trans-4-hydroxy-2-nonenal, induced DNA adducts in nucleotide excision repair-proficient and -deficient human cells.

Feng Z, Hu W, Amin S, Tang MS.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.

trans-4-Hydroxy-2-nonenal (4-HNE), a major product of lipid peroxidation, is able to interact with DNA to form 6-(1-hydroxyhexanyl)-8-hydroxy-1,N(2)-propano-2'-deoxyguanosine (4-HNE-dG) adducts, but its genotoxicity and mutagenicity remain elusive. It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers, particularly in hepatocellular carcinoma. This G.C to T.A transversion at codon 249, however, has been thought to be caused by etheno-DNA adducts induced by the endogenous metabolite of 4-HNE, 2,3-epoxy-4-hydroxynonanal. We have recently found that 4-HNE preferentially forms 4-HNE-dG adducts at the GAGG*C/A sequence in the p53 gene including codon 249 (GAGG*C). Our finding supports the possibility that G.C to T.A mutations at codon 249 may be induced by 4-HNE-dG adducts. To investigate this possibility, we determined the mutational spectrum induced by 4-HNE-dG adducts in the supF gene of shuttle vector pSP189 replicated in human cells. We have found that 4-HNE-dG adducts are mutagenic and genotoxic in human cells, and that G.C to T.A transversions are the most prevalent mutations induced by 4-HNE-dG adducts. Furthermore, 4-HNE-dG adducts induce a significantly higher level of genotoxicity and mutagenicity in nucleotide excision repair (NER)-deficient human and Escherichia coli cells than in NER-proficient cells, indicating that NER is a major pathway for repairing 4-HNE-dG adducts in both human and E. coli cells. Together, these results suggest that 4-HNE-dG adducts may contribute greatly to the G.C to T.A mutation at codon 249 of the p53 gene, and may play an important role in carcinogenesis.

PMID: 12820894 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Chem Res Toxicol. 2002 Mar;15(3):367-72. Related Articles, Links
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Formation of cyclic deoxyguanosine adducts from omega-3 and omega-6 polyunsaturated fatty acids under oxidative conditions.

Pan J, Chung FL.

Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, Valhalla, New York 10595, USA.

The discovery of the cyclic 1,N(2)-propanodeoxyguanosine adducts of acrolein (Acr), crotonaldehyde (Cro), and t-4-hydroxy-2-nonenal (HNE) as endogenous DNA lesions from lipid peroxidation has raised questions regarding the role of different types of fatty acids as sources for their formation. In this study, we carried out reactions at pH 7 and 37 degrees C with deoxyguanosine 5'-monophosphate and omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA), linolenic acid (LNA), and eicosapentaenoic acid (EPA); or omega-6 PUFAs, including linoleic acid (LA) and arachidonic acid (AA), each in the presence of ferrous sulfate. The formation of Acr, Cro, and HNE-derived 1,N(2)-propanodeoxyguanosine adducts (Acr-, Cro-, and HNE-dG) in the incubation mixture was determined by reversed-phase HPLC analysis. The results showed that Acr and Cro adducts are primarily derived from omega-3 PUFAs, although Acr adducts are also formed, to a lesser extent, from oxidized AA and LA. HNE-dG adducts were detected exclusively in incubations with AA. The kinetics of the formation of these adducts was determined during incubations for 2 weeks and 5 days. The rate of Acr adduct formation was about 5-10-fold that of Cro adducts, depending on the type of PUFAs, and the rate of formation of HNE adducts from AA was also considerably slower than that of Acr adducts. Unlike other cyclic adducts, the formation of Acr adducts was independent of types of PUFAs, but its yield was proportional to the number of double bonds in the fatty acid. Only one of the isomeric Acr adducts was detected, and its stereoselective formation is consistent with that observed previously in vivo. Two previously unknown cyclic adducts, one derived from pentenal and the other from heptenal, were also detected as products from omega-3 and omega-6 fatty acids, respectively. This study demonstrated the specificity for the formation of the cyclic adducts of Acr, Cro, and HNE and other related enals by oxidation of omega-3 and omega-6 PUFAs. These results may be important for the understanding of the specific roles of different types of fatty acids in tumorigenesis.


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Mutat Res. 2003 Oct 29;531(1-2):25-36. Related Articles, Links
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Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.

Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS.

Division of Carcinogenesis and Molecular Epidemiology, Institute for Cancer Prevention, American Health Foundation Cancer Center, Valhalla, NY 10595, USA. fchung@ifcp.us

The cyclic 1,N(2)-propanodeoxyguanosine adducts, derived from alpha,beta-unsaturated aldehydes or enals, including acrolein (Acr), crotonaldehyde (Cro), and trans-4-hydroxy-2-nonenal (HNE), have been detected as endogenous DNA lesions in rodent and human tissues. Collective evidence has indicated that the oxidative metabolism of polyunsaturated fatty acids (PUFAs) is an important pathway for endogenous formation of these adducts. In a recent study, we examined the specific role of different types of fatty acids, omega-3 and omega-6 PUFAs, in the formation of cyclic adducts of Acr, Cro, and HNE. Our studies showed that the incubation of deoxyguanosine 5'-monophosphate with omega-3 or omega-6 fatty acids under oxidative conditions in the presence of ferrous sulfate yielded different amounts of Acr, Cro, and HNE adducts, depending on the types of fatty acids. We observed that Acr- and Cro-dG adducts are primarily formed from omega-3, and the adducts derived from longer chain enals, such as HNE, were detected exclusively from omega-6 fatty acids. Acr adducts are also formed from omega-6 fatty acids, but to a lesser extent; the yields of Acr adducts are proportional to the number of double bonds present in the PUFAs. Two previously unknown cyclic adducts, one from pentenal and the other from heptenal, were detected as products from omega-3 and omega-6 fatty acids, respectively. Because omega-6 PUFAs are known to be involved in the promotion of tumorigenesis, we investigated the role of HNE adducts in p53 gene mutation by mapping the HNE binding to the human p53 gene with UvrABC nuclease and determined the formation of HNE-dG adducts in the gene. The results showed that HNE-dG adducts are preferentially formed in a sequence-specific manner at the third base of codon 249 in the p53 gene, a mutational hotspot in human cancers. The DNA repair study using plasmid DNA containing HNE-dG adducts as a substrate in HeLa cell extracts showed that HNE adducts are readily repaired, and that nucleotide excision repair appears to be a major pathway involved. Together, results of these studies provide a better understanding of the involvement of different PUFAs in DNA damage and their possible roles in tumorigenesis.

Publication Types:

* Review


PMID: 14637245 [PubMed - indexed for MEDLINE]

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Old 07-10-2006, 06:42 AM   #56
Mary Anne in TX
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Smile Simple explanation of 6 to 3!

http://en.wikipedia.org/wiki/Omega-6_fatty_acid

This made it simple to me. I followed the other links on the page and found more good information to help me understand (at least these people's opinion) the importance of 6 to3. I'm still reading and I'm beginning to understand. I'm getting why my husband's health changed and the doctors thought he'd been on statins when he had just eaten and supplemented right. If he can do it, I can too. Thanks to all who keep making me learn!
ma

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Old 07-10-2006, 09:12 AM   #57
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The Blame Game

I just received my copy of "Cure" magazine, Summer issue Volume 5, Number 2 2006.

On page 14 there is an article entitled "The Blame Game, Moving past myriad rationales for cancer guilt"

Here is an excerpt from the article:

"Labels lead to guilt, which can be a huge burden for newly diagnosed patients because it lurks around almost every turn. We feel guilt about causing our cancer, about having our families go through it, about not being able to do what we did before, if only for a short time. Then there are the financial burdens, and the list goes on. Particular guilt comes with behaviors linked to cancer: smoking, sun overexposure, a common sexually transmitted disease and obesity.

It's not unusual to try and find an answer to why cancer occurs, says Kymberley Bennett, PhD, assistant professor of psychology at Indiana State University in Terre Haute. "With any stressor, and cancer is a big stressor, we try to figure out why it happened to us," she says. "Ultimately, we want to try to identify something that we can, in turn, control."

And stressing about the cause of cancer can lead to additional stress, says Dr. Bennett, who recently led a study of 115 women newly diagnosed with breast cancer that showed that those who blamed themselves for their cancer showed higher levels of distress than those who didn't. The findings also suggested that self-blame negatively affected a patient's ability to psychologically adjust throughout the year following diagnosis."

I think the danger here is that of blaming the victim. The unpalatable truth is, no one knows what causes cancer. Period.

R.B. may be correct in his(?) assertions that Omega 3's and 6's play some sort of a role in cancer development/treatment. The fact is, however, that despite all of our very best efforts many of us here on this forum will die untimely deaths and that is not our fault. I can't help but bristle whenever I catch a nasty whif of blame.

Yes, R.B., I am taking Fish Oil supplements. I will probably die from breast cancer anyway.

I admire your dedication to research, however, perhaps on your wife's behalf? Unless I am mistaken, and you a a female. Clearly you are a warrior, and every country needs its warriors, whatever your sex may be.

Mary
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Old 07-10-2006, 10:23 AM   #58
RhondaH
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Angry I don't see WHAT difference it makes as to RB's sex...

a wealth of information comes from this source and I for one am PISSED off as to the negativity that comes out on the board (we have lost a lot of good members...Gina, ALMOST lost AL and many others...due to people not just voicing their opinion and offering constructive criticism, but adding unnecessary comments) not to mention that there ARE male breast cancer survivors on the board. I belive that cancer has MANY causes (ie, smoking, poor diet, genetics, environment, lack of exercise, etc.) and while some of us may have gotten it because of 1 cause, others may have gotten it for another (or MANY causes). I choose to do EVERYTHING I can to not get it again (surgery, drugs, diet, exercise, yoga, prayer) and do offer myself 1 cheat day a week so as to not feel deprived. Mary, you go ahead and die of cancer (since that's what you choose to believe), but I and all the OTHER survivors choose to LIVE, some WITH cancer and others WITHOUT. Understand that there are SEVERAL people on the board who offer helpful information that have not had breast cancer, BUT they provide valuable information for those that do. I'm done.

Rhonda
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Rhonda

Dx 2/1/05, Stage 1, 0 nodes, Grade 3, ER/PR-, HER2+ (3.16 Fish)
2/7/05, Partial Mastectomy
5/18/05 Finished 6 rounds of dose dense TEC (Taxotere, Epirubicin and Cytoxan)
8/1/05 Finished 33 rads
8/18/05 Started Herceptin, every 3 weeks for a year (last one 8/10/06)

2/1/13...8 year Cancerversary and I am "perfect" (at least where cancer is concerned;)


" And in the end, it's not the years in your life that count. It's the life in your years."- Abraham Lincoln

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Old 07-10-2006, 10:36 AM   #59
R.B.
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Thank you for your response.

Blame.

I apologise if my posts allow interpretation as blame. This is not in any way my intention. In life we are where we are - changing the past is not an option.


Control.

It is widely accepted that diet can influence health.

IF improved diet gives people something they have some small sense of control over it seems to me providing it is not obsessive that any sense of control must be good news.

If it achieve really positive benefit so much the better.


Implication of fats in cancer.

I am certain fats are implicated in the risk of some cancers and a wide number of other inflammatory based diseases, a number of issues of the nervous system including depression, as well as the immune system and general health. This is based on extensive reading of trials and the works of others. I would challenge anybody with the time to read what I have seen to come to a different conclusion

Gender.

Thanks for the compliment but definatively male, and always so.


Reasons for posting

Various including previous contact with BC sufferer, time on my hands, a need to be kept mentally occupied, a sense that the issue of fats is one that needs airing and the answers found, the implications are too enormous to ignore, and once you have glimpsed them they are not easily put back in the box. Answering questions make one check things, prompts new directions of thought, and gives one a sense of being of a little use.


Causes of cancer.

Human nature and the human dynamic. There is no "profit" (in the widest sense job opportunities, praise, conferences, funding etc.) in finding cancer causes, except where so obvious that they may involve the companies in a law suit. There have been suggestions that trans fats may be problematic for human consumption and yet the level of research on trans fats is moderate. For example a search on PubMed for trans fats and herceptin produces about 1700 for both but trans fats are consumed by probably billions and if as suggested they have negative health impacts the health / life cost will be truly huge huge in global terms. But there is not "profit" in researching / restricting trans fats and the situation will not change except by government intervention, public outcry, or sufficient potential medical downsides to justify the rsik of lawyers involving themselves in a group action. It is suggested they have no nutritional advantage so why are we conducting an experiment on global health?

I am not complaining about the amount of research on herceptin which is clearly making a huge difference to many women. I merely making the point that research and new products is "sexier" than prevention at very many levels - and the reality is we to give equal attention to both side of the problem cause and treatment. How that is to be achieved is another issue.


RB

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Old 07-10-2006, 02:33 PM   #60
marymary
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Of course, Rhonda, none of us on this board have chosen or ever would have chosen breast cancer. My friend Katie, who died two weeks back, never chose to have this horrible disease. I am not trying to be negative, but I did find the article in Cure magazine to be thought provoking.

Personally speaking, from the day I was diagnosed I asked myself "Why has this disease happened to me?". Further I wondered "and why did I get the worst variety (Her2Neu) of the worst?" I think it's probably the number one question we all ask ourselves. There's even a group called "Why Me?".

Like so many other sufferers, I would try just about anything to get a survival advantage. I am currently taking Herceptin, A/I's, have had radiation of my body and my brain. I even sought the help of a faith healer. Much to my husband's chagrin I am eating broccoli and salads like a rabbit and do take fish oil. But I can't believe that this is my fault. Or your fault. Or Katie's fault. Faults, I think, are character defects and not diseases.

This is a wonderful site and I have gained much support and inspiration here. For me the struggle and the challenge of breast cancer is not just physical, although it certainly is that. Today I am struggling with pain and this is a brand new thing for me. The bigger struggle is psychological, feeling like I have any control at all in a situation where there is none. Trying to move past anger that this has happened to me at all. Trying to feel like cancer is not my fault, that it is not something I have mistakenly brought on myself by some unknown means. Struggling to feel valuable to my family, my friends and society, that I still have value even though my body may be under assault. That I am inherently valuable, not only for the services that I provide but just by being me. I imagine that these struggles are not isolated to me alone, but are common to everyone who comes to the board. They are the tie that binds.

Mary
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