Partnersuche: [NiCl2(PCy3)2] katalysiert die Titelreaktion zur Aryl‐Aryl‐ und Vinyl‐Aryl‐Kupplung hoch effizient. Die erste katalytische Kreuzkupplung von Pivalaten mit Organozinkreagentien als Partnern wird beschrieben (siehe Schema; Cy=Cyclohexyl, Piv=Pivalat).

The expression of ␣V integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of ␣V integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of ␣V integrins in hepatocellular carcinoma. We first analyzed the expression of ␣V integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. ␣V integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 ␣V-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study ␣V integrin regulation and function. HepG2 and Hep3B cells expressed ␣V integrin chain and used ␣V␤1 and ␣V␤5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) ␣ and transforming growth factor (TGF) ␤ significantly increased the expression levels of ␣V integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an ␣V integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor. (HEPATOLOGY 2002;36:418-426.)

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The pathogenesis of idiopathic and heritable forms of pulmonary arterial hypertension is still not completely understood, even though several causative genes have been proposed, so that a third of patients remains genetically unresolved. Here we applied a multistep approach to extend identification of the genetic bases of such a disease by searching for novel candidate genes/pathways. Twenty-eight patients belonging to 18 families were screened for BMPR2 mutations and BMPR2-negative samples were tested for 12 additional candidate genes by means of a specific massive parallel sequencing-based assay. Finally, whole exome sequencing was performed on four patients showing no mutations at known disease genes, as well as on their unaffected parents. In addition to EIF2AK4, which has been already suggested to be associated with pulmonary veno-occlusive disease, we identified the novel candidate genes ATP13A3, CD248, EFCAB4B, involved in lung vascular remodeling that represent reliable drivers contributing to the disease according to their biological functions/inheritance patterns. Therefore, our results suggest that combining gene panel and whole exome sequencing provides new insights useful for the genetic diagnosis of familial and idiopathic pulmonary arterial hypertension, as well as for the identification of biological pathways that will be potentially targeted by new therapeutic strategies.