The traditional diet of Greece and cancer.

[R.B.]

Where n6 - n3 is high genes have been shon in trials to be regulated by a factor of 10. Genes regulated include HER2.

RB


"n-3 polyunsaturated fatty acids, usually provided as fish oil, modulate expression of a number of genes with such broad functions as DNA binding, transcriptional regulation, transport, cell adhesion, cell proliferation, and membrane localization. These effects, in turn, may significantly modify cell function, development and/or maturation."


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


1: Curr Opin Clin Nutr Metab Care. 2004 Mar;7(2):151-6.Click here to read Links
Polyunsaturated fatty acids and gene expression.

* Lapillonne A,
* Clarke SD,
* Heird WC.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2600, USA.

PURPOSE OF REVIEW: This review focuses on the effect(s) of n-3 polyunsaturated fatty acids on gene transcription as determined by data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneously and, hence, is a potentially powerful tool for studying the regulation of physiological mechanisms that are triggered or inhibited by nutrients. RECENT FINDINGS: Recent data generated with cDNA microarrays not only confirm the effects of n-3 polyunsaturated fatty acids on regulation of lipolytic and lipogenic gene expression as determined by more traditional methods but also emphasize the tissue specificity of this regulation. cDNA microarray experiments also have expanded our understanding of the role of n-3 polyunsaturated fatty acids in regulation of expression of genes involved in many other pathways. These include: oxidative stress response and antioxidant capacity; cell proliferation; cell growth and apoptosis; cell signaling and cell transduction. SUMMARY: The cDNA microarray studies published to date show clearly that n-3 polyunsaturated fatty acids, usually provided as fish oil, modulate expression of a number of genes with such broad functions as DNA binding, transcriptional regulation, transport, cell adhesion, cell proliferation, and membrane localization. These effects, in turn, may significantly modify cell function, development and/or maturation.

PMID: 15075705 [PubMed - indexed for MEDLINE]

[R.B.]

Generally beyond me and I do not have the time to delve but does this help explain why omega three has synergistic effects with some chemos etc.

At simplest level in colon cancer was shown to "In view of the central role of oncogenic Ras in the development of colon cancer, the finding that n-3 and n-6 PUFA differentially modulate Ras activation may partly explain why dietary fish oil protects against colon cancer development."

As far as this site goes just another hint that balancing the omega threes and sixes and having regard to omega three intake is worth consideration.

RB






http://ajpcell.physiology.org/cgi/co...ll/280/5/C1066


ABSTRACT

Ras proteins are critical regulators of cell function, including growth, differentiation, and apoptosis, with membrane localization of the protein being a prerequisite for malignant transformation. We have recently demonstrated that feeding fish oil, compared with corn oil, decreases colonic Ras membrane localization and reduces tumor formation in rats injected with a colon carcinogen. Because the biological activity of Ras is regulated by posttranslational lipid attachment and its interaction with stimulatory lipids, we investigated whether docosahexaenoic acid (DHA), found in fish oil, compared with linoleic acid (LA), found in corn oil, alters Ras posttranslational processing, activation, and effector protein function in young adult mouse colon cells overexpressing H-ras (YAMC-ras). We show here that the major n-3 polyunsaturated fatty acid (PUFA) constituent of fish oil, DHA, compared with LA (an n-6 PUFA), reduces Ras localization to the plasma membrane without affecting posttranslational lipidation and lowers GTP binding and downstream p42/44ERK-dependent signaling. In view of the central role of oncogenic Ras in the development of colon cancer, the finding that n-3 and n-6 PUFA differentially modulate Ras activation may partly explain why dietary fish oil protects against colon cancer development.

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

Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance.

* McCubrey JA,
* Steelman LS,
* Abrams SL,
* Lee JT,
* Chang F,
* Bertrand FE,
* Navolanic PM,
* Terrian DM,
* Franklin RA,
* D'Assoro AB,
* Salisbury JL,
* Mazzarino MC,
* Stivala F,
* Libra M.

Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA; Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA.

The Ras/Raf/MEK/ERK and PI3K/PTEN/AKT signaling cascades play critical roles in the transmission of signals from growth factor receptors to regulate gene expression and prevent apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf, PI3K, PTEN, Akt). Also, mutations occur at genes encoding upstream receptors (e.g., EGFR and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL) which transmit their signals through these cascades. These pathways interact with each other to regulate growth and in some cases tumorigenesis. For example, in some cells, PTEN mutation may contribute to suppression of the Raf/MEK/ERK cascade due to the ability of elevated activated Akt levels to phosphorylate and inactivate Raf-1. We have investigated the genetic structures and functional roles of these two signaling pathways in the malignant transformation and drug resistance of hematopoietic, breast and prostate cancer cells. Although both of these pathways are commonly thought to have anti-apoptotic and drug resistance effects on cells, they display different cell-lineage-specific effects. Induced Raf expression can abrogate the cytokine dependence of certain hematopoietic cell lines (FDC-P1 and TF-1), a trait associated with tumorigenesis. In contrast, expression of activated PI3K or Akt does not abrogate the cytokine dependence of these hematopoietic cell lines, but does have positive effects on cell survival. However, activated PI3K and Akt can synergize with activated Raf to abrogate the cytokine dependence of another hematopoietic cell line (FL5.12) which is not transformed by activated Raf expression by itself. Activated Raf and Akt also confer a drug-resistant phenotype to these cells. Raf is more associated with proliferation and the prevention of apoptosis while Akt is more associated with the long-term clonogenicity. In breast cancer cells, activated Raf conferred resistance to the chemotherapeutic drugs doxorubicin and paclitaxel. Raf induced the expression of the drug pump Mdr-1 (a.k.a., Pgp) and the Bcl-2 anti-apoptotic protein. Raf did not appear to induce drug resistance by altering p53/p21(Cip-1) expression, whose expression is often linked to regulation of cell cycle progression and drug resistance. Deregulation of the PI3K/PTEN/Akt pathway was associated with resistance to doxorubicin and 4-hydroxyl tamoxifen, a chemotherapeutic drug and estrogen receptor antagonist used in breast cancer therapy. In contrast to the drug-resistant breast cancer cells obtained after overexpression of activated Raf, cells expressing activated Akt displayed altered (decreased) levels of p53/p21(Cip-1). Deregulated expression of the central phosphatase in the PI3K/PTEN/Akt pathway led to breast cancer drug resistance. Introduction of mutated forms of PTEN, which lacked lipid phosphatase activity, increased the resistance of the MCF-7 cells to doxorubicin, suggesting that these lipid phosphatase deficient PTEN mutants acted as dominant negative mutants to suppress wild-type PTEN activity. Finally, the PI3K/PTEN/Akt pathway appears to be more prominently involved in prostate cancer drug resistance than the Raf/MEK/ERK pathway. Some advanced prostate cancer cells express elevated levels of activated Akt which may suppress Raf activation. Introduction of activated forms of Akt increased the drug resistance of advanced prostate cancer cells. In contrast, introduction of activated forms of Raf did not increase the drug resistance of the prostate cancer cells. In contrast to the results observed in hematopoietic cells, Raf may normally promote differentiation in prostate cells which is suppressed in advanced prostate cancer due to increased expression of activated Akt arising from PTEN mutation. Thus in advanced prostate cancer it may be advantageous to induce Raf expression to promote differentiation, while in hematopoietic cancers it may be beneficial to inhibit Raf/MEK/ERK-induced proliferation. These signaling and anti-apoptotic pathways can have different effects on growth, prevention of apoptosis and induction of drug resistance in cells of various lineages which may be due to the expression of lineage-specific factors.

PMID: 16854453 [PubMed - as supplied by publisher]


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


1: Cancer Res. 2006 Aug 1;66(15):7540-7547.Click here to read Links
p38{gamma} Mitogen-Activated Protein Kinase Integrates Signaling Crosstalk between Ras and Estrogen Receptor to Increase Breast Cancer Invasion.

* Qi X,
* Tang J,
* Loesch M,
* Pohl N,
* Alkan S,
* Chen G.

Departments of Radiation Oncology, Pharmacology and Experimental Therapeutics, and Pathology and Program in Molecular Biology, Loyola University Chicago, Maywood, Illinois and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Ras is believed to stimulate invasion and growth by different effector pathways, and yet, the existence of such effectors under physiologic conditions has not been shown. Estrogen receptor (ER), on the other hand, is both anti-invasive and proliferative in human breast cancer, with mechanisms for these paradoxical actions remaining largely unknown. Our previous work showed an essential role of p38gamma mitogen-activated protein kinase in Ras transformation in rat intestinal epithelial cells, and here, we show that p38gamma integrates invasive antagonism between Ras and ER to increase human breast cancer invasion without affecting their proliferative activity. Ras positively regulates p38gamma expression, and p38gamma in turn mediates Ras nonmitogenic signaling to increase invasion. Expression of the Ras/p38gamma axis, however, is trans-suppressed by ER that inhibits invasion and stimulates growth also by distinct mechanisms. Analysis of ER and its cytoplasmic localized mutant reveals that ER additionally binds to p38gamma protein, leading to its specific down-regulation in the nuclear compartment. A p38gamma-antagonistic activity of ER was further shown in a panel of breast cancer cell lines and was shown independent of estrogens by both ER depletion and ER expression. These results revealed that both Ras and ER use distinct pathways to regulate breast cancer growth and invasion, and that p38gamma specifically integrates their antagonistic activity to stimulate cell invasion. Selective targeting of p38gamma-dependent invasion pathways may be a novel strategy to control breast cancer progression. (Cancer Res 2006; 66(15): 7540-7).

PMID: 16885352 [PubMed - as supplied by publisher]

[R.B.]

This was interesting in that it confirms in rats that the breast does manifacture long chain fats eg DHA and not just accumulate them.

AND linoleic acid. the omega six mother fat in excess in the diet inhibits that ability.

WHICH ties in with what is being observed in general trends in mothers production of long chain fats in breast milk.

It links to BC in that one could postulate that the same characterisitics might be seen carried into proliferating cells....

RB



http://www.jlr.org/cgi/content/abstract/47/3/553


Synthesis of long-chain polyunsaturated fatty acids in lactating mammary gland
: role of {Delta}5 and {Delta}6 desaturases, SREBP-1, PPAR{alpha}, and PGC-1

Maricela Rodriguez-Cruz*,{dagger}, Armando R. Tovar§, Berenice Palacios-González§, Martha del Prado* and Nimbe Torres1,§

* Unidad de Investigación Médica en Nutrición, Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, DF 06720 Mexico
{dagger} Posgrado en Ciéncias Biológicas, Facultad de Medicina, UNAM, Mexico City, DF 04510, Mexico
§ Departamento de FisiologÃ*a de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, DF 14000 Mexico

Published, JLR Papers in Press, December 6, 2005.

1 To whom correspondence should be addressed. e-mail: nimbet@quetzal.innsz.mx

The purpose of this work was to study whether rat lactating mammary gland can synthesize PUFAs through the expression of {Delta}5 and {Delta}6 desaturases ({Delta}5D and {Delta}6D), whether these enzymes are regulated by the transcription factors sterol-regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) and the coactivator peroxisome proliferator-activated receptor {gamma} coactivator 1ß (PGC-1ß), and whether these desaturases are regulated by the lipid concentration in the diet. The results showed that on day 12 of lactation, ~35% of the linoleic acid in the diet, which is the precursor of PUFAs, is transferred to the mammary gland. There was expression of {Delta}5D and {Delta}6D in mammary gland, and it was regulated by the corn oil content in the diet. The higher the corn oil content in the diet, the lower the expression of both desaturases. Induction of {Delta}5D and {Delta}6D was associated positively with similar changes in SREBP-1 and PGC-1ß. Expression of PPAR{alpha} was barely detected and was not affected by the corn oil content in the diet, whereas PGC-1ß expression increased as the corn oil in the diet increased. These results indicate that the lactating mammary gland has the capacity to synthesize PUFAs and can be regulated by the lipid content in the diet.

Supplementary key words sterol-regulatory element binding protein 1 • peroxisome proliferator-activated receptor {alpha} • peroxisome proliferator-activated receptor {gamma} coactivator 1

[R.B.]

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


1: J Dent Res. 2006 Jul;85(7):648-52.Click here to read Links
Omega-3 Fatty Acid effect on alveolar bone loss in rats.

* Kesavalu L,
* Vasudevan B,
* Raghu B,
* Browning E,
* Dawson D,
* Novak JM,
* Correll MC,
* Steffen MJ,
* Bhattacharya A,
* Fernandes G,
* Ebersole JL.

Center for Oral Health Research, College of Dentistry, 159 HSRB, University of Kentucky, Lexington, KY 40536-0305, USA; and.

Gingival inflammation and alveolar bone resorption are hallmarks of adult periodontitis, elicited in response to oral micro-organisms such as Porphyromonas gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary supplementation would modulate inflammatory reactions leading to periodontal disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6 FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3 FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses demonstrated that rats were orally colonized by P. gingivalis; increased IgG antibody levels substantiated this infection. P. gingivalis-infected rats treated with omega-3 FA had significantly less alveolar bone resorption. These results demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating alveolar bone resorption following P. gingivalis infection, and supported that omega-3 FA may be a useful adjunct in the treatment of periodontal disease. Abbreviations: PUFA, polyunsaturated fatty acid; EPA, eicosapentanoic acid; DHA, docosahexanoic acid; and PCR, polymerase chain-reaction.

PMID: 16798867 [PubMed - in process]

[R.B.]

This is a useful and thought provoking article on those looking at their hormone levels in relation to BC..

"Recent prospective studies have provided strong evidence that the risk of developing breast cancer in postmenopausal women is increased by high serum levels of testosterone and estradiol, low levels of sex hormone-binding globulin, and, hence, high circulating levels of free steroid sex hormones (1, 2, 3, 4, 5, 6, 7) . Evidence is accumulating that Western dietary habits contribute this high-risk hormonal profile, but the efficacy of changes in diet in reducing the availability of sex hormones has not been sufficiently investigated."

The trial looks at the impact of some dietary changes on hormone levels.

RB


http://cebp.aacrjournals.org/cgi/content/full/10/1/25

(FULL ARTICLE LINK)


Reducing Bioavailable Sex Hormones through a Comprehensive Change in Diet: the Diet and Androgens (DIANA) Randomized Trial1
Franco Berrino2, Cristina Bellati, Giorgio Secreto, Edgarda Camerini, Valeria Pala, Salvatore Panico, Giovanni Allegro and Rudolf Kaaks

Unit of Epidemiology (F. B., C. B.,V. P.), Unit of Nuclear Medicine (G. S.), Unit of Laboratory Medicine (E. C.), Istituto Nazionale Tumori, 20133 Milan, Italy; Department of Clinical and Experimental Medicine, Federico II University, 80131 Naples, Italy (S. P.); Association Le Cinque Stagioni, 10018 Ivrea, Italy (G. A.); and Nutrition and Cancer Unit, International Agency for Research on Cancer, 69372 Lyon, France (R. K.)


Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References

High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.......................MORE

[R.B.]

Please excuse me pushing this thread back up for any who may be new to the Forum.

There is also the "cancer Diet" thread for those looking for diet ideas.

RB

[R.B.]

1771 views for both the Greek Diet, and Cancer Diet when I visited just now.

I wonder what the chances of that are.


RB

[chrisy]

Pretty good, since each of these "timeless topics" have a great sponsor bumping them up to keep them visible. Thanks!

p.s. I visited both, too...just trying to keep my "Breast cancer diet/Greek diet" balance correct. I know you would approve!

[RobinP]

What about other diet measures beside omega 3 fats. I use olive oil to bind the her2 receptor, use genistein ( yes I know it's contraversial as a phytoestrogen) for the Her1(yes I know by testing I am her1+), use quercetin natural products for the her 3 (again I am her3+ too), green tea as a general antioxidant, vitamin A products and oatmeal to bind the estrogen receptor, tumeric also to prevent spread and seeding of her2. Finally, I use vit. D and calcium for bone health but it may also play a role in preventing some cancers too, especially colon.

[R.B.]

Just a reminder for new members that diet can impact on your cancer risk profile.

Diet does change the way you express your genes, a bit like you can change the tonal nature of your music using a graphic equaliser on your stereo.

I accept it is difficult.

I am sorry to keep labouring it but talking with women giving their time to collect for a support group reminded my how many evidently are not convinced, almost to the point of being hostile to suggestions diet is significant even (if not more so) after contracting BC.

It was saddly evident of possibly how few people are aware of the significant potential of diet to reduce rsik profiles, and the resistance to it as an idea among significnat numbers.

RB

[Mary Anne in TX]

Thanks for keeping this "front and center"! Everytime I read the information (new and old) it reminds me how much better I feel when I pay close attention to what goes in my mouth!!!! And it gets me back on track!

ma

[chrislmelb]

always good to read your thoughts and answers to others' questions.
Take care
Christine

[RhondaH]

MIA for a while. Good to see you. Take care and God bless.

Rhonda

[R.B.]

Rhonda, Christine, Mia, thanks for the comments. I'm touched.

Marbles Institute Associate (as in lost a few) is closer some might say. Nothing as gallant as MIA I'm afraid.

Thanks.

RB

[R.B.]

Just to put the thread back on the current map for any that may not have seen it.

Diet can and does alter the way you express your genes including BRAC and HER2.

Rhonda breast cancer diet thread in another useful nutritional thread.

RB

[julierene]

I used to read my pH and only once in the first 2 years of reading my monthly pH did I have anything past normal. I had normal pH even when my cancer came back... and just to disprove the pregnancy test theory - I got a negative pregnancy test too... I honestly don't know who comes up with this stuff. But these two tests were a waste of my money. Is there anyone who can show that the pH strips or the pregnancy tests actually WORKED for them?

[StephN]

Another interesting topic. We had a thread going on acid/alkaline when Lyn was here contributing months back. I am sure a search here will turn it up.

I have no experience with those test strips myself, but DO try to stay to the less acid side in my diet. It can be very surprising what foods you think are acid that really do not fall into that category.

Start a new thread with this subject, OK?

P.S. Looks like your tests are coming out negative for active disease - YAY!

[heblaj01]

I have no personal opinion on the validity of the acid/alkaline theory but here is a contrary position by an MD:

http://www.quackwatch.org/01Quackery...SH/coral2.html
Acid/Alkaline Theory of Disease Is Nonsense

I also read somewhere in the distant past that the theory of the acidic environment as enhancing cancer progression was based on the wrong assessment of the cause & effect in the fact that cancer cells release lactic acid ( not the acid causing cancer).

[R.B.]

Just bringing this thread back in case of interest to those new to the site, or with a new interest in diet etc.

The links do emphasise the importance of diet, and even if a tiny bit of use to anyone contribution makes me feel better.

RB

[R.B.]

Just to bring this forward again as diet is a topic at the moment.

RB