The traditional diet of Greece and cancer.

[R.B.]

: Clin Chim Acta. 2006 Nov;373(1-2):1-8. Epub 2006 May 16.

Omega-3 fatty acid effects on biochemical indices following cancer surgery.
Stehr SN, Heller AR.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Fetscherstrasse 74, D-01309 Dresden, Germany.

Epidemiological studies have indicated that a high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Laboratory and clinical investigations have shown a reduced risk of colon carcinogenesis after alimentation with omega-3 fatty acids, as found in fish oil. Mechanisms accounting for these anti-tumor effects are reduced levels of PGE(2) and inducible NO synthase as well as an increased lipid peroxidation, or translation inhibition with subsequent cell cycle arrest. Further, omega-3 eicosapentaenoic acid is capable of down-regulating the production and effect of a number of mediators of cachexia, such as IL-1, IL-6, TNF-alpha and proteolysis-inducing factor. In patients with advanced cancer, it is possible to increase energy and protein intake via an enteral or parenteral route, but this seems to have little impact on progressive weight loss. Fish oil administration improved patients' conditions in cancer cachexia and during radio- and chemotherapy. In patients undergoing tumor resection surgery we observed improvement of liver and pancreas biochemical indices when omega-3 fatty acids were administered. This paper is a review of recent developments in the field of nutrition in cancer patients with emphasis on the acute phase response following cancer surgery and the beneficial aspects of fish oil administration.

[R.B.]

They have inserted genes into mice that allows them to make their own omega three.

The breasts of these mice make high levels of Omega 3.

Babies have a high need for Omega 3s.

Humans cannot make Omega 3 from scratch, but it would be reasonable to assume human breasts would make high levels of Omega 3s if they have the raw materials to do so. A possible consequences of a deficit of Omega 3 could be cellular misfunction.




http://www.ncbi.nlm.nih.gov/pubmed/1...med_RVDocSum1: Lipids. 2006 Jan;41(1):35-9.Links
N-3 polyunsaturated fatty acids endogenously synthesized in fat-1 mice are enriched in the mammary gland.
Ma DW, Ngo V, Huot PS, Kang JX.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada. davidwl.ma@utoronto.ca

In this study, we determined the phospholipid FA composition in the mammary gland of the transgenic Fat-1 mouse. This is the first animal model developed that can endogenously synthesize n-3 PUFA. The synthesis of n-3 PUFA is achieved through the expression of the fat-1 transgene encoding for an n-3 desaturase from Caenorhabditis elegans, which utilizes n-6 PUFA as substrate. Wild-type and Fat-1 female mice were terminated at 7 wk of age and the fifth mammary gland was removed. Lipids were extracted and phospholipids were separated by TLC and converted to FAME for analysis by GC. There was no significant change in total saturated, monounsaturated, and PUFA composition. However, there was a significant increase in total n-3 PUFA and a corresponding decrease in n-6 PUFA. The major n-3 PUFA that were enriched included 20:5n-3 and 22:6n-3. The n-6 PUFA that were reduced included 20:4n-6, 22:4n-6, and 22:5n-6. Overall, these findings demonstrate that female Fat-i mice have elevated levels of n-3 PUFA in the mammary gland. Moreover, the n-3 desaturase products are the same n-3 PUFA found in fish oil, which have been shown to have chemoprotective properties against breast cancer. Therefore, this newly developed mouse model may be highly useful for investigating molecular and cellular mechanisms by which n-3 PUFA prevents and inhibits breast cancer growth.

PMID: 16555469 [PubMed - indexed for MEDLINE]

[Becky]

Bumping up

[R.B.]

From one of the leaders in the Omega 3 6 field

Omega 6 in excess increases inflammatory pressures.


Asia Pac J Clin Nutr. 2008;17 Suppl 1:131-4.Links
The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease.
Simopoulos AP.

The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009 USA. cgnh@bellatlantic.net

A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.

PMID: 18296320 [PubMed - in process]

[R.B.]

This is about cardiac health and not BC. I post it because it is unusually unequivocal in its statements on the benefits of omega 3s.

It seems to me that anything that assists with cardiac health is good news; it would be nice if they looked to see if omega 3s helped reduce any cardiac implications of Herceptin.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Am J Clin Nutr. 2008 Jun;87(6):1991S-6S.
Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death.
Mozaffarian D.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Department of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA, USA. dmozaffa@hsph.harvard.edu

Large observational studies, randomized clinical trials, and experimental studies have evaluated the effects of fish and n-3 fatty acid consumption on fatal coronary heart disease (CHD) and sudden cardiac death (SCD), clinically defined events that most often share the final common pathway of fatal ventricular arrhythmia. These different study designs, each having complementary strengths and limitations, provide strong concordant evidence that modest consumption of fish or fish oil (1-2 servings/wk of oily fish, or approximately 250 mg/d of EPA+DHA) substantially reduces the risk of CHD death and SCD. Pooled analysis of prospective cohort studies and randomized clinical trials demonstrates the magnitude and dose-response of this effect, with 36% lower risk of CHD death comparing 0 and 250 mg/d of EPA+DHA consumption (P < 0.001), but then little additional benefit with higher intakes. Reductions in risk are even larger in observational studies utilizing tissue biomarkers of n-3 fatty acids that more accurately measure dietary consumption. The concordance of findings from different studies also suggests that effects of fish or fish oil on CHD death and SCD do not vary depending on presence or absence of established CHD. The strength and consistency of the evidence, and the magnitude of this effect are each notable. Because more than one-half of all CHD deaths and two-thirds of SCD occur among individuals without recognized heart disease, modest consumption of fish or fish oil, together with smoking cessation and regular moderate physical activity, should be among the first-line treatments for prevention of CHD death and SCD.

[TSund]

RB,

Thanks for this.

Do I remember you posting some helpful relationship between Omega 3's and Auto-Immune disease?

THX

TRS

[R.B.]

Tsund - thanks for the thanks,

I do not recall doing so, but there may have been a post that was looking at inflammation that also considered auto immune conditions.

Here are two trials that suggest that fish oil / Omegas 3 may assist reduce the risk of auto immune conditions.

RB


http://www.jacn.org/cgi/content/full/21/6/495

Journal of the American College of Nutrition, Vol. 21, No. 6, 495-505 (2002)
Published by the American College of Nutrition
REVIEW
Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases
Artemis P. Simopoulos, MD, FACN

The Center for Genetics, Nutrition and Health, Washington, D.C

Abstract

"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."


http://www.ncbi.nlm.nih.gov/pubmed/11802309
Isr Med Assoc J. 2002 Jan;4(1):34-8.Links
n-3 fatty acids and the immune system in autoimmunity.
Ergas D, Eilat E, Mendlovic S, Sthoeger ZM.

Department of Internal Medicine B, Kaplan Medical Center, Rehovot, Israel. ergaz@clalit.org.il

"Therefore, the use of n-3 fatty acids can be recommended to the general healthy population, not only to prevent atherosclerosis but possibly also to reduce the risk of autoimmunity."

[R.B.]

(I re-copied this to this thread as it is significant I suspect)


It all interconnects - what happy coincidences - The post on MS by Bill, and Hopeful of an MMP9 all come together at the same moment in a search for an article on MMP9 omega six and gene expression.

Conclusion Omega 3 suppresses MMP-9 which is a marker of MS and BC

http://www.springerlink.com/content/963788775224p348/

"The treatment with both ω-3 PUFA and fish oil dose-dependently inhibited the LPS-induced production of MMP-9. Our results suggest that a low fat diet supplemented with ω-3 PUFA may become recommended for the well being of MS patients under therapy."

MMP9 has been on my list of interest. I do not know exactly what it is, but saw a trial a long time ago that I will dig out that suggested the omega 3 and 6 significantly change gene expression of MMP9. I have been wondering ever since about MMP 9.



This was posted in articles of interest
http://breastcancersource.com/breast...48_0_0_0.aspx?
2 June 2008
Urine biomarker test confirms breast cancer precursor lesions
MedWire News: Matrix metalloproteinases can be detected in the urine of women with atypical breast hyperplasia and could form the basis for an accurate and convenient test for invasive breast cancer risk, researchers claim.

"Once validated in larger studies, such a test could potentially provide a useful adjunct for breast cancer risk assessment," Marsha Moses (Harvard Medical School, Boston, Massachusetts, USA) and colleagues comment, adding: "The goal of identifying women at high risk of developing breast cancer and providing safe effective risk reduction to this group is compelling."

Matrix metalloproteinases are required for the "angiogenic switch" - an early and critical event in breast cancer growth and progression, Moses et al explain in the journal Cancer Epidemiology, Biomarkers and Prevention.

Matrix metalloproteinase 9 (MMP-9) and a disintegrin and metalloprotease 12 (ADAM 12) are two established serum biomarkers in breast cancer.

[R.B.]

More evidence Omega 6 LA is implicated in BC.

And why COX blockers may have an impact as the block these pathways.

And more PGE2 may = more aromatase = more oestrogen products

More oestrogen would result in more conversion of LA to AA the raw material for this process be enhancing long chain fat conversion.

SO this could be a self fuelling tumour loop where Omega 6 is present in excess and there is no Omega 3 to moderate the process.

RB




http://www.springerlink.com/content/n547j2538p317388/

Xin-Hua Liu1, Jeanne M. Connolly1 and David P. Rose1 Contact Information
(1) Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, New York, USA
(2) Division of Nutrition and Endocrinology, American Health Foundation, 10595 Valhalla, NY, USA

Received: 21 August 1995 Accepted: 27 October 1995

Diets rich in linoleic acid (LA) stimulate the metastasis of MDA-MB-435 human breast cancer cells from the mammary fat pads of nude mice. This omega-6 fatty acid is metabolized to various cyclo-oxygenase and lipoxygenase products, several of which have been previously associated with tumor cell invasion and metastasis. We now report that MDA-MB-435 cells secreted increased levels of prostaglandin E2 (PGE2),

[R.B.]

Striking figures for COX blockers.

DHA is a cox blocker.

It is suggested COX blockers seek to moderate the downstream effect of excess Omega 6.

So balancing Omega 3s and 6s may assist in any COX blocking based strategy.

Please discuss dietary change with your doctor. The posts are only intended to inform debate.



Chemoprevention of Breast Cancer in Rats by Celecoxib, a Cyclooxygenase 2 InhibitorRandall E. Harris2, Galal A. Alshafie, Hussein Abou-Issa and Karen Seibert

School of Public Health [R. E. H., G. A. A., H. A-I.], Comprehensive Cancer Center [R. E. H., H. A-I.], and Department of Surgery [H. A-I.], The Ohio State University College of Medicine, Columbus, Ohio 43210, and Searle Monsanto Research and Development, St. Louis, Missouri 63137 [K. S


Nonsteroidal anti-inflammatory drugs (NSAIDs) have been observed to reduce the relative risk of breast cancer. This prompted our investigation of the chemopreventive potential of celecoxib, a specific cyclooxygenase 2 blocker, against mammary carcinogenesis induced by 7,12-dimethyl-benz(a)anthracene in female Sprague Dawley rats. Treatment with celecoxib was examined and compared to treatment with the general NSAID, ibuprofen, and to a control group receiving only dimethylbenz(a)anthracene. Dietary administration of celecoxib (1500 ppm) produced striking reductions in the incidence, multiplicity, and volume of breast tumors relative to the control group (68%, 86%, and 81%, respectively; P < 0.001). Ibuprofen also produced significant effects, but of lesser magnitude (40%, 52%, and 57%, respectively; P < 0.001). These results help confirm the chemopreventive activity of NSAIDs against breast cancer and provide the first evidence that a cyclooxygenase 2 blocking agent, celecoxib, possesses strong chemopreventive activity against mammary carcinogenesis.

[R.B.]

Cancer therapy for animals

http://www.huntsvillecompounding.com/vet%20cancer.pdf
Gigi Davidson, BSPh, RPh, FSVHP, DICVP
North Carolina State University College of Veterinary Medicine
Raleigh, North Carolina

"Matrix metalloproteinases (especially MMP-2 and MMP-9) are
enzymes that are secreted to degrade the ECM. Any new blood
vessels formed by angiogenesis can migrate only after the ECM is
degraded. MMP-2 and MMP-9 have long been associated with
tumor progression and metastasis.6-8 Although mechanisms of MMP
inhibition remain obscure, n-3 omega fatty acids have been shown
to be very effective MMP inhibitors,"

[R.B.]

Very largely outside my reading but another mechanism by which Omega 3s may reduce the risk of BC.

RB

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

1: Cancer Res. 2008 Apr 15;68(8):2912-9.Click here to read Links
Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells.
Sun H, Berquin IM, Owens RT, O'Flaherty JT, Edwards IJ.

Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-regulation of SDC-1 induces apoptosis. DHA was delivered to MCF-7 cells by n-3 PUFA-enriched low-density lipoproteins (LDL) or by albumin in the presence or absence of SDC-1 small interfering RNA. The n-3 PUFA induced apoptosis, which was blocked by SDC-1 silencing. We also confirmed that SDC-1 up-regulation and apoptosis promotion by n-3 PUFA was mediated by peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a luciferase gene driven by either a PPAR response element or a DR-1 site present in the SDC-1 promoter, reporter activities were enhanced by n-3 LDL, DHA, and PPAR gamma agonist, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. Cotransfection with dominant-negative PPAR gamma DNA eliminated the increase in luciferase activity. These data provide strong evidence that SDC-1 is a molecular target of n-3 PUFA in human breast cancer cells through activation of PPAR gamma and that n-3 PUFA-induced apoptosis is mediated by SDC-1. This provides a novel mechanism for the chemopreventive effects of n-3 PUFA in breast cancer.

PMID: 18413760 [PubMed - indexed for MEDLINE]

[R.B.]

Complicated but interesting.

Prostaglandins and leukotrienes are products of Omega Six.

It is an interesting suggestion that CLA may inhibit the downstream products of Omega 6. But as ever it is easier to cut down on excess Omega Six and balance with 3s, so avoiding excess Omega 6 products in the first place.

RB



Proliferative responses of normal human mammary and MCF-7 breast cancer cells to linoleic acid, conjugated linoleic acid and eicosanoid synthesis inhibitors in culture

Anticancer Research (Greece) , 1997, 17/1 A (197-203)

Potential mechanisms for the stimulation or inhibition of cell growth by linoleic acid (LA) and conjugated linoleic acid (CLA) were investigated by using eicosanoid linoleic acid (CLA) were investigated by using eicosanoid synthesis inhibitors. Normal human mammary epithelial cells (HMEC) and MCF-7 breast cancer cells were incubated in serum-free medium supplemented with LA or CLA and cyclooxygenase (indomethacin; INDO) or lipoxygenase (nordihydroguaiaretic acid; NDGA) inhibitors. Linoleic acid stimulated the growth and (3H)thymidine incorporation of normal HMEC and MCF-7 cancer cells, while CLA was inhibitory. Supplementation with LA increased intracellular lipid peroxide concentrations in normal HMEC and MCF-7 cancer cells, whereas CLA did not affect lipid peroxide formation. Normal HMEC and MCF-7 cells supplemented with LA and INDO or NDGA resulted in growth inhibition. The treatment of normal HMEC with CLA and INDO or NDGA, and MCF-7 cells with CLA and INDO stimulated cell growth. However, the addition of CLA and NDGA to MCF-7 cells resulted in synergistic growth suppression suggesting that CLA effects were mediated through lipoxygenase inhibition. Although NDGA was more inhibitory of cell growth in the presence of LA or CLA than INDO, growth was associate with both prostaglandin and leukotriene production. Additional studies are warranted to elucidate the mechanism(s)

whereby LA or CLA affect breast cell growth.

[madubois63]

RB - I've mentioned that I am working on helping heal my best friends lymphadema and also have been working very hard on fixing my iron over load in my liver. I grew eating the Mediterranean diet , as both my parents are from Greece. I never had a tv dinner or frozen food until I lived on my own in my 20's. Fast food was unheard of in my household. We only had "spaceburgers" or Jack in the Box the night we decorated the Christmas tree and Chinese in the restaurant on New Years. We fished and clammed all summer and ate our fish in the winter, grew our own veggies and picked our own fruit off the apple. cherry, pear, peach plum and quince trees (native to the Island of Create and my back yard). My mom cooked dandelion, and lentil soups from scratch. The only soup I ever ate from a can was tomato and everything was cooked in olive oil.

I have strayed over the years from a clean diet and paid the price. I have from time to time went back to the old ways, but have strayed many times over. Since becoming sick I have added supplements and herbs to my Mediterranean diet. This time around (the last 2 -3 months) I have really payed attention to everything going in to my body and when (because of my sugar level). The omega's are really important as are the anti-inflammatory herbs and spices. I have scanned your information because I can't always get my head in to reading and retaining information, but I will read it again. Thanks for all the information. This diet has really helped me get my liver functions under control and reducing the iron in my blood.

[R.B.]

The omega 3:6 balance, inflammation, COX 2 pathways and downstream products are factors in BC.

See also COX 2 posts.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum




1: Nutr Cancer. 2007;59(1):14-20.Links
Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer.
Cerchietti LC, Navigante AH, Castro MA.

Translational Research Unit, Angel H Roffo Cancer Institute, Universidad de Buenos Aires, Buenos Aires, Argentina. lcerchie@aecom.yu.edu

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.

[TSund]

RB- what is celecoxib? A Cox2 inhibitor of some sort I assume?

And, do you think this would applicable to mom who suffers multiple immune system problems, probably stemming from her chronic leukemia, along with muscle wasting/fibromylagia.
Thanks

TRS

[R.B.]

Hi T Sund

Here is a link for celecoxib.

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

I cannot in any way give advice on specific conditions in relation to individual circumstances. I have no training to do so. I can only draw your attention to the generality of relevant trials for your consideration.

Omega 3 and 6 do impact on the immune function through a number of mechanisms. IF there is dietary excess of Omega 6 and a lack of Omega 3 fats from plant sources (eg vegetable oils) AND a lack of long chain Omega 3s DHA and EPA or blocked conversion pathways there is significant evidence this can negatively impact on the immune function.

As posted already there is some evidence that increasing the intake of long chain omega 3s may help in some circumstances with fatigue etc.

These are listed as symptoms of CFS

http://www.spineuniverse.com/display...rticle155.html

Symptoms of Fibromyalgia include:

—Multiple tender points and muscle pain

—Disturbed sleep with morning fatigue and stiffness

—Aggravation of signs and symptoms by modulating factors (emotional stress, temperature changes)

—Subjective swelling and numbness

—Chronic headaches

—Irritable bowel syndrome

—Cold intolerance (Raynaud's Phenomenon)

—Dysmenorrhea - painful menstruation

—Exercise intolerance

—Weakness

A number of them have also been linked at some level with Omega 3:6 imbalances.


A search under leukemia or CFS and DHA or Omega 3 etc on Pubmed http://www.ncbi.nlm.nih.gov/ will produce some trials.


CFS
There are a few for CFS. This is an example suggesting CFS sufferers have a lack of Omega 3 and excess Omega 6

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.

ABSTRACT

"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."

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

So have a look at some more.

LEUKEMIA

There has been some work in the area of leukemia which seems to suggest possible benefits for EPA for example or usage as a treatment adjunct.

http://www.ncbi.nlm.nih.gov/sites/en...20%20omega%203


GOOD CLINICAL BOOK ON ACUTE INFLAMMATION

This is expensive but an excellent book you could give to your doctor. It is rare in being clinically orientated It is a powerful book. It is not an easy read but your friend just needs to get the jist and give it to her doctor as a basis for dietary discussion.

Omega 3 Fatty Acids in Clinical Nutrition by Heller, Stehr and Koch.

AND FINALLY

Your friend must tell to her doctor before any significant change in diet. I would suggest doing some more reading on Omega 3 and 6 and CFS etc printing the information and taking it to the doctor at the time of visit.

[R.B.]

Another mechanism by which Omega 6 linoleic acid induces tissue formation , migration and proliferation.

Oxidised Omega 6 linoleic acid induces rapid dose dependent upregulation of Syndecan-4

http://www.ncbi.nlm.nih.gov/pubmed/16636895

Breast Cancer Res Treat. 2006 Jul;98(1):91-8. Epub 2006 Apr 25.Click here to read Links
Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype.
Baba F, Swartz K, van Buren R, Eickhoff J, Zhang Y, Wolberg W, Friedl A.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA.

Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.

http://www.asco.org/ASCO/Abstracts+&...tractID=202291



Specific Induction of Syndecan-4 in Vascular Endothelial Cells of Breast Cancer - Implications for FGF-2-Induced Angiogenesis.
Sub-category:


Proc Am Soc Clin Oncol 19: 2000 (abstr 2603)
Author(s):

Christoph Mundhenke, Sally Drew, Zhen Chang, Aung Choon, Andreas Friedl
Abstract:

Introduction: Fibroblast growth factor-2 (FGF-2) is a potent angiogenic stimulator. Binding of FGF-2 to its receptor tyrosine kinases (RTKs) and cellular signaling are modulated by heparan sulfate proteoglycans (HSPGs) via their heparin-like heparan sulfate (HS) side chains. HS can be specific positive or negative regulators of FGF signaling depending on their ability to bind to both FGF ligand and RTK. Aim: The goal of this study was to localize different cell surface HSPGs in breast cancer and normal breast tissue and to examine their roles in FGF signaling. Materials and Methods: HSPGs were detected immunohistochemically in paraffin embedded tissues using antibodies directed against the HSPG core proteins of glypican-1, syndecan-1 and syndecan-4. The ability of HSPGs to promote FGF-2 signaling complex assembly was tested by using FGF-2 ligand and soluble RTK fusion protein (FR1-AP) as binding probes (Chang et al. FASEB J., in press). Results: HSPGs are induced in the stroma of infiltrating carcinomas in a striking tissue compartment and cell type-specific fashion. Syndecan-4 is dramatically induced in activated endothelial cells within infiltrating carcinoma tissue, while endothelial cells in normal breast gland are syndecan-4 negative. Syndecan-1 is strongly up-regulated in fibroblasts within the desmoplastic stroma surrounding infiltrating cancer cells. Glypican-1 is found in stromal fibroblasts in the immediate vicinity of cancer cells. FGF-2 binds to HSPGs in all stromal compartments. FR1-AP binds to FGF-2 immobilized on stromal fibroblast and endothelial cell HSPGs, suggesting, that syndecan-1 on fibroblasts and syndecan-4 on endothelial cells promote FGF-2 signaling complex assembly. Summary: Syndecan-4 is induced in tumor vessel endothelial cells of infiltrating carcinomas of the breast, facilitating FGF-2 signaling and thereby likely promoting angiogenesis.




http://ajpcell.physiology.org/cgi/co...ull/288/2/C458
ABSTRACT

Syndecan-4, a heparan sulfate proteoglycan that is widely expressed in the vascular wall and as a cell surface receptor, modulates events relevant to acute tissue repair, including cell migration and proliferation, cell-substrate interactions, and matrix remodeling. While syndecan-4 expression is regulated in response to acute vascular wall injury, its regulation under chronic proatherogenic conditions such as those characterized by prolonged exposure to oxidized lipids has not been defined. In this investigation, arterial smooth muscle cells were treated with 13-hydroperoxy-9,11-octadecadienoic acid (HPODE) and 13-hydroperoxy-10,12-octadecadienoic acid, oxidized products of linoleic acid, which is the major oxidizable fatty acid in LDL. Both oxidized fatty acids induced a dose-dependent, rapid upregulation of syndecan-4 mRNA expression that was not attenuated by cycloheximide. This response was inhibited by pretreatment with N-acetylcysteine, catalase, or MEK1/2 inhibitors, but not by curcumin or lactacystin, known inhibitors of NF-{kappa}B. These data suggest that oxidized linoleic acid induces syndecan-4 mRNA expression through the initial generation of intracellular hydrogen peroxide with subsequent activation of the extracellular signal-regulated kinase signaling pathway via MEK1/2. Notably, the HPODE-induced enhancement of syndecan-4 mRNA was accompanied by accelerated shedding of syndecan-4. In principle, alterations in both the cell surface expression and shedding of syndecan-4 may augment a variety of proatherogenic events that occur in response to oxidized lip

[R.B.]

PPAR gamma has made a previous appearance as having a link with BC. The trial below suggest that the products of oxidation of Omega 6 linoleic acid promote PPAR gamma which is suggested to be a tumour promoter in BC.



http://genesdev.cshlp.org/cgi/content/abstract/18/5/528

ABSTRACT

"These results suggest that once an initiating event has taken place, increased PPAR{gamma} signaling serves as a tumor promoter in the mammary gland."


http://carcin.oxfordjournals.org/cgi...act/24/11/1717

ABSTRACT

Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma}

Arthur W. Bull1,4, Knut R. Steffensen2, Jörg Leers2 and Joseph J. Rafter3

1 Oakland University, Department of Chemistry, Rochester MI 48309-4477, USA, 2 Center for Biotechnology, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden and 3 Department of Medical Nutrition, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) {gamma} plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for {gamma}1, {gamma}2 and {gamma}3, in Caco-2 and HCT-116 colon cell lines showed that {gamma}3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR {gamma} by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR {gamma}1 or {gamma}2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR {gamma} and that PPAR {gamma} plays an important role in the differentiation of intestinal cells.

[R.B.]

Linoleic Acid-Induced VCAM-1 Expression in Human Microvascular Endothelial Cells Is Mediated by the NF-κβ-Dependent Pathway
Authors: Hyen Joo Park; Yong Woo Lee; Bernhard Hennig; Michal Toborek
DOI: 10.1207/S15327914NC41-1&2_18
Publication Frequency: 6 issues per year
Published in: journal Nutrition and Cancer, Volume 41, Issue 1 & 2 September 2001 , pages 126 - 134


Abstract
Vascular cell adhesion molecule-1 (VCAM-1) has been reported to play an important role in cancer metastasis via the adhesive interaction between tumor cells and endothelial cells. In this study, we examined the effects of linoleic acid on VCAM-1 expression and its transcriptional regulatory mechanism in human microvascular endothelial cells (HMEC-1). Time- and dose-dependent increases of VCAM-1 mRNA levels were observed in linoleic acid-treated HMEC-1 as detected by reverse transcriptase-polymerase chain reaction. Flow cytometry analysis showed a significant and dose-dependent upregulation of VCAM-1 expression in HMEC-1 stimulated with linoleic acid compared with controls. To clarify the transcriptional regulatory pathway, we investigated the role of nuclear factor-κβ (NF-κβ) in the expression of VCAM-1 by linoleic acid in HMEC-1. Nuclear extracts from HMEC-1 stimulated with linoleic acid showed a dose-dependent increase in binding activity to the NF-kB consensus sequences. These effects were preventable by cotreatment with inhibitors of NF-κβ activity, such as sodium salicylate, aspirin, or pyrrolidine dithiocarbamate. In addition, pretreatment with NF-κβ inhibitors markedly suppressed the ability of linoleic acid to induce VCAM-1 gene expression. The role of NF-κβ in linoleic acid-induced VCAM-1 expression was confirmed by functional promoter studies in HMEC-1 transfected with reporter constructs of the VCAM-1 promoter with or without mutated NF-κβ binding site. These results indicate that linoleic acid upregulates VCAM-1 expression in HMEC-1 through the NF-κβ-dependent pathway.