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Dicembre 2005

Gli articoli di questo mese:

- Artrosi e Ipertermia del prof. Giuseppe di Fede>>
- Acidi grassi (PUFA) marcatori biologici nella valutazione di pazienti oncologici >>

Versione Italiana

ISTITUTO DI MEDICINA BIOLOGICA
dr G. Di Fede

PUFA biomarkers in assessment of cancer patients.
A proposal

B. Berra, G. Montorfano, A.M. Rizzo

Institute of General Physiology and Biochemistry "G. Esposito"
University of Milano Via D. Trentacoste, 2 - 20134 Milano Italy

INTRODUCTION
Omega 3 are important molecules for membrane order; they can also modify gene-expression, content of inflammation-inducible cytokines, regulation of eicosanoid production, plasma triglycerides level, blood pressure, and ion flux in cardiac cells. So there have been successful trials with eicosapentaenoic acid (C20:5 ω-3, EPA) and docosaexahaenoic acid (C22:6 ω-3, DHA) of secondary prevention of myocardial infarction, fatal arrhytmias and coronary hearth disease. These observations show they play an important role in the cardiovascoular system.
The effects of ω -3 in patients with cardiovascular diseases (CVD) were the driving force for the valuation of PUFA-based biomarker for the assessment of coronary heart diseases, which could serve as measures of the risk for developing CVD and SCD.

Colorectal cancer
Omega-3 have been hypothesized to influence colorectal carcinogenesis through many mechanisms (e.g. inhibiting COX2, increasing apoptosis, reducing angiogenesis). Low dose of DHA synergistically interacts with araC, suggesting that dietary supplementation of DHA might achieve therapeutic gain.

Breast cancer
Supplementation with DHA synergistically enhances toxane cytotoxicity, down regulate HER-2/neu (c-erb B-2) oncogene expression, modifies the production of the heparansulfate syndecan-1, suggesting a gene-nutrient interaction of critical importance for mammary carcinogenesis and supporting the hypothesis that ω-3 can be used as modulators of tumor cell chemiosensitivity.

AIM OF THE STUDY
We would like to evaluate the potential value of tumor risk assessment in colon and breast cancer patients by determining ω-3 concentration in blood in healthy subjects, cancer free patients and patients with colon or breast cancer, before and after supplementation with (ω-3, evaluating the potential correlation with the clinical conditions.

MATERIALS AND METHODS
Arachidonic acid (AA) and eicosapentaenoic acid (EPA) content in blood were determined by gaschromatographic analysis. The methylesters fatty acids were obtained with sodium methoxide in methanol 3.33% w/v and injected into an Agilent gaschromatograph (HP 6850, series II plus), equipped with FID detector under the following experimental conditions: Capillary column: AT Silar ALLTECH (50% cyanopropyl - 50% methyl polysiloxane) length 30 m, i.d. 0.32 mm, film thickness 0.25 μm. Gas carrier: helium, flow rate 2.7 ml/min. Temperature: injector 250°C, detector 275°C, oven 50°C for 2 minutes, rate of 10°C/minute until 200°C for 20 minutes. Standard: a standard mixture containing arachidonic acid and eicosapentaenoic acid was injected to identify sample peaks. The procedure was validated according the more recent rules (ISO 9001:2000).
The AA/EPA ratio was calculated on blood samples from 600 healthy subjects and 46 pathological subjects.

RESULTS AND DISCUSSION
We analyzed 295 healthy subjects, on a normal diet and 268 after omega-3 supplementation. The ratio AA/EPA was 15.25±10.36 and 4.07±3.44 respectively in the 1st and 2nd group. We have also analyzed 38 and 6 patients respectively with breast and colon cancer. The ratio AA/EPA was 18.20±9.36 in patients with tumors without supplementation and 4.07±3.44 in patients after supplementation. In 150 subjects the AA/EPA ratio in blood correlate with the AA/EPA ratio in cell membrane phospholipids of erythrocytes (RBC).

CONCLUSIONS
Conclusion 1: the correlation between plasma and RBC phospholipids we found suggests that the easier analysis in blood samples is a good tool for the evaluation of the ratio AA/EPA.
Conclusion 2: in colon and breast cancer patients the concentration of omega-3 LCPUFA is lower in comparison with normal subjects.
Conclusion 3: the supplement with omega-3 results in restablishing normal value of the ratio ω3 / ω6.
Conclusion 4: the preliminary results in colon and breast cancer patients obtained seems to indicate that the ratio AA/EPA. could be included as a new biomarker in the follow-up of patients under traditional chemotherapy supplemented, according to the recent data of literature with PUFA omega-3 fatty acids (Wu M. et al. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int. J. Cancer, 117, 340-348 2005; Astorg P., Dietary fatty acids and colorectal and prostate cancers: epidemiological studies. Bull Cancer. 2005 Jul;92(7):670-84).
 

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