Alcohol and wine in relation to cancer and other diseases.

Heavy alcohol consumption is associated with increased overall mortality, cancer, liver, and cardiovascular diseases; but low doses of alcohol (up to one drink per day) are not associated with the risk of any cancer site with the exception of breast cancer and possibly of oral and pharyngeal cancers. Moreover, recent evidence indicates that moderate alcohol and specifically wine intake provides cardioprotection and neuroprotection and may increase longevity. Various experimental data hypothesize a potential cancer chemopreventive role of some grape extracts, and complete sequencing of the grapevine genome has revealed genes responsible for the synthesis of health-promoting compounds (resveratrol and other polyphenols), thus advocating the development of future potential nutraceutical strategies. This focuses on the pros and cons of moderate alcohol and wine consumption and opens a debate on this topic.

Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation.

Angiostatin effectively blocks tumor angiogenesis through still poorly understood mechanisms. Given the close association between immune and vascular regulation, we investigated the effects of angiostatin on angiogenesis-associated leukocytes. Angiostatin inhibited the migration of monocytes and, even more markedly, neutrophils. Angiostatin blocked chemotaxis of neutrophils to CXCR2 chemokine receptor agonists (IL-8, MIP-2, and GROalpha), formyl-Met-Leu-Phe (fMLP), and 12-O-tetradecanoylphorbol 13-acetate, and repressed fMLP-induced mitochondrial activity. Two different angiostatin forms (kringles 1-4 and 1-3) were effective, whereas whole plasminogen had no effect. IL-8, MIP-2, and GROalpha induced intense angiogenic reactions in vivo, but no angiogenic response to these factors was observed in neutropenic mice, demonstrating an essential role for neutrophils. Angiostatin potently inhibited chemokine-induced angiogenesis in vivo, and consistent with in vitro observations, both angiostatin forms were active and whole plasminogen had little effect. Angiostatin inhibition of angiogenesis in vivo was accompanied by a striking reduction in the number of recruited leukocytes. In vivo, the inflammatory agent lipopolysaccharide also induced extensive leukocyte infiltration and angiogenesis that were blocked by angiostatin. Neutrophils expressed mRNAs for ATP synthase and angiomotin, two known angiostatin receptors. These data show that angiostatin directly inhibits neutrophil migration and neutrophil-mediated angiogenesis and indicate that angiostatin might inhibit inflammation.