S. Shimoda

Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination

Block copolymer of poly(ethylene glycol)-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-P[Asp(DET)]) has been originally introduced as a promising gene carrier by forming a nanomicelle with plasmid DNA. In this study, the polyplex micelle of PEG-SS-P[Asp(DET)], which disulfide linkage (SS) between PEG and cationic polymer can detach the surrounding PEG chains upon intracellular reduction, was firstly evaluated with respect to in vivo transduction efficiency and toxicity in comparison to that of PEG-P[Asp(DET)] in peritoneally disseminated cancer model. Intraperitoneal (i.p.) administration of PEG-SS-P[Asp(DET)] polyplex micelles showed a higher (P<0.05) transgene expression compared with PEG-P[Asp(DET)] in tumors. In contrast, the delivered distribution of the micelles was not different between the two polyplex micelles. PEG-SS-P[Asp(DET)] micelle encapsulating human tumor necrosis factor α (hTNF-α) gene exhibits a higher antitumor efficacy against disseminated cancer compared with PEG-P[Asp(DET)] or saline control. No hepatic and renal toxicities were observed by the administration of polyplex micelles. In conclusion, PEG-detachable polyplex micelles may represent an advantage in gene transduction in vivo over PEG-undetachable polyplex micelles after i.p. administration for peritoneal dissemination of cancer.

Effectiveness and safety of daclatasvir plus asunaprevir for HCV genotype 1b patients aged 75 and over with or without cirrhosis

The aim of this study was to evaluate the efficacy and safety of 24‐week daclatasvir (NS5A inhibitor) plus asunaprevir (NS3/4 A protease inhibitor) treatment for elderly patients with hepatitis C virus (HCV) genotype 1b infection.

Impaired activities of cyclic adenosine monophosphate-responsive element binding protein, protein kinase A and calcium-independent phospholipase A2 are involved in deteriorated regeneration of cirrhotic liver after partial hepatectomy in rats.

Aims:  This study is to elucidate whether cyclic adenosine monophosphate (cAMP)‐mediated signal is involved in lower regenerative potential of cirrhotic liver.

P1108 EFFICACY AND TOLERABILITY OF TELAPREVIR-BASED TRIPLE THERAPY FOR ADVANCED FIBROSIS STAGE CHRONIC HEPATITIS C PATIENTS: RESULTS OF THE KYUSHU UNIVERSITY LIVER DISEASE STUDY GROUP

response rate. This study aimed to detect types and predictors of interferon induced cardiac complications in Egyptian hepatitis-Cvirus infected patients treated with pegylated interferon/ribavirin combination therapy. Methods: A total of 194, chronic HCV patients were followed up from the time of receiving treatment till one year after end of treatment, to detect cardiac disorders and to determine the response status. Patients were assessed by through history taking, full clinical examination, full laboratory parameters and cardiac assessment using the standard 12 lead ECG and Transthoracic Doppler Echocardiography. Patients in the final analysis were divided into: Group A (who developed cardiac disorders) and group B (who did not develop cardiac disorders). Results: The baseline clinical features (cardiovascular risk factors and hemodynamics) were comparable in both groups. Patients who developed cardiac disorders had higher baseline ALT level, hepatic fibrosis and histologic activity than patients without cardiac disorders (P < 0.05). The confirmed cardiac complications represented 19.6% (n =38) and included left ventricular systolic and diastolic dysfunction, pericardial effusion, arrhythmia, myocardial ischemia and heart failure. Hepatic activity in the liver biopsy, ejection fraction (EF) and left ventricular end diastolic dimension (LVEDD) were independent predictors of the cardiovascular complications. Conclusions: Pegylated interferon therapy of chronic HCV is associated with many types of cardiac complications. Predictors of which are hepatic activity in the liver biopsy, EF and LVEDD in Echocardiography.