46 research outputs found
The angiopoietin/tie2 pathway in hepatocellular carcinoma
Due to the usually late diagnosis and lack of effective therapies, hepatocellular carcinoma (HCC), which poses a growing global health problem, is characterized by a poor prognosis. Angiogenesis plays an important role in HCC progression, and vascular endothelial growth factor (VEGF) and angiopoietins (Angs) are key drivers of HCC angiogenesis. VEGF-targeting strategies already represent an important component of today's systemic treatment landscape of HCC, whereas targeting the Ang/Tie2 signaling pathway may harbor future potential in this context due to reported beneficial anticancer effects when targeting this pathway. In addition, a better understanding of the relation between Angs and HCC angiogenesis and progression may reveal their potential as predictive factors for post-treatment disease progression and prognosis. In this review, we give a comprehensive overview of the complex role of Ang/Tie2 signaling in HCC, pinpointing its potential value as biomarker and target for HCC treatments, aiding HCC diagnosis and therapy
NOX1 inhibition attenuates the development of a proâtumorigenic environment in experimental hepatocellular carcinoma
BackgroundThe poor prognosis of advanced HCC and limited efficacy of current systemic treatments emphasize the need for new or combined targeted therapies. The development of HCC is a multistage process in which liver injury appears in a complex microenvironment associated with oxidative stress. NOX enzymes are the main source of ROS during hepatocarcinogenesis and NOX1 in particular has shown correlation with poor prognosis of HCC patients. This study evaluates the effect of pharmacological NOX1 inhibition on the development and progression of HCC and its effect on the tumor microenvironment.MethodsThe in vitro cytotoxic effects of the NOX1 inhibitor GKT771 (Genkyotex) on human Huh7 and Hep3B and murine Hepa1-6 HCC cell lines, the human THP1 monocyte cell line and mouse macrophages were evaluated via MTT, LDH activity and CaspGlo (R) assays. In order to induce in vivo HCC, male SV129 wild-type mice received weekly IP injections of diethylnitrosamine (DEN) (35 mg/kg) for 20-25 weeks. Mice were treated with vehicle or GKT771 (30 mg/kg) via oral gavage, daily or twice daily, in preventive and therapeutic studies. The liver damage was evaluated for inflammation, angiogenesis, fibrosis and HCC development via histology, RT-qPCR, multiplex analyses and ROS levels.ResultsA concentration-dependent reduction in cellular activity of the human HCC cell lines without cytotoxicity was observed. GKT771 treatment reduced LPS-induced pro-inflammatory bone-marrow derived macrophage polarization. DEN injections resulted in 100% tumor formation and the induction of HCC markers which could be reduced by twice daily dosing of GKT771 at early onset of advanced HCC. DEN-induced HCC resulted in an upregulation of pro-inflammatory, angiogenic and fibrotic markers which was less pronounced in GKT771 treated mice in all treatment regimens. In line, liver fibrosis was induced in HCC mice and this to a lesser extend upon GKT771 treatment.ConclusionsNOX1 inhibition showed to be safe and well tolerated and was able to attenuate the induction of a pro-inflammatory, angiogenic and pro-fibrotic microenvironment suggesting that this might be a promising adjuvant therapeutic strategy in the treatment of advanced HCC
Effect of isoform-specific HIF-1α and HIF-2α antisense oligonucleotides on tumorigenesis, inflammation and fibrosis in a hepatocellular carcinoma mouse model
Hepatitis C prevalence and risk factors in hemodialysis patients in Central Brazil: a survey by polymerase chain reaction and serological methods
Targeting angiogenic and inflammatory components of the tumor microenvironment in hepatocellular carcinoma
L'Europe sociale en Belgique: emploi et inclusion sociale au prisme de l'européanisation
La prĂ©sente contribution vise Ă synthĂ©tiser les principaux acquis de la recherche multidisciplinaire « Outils europĂ©ens et politique sociale belge » (« ETOS.be ») menĂ©e dans le cadre du programme « SociĂ©tĂ© et avenir » de la Politique scientifique fĂ©dĂ©rale, et prĂ©sentĂ©s dans un livre paru en juin 2011. Cette recherche portait sur lâeuropĂ©anisation des politiques sociales au cours de la pĂ©riode 1989-2009. Cet article est focalisĂ© sur le droit europĂ©en classique (directives et rĂšglements), les mĂ©thodes ouvertes de coordination (MOC) et les instruments financiers (notamment le Fonds social europĂ©en, FSE). Lâanalyse est menĂ©e au travers de deux grandes thĂ©matiques relevant de lâaction actuelle de lâUE en matiĂšre sociale : lâemploi et les conditions de travail dâune part, et lâinclusion sociale dâautre part