AdTIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice.

TIMP-2 is a natural matrix metalloproteinase (MMP) inhibitor that prevents the degradation of extracellular matrix proteins. It abolishes the hydrolytic activity of all activated members of the metalloproteinase family and in particular that of MT1-MMP, MMP-2, and MMP-9, which are selective for type IV collagenolysis. Since MMPs have been implicated in both cancer progression and angiogenesis, we generated a recombinant adenovirus to deliver human TIMP-2 (AdTIMP-2) and evaluated its anticancer efficiency in three murine models. Our results demonstrated that overexpression in vitro of TIMP-2 inhibited the invasion of both tumor and endothelial cells without affecting cell proliferation. Its in vivo efficiency has been evaluated in murine lung cancer LLC, and colon cancer C51 in syngeneic mice as well as in human breast cancer MDA-MB231 in athymic mice. Preinfection of tumor cells by AdTIMP-2 resulted in an inhibition of tumor establishment in more than 50% of mice in LLC and C51 models and in 100% mice in the MDA-MB231 model. A single local injection of AdTIMP-2 into preestablished tumors of these three types significantly reduced tumor growth rates by 60--80% and tumor-associated angiogenesis index by 25--75%. Lung metastasis of LLC tumor was inhibited by >90%. In addition, AdTIMP-2-treated mice showed a significantly prolonged survival in all the cancer models tested. These data demonstrate the potential of adenovirus-mediated TIMP-2 therapy in cancer treatment.

[Dormant tumors and organs resistant to metastasis after gene transfer: dream and reality of anti-angiogenic gene therapy]. / Tumeurs dormantes et organes résistants aux métastases après transfert de gènes: rêve et réalité de la thérapie génique anti-angiogénique.

Treating cancer by targeting its vasculature is a recent conceptual revolution. The use of newly discovered potent antiangiogenic factors has confirmed the anti-growth and anti-metastatic efficiency of anti-angiogenic therapy in a variety of experimental solid tumour models. Using gene transfer technique to deliver anti-angiogenic molecules in vivo is becoming a widely accepted new approach. This review summarizes the biological basis, current situation and development trends of this new therapy, as well as its promising perspectives in cancer treatment.

[Blood glucose and insulin secretion after meals rich in simple and complex carbohydrates, in non-insulin-dependent diabetics]. / Glycémies et insulino-sécrétion après des repas riches en sucres simples et complexes chez des diabétiques non insulino-dépendants.

In 10 well controlled non insulin-dependent diabetics, 25 g of complex sugars were replaced by the same amount of simple sugars in each of two isocaloric meals identical in their lipid, protein and carbohydrate contents. This had no detrimental effect on postprandial glycaemic and insulin responses. There were no statistically significant changes in areas under the curve and kinetics of glycaemic, insulin and peptide C responses after ingestion of limited amounts of simple sugars. It appears from these results that well controlled, non insulin-dependent diabetic patients without marked postprandial fluctuations in glycaemia (as confirmed by self-performed capillary blood tests) can be authorized to take 25 to 40 g of simple sugars (preferably fructose) during meals.