A comparative effectiveness trial indicates that dorsal root ganglion stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to spinal cord stimulation.

Vitamin D has pleiotropic effects that go beyond its traditional role in calcium homeostasis. Hundreds of genes with vitamin D receptor response elements directly or indirectly influence cell cycling and proliferation, differentiation, and apoptosis. Vitamin D compounds also have effects on cell function that are nongenomic. The noncalcemic actions of vitamin D influence normal and pathological cell growth, carcinogenesis, immune function, and cardiovascular physiology. This review examines many of the various mechanisms by which vitamin D alters cellular growth and differentiation and explores cell-specific factors that influence responsiveness to vitamin D.

BackgroundThere is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC).MethodsUsing SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01.ResultsOut of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively.ConclusionPapillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma.

to respond to heat shock in the expected manner. FiPrevious studies from this laboratory identified a 28-nally, the amount of Hrp12 protein was also found to kd nonreducible protein, liver-derived immunoinhibiincrease after heat shock in a manner that was consistory factor (LDIF) from the mouse liver. Isolation The adult liver is a mitotically quiescent organ with most in all of the mammalian species tested. Analysis of the of hepatocytes resting in the G o stage of the cell cycle. 14 When protein structure of Hrp12 revealed motifs predicted to the liver is subject to partial hepatectomy, hepatocytes rebe targets for protein kinase C (PKC). More importantly, enter the cell cycle and proliferate. Thus, it is not surprising purified mouse Hrp12 could be phosphorylated in vitro that the liver is an abundant source of auto-inhibitory molewith PKC. The protein had significant similarity to cules that suppress protein synthesis and DNA replication; DnaK heat shock protein (Hsp)70 and contained a 54-however, only a few of these molecules have been fully characamino acid stretch with sequence similarity to Hsp90.terized. Delaunay et al. 15 isolated a liver inhibitory protein This prompted us to investigate the heat shock response from the rat with properties similar to that of heme-regulated of Hrp12. Isolated hepatocytes and hepatoma cells were translation inhibitor (HRI). Liver inhibitory protein supexposed to different heat shock temperatures (39.5ЊC, pressed the initiation of protein synthesis in rabbit reticulo-42.5ЊC, and 44.5ЊC); and then total RNA was extracted cyte lysates. Recently, Oka et al. 16 characterized a 136-amino and Northern analysis carried out. The message for this acid perchloric acid-soluble protein (PSP) from the rat liver novel protein responded atypically to heat shock. Althat strongly inhibited protein synthesis in a rabbit reticulothough the steady-state level of the message increased cyte lysate system. The kinetics of protein synthesis inhibiafter heat shock, a marked oscillatory pattern was sution exhibited by PSP was identical to liver inhibitory protein. perimposed on it. In contrast, the steady-state levels of PSP was also found to be identical to a previously isolated Hsp90 and Hsp70 messenger RNA (mRNA) were found rat liver-kidney perchloric acid-soluble protein (LKPS). 17 The liver contains two other proteins that inhibit cell proliferation: arginase and very low-density lipoprotein. 18 with a 27% identity and 60% similarity to a highly conserved

Brief (1-2 h) exposure of Clone 9 cells to inhibitors of oxidative phosphorylation such as azide is known to markedly increase glucose uptake. Clone 9 cells express GLUT1 but not GLUT2, -3, and -4, and the azide effect was not accompanied by any increase in cellular or plasma membrane GLUT1 level. To identify the molecular event underlying this apparent increase in GLUT1 intrinsic activity, we studied the acute effects of azide on the substrate binding activity of GLUT1 in Clone 9 cells by measuring glucose-sensitive cytochalasin B binding. The glucose-displaceable, cytochalasin B binding activity was barely detectable in membranes isolated from Clone 9 cells under control conditions but was readily detectable after a 60-min incubation of cells in the presence of 5 mM azide showing a 3-fold increase in binding capacity with no change in binding affinity. Furthermore, the cytochalasin B binding activity of purified human erythrocyte GLUT1 reconstituted in liposomes was significantly reduced in the presence of cytosol derived from azide-treated Clone 9 cells but not in the presence of cytosol from control cells; this effect was heat-labile and abolished by the presence of the peptide corresponding to the GLUT1 COOH-terminal sequence. These results suggest that a cytosolic protein in Clone 9 cells binds to GLUT1 at its COOH-terminal domain and inhibits its substrate binding and that azide-induced metabolic alteration releases GLUT1 from this inhibitory interaction. Studying the binding of cytosolic proteins derived from 35 S-labeled Clone 9 cells to glutathione S-transferase fusion protein containing glucose transporter COOH-terminal sequences, we identified 28-and 70-kDa proteins that bind specifically to the cytoplasmic domain of GLUT1 and GLUT4 in vitro. We also found a 32 P-labeled, 85-kDa protein that binds to GLUT4 but not to GLUT1 and only in cytosol derived from azidetreated cells. The roles, if any, of these glucose transporter-binding proteins in the azide-sensitive modulation of GLUT1 substrate binding activity in Clone 9 cells are yet to be determined.