The kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma

The kringle 1 domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial cell proliferation, suggesting that it might be an antiangiogenic molecule. Here, we evaluated the in vivo efficacy of a recombinant adenoassociated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model and explored its molecular mechanisms in vitro in both endothelial and tumor cells. We first showed that rAAV-HGFK1 treatment significantly prolonged the survival time of rats transplanted with tumor cells. Treatment with rAAV-HGFK1 inhibited tumor growth, decreased tumor microvessel density, and completely prevented intrahepatic, lung, and peritoneal metastasis in this in vivo model. In vitro, rAAVHGFK1 exhibited both antiangiogenic and antitumor cell effects, inhibiting the proliferation of both murine microvascular endothelial cells (MEC) and tumor cells, and inducing apoptosis and G 0-G 1 phase arrest in these cells. To our surprise, rAAV-HGFK1 did not act through the hepatocyte growth factor/hepatocyte growth factor receptor pathway. Instead, it worked mainly through epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling, with more minor contributions from vascular endothelial growth factor/vascular endothelial growth factor receptor and β fibroblast growth factor (bFGF)/β fibroblast growth factor receptor (bFGFR) signaling. In both MECs and tumor cells, rAAV-HGFK1 acted through two pathways downstream of EGFR, namely inhibition of extracellular signal-regulated kinase activation and stimulation of p38 mitogen-activated protein kinase/c-Jun-NH 2-kinase activation. These results suggest for the first time that HGFK1 exerts both antiangiogenic and antitumor cell activities mainly through EGF/EGFR signaling, and may thus be considered as a novel therapeutic strategy for the treatment of HCC. ©2008 American Association for Cancer Research.link_to_OA_fulltex

Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments

Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOSþ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θμe mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm2 41, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CLs for Δm2 41 < 13 eV2. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CLs for Δm2 41 < 1.6 eV2

Conducting Polymer Nanomaterials and Their Applications

A paradigm shift takes place in the fabrication of conducting polymers from bulky features with microsize to ultrafine features with nanometer range. Novel conducting polymer nanomaterials require the potential to control synthetic approaches of conducting polymer on molecular and atomic levels. In this article, the synthetic methodology of conducting polymer has been briefly considered with chemical oxidation polymerization and electrochemical polymerization. The recent achievements in the fabrication of conducting polymer nanomaterials have been extensively reviewed with respect to soft template method, hard template method and template-free method. It also details the morphological spectrum of conducting polymer nanomaterials such as nanoparticle, core-shell nanomaterial, hollow nanosphere, nanofiber/nanorod, nanotube, thin film and nanopattern and nanocomposite. In addition, their applications are discussed under nanometer-sized dimension.This work has been financially supported by the Brain Korea 21 program of the Korean Ministry of Education and the Hyperstructured Organic Materials Research Center supported by Korea Science and Engineering Foundation