A number of chromosomal abnormalities including 19q deletions have been associated with the formation of human gliomas. In this study, we employed a proteomics-based approach to identify possible genes involved in glioma tumorigenesis which may serve as potential diagnostic molecular markers for this type of cancer. By comparing protein spots from gliomas and non-tumor tissues using two-dimensional (2D) gel electrophoresis, we identified 11 up-regulated proteins and four down-regulated proteins in gliomas. Interestingly, we also discovered that a group of cytoskeleton-related proteins are differentially regulated in gliomas, suggesting the involvement of cytoskeleton modulation in glioma pathogenesis. We then focused on the cytoskeleton-related protein, SIRT2 (sirtuin homologue 2) tubulin deacetylase, which was down-regulated in gliomas. SIRT2 is located at 19q13.2, a region known to be frequently deleted in human gliomas. Subsequent Northern blot analysis revealed that RNA expression of SIRT2 was dramatically diminished in 12 out of 17 gliomas and glioma cell lines, in agreement with proteomic data. Furthermore, ectopic expression of SIRT2 in glioma cell lines led to the perturbation of the microtubule network and caused a remarkable reduction in the number of stable clones expressing SIRT2 as compared to that of a control vector in colony formation assays. These results suggest that SIRT2 may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network and may serve as a novel molecular marker for gliomas. Additional proteins were also identified, whose function in gliomas was previously unsuspected.

We previously Isolated from a rat regeneratbig islet cDNA library a gene named Reg, which Is expressed in regenerating Islets but is not expressed in normal islets. Here we examined the effect of rat Reg protein on pancreatic beta-cell replication using both 90% depancreatized rats and isolated Islets. The depancreatized rats that received i. Hydrated 5-pm sections of paraffin-embedded pancreatic tissues were stained for insulin by the labeled streptavidinbiotin method, using an LSAB kit (Dakopatts, Glostrup, Denmark). After being stained, the relative volumes of beta cells were measured by the point-counting method (1, 13).In Vitro Experiment. Pancreatic islets were isolated from male Wistar rats (body weight 200-250 g) by using density separation on a dextran gradient and cultured free-floating in RPMI 1640 medium/10%o fetal calf serum/penicillin G at 100 pg/ml/streptomycin at 100 g/ml for 48 hr to allow recovery from the isolation procedure (14). After this initial period, islets were transferred to 24-well culture dishes in groups of 50 islets. The islets were cultured in RPMI 1640 medium/2.7 mM D-glucose/2% fetal calf serum/penicillin G at 100 ;g/ ml/streptomycin at 100 ;g/ml in the presence of increased concentrations of Reg protein for 72 hr. During the last 24 hr, the islets were cultured in the above medium to which [methyl-3H]thymidine at 10 puCi/ml (Amersham; 1 Ci = 37 GBq) had been added. To estimate the amount of [3H]thymidine incorporated into newly synthesized DNA, the islets were washed as described (14) after the culture period and sonicated in 10 mM Tris.HCl/5 mM EDTA. DNA was precipitated by the addition of 7% ice-cold trichloroacetic acid and trapped by filtration on a glass-fiber disc (Whatman GF/C). The discs were dried, and radioactivity was counted after the addition of scintillation fluid (Packard Ultima Gold F). The DNA content of the islets was measured by a flurometric DNA assay using Hoechst 33258. To estimate labeling indices for insulin-positive cells, the [3H]thymidinelabeled islets were fixed in 4% paraformaldehyde for 20 min and embedded in OCT compound. Ten-micrometer sections were cut with a cryostat and immunostained with antiporcine insulin guinea pig antiserum (DAKO, 1:500) and Vectastain ABC-GO kit (Vector Laboratories). Autoradiography of the immunostained sections was performed by using lTo whom reprint requests should be addressed at:

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.

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Pancreatic cancer is characterized by excessive desmoplastic reaction and by a hypoxic microenvironment within the solid tumor mass. Chronic pancreatitis is also characterized by fibrosis and hypoxia. Fibroblasts in the area of fibrosis in these pathological settings are now recognized as activated pancreatic stellate cells (PSCs). Recent studies have suggested that a hypoxic environment concomitantly exists not only in pancreatic cancer cells but also in surrounding PSCs. This study aimed to clarify whether hypoxia affected the cell functions in PSCs. Human PSCs were isolated and cultured under normoxia (21% O(2)) or hypoxia (1% O(2)). We examined the effects of hypoxia and conditioned media of hypoxia-treated PSCs on cell functions in PSCs and in human umbilical vein endothelial cells. Hypoxia induced migration, type I collagen expression, and vascular endothelial growth factor (VEGF) production in PSCs. Conditioned media of hypoxia-treated PSCs induced migration of PSCs, which was inhibited by anti-VEGF antibody but not by antibody against hepatocyte growth factor. Conditioned media of hypoxia-treated PSCs induced endothelial cell proliferation, migration, and angiogenesis in vitro and in vivo. PSCs expressed several angiogenesis-regulating molecules including VEGF receptors, angiopoietin-1, and Tie-2. In conclusion, hypoxia induced profibrogenic and proangiogenic responses in PSCs. In addition to their established profibrogenic roles, PSCs might play proangiogenic roles during the development of pancreatic fibrosis, where they are subjected to hypoxia.

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Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries.