Purpose: We determined the antiangiogenic and anticancer activity of VEGI-192, a new isoform of TNFSF15 (VEGI,TL1), with a Lewis lung cancer murine tumor model. Experimental Design: Recombinant human VEGI-192 was produced in Escherichia coli and purified to apparent homogeneity.The protein was given systemically via i.p., i.v., or s.c. injections to tumor-bearing C57BL/6 mice. Tumor growth rates, animal survival rates, and general toxicity were determined. Effect on endothelial cell/smooth muscle cell ratio of the tumor vasculature was analyzed. Results: Systemic administration ofVEGI-192 gave rise to a marked inhibition of tumor growth. As much as 50% inhibition of the tumor growth rate was achieved with treatment initiated when the tumor volumes reached nearly 5% of the body weight. Inhibition of tumor formation was also observed when VEGI-192 was given at the time of tumor inoculation. Consistently, we observed an increased survival time of the treated animals.TheVEGI-192-treated animals showed no liver or kidney toxicity. The treatment eliminated tumor endothelial cells but not vascular smooth muscle cells, which remained associated with a residual vascular structure consisting of the basement membrane. In addition, we carried out immunohistochemical analysis of rat kidneys and found that vascular endothelial cell growth inhibitor (VEGI) expression is largely limited to endothelial cells. Conclusions: Our findings indicate thatVEGI is an endogenous inhibitor of angiogenesis, and that systemic administration of the VEGI-192 isoform resulted in inhibition of tumor angiogenesis and growth.The recent success of applying an antiangiogenic agent Avastin (1) in clinical settings for cancer treatment provided the first set of evidence to support the hypothesis that inhibition of tumor neovascularization can bring significant benefit to cancer therapy (2). Because neovascularization under either physiologic or pathologic conditions is controlled by a balance of endogenous proangiogenic and antiangiogenic factors, an important approach to develop therapeutic agents for cancers and other angiogenesis-driven diseases is to use endogenous antiangiogenic factors (3).We previously reported the discovery of an endothelial cellspecific gene product, vascular endothelial cell growth inhibitor (VEGI, TNFSF15), which exhibits 20% to 30% sequence homology to the tumor necrosis factor superfamily (4, 5). VEGI mRNA was found in many normal adult tissues, suggesting a physiologic role for this unique gene in the maintenance of the normal vasculature (6). We showed that VEGI is a potent and specific inhibitor of endothelial cell growth (4 -6). VEGI exhibits two distinctly different activities on endothelial cells: growth arrest of G 0 -G 1 cells and apoptosis of proliferating cells (7). These findings suggest that VEGI may have an important role in the regulation of vascular homeostasis.There are three differential splicing variants of VEGI (7). The initially reported VEGI protein is composed of 174 amino acids (4, 5). Hydr...

Full utilization of oxygen in biomass can greatly improve its atomic efficiency because of its nature of containing 40%–45% oxygen. In this work, we achieved a complete conversion of ethylene glycol toward glycolic acid with accompanying evolution of hydrogen via a cascade dehydrogenation and Cannizzaro reaction in water without any external oxidant. The yield of glycolic acid can reach 81%, and the whole homogeneous catalytic system displays a long-term continuous reaction stability. Moreover, this dehydrogenative oxidation process can be applied into the one-pot conversion of biomass carbohydrates toward α-hydroxyl acid. This finding provides a closer insight into the application of catalytic dehydrogenative oxidation techniques in designing value-added products from biomass-derived compounds as well as hydrogen evolution as a byproduct.

C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.

Methyl glycerate (MGLY) and methyl glycolate (MG) are directly produced in maximum yield by the one-pot conversion of hexose, and the formation of MGLY and MG experience different reaction routes.