Histidine-Rich Glycoprotein Can Prevent Development of Mouse Experimental Glioblastoma

Extensive angiogenesis, formation of new capillaries from pre-existing blood vessels, is an important feature of malignant glioma. Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma. However, the modest efficacy of these drugs and emerging problems with anti-VEGF treatment resistance welcome the development of alternative antiangiogenic therapies. One potential candidate is histidine-rich glycoprotein (HRG), a plasma protein with antiangiogenic properties that can inhibit endothelial cell adhesion and migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the effect of HRG on brain tumor development. Tumors were induced with platelet-derived growth factor-B (PDGF-B), in the presence or absence of HRG. We found that HRG had little effect on tumor incidence but could significantly inhibit the development of malignant glioma and completely prevent the occurrence of grade IV tumors (glioblastoma)

Molecules as tracers of galaxy evolution: an EMIR survey. I. Presentation of the data and first results

We investigate the molecular gas properties of a sample of 23 galaxies in order to find and test chemical signatures of galaxy evolution and to compare them to IR evolutionary tracers. Observation at 3 mm wavelengths were obtained with the EMIR broadband receiver, mounted on the IRAM 30 m telescope on Pico Veleta, Spain. We compare the emission of the main molecular species with existing models of chemical evolution by means of line intensity ratios diagrams and principal component analysis. We detect molecular emission in 19 galaxies in two 8 GHz-wide bands centred at 88 and 112 GHz. The main detected transitions are the J=1-0 lines of CO, 13CO, HCN, HNC, HCO+, CN, and C2H. We also detect HC3N J=10-9 in the galaxies IRAS 17208, IC 860, NGC 4418, NGC 7771, and NGC 1068. The only HC3N detections are in objects with HCO+/HCN<1 and warm IRAS colours. Galaxies with the highest HC3N/HCN ratios have warm IRAS colours (60/100 {\mu}m>0.8). The brightest HC3N emission is found in IC 860, where we also detect the molecule in its vibrationally excited state.We find low HNC/HCN line ratios (<0.5), that cannot be explained by existing PDR or XDR chemical models. Bright HC3N emission in HCO+-faint objects may imply that these are not dominated by X-ray chemistry. Thus the HCN/HCO+ line ratio is not, by itself, a reliable tracer of XDRs. Bright HC3N and faint HCO+ could be signatures of embedded starformation, instead of AGN activity

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology characterised by inflammation and fibrosis of the biliary tree. The mean age at diagnosis is 40 years and men are affected twice as often as women. There is a reported annual incidence of PSC of 0.9–1.31/100,000 and point prevalence of 8.5–13.6/100,000. The onset of PSC is usually insidious and many patients are asymptomatic at diagnosis or have mild symptoms only such as fatigue, abdominal discomfort and pruritus In late stages, splenomegaly and jaundice may be a feature. In most, the disease progresses to cirrhosis and liver failure. Cholangiocarcinoma develops in 8–30% of patients. PSC is thought to be immune mediated and is often associated with inflammatory bowel disease, especially ulcerative colitis. The disease is diagnosed on typical cholangiographic and histological findings and after exclusion of secondary sclerosing cholangitis. Median survival has been estimated to be 12 years from diagnosis in symptomatic patients. Patients who are asymptomatic at diagnosis, the majority of whom will develop progressive disease, have a survival rate greater than 70% at 16 years after diagnosis. Liver transplantation remains the only effective therapeutic option for patients with end-stage liver disease from PSC, although high dose ursodeoxycholic acid may have a beneficial effect