Investigations into rates and mechanisms of mercury depuration in the Killifish, Fundulus Heteroclitus

Metallothionein (MT) and glutathione (GSH) have been shown in mammalian research to play a role in the sequestration and depuration of mercury. The sulfhydryl groups on both these peptides have a strong affinity for mercury, MT for Hg2+ and GSH for CH3Hg+. In this study, killifish (Fundulus heteroclitus) were force-fed one piece of squid laced with labelled mercuric nitrate to give a final food concentration of 20 ppm 203Hg2+ and 0.03 -0.05 µg g-1 Hg2+ total dose. Most of the mercury, 84.1 ± 12.1% (mean ± standard deviation), is depurated within the first 24 hours; of that retained, most was found in the intestine. There was little change over the next 6 days. The feces contained high amounts of mercury and can be considered the main route of excretion. Thin-layer chromatography of bile showed no noticeable amounts of mercury bound to GSH in the bile. But no conclusions regarding bile and enterohepatic circulation can be made since the killifish is too small a model in which to monitor it. MT was found in appreciable amounts in the liver and intestine homogenates by gel electrophoresis but autoradiography did not demonstrate the binding of Hg2+ to the MT. Most of the mercury which had been retained was associated with both soluble and insoluble proteins of high molecular weight (\u3e90,000 daltons). Therefore the first line of defense for this organism appears to be the intestine, as 90% of the mercury did not get beyond this organ

Zapomniany tłumacz Odysei Homerowej

Zapomniany tłumacz Odysei Homerowe

Molecular and Clinical Aspects of Targeting the VEGF Pathway in Tumors

Tumor angiogenesis is a complex process resulting from many signals from the tumor microenvironment. From preclinical animal models to clinical trials and practice, targeting tumors with antiangiogenic therapy remains an exciting area of study. Although many scientific advances have been achieved, leading to the development and clinical use of antiangiogenic drugs such as bevacizumab, sorafenib, and sunitinib, these therapies fall short of their anticipated benefits and leave many questions unanswered. Continued research into the complex signaling cascades that promote tumor angiogenesis may yield new targets or improve upon current therapies. In addition, the development of reliable tools to track tumor responses to antiangiogenic therapy will enable a better understanding of current therapeutic efficacy and may elucidate mechanisms to predict patient response to therapy

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

Purpose The current treatment outcomes in cholangiocarcinoma are poor with cure afforded only by surgical extirpation. The efficacy of targeting the tumoural endothelial marker CD105 in cholangiocarcinoma, as a basis for potential microbubble-based treatment, is unknown and was explored here. Methods Tissue expression of CD105 was quantified using immunohistochemistry in 54 perihilar cholangiocarcinoma samples from patients who underwent resection in a single centre over a ten-year period, and analysed against clinicopathological data. In vitro flow assays using microbubbles functionalised with CD105 antibody were conducted to ascertain specificity of binding to murine SVR endothelial cells. Finally, CD105-microbubbles were intravenously administered to 10 Balb/c nude mice bearing heterotopic subcutaneous human extrahepatic cholangiocarcinoma (TFK-1 and EGI-1) xenografts after which in vivo binding was assessed following contrast-enhanced destruction replenishment ultrasound application. Results Though not significantly associated with any examined clinicopathological variable, we found that higher CD105 expression was independently associated with poorer patient survival (median 12 vs 31 months; p = 0.002). In vitro studies revealed significant binding of CD105-microbubbles to SVR endothelial cells in comparison to isotype control (p = 0.01), as well as in vivo to TFK-1 (p = 0.02) and EGI-1 (p = 0.04) mouse xenograft vasculature. Conclusion Our results indicate that CD105 is a biomarker eminently suitable for cholangiocarcinoma targeting using functionalised microbubbles