14, 15 The present study confirms the safety profile of αPlGF (Supporting Information Results and Supporting Information Fig. 11). Furthermore, αPlGF did not compensatorily up-regulate the expression of VEGF; selleck such up-regulation has been suggested to represent a possible cause of resistance to antiangiogenic treatment (Supporting Information Results and Supporting Information Fig. 11). In conclusion, this experimental study characterized the pathophysiological mechanisms and molecular effects that PlGF exerts on murine and human cirrhotic livers and on HSCs. Blockade of the PlGF pathway in cirrhotic mice by monoclonal antibodies or by genetic deficiency of PlGF decreased

hepatic and mesenteric angiogenesis, mesenteric arterial blood flow, fibrosis, and inflammation, as well as portal pressure. Also because of its safety profile, αPlGF may be considered as an attractive candidate for treating patients with chronic liver disease. We thank Julien Dupont and Huberte Moreau for technical assistance,

Kin Jip Cheung for compiling the demographic data of the patients, and Susana Kalko for technical assistance with bioinformatic analysis. LX-2 cells were generously supplied by Scott L. Friedman; αPlGF was kindly provided by ThromboGenics NV. Additional Supporting Information may be found in the online Antiinfection Compound Library cell line version of this article. “
“Background and Aim:  Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization

(TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE. Methods:  We evaluated 264 patients with intermediate-stage HCC who underwent TACE between January 2006 and September 2009. We designated the development of vascular invasion or extrahepatic see more spread during follow up as “stage progression” (SP), and hypothesized that SP might be the surrogate end-point for TACE refractoriness. Results:  The median follow up was 18.2 months, and median number of TACE was 3.0 (range, 1–13). Median time-to-progression was 5.5 months (95% confidence interval, 4.8–6.2), and median overall survival was 25.3 months (95% confidence interval, 21.6–29.0). We classified the patients according to disease course as: no progressive disease (PD(−); n = 33); PD without SP (PD(+)SP(−); n = 113); PD followed by SP (PDSP; n = 47); and simultaneous PD and SP (PD&SP; n = 64). PD(−) and PD(+)SP(−) groups showed no difference in overall survival, PDSP group had worse overall survival than PD(−) and PD(+)SP(−) groups, and PD&SP group had the worst overall survival. The significant prognostic factors for SP-free survival were development of PD and need for three sessions of TACE during the first 6 months.