Another trial I have come across suggesting synergy between DHA and chemo outcome.
I know nothing of the pathways by which chemo works.
Why should different chemo regeimes be influenced by DHA.
Is the DHA allowing the chemo to work or is the chemo allowing the DHA or a mix.
Intrigueing.
Why is DHA supplementation not checked out to detemine if it should be standard practice.
RB
http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum
1: Br J Cancer. 1999 Apr;79(11-12):1765-9. Related Articles, Links
Click here to read
Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma.
Bougnoux P, Germain E, Chajes V, Hubert B, Lhuillery C, Le Floch O, Body G, Calais G.
Laboratoire de Biologie des Tumeurs et Clinique d'Oncologie-Radiotherapie, Hopital Bretonneau, Tours, France.
Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response of the tumour to chemotherapy in 56 patients with an initially localized breast carcinoma. Adipose breast tissue was obtained at the time of biopsy, and individual fatty acids were measured as a percentage of total fatty acids using capillary gas chromatography. Patients then received primary chemotherapy, combining mitoxantrone, vindesine, cyclophosphamide and 5-fluorouracil every 4 weeks. Tumour size was reassessed after three cycles of chemotherapy. Tumour response was evaluated according to World Health Organization criteria. Complete or partial response to chemotherapy was achieved in 26 patients (47%). Level of n-3 polyunsaturated fatty acids in adipose tissue was higher in the group of patients with complete or partial response to chemotherapy than in patients with no response or with tumour progression (P < 0.004). Among n-3 polyunsaturated, only docosahexaenoic acid (22:6n-3) was significantly associated with tumour response (P < 0.005). In a logistic regression analysis taking into account age, body mass index and tumour size, 22:6 n-3 level proved to be an independent predictor for chemosensitivity (P = 0.03). These results suggest that, in breast cancer, 22:6 n-3 may increase the response of the tumour to the cytotoxic agents used.
PMID: 10206290 [PubMed - indexed for MEDLINE]
AND one I posted some time ago
1: Eur J Cancer Prev. 2005 Jun;14(3):263-70. Related Articles, Links
Exogenous supplementation with omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells.
Menendez JA, Lupu R, Colomer R.
Department of Medicine, Breast Cancer Translational Research Laboratory, Evanston Northwestern Healthcare Research Institute, Evanston, Illinois 60201, USA.
jmenendez@enh.org
Omega-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA; 22:6n-3) and other omega-3 and omega-6 PUFAs have raised interest as novel anticancer agents by exerting selective cytotoxic effects on human cancer cells without affecting normal tissues. Here, we examined the in vitro relationship between exogenous supplementation with DHA and breast cancer chemosensitivity to taxanes. We measured cell viability in the highly metastatic human breast cancer cell line MDA-MB-231 exposed sequentially to DHA followed by paclitaxel (Taxol) or docetaxel (Taxotere). As DHA by itself showed cytotoxic effects, possible synergistic interactions between DHA and taxanes were assessed, employing the combination index (CI) method and the isobologram analysis. Both methods showed a strong synergism (CI approximately 0.5; P<0.005) between DHA and taxanes in MDA-MB-231 cells. When the increase in taxanes efficacy was measured by dividing the IC50 values (50% inhibitory concentrations) obtained when the cells were exposed to taxanes alone by those after DHA pre-exposure, we found that DHA enhanced the cytotoxic activity of taxanes against MDA-MB-231 cells in a dose-dependent manner (up to 13- and 5-fold increase in Taxol and Taxotere efficacy, respectively). Importantly, sequential exposure to DHA followed by taxanes also yielded strong synergism in Her-2/neu (c-erbB-2)-overexpressing and taxanes-resistant SK-Br3 and BT-474 breast cancer cells. Moreover, exogenous supplementation with DHA significantly decreased the expression of Her-2/neu-codified p185(Her-2/neu) oncoprotein (up to 78% reduction in BT-474 cells). Our results provide experimental support to the hypothesis that omega-3 PUFAs can be used as modulators of tumor cell chemosensitivity and provide the rationale for in vivo preclinical investigation. In addition, this is the first study demonstrating that omega-3 PUFA DHA downregulates Her-2/neu oncogene expression in human breast cancer cells.
PMID: 15901996 [PubMed - indexed for MEDLINE]
Linear Mode
