Approches d'immunothérapie anti-mélanome sur la base de l'inhibition du facteur de croissance IGF-1 modulant l'expression du CD9

Nous avons inhibé l expression de l insulin-like growth factor I sur une lignée de cellules de mélanome (la lignée B16-F0 des souris C57Bl/6). Les molécules impliquées dans l immunité (CMH-I, B7.1) n ont montré aucune variation d expression suite à la modulation de IGF-I. Par contre, la molécule de tétraspanine CD9, impliquée dans les interactions cellulaires, s est trouvée fortement inhibée. En parallèle, l inoculation in vivo de la lignée modifiée (B16-F0.MOD) induit une diminution de la tumorigénicité et améliore la survie. La vaccination par B16-F0.MOD entraîne la formation d effecteurs humoraux lytiques en présence de complément dirigés contre la lignée parentale, mais également d effecteurs cellulaires. En particulier, la sous-population CD8+ a la capacité d inhiber la croissance tumorale in vivo et la prolifération cellulaire in vitro. En conclusion, l inhibition de l IGF-I a provoqué la production d effecteurs immuns anti-mélanomeWe developed a strategy of immunological treatment based on inhibition of the insulin-like growth factor I (IGF-I) in melanoma cell line (B16-F0 from C57Bl/6 mice). Immunological molecules (CMH-I, B7.1) weren t modulated by targeting IGF-I. On the other hand, downregulation of the tetraspanin molecule named CD9, implicated in cellular interactions, was observed. Moreover, delayed outgrowth and increased survival were evaluated after inoculation of modified cells in syngeneic hosts. Vaccines were realised using these blocked modified cells. Cytotoxic antibodies were shown to be present in the sera of mice that were able to lyse parental cells in the presence of rabbit complement. Moreover, spleen cells from CD8 subpopulation harvested from hosts vaccinated were able to inhibit in vivo outgrowth and in vitro proliferation of parental B16-F0. Consequently promising results were reported using IGF-I inhibition strategy leading to stimulate anti-melanoma immune effectorsPARIS-BIUP (751062107) / SudocSudocFranceF

Le mélanome (aspects biologiques et cliniques, approches expérimentales contrôlant la prolifération tumorale par inhibition du facteur de croissance IGF-I (Insuline-like growth factor I))

PARIS-BIUP (751062107) / SudocSudocFranceF

Impact of grapefruit flavanone consumption on vascular protection and bone metabolism: Clinical and nutrigenomic study

International audienc

Effect of High-Fat Diet and its Reversal on the Thoracic Duct Lymph Composition in Pigs

National audienceHigh-fat, carbohydrate and low fiber diet is linked to increased CV risk as demonstrated in both experimental animals and epidemiological studies. Reversal to the healthy diet is known to decrease CV risk. Lymph transports both lipids absorbed in intestine and cholesterol from tissues (reverse cholesterol transport). Lipid composition of both post-nodal and pre-nodal lymph is affected by several pathophysiological conditions. Thus, the aim of the presents study was to evaluate how long-term changes in dietary fat intake in pigs alter the lymph lipid and lipoproteins. MATERIALS AND METHODS: Thirty-two female pigs were divided into three experimental groups: Group 1 - control: regular diet (RD - low fat – 3%) for 12 months; Group 2 – increased fat diet ad libitum (HFD) for 12 months (first 6 months moderate-fat (7.5%) diet and following 6 months high-fat diet (16% fat); Group 3: Reversal diet (HRD): HFD for 9 months followed by RD for 3 months. Pigs were examined every 3 months for: body weight, blood pressure, lipidemia, arterial stiffness and elasticity, intima-media complex (IMC) measured by ultrasound. After 12 months on the respective diets, all animals were killed after 24 hours fasting and thoracic duct lymph was collected. Samples from eight animals from each group were used for lymph lipid and lipoprotein distribution analysis by density gradient ultracentrifugation. RESULTS: Lipid lymph analysis revealed higher total cholesterol concentration in HFD fed animals than in these on the control diet. Lymph lipoprotein distribution showed that HFD caused an increase in chylomicron and HDL cholesterol levels, but did not affected VLDL and LDL cholesterol. The return from the HFD to the RD partly restored lymph cholesterol levels to values found in the control (RD) group. In conclusion, our findings support that the level of dietary fat affects lymphatic reverse cholesterol transport