More links between repoduction and prostaglandins. " Although the mechanism by which prostaglandins modulate these changes remains unclear, much evidence suggests that prostaglandins and their receptors and downstream signalling pathways are involved in angiogenesis and in alterations in cell adhesion, morphology, motility, invasion and metastases. "

Whilst omega threes and GLA both produce separte series of prosaglandins series 1 and series 3 the limited materila I have read links 1 and 3 to moderating roles in cell maturation etc, and series 2 which are derived from omega six and AA are the drivers.

More questions

RB



http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15380812

1: Trends Endocrinol Metab. 2004 Oct;15(8):398-404.Click here to read Links
Prostaglandin receptor signalling and function in human endometrial pathology.

* Jabbour HN,
* Sales KJ.

MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The University of Edinburgh Academic Centre, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK. h.jabbour@hrsu.mrc.ac.uk

Prostaglandins are bioactive lipids that exert an autocrine or paracrine function by binding to specific G-protein-coupled receptors (GPCRs) to activate intracellular signalling and gene transcription. Prostaglandins are key regulators of reproductive processes, including ovulation, implantation and menstruation. Prostaglandins have been ascertained to have a role in various pathological changes of the reproductive tract including menorrhagia, dysmenorrhea, endometriosis and cancer. Although the mechanism by which prostaglandins modulate these changes remains unclear, much evidence suggests that prostaglandins and their receptors and downstream signalling pathways are involved in angiogenesis and in alterations in cell adhesion, morphology, motility, invasion and metastases. The potential role of prostaglandin receptors in pathological changes of the endometrium has significance for the future development of therapeutic interventions.

PMID: 15380812 [PubMed - indexed for MEDLINE]

|More linking Cancer pathways and reproduction.
 

http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16310177

Fishing for prostanoids: deciphering the developmental functions of cyclooxygenase-derived prostaglandins.

* Cha YI,
* Solnica-Krezel L,
* DuBois RN.

Department of Medicine and Cancer Biology, Cell and Developmental Biology, Vanderbilt University Medical Center and Vanderbilt Ingram-Cancer Center, Nashville, TN 37232-2279, USA.

Prostaglandin G/H synthases (PGHS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze a key step in the synthesis of biologically active prostaglandins (PGs), the conversion of arachidonic acid (AA) into prostaglandin H(2) (PGH(2)). PGs have important functions in a variety of physiologic and pathologic settings, including inflammation, cardiovascular homeostasis, reproduction, and carcinogenesis. However, an evaluation of prostaglandin function in early development has been difficult due to the maternal contribution of prostaglandins from the uterus. The emergence of zebrafish as a model system has begun to provide some insights into the roles of this signaling cascade during vertebrate development. In zebrafish, COX-1 derived prostaglandins are required for two distinct stages of development, namely during gastrulation and segmentation. During gastrulation, PGE(2) signaling promotes cell motility, without altering the cell shape or directional migration of gastrulating cells. During segmentation, COX-1 signaling is also required for posterior mesoderm development, including the formation of vascular tube structures, angiogenesis of intersomitic vessels, and pronephros morphogenesis. We propose that deciphering the role for prostaglandin signaling in zebrafish development could yield insight and ultimately address the mechanistic details underlying various disease processes that result from perturbation of this pathway.

PMID: 16310177 [PubMed - indexed for MEDLINE]

A different cancer but same general direction of importance of omega three six balance.

I am scratching my head over aspects of the diagram but will work on it.


RB



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

1: J Carcinog. 2006 Mar 27;5:9.Click here to read Click here to read Links
The yin and yang of 15-lipoxygenase-1 and delta-desaturases: Dietary omega-6 linoleic acid metabolic pathway in prostate.

* Kelavkar U,
* Lin Y,
* Landsittel D,
* Chandran U,
* Dhir R.

Department of Urology and University of Pittsburgh Cancer Institute, 5200 Center Ave,, SHMC-Suite G-37, Pittsburgh, PA, 15232, USA. kelavkarup@upmc.edu.

ABSTRACT : One of the major components in high-fat diets (Western diet) is the omega (omega, n)-6 polyunsaturated fatty acid (PUFA) called linoleic acid (LA). Linoleic acid is the precursor for arachidonic acid (AA). These fatty acids are metabolized to an array of eicosanoids and prostaglandins depending upon the enzymes in the pathway. Aberrant expression of the catabolic enzymes such as cyclooxygenases (COX-1 and/or -2) or lipoxygenases (5-LO, 12-LO, 15-LO-1, and 15-LO-2) that convert PUFA either AA and/or LA to bioactive lipid metabolites appear to significantly contribute to the development of PCa. However, PUFA and its cellular interactions in PCa are poorly understood. We therefore examined the mRNA levels of key enzymes involved in the LA and AA pathways in 18 human donor (normal) prostates compared to 60 prostate tumors using the Affymetrix U95Av2 chips. This comparative (normal donor versus prostate cancer) study showed that: 1) the level of 15-LO-1 expression (the key enzyme in the LA pathway) is low (P < 0.001), whereas the levels of delta-5 desaturase (P < 0.001, the key enzyme in the AA pathway), delta-6 desaturase (P = 0.001), elongase (P = 0.16) and 15-lipoxygenase-2 (15-LO-2, P = 0.74) are higher in donor (normal) prostates, and 2) Contrary to the observation in the normal tissues, significantly high levels of only 15-LO-1; whereas low levels of delta-6 desaturase, elongase, delta-5 desaturase and 15-LO-2 respectively, were observed in PCa tissues. Although the cyclooxygenase (COX)-1 and COX-2 mRNA levels were high in PCa, no significant differences were observed when compared in donor tissues. Our study underscores the importance of promising dietary intervention agents such as the omega-3 fatty acids as substrate competitors of LA/AA, aimed primarily at high 15-LO-1 and COX-2 as the molecular targets in PCa initiation and/or progression.

PMID: 16566819 [PubMed - in process]

More of the same.

RB



http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16611404

1: Neoplasia. 2006 Feb;8(2):112-24.Click here to read Links
Prostate Tumor Growth and Recurrence Can Be Modulated by the omega-6:omega-3 Ratio in Diet: Athymic Mouse Xenograft Model Simulating Radical Prostatectomy.

* Kelavkar UP,
* Hutzley J,
* Dhir R,
* Kim P,
* Allen KG,
* McHugh K.

Department of Urology and Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA, Email: kelavkarup@upmc.edu.

Evidence indicates that a diet rich in omega (omega)-6 polyunsaturated fatty acids (PUFAs) [e.g., linoleic acid (LA)] increases prostate cancer (PCa) risk, whereas a diet rich in omega-3 decreases risk. Precisely how these PUFAs affect disease development remains unclear. So we examined the roles that PUFAs play in PCa, and we determined if increased omega-3 consumption can impede tumor growth. We previously demonstrated an increased expression of an omega-6 LA-metabolizing enzyme, 15-lipoxygenase-1 (15-LO-1, ALOX15), in prostate tumor tissue compared with normal adjacent prostate tissue, and that elevated 15-LO-1 activity in PCa cells has a protumorigenic effect. A PCa cell line, Los Angeles Prostate Cancer-4 (LAPC-4), expresses prostate-specific antigen (PSA) as well an active 15-LO-1 enzyme. Therefore, to study whether or not the protumorigenic role of 15-LO-1 and dietary omega-6 LA can be modulated by altering omega-3 levels through diet, we surgically removed tumors caused by LAPC-4 cells (mouse model to simulate radical prostatectomy). Mice were then randomly divided into three different diet groups-namely, high omega-6 LA, high omega-3 stearidonic acid (SDA), and no fat-and examined the effects of omega-6 and omega-3 fatty acids in diet on LAPC-4 tumor recurrence by monitoring for PSA. Mice in these diet groups were monitored for food consumption, body weight, and serum PSA indicative of the presence of LAPC-4 cells. Fatty acid methyl esters from erythrocyte membranes were examined for omega-6 and omega-3 levels to reflect long-term dietary intake. Our results provide evidence that prostate tumors can be modulated by the manipulation of omega-6:omega-3 ratios through diet and that the omega-3 fatty acid SDA [precursor of eicosapentaenoic acid (EPA)] promotes apoptosis and decreases proliferation in cancer cells, causing decreased PSA doubling time, compared to omega-6 LA fatty acid, likely by competing with the enzymes of LA and AA pathways, namely, 15-LO-1 and cyclooxygenases (COXs). Thus, EPA and DHA (major components of fish oil) could potentially be promising dietary intervention agents in PCa prevention aimed at 15-LO-1 and COX-2 as molecular targets. These observations also provide clues as to its mechanisms of action.

PMID: 16611404 [PubMed - in process]

"Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver."


http://www.ncbi.nlm.nih.gov/entrez/q...ubmed_DocSum1: Lipids. 2004 Oct;39(10):963-76. Links
Dietary modulation of fatty acid profiles and oxidative status of rat hepatocyte nodules: effect of different n-6/n-3 fatty acid ratios.

* Abel S,
* De Kock M,
* Smuts CM,
* de Villiers C,
* Swanevelder S,
* Gelderblom WC.

Medical Research Council, Tygerberg, South Africa. stefan.abel@mrc.ac.za

Male Fischer rats were fed the AIN 76A diet containing varying n-6/n-3 FA ratios using sunflower oil (SFO), soybean oil (SOY), and SFO supplemented with EPA-50 and GLA-80 (GLA) as fat sources. Hepatocyte nodules, induced using diethylnitrosamine followed by 2-acetylaminofluorene/partial hepatectomy promotion, were harvested, with surrounding and respective dietary control tissues, 3 mon after partial hepatectomy. The altered growth pattern of hepatocyte nodules in rats fed SFO is associated with a distinct lipid pattern entailing an increased concentration of PE, resulting in increased levels of 20:4n-6. In addition, there is an accumulation of 18:1 n-9 and 18:2n-6 and a decrease in the end products of the n-3 metabolic pathway in PC, suggesting a dysfunctional delta-6-desaturase enzyme. The hepatocyte nodules of the SFO-fed rats exhibited a significantly reduced lipid peroxidation level that was associated with an increase in the glutathione (GSH) concentration. The low n-6/n-3 FA ratio diets significantly decreased 20:4n-6 in PC and PE phospholipid fractions with a concomitant increase in 20:5n-3, 22:5n-3, and 22:6n-3. The resultant changes in the 20:4/20:5 FA ratio and the 20:3n-6 FA level in the case of the GLA diet suggest a reduction of prostaglandin synthesis of the 2-series. The GLA diet also counteracted the increased level of 20:4n-6 in PE by equalizing the nodule/surrounding ratio. The low n-6/n-3 ratio diets significantly increased lipid peroxidation levels in hepatocyte nodules, mimicking the level in the surrounding and control tissue while GSH was decreased. An increase in n-3 FA levels and oxidative status resulted in a reduction in the number of glutathione-S-transferase positive foci in the liver of the GLA-fed rats. Modulation of cancer development with low n-6/n-3 ratio diets containing specific dietary FA could be a promising tool in cancer intervention in the liver.

PMID: 15691018 [PubMed - indexed for MEDLINE]

Melatonin plus fish oil 63% showed weight stabilisation in adv. gastro cancer
 

Interesting RB



http://grande.nal.usda.gov/ibids/index.php


Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomized pilot study.
Author: Persson,-C; Glimelius,-B; Ronnelid,-J; Nygren,-P
Citation: Nutrition. 2005 Feb; 21(2): 170-8
Abstract: OBJECTIVE: The effect of fish oil (FO), melatonin (MLT), or their combination and dietary advice on cachexia and biochemistry variables reflecting cachexia were investigated in patients with advanced gastrointestinal cancer. METHODS: Twenty-four patients not amenable to standard anticancer treatment and with documented weight loss and/or decreased serum albumin were included. They were randomized to 30 mL/d of FO, which provided 4.9 g of eicosapentaenoic acid and 3.2 g of docosahexanoic acid, or 18 mg/d of MLT for 4 wk. During the next 4 wk, all patients had FO and MLT. Serum or plasma was analyzed for tumor necrosis factor-alpha, interleukin-1beta, soluble interleukin-2 receptor, interleukin-6, and interleukin-8 and the fatty acids eicosapentaenoic acid, docosahexanoic acid, arachidonic acid, and linoleic acid. RESULTS: Serum levels of eicosapentaenoic acid and docosahexanoic acid increased as expected with FO. No major changes in biochemical variables and cytokines were observed with any intervention. In the FO group, 5 of 13 patients (38%) showed weight stabilization or gain compared with 3 of 11 patients (27%) in the MLT group. After combining interventions, approximately 63% of patients showed such responses. CONCLUSIONS: FO, MLT, or their combination did not induce major biochemical changes indicative of a strong anticachectic effect. Nonetheless, the interventions used may have produced a weight-stabilizing effect.

Re ability of omega three to alter gene expression
 

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

RB


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


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


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

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

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

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

PMID: 15075705 [PubMed - indexed for MEDLINE]

Omega three reduces RAS in colon cancer and relates to PI3K etc in BC
 

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

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

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

RB






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


ABSTRACT

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

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

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

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

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

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

PMID: 16854453 [PubMed - as supplied by publisher]


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


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

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

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

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

PMID: 16885352 [PubMed - as supplied by publisher]

Excess LA reduces ability of breast to produce LCPUFAs
 

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

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

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

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

RB



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


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

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

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

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

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

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

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

omega-3 FA may be a useful adjunct in the treatment of periodontal disease.
 

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


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

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

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

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

PMID: 16798867 [PubMed - in process]

Reducing Bioavailable Sex Hormones through a Comprehensive Change in Diet
 

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

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

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

RB


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

(FULL ARTICLE LINK)


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

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


Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References

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

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

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

RB

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

I wonder what the chances of that are.


RB

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

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

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

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

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

I accept it is difficult.

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

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

RB

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

ma

R.B., i thought you had disappeared!
 

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

I know...RB had been
 

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

Rhonda

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

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

Thanks.

RB

I guess one of my main concerns is that we don't know WHAT diet does to our gene expression. We are so on the edge of what diet can do. Look at the Beta Carotene study they did. That is one of the reasons I would caution anyone taking megadoses of anything that is supposedly "good" for you. There is such a thing as "too much of a good thing".

Good point

I wish they would fund trials. An animal trial on skeletal muscle did show high omega six increased HER2 expression. But I agree with you and again wish they would fund trials to sort out these basics.

We do know our ancestors did not have access to large quantities of cheap vegetable oils, trans fats etc. Or necessarily clean water, better all year round food availability, better housing and some fantastic medical advances.

RB

Kat in the delta
 

All I know is that Cancer seems to GROW in an ACIDIC BODY. WE need to find out ALL the foods that NEUTRALIZE the acid to make our bodies MORE ALKALINE. You would not believe Which foods they are--example apples and oranges...Who will make the list ? gotta get off --kat in the delta

Kat in the delta
 

1. Eat food to make our bodies more alkaline.

2. get rid of the magnetic chaos around us

3. Detox our bodies--colon, liver,,,,,etc

4. Learn to deal or get rid of stress

Really all of these can make our bodies acidic which we want to REVERSE-kat in the delta

rsvp what do YOU ALL think ??????????

This is an abstract from an article I saved.

I will try and find the link to it and post it.

Thank you for bringing it up as a subject.

This seems to sum it up plus carbonated drinks, and I wonder about vitamin C unbuffered when used as a preservative etc. I also cannot recall the situation re orange juice etc, which in addition in high quantities is a source of fruit sugars which in excess - all healthy things in moderation. I have started significantly diluting all purchased fruit juices.

"fish, meat, poultry, eggs, shellfish, cheese, milk, and cereal grains are net acid producing, whereas fresh fruit, vegetables, tubers, roots, and nuts are net base producing. Legumes yield near-zero mean acid values. Salt is net acid producing because of the chloride ion."



“fish, meat, poultry, eggs, shellfish, cheese, milk, and cereal grains are net acid producing, whereas fresh fruit, vegetables, tubers, roots, and nuts are net base producing. Legumes yield near-zero mean acid values. Salt is net acid producing because of the chloride ion. …As a result, healthy adults consuming the standard US diet sustain a chronic, low-grade pathogenic metabolic acidosis that worsens with age as kidney function declines. Virtually all preagricultural diets were net base yielding because of the absence of cereals and energy-dense, nutrient-poor foods—foods that were introduced during the Neolithic and Industrial Eras and that displaced base-yielding fruit and vegetables �


I hope this helps a little.

RB

I did a google search of alkaline & acid foods and found some charts that were really good, but on some items them differed! It really did help though! I'll keep reading them to find the ones that most often agree!
Watching what I eat has helped me so much these past 10 months!

Mary Anne.

If you find some particularly interesting ones could you post the links.

Many thanks

RB

Alkaline/Acid Food Charts
 

http://www.thewolfeclinic.com/acidalkfoods.html
Here is one chart that is easy to read and fairly complete.

http://www.liferesearchuniversal.com/acid.html
Here is one other that is easy to use.

Now, I just have to do it!
mary anne

kat in the delta
 

Thanks for looking us the info on foods--WE all need foods that Neutralize the acid in our bodies because cancer and most diseases love to live in an acidic body. I found that you can replace reg.salt with Sea Salt which is more alkaline(NONacid).
What about MILK----
Cancer craves SUGAR--so refined sugar should be a NO-NO for all of us. I guess someone or all of Us can make a list of Acid forming foods and a list of Foods that neutalize acid
--Any volunteers ??? I cannot stay on net long now......
Which are good site ?? from the Mayo Clinic, or MDAnderson, or Memorial Sloan Kettering Cancer Center or some dietician page or nutrition page.....Let me know what you all find out and we can all help each other ....................kat in the delta

kat in the delta
 

Mary Ann, Those sites you found were both excellant..& don't forget to drink Water--(mineral,spring,purified ??? )&..what other foods are missing? gotta run now...thanks for info for all...kat in the delta

keep looking if you can.......
Also look at what would prevent Magnetic interference with our bodies....We all may need to buy a bracelet or such......
I know that microwaves are NOT good,,,,and Cell Phones.....what else ???
And we need to detox. our bodies of toxins--colon -liver and more.....
To eliminate STRESS is a hard one for me.......really need to run now, but could go on .....kat.

food charts
 

http://www.essense-of-life.com/info/foodchart.htm


Ok, here is a chart that points out the unknown foods that I referred to earlier.
Good charts!

mary anne

Mary Anne

Thank you for those great links - exellent additions to this thread.

Sugar has the potential to create problems at all sorts of levels, poor digestion, upsetting of the fat metabolism, empty calories....

Sugar sucrose which breaks down into glucose and fructose from memory. It is a huge subject on its own.

It is clear from papers that consumption of refined sugars, particularly above a minimum can potentially have significant negative effects in the body.

Some are suggesting it is in general terms possibly a bigger factor in IBS than gluten etc. It certainly makes thought provoking reading. Good digestion is essential to health. And yes I could do better too.

Here is one link by way of example.

http://www.bashaar.org.il/files/101022005111814.pdf


RB

kat in the delta
 

Help me Robbie,
So is olive oil good or NOT good for you..Can you tell me some common foods and oils that ARE GOOD for you...Then, tell me those that are NOT as good for you
I would appreciate your help.........this has been alot for me to absorb as I just started from the top of this thread...thanks,
KAT

Well done for making the effort to try and understand this huge subject.

It is as usual complicated, but I will try and deal with the basics.

Olive oil is a complex mix of a lot of fats and chemicals.

This link gives an idea as to the mix of fats it contains. http://www.nutritiondata.com/facts-C00001-01c208D.html
18:1 is likely to be mainly oleic, 18:2 linoleic (omega six) 18:3 linolenic (omega three). So in olive oil you are getting a mix of fats, and mainly mono saturates (1 double bond eg 18:1 - 18 the number of carbons - 1 the number of double bonds.)

Mono saturates are better to cook with as they oxidise less, but add what you need for taste etc at end,

But if you use a lot it is important to rember 10% - 15% of a virgin oil and up to 50% of a processed oil is omega six.

There are also other chemicals in olive oil that are reported to have a benificial effect.

http://www.her2support.org/vbulletin...ight=olive+oil


So in general terms,
- moderation - less is probably more in general terms
- be very aware to add in the omega six it contains in working out approx your three six intake.
- use only quality virgin oils
- remember the body can make omega nines but it is complex and your body may appreciate a helping hand with provision of a little

Every body is different and will metabolise fats differently. If it is a choice becuase you do not tolerate fat or some other reason I would put fish oil first, and include a little olive oil now and then.


This thread may help too

http://www.her2support.org/vbulletin...ight=olive+oil


And this one.

http://www.her2support.org/vbulletin...ight=olive+oil



In general diet terms on diet - there are lots of books many of which cover more or less the same ground. Here are some thoughts but best check out some book at the library if you get time.

- as wide a variety as possible (a green food supplement is a way of getting some things you would not usually include in your diet Green Frog as a make is quite good)
- Green things and lots of them, frozen if fresh is not available spinach, broccoli etc. highly coloured fruit and veg, some dried seaweed.
- Some nuts mixed as much as will fit on your palm.
- Some pulses if your digestion will tolerate them
- Whole grain but in strict moderation and better pre germinated as reportedly easier to digest.
- a little occasional grass fed meat, farm raised chicken, offal etc if you are not vegitarian - corn fed animals have higher level of omega six
- fish including oily - small quick growing are less likely to be polluted sardines, mackerel - but again variety - all fish is good but wild is better.
- a variety of herbs and spices, ginger, curcumin, .....
- cut out vegetable oils except a little flaxseed (do not cook), maybe canola, perillia etc but you must watch the six content and strictly in moderation
- some fish oil to bring your intake of DHA up to about 2 grams a day.

Avoid "processed food" as in manifiactures prepreapred etc as far as is practicable - just because they usually contain vegetable oils etc. or at least read the label first, and regretabl they end up sadly going back on the shelf most times.

Sugar, sugar subsitutes, high salt levels, are very definate avoids.

So between sugars and vegetable oils most processed food is out.

Rhonda's "Cancer Diet" posted on this site is thought provoking.

Some suggest dairy and some say no. For those that tolerate it maybe a tiny bit of butter, maybe yogourt, maybe goats cheese, but small quantities.

You will find your taste changes and previous treats like crisps etc strangely end up tasting less desireable.

Getting ones digestion sorted out is key, which may mean no sugar, avoiding grains which can be difficult to digest for some, (Breaking the Vicious Cycle Elaine Gotterschall - is an interesting book on digestion - but may not be ideal receipies in respect of balancing omega threes and sixes, (high omega six in almonds) and I would have concern about too much honey....) for a bit etc.

Etc.

Do talk to your doctor about significant dietary change.

I hope the above helps. I am afraid beyond the basics you will have to find what suits you.

RB

Diet and body function
 

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

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

Rhonda breast cancer diet thread in another useful nutritional thread.

RB

OK...about Alakine bodies and pH
 

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

Hey Julierene
 

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

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

Start a new thread with this subject, OK?

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

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

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

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

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

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

RB

Hi,

Thought I would look up The Lyon Study, since it was quoted as reducing coronary disease, and cancer mortality.

Alas, I could find no reference to cancer within the study.

Maybe I found the wrong one? Seems like all roads point back to this one study, and it was designed to rate coronary disease recurrance.
The study had flaws. Mainly lack of control of its "control" group, and exceedingly small sample. 300+ each of experimental and control individuals. The diet of either group was assessed once. Less than a third of the control, and less than half of the experimental group, provided dietary data at the final meeting.

The conclusion is that the role of diet is uncertain regarding this particular study of recurrant coronary events(!) Encouraging results were had, but the study was flawed enough to make it no more than interesting...far from conclusive. Again, nothing at all about cancer.

So, maybe I found the wrong study. There was another one based in France by the same name, but it was also a study of coronary illness, and no mention is made of cancer.

There does seem to be quite an interest in diet and cancer links.
There must be more carefully conducted studies somewhere of this topic.

Whenever a study is quoted, it's good to review the source of the study. There are a lot of claims out there...