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P Bougnoux

Publications and source records attributed to P Bougnoux.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of an alpha-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status.

To investigate whether the oxidative status of an 18:3(n-3) polyunsaturated fatty acid (PUFA)-enriched diet could modulate the growth of chemically induced rat mammary tumors, three independent experiments were performed. Experiments I and II examined the variation of tumor growth by addition of antioxidant (vitamin E) or a prooxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to a 15% linseed oil diet rich in 18:3(n-3). Experiment III addressed the role of PUFA in the tumor growth modulation by vitamin E. For this purpose, we compared the effect of vitamin E in 15% fat diets containing a high level of 18:3(n-3) (linseed oil, high-PUFA diet) or devoid of 18:3(n-3) (hydrogenated palm/sunflower oil, low-PUFA diet). In Experiments I-III, tumor growth increased in the presence of vitamin E compared with control (without vitamin E). Furthermore, it decreased when prooxidant was added. In contrast, no difference was observed when the diet was low in PUFA, suggesting that sensitivity of PUFA to peroxidation may interfere with tumor growth. This observation was supported by growth kinetic parameter analysis, which indicated that tumor growth resulted from variations in cell loss but not from changes in cell proliferation. These data show that, in vivo, PUFA effects on tumor growth are highly dependent on diet oxidative status.

Animals↗
PubMed1999

Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma.

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.

Adipose Tissue↗
PubMed1999

n-3 polyunsaturated fatty acids and cancer.

n-3 Polyunsaturated fatty acids are promising molecules in cancer prevention and the potentiation of cancer treatment. Recent studies have highlighted the importance of their interactions with other food components. Their effects on tumor growth depend upon background levels of n-6 polyunsaturated fatty acids and antioxidants, and this could account for previously inconsistent results in experimental carcinogenesis. Recognition of the role of lipoperoxidation in the anti-tumor effects of polyunsaturated fatty acids, which is apparent in a variety of in-vitro or in-vivo systems, has been a major advance in the field. Consequently, n-3 polyunsaturated fatty acids appear to be excellent substrates for lipid peroxidation in situations where an oxidative stress is involved, such as in the action of several cytotoxic agents in the treatment of cancer.

Antineoplastic Agents↗
PubMed1998

Suicide gene therapy of chemically induced mammary tumor in rat: efficacy and distant bystander effect.

We examined the efficacy of suicide gene therapy for nitrosomethylurea-induced mammary tumors in rats. Individual tumors were directly injected with a retrovirus-producing cell line that releases retroviral vectors that transduce the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene. HSV1-TK specifically converts the nucleoside analogue ganciclovir (GCV) into a toxic metabolite. Compared to control rats receiving saline, we observed a significant tumor regression of the injected tumors following GCV administration, accompanied by a stromal inflammation and an extensive lymphocyte infiltration invading the tumor epithelium. It is noteworthy that the neighboring uninjected tumors also regressed, demonstrating the occurrence of a distant bystander effect. This is the first demonstration that HSV1-TK/GCV can efficiently treat multiple solid tumors directly generated from an epithelial tissue.

Animals↗
PubMed1998

Enhancement of doxorubicin cytotoxicity by polyunsaturated fatty acids in the human breast tumor cell line MDA-MB-231: relationship to lipid peroxidation.

Exogenous polyunsaturated fatty acids modulate the cytotoxic activity of anti-cancer drugs. In this study, we examined whether lipid peroxidation is a potential mechanism through which fatty acids enhance drug cytotoxicity. We measured cell viability in the human breast cancer cell line MDA-MB-231 exposed to doxorubicin in the presence of non-cytotoxic concentrations of various polyunsaturated fatty acids for 6 days. To determine the role of lipid peroxidation, the hydroperoxide level was measured in cell extracts. Among all polyunsaturated fatty acids tested, docosahexaenoic acid (DHA, 22:6n-3) was the most potent in increasing doxorubicin cytotoxicity: cell viability decreased from 54% in the presence of 10(-7) M doxorubicin alone to 21% when cells were incubated with doxorubicin and DHA. After addition of an oxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to cells incubated with doxorubicin and DHA, cell viability further decreased to 12%. Cell hydroperoxides increased commensurately. The effect of DHA on doxorubicin activity and lipid hydroperoxide formation was abolished by a lipid peroxidation inhibitor (dl-alpha-tocopherol) or when oleic acid (a non-peroxidizable fatty acid) was used in place of DHA. No effect was observed with mitoxantrone, a drug with a low peroxidation-generating potential. Thus, DHA may increase the efficacy of oxyradical-producing drugs through a mechanism involving a generation of lipoperoxides. This may lead in vivo to a modulation of tumor cell chemosensitivity by DHA and oxidant agents.

Breast Neoplasms↗
PubMed1997

Suppression of the promoter effect of polyunsaturated fatty acids by the absence of dietary vitamin E in experimental mammary carcinoma.

Because lipoperoxides seem able to modulate tumor growth, we have examined the concomitant effects of dietary antioxidant (vitamin E) and of a high amount of polyunsaturated fatty acids (PUFA) in a model of chemically-induced mammary carcinogenesis. Two groups of rats received a high fat diet with or without added vitamin E and mammary tumors were initiated in both groups by an injection of carcinogen. Tumor growth was followed in both groups. We found that tumor incidence and growth were decreased in rats with no added vitamin E in diet, suggesting a protective role of oxidized PUFA at later stages of carcinogenesis.

Animals↗
PubMed1997

Supplementation of MCF-7 cells with essential fatty acids induces the activation of protein kinase C in response to IGF-1.

The effects of changing the composition of membrane lipids on protein kinase C (PKC) activation were studied in MCF-7 human breast cancer cells. The supply of linoleate or alpha-linolenate to MCF-7 cells altered cell membranes fatty acid composition but did not affect PKC activity. When the cells were additionally exposed to IGF-1, the same fatty acids caused a dramatic increase in membrane-bound PKC activity. We also found that the mitogenic response induced by IGF-1 was not enhanced in those conditions when PKC becomes activated by linoleate and alpha-linolenate. These data show that these fatty acids elicit a distinct route for the transmission of IGF-1 signal by inducing the PKC pathway. They suggest that linoleate and alpha-linolenate could control the biological response of MCF-7 cells to IGF-1.

Breast Neoplasms↗
PubMed1996

Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.

The study of the relationship between dietary intake of vitamin E and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly due to methodological issues inherent to nutritional epidemiology. To avoid the pitfalls of dietary recalls, alpha-tocopherol content of adipose tissue was used as a biochemical indicator of long-term dietary intake of vitamin E. alpha-tocopherol and hydroperoxides were measured in breast adipose tissue obtained at the time of diagnosis from 70 patients with early breast cancer. Thirty women with non-malignant breast tumors served as control. Lipid peroxidation was monitored by quantifying conjugated dienes spectrophotometrically and by assaying hydroperoxides with an iodometric method; alpha-tocopherol was measured by HPLC associated with fluorescence detection. Mean alpha-tocopherol value in breast adipose tissue was significantly lower in breast cancer patients than in control patients, whereas the hydroperoxide content was significantly higher in cancer patients than in controls. The alpha-tocopherol concentration in adipose tissue was not correlated with the clinical status of the patients with respect to age, menopausal status or body mass index. We conclude from this pilot study that breast cancer is associated with a low content of alpha-tocopherol in breast adipose tissue, and with an altered lipid oxidation pattern, which might be related to a low antioxidant status.

Adipose Tissue↗
PubMed1996

Inhibition of Na+/H+ exchanger activity by an alkyl-lysophospholipid analogue in a human breast cancer cell line.

The mechanisms by which ET-18-OCH3 (1-O-octadecyl-2-O-methyl-sn-glycero-3 -phosphocholine) and other analogues of alkyl-lysophospholipids exert their antineoplastic effects are not yet fully elucidated. Possible interference with mechanisms involving intracellular pH (pHi) regulation was examined by measuring the effect of ET-18-OCH3 on the activity of the Na+/H+ exchanger in the breast cancer-derived cell line MCF-7. When ET-18-OCH3 was added to culture medium at 10 muM (determined as a noncytotoxic but cytostatic concentration), it led to an intracellular acidification (0.15 pH unit). It also decreased the rate of pHi recovery by Na+/H+ exchange following artificial acidification. Kinetic parameters of the exchange indicated that this was due to a decrease in the affinity of the exchanger for both transported ions, rather than to a decrease in the number of exchanger proteins in the membrane (same maximal efflux rate for treated and untreated cells). These results suggest that Na+/H+ exchanger inhibition and subsequent cytoplasmic acidification participate in the mode of action of ET-18-OCH3, and could be used for modulation of tumor-cell chemosensitivity or their subsequent commitment into programmed cell death.

Antineoplastic Agents↗
PubMed1996

[Indications for castration in women treated for breast cancer].

Historically, castration has been the first endocrine treatment in breast carcinoma. In premenopausal metastatic patients, castration improves quality of survival during a median period of 10 months, in one third of patients. As adjuvant treatment, prophylactic castration can be an alternative to chemotherapy in patients with positive receptors. Prospective randomized trials are being conducted to define indications of each adjuvant treatment.

Antineoplastic Agents, Hormonal↗
PubMed1995

Membrane fatty acids of breast carcinoma: contribution of host fatty acids and tumor properties.

To assess the part that host fatty-acid supply and tumor-specific fatty-acid utilization contribute to the membrane lipid composition of tumor tissue, intra-individual comparisons of membrane fatty acids were carried out between breast-carcinoma tissue and non-tumorous breast tissue adjacent to the tumor and taken as reference. Phospholipids were purified by thin-layer chromatography from tumor biopsies obtained from 59 patients with a localized presentation of breast cancer, and fatty acids analyzed by capillary gas chromatography. Elevated levels of palmitic, palmitoleic and arachidonic acids, along with a low level of linoleic acid, were observed in membrane phospholipids of tumors with poor histoprognostic grade. The level of mono-unsaturated fatty acids was higher, and the level of essential fatty acids was lower in the tumor than in the reference breast tissue. Fatty-acid-desaturating activity was not detectable in tumors. A positive relationship was observed among patients for most of the fatty acids between carcinoma and non-tumorous breast tissue, except for mono-unsaturated and essential fatty-acid levels, which were not correlated between both tissues. These data suggest that mechanisms specifically related to malignant transformation and tumor progression influence the membrane fatty-acid profile of breast carcinoma. Fatty acid supply to the tumor, possibly modified by metabolic conditions related to the host, also seems to play a decisive role in this composition.

Adult↗
PubMed1995

Developing Yoshida sarcoma does not influence the fatty acid composition of adipose tissues in the rat.

The potential involvement of individual fatty acids from diet or from adipose tissue in the outcome of cancer emphasizes the need for more insight into the relationship between fatty acids and tumor growth. The main objective of the present study was to examine whether rapid tumor growth would induce changes in the fatty acid composition of adipose tissue, indicating selective use and thus deposition of dietary fatty acids and/or selective removal of stored fatty acids from adipose tissue. We used a rodent model of transplanted solid tumor (Yoshida sarcoma) and measured the fatty acid composition from different adipose sites in the absence and in the presence of tumor but at the same intake of dietary fatty acids. We found that Yoshida sarcoma could grow rapidly without significantly altering the fatty acid composition of adipose tissue, irrespective of its location. These results do not favor the hypothesis of a selective removal of fatty acids from adipose tissue by growing tumors. They moreover indicate that tumors do not modify the storage of individual dietary fatty acids.

Adipose Tissue↗