The traditional diet of Greece and cancer.

[R.B.]

Mary mary

A powerful comment. We are all "frail" flawed and human it is part of our condition.

At the risk of being repetitive I note that many posts say I take threes or fish oil etc as part of their personal program, but few make reference to balancing the sixes.

Please excuse the "shout" but I wonder if I am managing to convey the other half of the omega 3/EPA DHA message which is

PLEASE BALANCE THE SIXES AND THREES.

Please do excuse me if you have already more than got that part of the message too.

Fish oil together with flaxseed or oil (personal preference see flax seed debate) according to reports is really beneficial at lots of levels, BUT the one that is at the root of the INFLAMMATORY PATHWAYS, and IN VAST excess in the average diet is OMEGA SIX family which includes the key player AA Arachidonic acid. Omega three six ratios in the US are reported as in some cases up to 1:50. The often suggested best average is 1:1. The pathways to make the longer chain omega threes are reported to go astray around one 1:7.

So for most it is necessary to look at your omega six intake, cut right down or out on vegetable, nut and seed oils except those exceptions that are high in three, moderate nut intake, and beware of processed food. (Me too - this is where this quest started when I realised how skewed my own intake was)

Thanks for your post. It sounds like you have been through a great deal.

RB

[R.B.]

"There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs."


By the same author as the initial posts.

RB





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

1: J Am Coll Nutr. 2002 Dec;21(6):495-505. Related Articles, Links
Click here to read
Omega-3 fatty acids in inflammation and autoimmune diseases.

Simopoulos AP.

The Center for Genetics, Nutrition and Health, Washington, DC 20009, USA. cgnh@bellatlantic.net

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

Publication Types:

* Review


PMID: 12480795 [PubMed - indexed for MEDLINE]

[R.B.]

This fits in with other trials but good to see it in writing.

No mention of looking at omega six intake and effect of reductions which could possibly going to produce significant effect as well.

Some trials please


RB





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


1: Br J Nutr. 2003 May;89(5):679-89.Click here to read Links
Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects.

* Wallace FA,
* Miles EA,
* Calder PC.

Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.

Studies on animal and human subjects have shown that greatly increasing the amount of linseed (also known as flaxseed) oil (rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALNA)) or fish oil (FO; rich in the long-chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in the diet can decrease a number of markers of immune function. The immunological effects of more modest doses of n-3 PUFA in human subjects are unclear, dose-response relationships between n-3 PUFA supply and immune function have not been established and whether ALNA has the same effects as its long-chain derivatives is not known. Therefore, the objective of the present study was to determine the effect of enriching the diet with different doses of FO or with a modest dose of ALNA on a range of functional responses of human monocytes and lymphocytes. In a randomised, placebo-controlled, double-blind, parallel study, forty healthy males aged 18-39 years were randomised to receive placebo or 3.5 g ALNA/d or 0.44, 0.94 or 1.9 g (EPA+DHA)/d in capsules for 12 weeks. The EPAHA ratio in the FO used was 1.0:2.5. ALNA supplementation increased the proportion of EPA but not DHA in plasma phospholipids. FO supplementation decreased the proportions of linoleic acid and arachidonic acid and increased the proportions of EPA and DHA in plasma phospholipids. The interventions did not alter circulating mononuclear cell subsets or the production of tumour necrosis factor-alpha, interleukin (IL) 1beta, IL-2, IL-4, IL-10 or interferon-gamma by stimulated mononuclear cells. There was little effect of the interventions on lymphocyte proliferation. The two higher doses of FO resulted in a significant decrease in IL-6 production by stimulated mononuclear cells. It is concluded that, with the exception of IL-6 production, a modest increase in intake of either ALNA or EPA+DHA does not influence the functional activity of mononuclear cells. The threshold of EPA+DHA intake that results in decreased IL-6 production is between 0.44 and 0.94 g/d.

PMID: 12720588 [PubMed - indexed for MEDLINE]

[R.B.]

"DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding."

PGE2 is a percusor of aromatase which is a percusor of oestrogens.

So as a preventative in terms of oestrogen restriction DHA at higher doses may be a useful dietary additive. See previous post as to DHA fish oil dosages. Low dosages were reported as not showing the same effects.

Again omega six intake / reduction not examined to determine impact.

Please see posts on balancing omega threes and sixes.

Please do talk to youe medical advisor about significant dietary changes.

You can always think about printing the trials to take i to save you trying to explain. Any feed back positive or negative is most welcome.

RB

http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract


1: Lipids. 1999 Apr;34(4):317-24. Related Articles, Links

Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men.

Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Ferretti A, Erickson KL, Yu R, Chandra RK, Mackey BE.

USDA, ARS, Western Human Nutrition Research Center, Presidio of San Francisco, California 94129, USA. Dkelley@whnrc.usda.gov

The purpose of this study was to examine the effects of feeding docosahexaenoic acid (DHA) as triacylglycerol on the fatty acid composition, eicosanoid production, and select activities of human peripheral blood mononuclear cells (PBMNC). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of Western Human Nutrition Reach Center. Four subjects (control group) were fed the stabilization diet throughout the study; the remaining seven subjects were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg D alpha-tocopherol acetate per day. PBMNC fatty acid composition and eicosanoid production were examined on day 30 and 113; immune cell functions were tested on day 22, 30, 78, 85, 106, and 113. DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding. These parameters remained unchanged in the subjects fed the control diet. B-cell functions as reported here and T-cell functions that we reported previously were not altered by DHA feeding. Our results show that inhibitory effects of DHA on immune cell functions varied with the cell type, and that the inhibitory effects are not mediated through increased production of PGE2 and LTB4.

Publication Types:

* Clinical Trial


PMID: 10443964 [PubMed - indexed for MEDLINE]

This is a link which sort of explains what a lippolysacceride is in this complex.
Something to get the prostaglandin out of bed (the membrane) and off to work (immune defence). If somebody can could confirm this it would be helpful.

http://en.wikipedia.org/wiki/Lipopolysaccharide

[R.B.]

Mice were fed a high omega six diet 43 % energy from corn oil (high omega six source).

Estrogen receptors up SIX fold.

And equally mind boggoling the potential fro offspring to carry a greater risk level. I have seen this suggested elsewhere.

(ER is not the same as HER which relates to growth factors - it took me a while to work that one out - please tell me if I am wrong!)




"In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice."


RB




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9485017

1: Cancer Res. 1998 Feb 15;58(4):654-60. Links
Consumption of a high-fat diet alters estrogen receptor content, protein kinase C activity, and mammary gland morphology in virgin and pregnant mice and female offspring.

* Hilakivi-Clarke L,
* Stoica A,
* Raygada M,
* Martin MB.

Lombardi Cancer Center, Department of Psychiatry, Georgetown University, Washington, DC 20007, USA.

Previous studies have shown that a diet high in polyunsaturated fatty acids increases mammary tumor incidence in adult and pregnant mice and rats and in the female offspring. The present study investigated whether a high-fat diet alters the number of estrogen receptor (ER) binding sites and protein kinase C (PKC) activity in the mammary gland of these animals. In the female offspring, the effects of maternal exposure to a high-fat diet during pregnancy on development of the mammary epithelial tree were studied also. BALB/c mice were kept on a diet containing either 43% (high-fat) or 16% (low-fat) calories from corn oil, which consists mostly of n-6 polyunsaturated fatty acids, for 1 month. In adult female mice, a 6-fold increase in the number of ER binding sites and 2-fold increase in PKC activity were found in the mammary glands of the high-fat mice when compared with the low-fat mice. In pregnant mice, a high-fat diet increased ER binding sites by 61% and PKC activity by 51%. In contrast to adult and pregnant mice, females exposed to a high-fat diet only in utero through their pregnant mother exhibited a significantly reduced number of mammary ER binding sites by age 45 days (78% decrease) and a reduction in PKC activity by ages 30 and 100 days (44 and 20% decrease, respectively). The mammary epithelial tree of the high-fat offspring contained more terminal end buds and was less differentiated than that of the low-fat offspring. These findings show that consumption of a high-fat diet increases ER and PKC in the adult and pregnant mouse mammary gland, perhaps contributing to the fat-induced promotion of mammary tumorigenesis. In contrast, reduced ER and PKC following a high-fat exposure in utero may be associated with increased susceptibility to carcinogenesis, possibly due to an increased number of terminal end buds that are the sites of neoplastic transformation in the mammary gland.

PMID: 9485017 [PubMed - indexed for MEDLINE]

i live in greece. unfortunately the hospitals here in greece are full of cancer patients, especially in crete.
my mother has metastatic breast cancer, since she was a child she followed a very healthy nutrition but unfortunately this did'nt helped to prevent the disease.
The truth is that -at the moment- she never had symptoms of the disease. she feels very good, full of energy, she does a lot of things every day.
from this point of view, maybe this could be a sign that greek diet helps cancer patients to have a good qol and live with dignity.
take care
lorenzo

[R.B.]

Thank you for your post.

I am glad your mother has a good qol.

I was sorry to hear of the suggestion of high numbers of cases in Crete. I would be positive to know of corners that had managed to avoid the increase that are being seen in numbers.

The articles do refer to the pre 1960 diet, and I guess was based on then (1960) statistics.

The introduction in dietary changes, vegetable oils, vegetable oils in processed foods etc may have changed the comparative cancer ratio bringin them more in line with other western countries since then.

It is not something I have specifically looked at.

Also sadly there are always going to be those for whom diet may offer better qol but have some sort of predisposition, exposure to other environmental factors etc.

Thank you agin for your post.

I hope your mother continues to enjoy a good qol. grape vines, Tavernas feta, juicy fresh peaches, local honey, feta basil and tomatoes come to mind but that was some years ago.

RB

[RobinP]

RB thanks so much for the omega three balancing dietary posts which are prudent for overall healthy living and to help prevent many disease conditions. I think it has made me more conscious of what I, my kids and husband eats which is a good thing. Afterall, we are what we eat to a certain degree, and also as the above abstracts suggests we are what mother ate while we were in utero as well. Of course, I agree that genetics and environment also plays into the equation and defines our weakness, strengths and our suspectibility to disease.

[R.B.]

I have see trial that suggest negative impacts for trans fats including blocking the pathways to make long chain fats which could compromise immune function, exacerbate related conditions, and as previously posted potentially impact on risks of cancer etc.

Margerines come in different "shapes" and sizes with different levels of polyunsaturates contents and thrans fats etc.

But you may like to try this with your brand, and some butter as a contol.

The author has a way with words.

RB





http://www.healthy-communications.co...margerine.html

Subject Butter or Parkay?
Date Sat, 18 Mar 2006

Margarine was originally manufactured to fatten turkeys. When it killed the
turkeys, the people who had put all the money into the research wanted a
payback so they put their heads together to figure out what to do with this
product to get their money back. It was a white substance with no food
appeal so they added the yellow coloring and sold it to people to use in
place of butter. How do you like it? They have come out with some clever
new flavorings.

DO YOU KNOW... the difference between margarine and butter?

Read on to the end...gets very interesting!

Both have the same amount of calories.

Butter is slightly higher in saturated fats at 8 grams compared to 5 grams.

Eating margarine can increase heart disease in women by 53% over eating
the same amount of butter, according to a recent Harvard Medical Study.

Eating butter increases the absorption of many other nutrients in other
foods.

Butter has many nutritional benefits where margarine has a few only because
they are added!

Butter tastes much better than margarine and it can enhance the flavors of
other foods.

Butter has been around for centuries where margarine has been around for
less than 100 years.

And now, for Margarine. Very high in trans fatty acids.

Triple risk of coronary heart disease.

Increases total cholesterol and LDL (this is the bad cholesterol) and
lowers HDL cholesterol, (the good cholesterol)

Increases the risk of cancers up to five fold.

Lowers quality of breast milk.

Decreases immune response.

Decreases insulin response.

And here's the most disturbing fact.... HERE IS THE PART THAT IS VERY
INTERESTING!

Margarine is but ONE MOLECULE away from being PLASTIC..

This fact alone was enough to have me avoiding margarine for life and
anything else that is hydrogenated (this means hydrogen is added, changing
the molecular structure of the substance).

You can try this yourself

Purchase a tub of margarine and leave it in your garage or shaded area.
Within a couple of days you will note a couple of things

* no flies, not even those pesky fruit flies will go near it (that should
tell you something)

* it does not rot or smell differently because it has no nutritional value
nothing will grow on it. Even those teeny weeny microorganisms will not a
find a home to grow.

Why? Because it is nearly plastic. Would you melt your Tupperware and
spread that on your toast?


Share This With Your Friends.....(If you want to "butter them up")

[RhondaH]

IF I "splurge" on my diet, I would rather use the REAL thing (i.e. butter, sugar) instead of the margarine, splenda, etc. as it seems that all the "stuff" they put in the food to lower the calories and/or fat, we have YET to know what it will do to our bodies and while YES, it may be helping us lose weight, do we REALLY know what it is doing to our bodies that's why everything is "real". It just seems like all the low fat, artificially sweetened food (with fewer) calories MAY be doing us more harm than good. Well, I have to go now as I'm off to the market to pick up my 40lbs of organic blueberries (sounds like a lot, BUT I use them as well as other berries...already froze 25lbs of strawberries...in Diana Dyers phytochemical shake that I have every day) AND I'm splurging and making a blueberry cobbler...mmm. Take care and God bless.

Rhonda

[R.B.]

See also previous post re DHA reducing bone loss and here a 2006 trial as well



"Bone marrow from LF-CO animals appeared to be more resistant to araC treatment than either MF group. Thus, DHA, fed as DHASCO, has advantages over low or moderate n-6 diets and chow as it is has both hypolipidemic- and bone marrow-enhancing properties in weanling Fischer 344 rats. This suggests that DHA supplementation may be useful in adjuvant chemotherapy."




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9076666

1: Lipids. 1997 Mar;32(3):293-302. Links
Incorporation of long-chain n-3 fatty acids in tissues and enhanced bone marrow cellularity with docosahexaenoic acid feeding in post-weanling Fischer 344 rats.

* Atkinson TG,
* Barker HJ,
* Meckling-Gill KA.

Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada.

We wanted to examine the effects of an oil rich in docosahexaenoic acid (DHA), without eicosapentaenoic acid, on the composition of membrane phospholipid in a variety of tissues. Our in vitro studies had previously shown that DHA could modify glucose and nucleoside transport in cells in culture and also increase selectivity of the nucleoside drug, arabinosylcytosine (araC) toward tumor cells. Here we wanted to examine what effect DHA supplementation would have in the whole animal in terms of the chemosensitivity of normal bone marrow, the dose-limiting tissue during chemotherapy, to araC. The purpose was to determine whether fatty acid supplementation might be useful as an adjuvant to chemotherapy. We fed diets containing 5% (w/w) low fat-corn oil (LF-CO group), 10% moderate fat-safflower oil (MF-SO group), or 10% DHASCO (MF-DHA group) to weanling Fischer 344 rats for 8-9 wk. Feed intake and growth were not different between the different diets. Similarly, treatment of animals with the chemotherapeutic drug araC did not differentially affect growth, feed intake, or tissue fatty acid composition for the different diet groups. Fatty acid compositions of bone marrow, liver, red blood cells, plasma phospholipid and triglyceride, as well as skeletal and cardiac muscle, were substantially different between the dietary groups. The DHASCO oil contained 46% DHA (22:6n-3) and resulted in profound incorporation of DHA in all tissues examined. The most dramatic response was seen in skeletal muscle of MF-DHA fed animals where DHA represented 46% of membrane phospholipid fatty acids. This is likely to have consequences to muscle function. Although DHASCO contains a similar level of saturated fatty acids (42%), few differences in saturates were noted between the various dietary groups for most of the tissues examined. Both LF-CO and MF-SO diets were hypercholesterolemic, and the LF-CO was also hypertriglyceridemic compared to the chow-fed animals. Animals fed the MF-DHA diet had the lowest triglyceride levels of any of the treatment groups and cholesterol levels comparable to chow-fed animals. MF-DHA had substantially higher numbers of colony-forming units-granulocyte macrophage (CFU-GM) as reflected in a twofold higher bone marrow cellularity than either chow or LF-CO animals, suggesting expansion of the bone marrow compartment with DHA feeding. Although higher than LF-SO, the number of CFU-GM in MF-SO animals was not significantly higher than animals fed chow. Bone marrow from LF-CO animals appeared to be more resistant to araC treatment than either MF group. Thus, DHA, fed as DHASCO, has advantages over low or moderate n-6 diets and chow as it is has both hypolipidemic- and bone marrow-enhancing properties in weanling Fischer 344 rats. This suggests that DHA supplementation may be useful in adjuvant chemotherapy.

PMID: 9076666 [PubMed - indexed for MEDLINE]



http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16102959


1: J Nutr Biochem. 2006 Apr;17(4):282-9. Epub 2005 Jun 21.Click here to read Links
Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats.

* Watkins BA,
* Li Y,
* Seifert MF.

Center for Enhancing Foods to Protect Health, Lipid Chemistry and Molecular Biology Laboratory, Purdue University, West Lafayette, IN 47907-2009, USA. baw@purdue.edu

Hypoestrogenic states escalate bone loss in animals and humans. This study evaluated the effects of the amount and ratio of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) on bone mineral in 3-month-old sexually mature ovariectomized (OVX) Sprague-Dawley rats. For 12 weeks, the rats were fed either a high-PUFA (HP) or a low-PUFA (LP) diet with a ratio of n-6/n-3 PUFAs of 5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided 110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended with n-3 PUFAs (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid analyses confirmed that the dietary ratio of 5:1 significantly elevated the amount of DHA in the periosteum, marrow and cortical and trabecular bones of the femur. Dual-energy X-ray absorptiometry measurements for femur and tibia bone mineral content (BMC) and bone mineral density showed that the DHA-rich diets (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at 12 weeks. Rats fed the LP diets displayed the lowest overall serum concentrations of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline, whereas the bone formation marker osteocalcin was lowest in the HP groups. Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5) preserved rat femur BMC in the absence of estrogen. This study indicates that the dietary ratio of n-6/n-3 PUFAs (LP5 and HP5) and bone tissue concentration of total long-chain n-3 PUFAs (DHA) minimize femur bone loss as evidenced by a higher BMC in OVX rats. These findings show that dietary DHA lowers the ratio of 18:2n-6 (linoleic acid)/n-3 in bone compartments and that this ratio in tissue correlates with reduced Pyd but higher bone alkaline phosphatase activity and BMC values that favor bone conservation in OVX rats.

PMID: 16102959 [PubMed - indexed for MEDLINE]

[R.B.]

"Taken together, these results indicate that {omega}-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma."


http://www.jlr.org/cgi/content/abstract/46/6/1278


Role of {omega}-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma

Yvonne Denkins1, Doty Kempf, Melissa Ferniz, Shilpa Nileshwar and Dario Marchetti

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803

Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400474-JLR200

1 To whom correspondence should be addressed. e-mail: 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 MatrigelTM 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 MatrigelTM invasion.

Taken together, these results indicate that {omega}-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

[R.B.]

For those of you who may have read the "very thought provoking" http://www.her2support.org/vbulletin...ight=provoking post on the man who claimed to have significantly impacted on lung cancer by balancing the omega threes and sixes here is some more evidence that would support such a possibility.

RB

http://carcin.oxfordjournals.org/cgi...tract/26/4/779

Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes
Shu-Hua Xia, Jingdong Wang and Jing X. Kang*

Departments of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA

* To whom correspondence should be addressed. Tel: +1 617 726 8509; Fax: +1 617 726 6144; Email: kang.jing@mgh.harvard.edu

Recent studies have shown opposing effects of n-6 and n-3 fatty acids on the development of cancer and suggest a role for the ratio of n-6 to n-3 fatty acids in the control of cancer. However, whether an alteration in the n-6/n-3 fatty acid ratio of cancer cells affects their invasive potential has not been well investigated. We recently developed a genetic approach to modify the n-6/n-3 ratio by expression of the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase that converts n-6 to n-3 fatty acids in mammalian cells. The objective of this study was to examine the effect of alteration in the n-6/n-3 fatty acid ratio on the invasive potential of human lung cancer A549 cells. Adenovirus-mediated gene transfer of the n-3 desaturase resulted in a marked reduction of the n-6/n-3 fatty acid ratio, particularly the ratio of arachidonic acid to eicosapentaenic acid. Cell adhesion assay showed that the cells expressing fat-1 gene had a delayed adhesion and retarded colonization. Matrigel assay for invasion potential indicated a 2-fold reduction of cell migration in the fat-1 transgenic cells when compared with the control cells. An increased apoptosis was also observed in the fat-1 transgenic cells. Microarray and quantitative polymerase chain reaction revealed a downregulation of several adhesion/invasion-related genes (MMP-1, integrin-{alpha}2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that a decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably downregulating the cell adhesion/invasion-related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in the prevention and treatment of cancer.

[R.B.]

Fats in milk will obviously depend on feed as cows like us are what they eat.

So I suppose you need to know what your organics cows ate but a Uk trial suggests organic milk has a better fat profile.

High levels of vegetable seed in feed are likely to produce high six contents.

Interestingly swiss cows from alpine pastures seem to have high omega three content.

RB


http://www.dairy-science.org/cgi/con...ract/89/6/1938

Comparing the Fatty Acid Composition of Organic and Conventional Milk
K. A. Ellis*,1, G. Innocent*, D. Grove-White{dagger}, P. Cripps{dagger}, W. G. McLean{ddagger}, C. V. Howard§ and M. Mihm#

* Division of Animal Production and Public Health, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow, G61 1QH, UK
{dagger} Division of Livestock Health and Welfare, University of Liverpool, Faculty of Veterinary Medicine, Leahurst, Neston, CH64 7TE, UK
{ddagger} Department of Pharmacology & Therapeutics School of Biomedical Sciences, Sherrington Buildings, Ashton Street, Liverpool, Merseyside, L69 3GE, UK
§ Centre for Molecular Biosciences, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, UK
# Division of Cell Sciences, Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow, G61 1QH, UK

1 Corresponding author: k.ellis@vet.gla.ac.uk

During a 12-mo longitudinal study, bulk-tank milk was collected each month from organic (n = 17) and conventional (n = 19) dairy farms in the United Kingdom. All milk samples were analyzed for fatty acid (FA) content, with the farming system type, herd production level, and nutritional factors affecting the FA composition investigated by use of mixed model analyses. Models were constructed for saturated fatty acids, the ratio of polyunsaturated fatty acids (PUFA) to monounsaturated fatty acids, total n-3 FA, total n-6 FA, conjugated linoleic acid, and vaccenic acid. The ratio of n-6:n-3 FA in both organic and conventional milk was also compared. Organic milk had a higher proportion of PUFA to monounsaturated fatty acids and of n-3 FA than conventional milk, and contained a consistently lower n-6:n-3 FA ratio (which is considered beneficial) compared with conventional milk. There was no difference between organic and conventional milk with respect to the proportion of conjugated linoleic acid or vaccenic acid. A number of factors other than farming system were identified which affected milk FA content including month of year, herd average milk yield, breed type, use of a total mixed ration, and access to fresh grazing. Thus, organic dairy farms in the United Kingdom produce milk with a higher PUFA content, particularly n-3 FA, throughout the year. However, knowledge of the effects of season, access to fresh grazing, or use of specific silage types could be used by producers to enhance the content of beneficial FA in milk.

Key Words: organic farming • fatty acid • n-3 fatty acid • conjugated linoleic acid



http://circ.ahajournals.org/cgi/cont...ract/109/1/103

Basic Science Reports
High {omega}-3 Fatty Acid Content in Alpine Cheese
The Basis for an Alpine Paradox
Christa B. Hauswirth, MD; Martin R.L. Scheeder, Dr sg agr; Jürg H. Beer, MD

From the Department of Medicine, Kantonsspital Baden, and the Federal Institute of Technology, Zürich, Switzerland.

Correspondence to J.H. Beer, MD, Department of Medicine, Kantonsspital Baden, 5404 Baden, Switzerland. E-mail hansjuerg.beer@ksb.ch

Received June 17, 2003; revision received August 21, 2003; accepted August 22, 2003.

Background— {alpha}-Linolenic acid (ALA) may protect from cardiovascular disease. Because fresh alpine grass contains high amounts of ALA, we hypothesized that the levels of {omega}-3 fatty acids would concentrate to nutritional relevance in the cheese of milk from cows with alpine grass feeding compared with cheese from silage and concentrate feeding; the newly available cheese produced from cows fed with linseed supplementation should contain even higher ALA concentrations.

Methods and Results— Forty different cheeses were analyzed by gas chromatography for their fatty acid profile: (1) 12 from well-defined alpine regions around Gstaad, Switzerland; (2) 7 commercially available English cheddar cheeses; (3) 6 cheeses from cows fed with linseed supplementation; (4) 7 industrial-type Emmentals; and (5) 8 alpine cheeses with partial silage feeding. The alpine cheese contained 4 times more linolenic acid (C18:3{omega}-3) compared with cheddar, more total {omega}-3 fatty acids, and showed a significantly lower n-6:{omega}-3 ratio. Conjugated linoleic acid (C18:2 c9/t11) was 3-fold higher, whereas the amount of palmitic acid was 20% lower. The Emmental reached 40% of the ALA content compared with alpine cheese, and surprisingly, cheese from linseed-supplemented cows contained only 49% of that of the alpine cheese (P<0.001 for each trait in the 5 cheese groups).

Conclusions— Cheese made of milk from cows grazed on alpine pastures had a more favorable fatty acid profile than all other cheese types. Alpine cheese may be a relevant source of ALA and other cardioprotective fatty acids.


Key Words: nutrition • fatty acids • coronary disease • diet • death, sudden

[R.B.]

ABSTRACT

"The omega-3 fatty acids continue to accumulate research that suggests that they may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In the first part of this article, the potential for these compounds to prevent certain cardiovascular conditions are discussed. In the second part, the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurologic diseases, osteoporosis, and other medical disciplines are also briefly covered. "








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

1: Urol Oncol. 2005 Jan-Feb;23(1):36-48.Click here to read Links
An introduction to dietary/supplemental omega-3 fatty acids for general health and prevention: part II.

* Moyad MA.

Phil F. Jenkins Director of Complementary & Alternative Medicine, Department of Urology, University of Michigan Medical Center, Ann Arbor, 48109-0330, USA. moyad@umich.edu

The correction of a subtle nutritional deficiency that may reduce the risk of a future chronic disease is indeed a challenge. However, some specific examples in the past, such as the addition of folic acid to prevent neural tube defects and calcium and vitamin D to prevent osteoporosis, should provide some encouragement that some conditions can be prevented with the appropriate addition of a deficient compound. One of the most intriguing current and future impacts on public health may come from a higher intake of omega-3 fatty acids, such as alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The omega-3 fatty acids continue to accumulate research that suggests that they may prevent a variety of diverse chronic diseases and potentially some acute clinical scenarios. In the first part of this article, the potential for these compounds to prevent certain cardiovascular conditions are discussed. In the second part, the potential for an impact in arthritis, numerous areas of cancer research, depression, maternal and child health, neurologic diseases, osteoporosis, and other medical disciplines are also briefly covered. The future appears bright for these agents, but specifically which conditions, who qualifies, testing, frequency, adequate sources, future trials, and numerous other questions need to be addressed and answered before the potential impact can catch up to the recent hype.

PMID: 15885582 [PubMed - indexed for MEDLINE]

[R.B.]

Blocking delta destaurase 5 will inhibit the formation of Archnidonic acid the omega six raw material for the eisosanoid pathways.

It may aslo push the omega six to DGLA conversion via the series one pathway which is reported as producing less inflamatory agents that the series two pathways.

This presumably acounts for its reported anti inflamatory properties.

But does it also block the 5 pathway for omegas threes long chain fabrication in the body (DHA and EPA)? (AMENDMENT I have just found a trial which suggests it does not which makes it a really interesting dietary adjunct) [Trial see below)

Also if excess omega six souces is a factor in inflamtion in a persons body the consequences in blocking the elongation pathways. The body has been supplied with the omega six and has to do something with it - burn it in exercise or for energy - store it in fat - and if there is too much of it in the circulation trials suggest things start going wrong with inapproriate oxidation leading heart conditions.

All of which might lead on to the conclusion that the easiest long term option is not getting to much in the first place.

RB




http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=1291640

1: J Nutr Sci Vitaminol (Tokyo). 1992 Aug;38(4):353-63. Links
Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid metabolism in primary cultured rat hepatocytes.

* Fujiyama-Fujiwara Y,
* Umeda R,
* Igarashi O.

Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo, Japan.

Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.

PMID: 1291640 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...t_uids=9610840

1: Prostaglandins Leukot Essent Fatty Acids. 1998 Mar;58(3):185-91. Links
Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.

* Chavali SR,
* Zhong WW,
* Forse RA.

Department of Surgery, Harvard Institute of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

PMID: 9610840 [PubMed - indexed for MEDLINE]

[R.B.]

1: Neuro Endocrinol Lett. 2005 Dec;26(6):745-51. Links
In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.

* Maes M,
* Mihaylova I,
* Leunis JC.

M-Care4U Outpatient Clinics, and the Clinical Research Center for Mental Health, Antwerp, Belgium.

There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.

PMID: 16380690 [PubMed - indexed for MEDLINE]

[R.B.]

If you are debating the best way to get your fish omega threes and sixes the articles below would provide arguments for fish oil or wild fish however humble, and thats without looking at other issues.

I must admit the figures made my draw drop.

The conversion rate from wild fish as food to farmed fish is apparently about 4 or 5 to 1.

A high price to fill our shelves with particular fish types?

I am not against farming fish to preserve wild stocks but where is the environmental "value" balance.

RB


Antarctic Krill: a case study on the ecosystem implications of fishing
http://72.14.221.104/search?q=cache:...ient=firefox-a


ABSTRACT

The fish farming industry already uses up
around 75% of the world’s fish oil and
around 40% of the world’s fish meal. By
2010, these figures might go up to 90% and
56% respectively, according to predictions
by the International Fish Meal and Fish Oil
Manufacturers Association (IFOMA). FAO
has indicated that by 2010, farmed salmon and trout alone could consume 620,000 tonnes
of fish oil (Staniford 2002). With demand exceeding supply and rising prices, fish oil has
been labelled “the new blue gold” (Staniford 2001).

http://72.14.221.104/search?q=cache:...ient=firefox-a


ABSTRACT

"Number 8
Winter 2001
Effects of Aquaculture on World Fish Supplies
SUMMARY
Global production of farmed fish, shrimp, clams, and oysters more than doubled in weight and value during the
1990s while landings of wild-caught fish remained level. Many people look to this growth in aquaculture to relieve
pressure on ocean fish stocks, most of which are now fished at or beyond capacity, and to allow wild populations to
recover. Production of farmed fish and shellfish does increase world fish supplies. Yet by using increasing amounts of wild-
caught fish to feed farmed shrimp and salmon, and even to fortify the feed of herbivorous fish such as carp, some sectors
of the aquaculture industry are actually increasing the pressure on ocean fish populations.
The available scientific evidence indicates that some types of aquaculture are on a destructive path that poses a
threat not only to wild fish stocks but also to the industry’s own long-term potential. One of the most disturbing trends is
the rapid expansion and intensification of shrimp and salmon farming and culture of other high-value carnivorous marine
fish such as cod, seabass, and tuna. Production of a single kilogram of these species typically uses two to five kilograms
of wild-caught fish processed into fish meal and fish oil for feed.
Besides this direct impact on wild fish stocks, some aquaculture as currently practiced degrades the marine
environment and diminishes the ecological life support services it provides to fish, marine mammals, and seabirds, as well
as humans. These impacts include
• Destruction of hundreds of thousands of hectares of mangrove forests and coastal wetlands for construction
of aquaculture facilities
• Use of wild-caught rather than hatchery-reared finfish or shellfish fry to stock captive operations, a practice
that often leads to a high rate of discarded bycatch of other species
• Heavy fishing pressure on small ocean fish such as anchovies for use as fish meal, which can deplete food for
wild fish such as cod, as well as seals and seabirds
• Transport of fish diseases into new waters and escapes of non-native fish that may hybridize or compete with
native wild fish
As aquaculture production continues to expand and intensify, both its reliance and its impact on ocean fisheries are
likely to increase. The balance between farmed and wild-caught fish, as well as the total supply of fish available for human
consumption, will depend on future trends in aquaculture practices. If the goal of aquaculture is to produce more fish for
consumers than can be produced naturally, then it will become increasingly counterproductive to farm carnivores that must
be fed large amounts of wild-caught fish that form the foundation of the ocean food chain. Indeed, non-carnivorous
species such as marine mollusks and carps account for most of the current net gain in world fish supplies from aquaculture.
Without clear recognition of its dependence on natural ecosystems, the aquaculture industry is unlikely to develop
to its full potential or continue to supplement ocean fisheries. We recommend the adoption of four priority goals for
aquaculture:
• Encourage farming of species lower on the food web – that is, fish with herbivorous or omnivorous diets or
filter feeders such as oysters
• Improve feed management and efficiency in industrial aquaculture systems and develop substitutes for fish-
derived feed ingredients
• Develop integrated fish farming systems that use multiple species to reduce costs and wastes while increasing
productivity
• Promote environmentally sound aquaculture practices and resource management
Governments have a key role to play in developing regulations to protect coastal ecosystems and in reexamining
subsidies to unsustainable marine fisheries. Development agencies are strategically placed to help in developing and
implementing sustainable production practices and in financing otherwise economically and socially unattainable reforms in
developing countries. If public and private interests act jointly to reduce the environmental costs generated by fish farm-
ing, present unsustainable trends can be reversed and aquaculture can make an increasingly positive contribution to global
fish supplies..............."
Cover (clockwise from top): shrimp ponds in Honduras (courtesy CODDEFFAGOLF); basket of milkfish (J. Primavera); harvesting catfish in
Mississippi (K. Hammond, courtesy USDA).

[R.B.]

Having done some more searches on the subject of fish farming there is contoversy about the "conversion" rate.

Here is another link to an article on conversion which contains three figues and one from the industry to balance things.



RB


http://www.davidsuzuki.org/Oceans/Fi...n/Net_Loss.asp

Net loss of wild fish to produce farmed salmon

A total of 2.7 to 3.5 tonnes of wild fish are used to make 1 tonne of farmed salmon

ABSTRACT



"Since a salmon farm in BC currently uses between 1.3 and 1.7 tonnes of dry feed (ie: FCR of 1.3 to 1.7) to make one tonne of farmed salmon, then the total amount of wild fish used to make one tonne salmon is between 2.7 and 3.5 tonnes (ie: the FCR multiplied by 2.08). It should be noted that in practice, BC salmon farms do not often reach the lower FCR of 1.3 which is achievable only when feed is used very efficiently on the farm. Rather than taking pressure off ocean resources then, salmon farming is currently adding greatly to that pressure..........................Much more research needs to be done and it is unclear when, or if the day will come when farmed salmon will be vegetarian. In the meantime, the stress on the ocean ecosystem will increase as salmon aquaculture expands globally. The consumption of 6.2 tonnes of wild fish for each tonne of salmon produced not only means less food for humans, but also for the many ocean species that rely on these fish as part of their food chain. Currently, the continued expansion of salmon farming is not sustainable.."



http://www.wfga.net/issues.asp?id=37

The Environmental Impact Of Salmon Farms

[R.B.]

Please also see prior posts on COX inhibitors and DHA.

This is prostate but there seems to be some communality of mechanisms in many cancers.

RB



1: Int J Cancer. 2006 Apr 27; [Epub ahead of print]Click here to read Links
Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells.

* Narayanan NK,
* Narayanan BA,
* Bosland M,
* Condon MS,
* Nargi D.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY.

The role of cyclooxygenase-2 (COX-2) and the mechanism by which it influences the development and behavior of prostate cancer is unclear. Selective COX-2 inhibitors may be effective against prostate cancer via COX-2-independent mechanisms. But administration of high doses of COX-2 inhibitors over longer period of time may not be devoid of side effects. There is increasing interest in using COX-2 inhibitors in combination with other chemopreventive agents to overcome the issue of toxicity. However, the molecular mechanisms underlying their combined actions are not well understood. Therefore, the present study was designed to determine the effects of low doses of docosahexaenoic acid (DHA) in combination with celecoxib on the molecular targets at the proteins level in rat prostate cancer cells. Two-dimensional gel electrophoresis, in combination with mass spectrometry analysis, was used for protein identification. Western blot analysis confirmed the proteins identified. Paraffin-embedded tissue sections from the rat prostate tumor were used to detect base level expression of heat shock protein 70 (HSP70) and p53. The rate of cancer cell growth was inhibited more effectively (p < 0.01) by DHA in combination with celecoxib at lower doses (2.5 muM each). A total number of twelve proteins were differentially expressed by the combined action of DHA and celecoxib at low doses. It was interesting to note that these agents activated both HSP70 and p53 proteins. Activation of HSP70 by the combined actions of DHA and celecoxib in the presence of wild-type p53 reveals a unique COX-2 independent mode of action against prostate cancer. (c) 2006 Wiley-Liss, Inc.

PMID: 16646082 [PubMed - as supplied by publisher]