Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin B2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now sanofi-aventis). Jerini AG is seeking a worldwide partner for the development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis and seeking a partner in Asia, North America, South America and Australia for angioedema. In August 2004, Aventis merged with Sanofi-Synthelabo to form sanofi-aventis. Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004. It was announced in September 2004 by Jerini that a pivotal registration study, known as FAST 1 (For Angioedema Subcutaneous Treatment), had been initiated in the US and Canada. The protocol of a European study, known as FAST 2, was submitted to the authorities in September 2004. Jerini is currently conducting pivotal/registration trials for angioedema in the US, Canada and Europe. During the 3rd Annual BioPartnering North America Conference (BPN-2005), Jerini announced that it expects to complete registration trials in the second half of 2005/first half of 2006, with a launch of icatibant for HAE in 2007. The US FDA granted fast-track status to icatibant in July 2004 for the treatment of HAE. Effective December 2003, icatibant gained orphan drug status in the US for the same indication. Previously, in January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema.
 ...
PMID:Icatibant: HOE 140, JE 049, JE049. 1599 85

Hepatitis B virus core protein (HBc) has been implicated in hepatocarcinogenesis through several mechanisms. Resistance of hepatitis B virus (HBV)-infected hepatocytes to apoptosis is considered one of the major contributors to the progression of chronic hepatitis to cirrhosis and ultimately to hepatocellular carcinoma. The Fas receptor/ligand (Fas/FasL) system plays a prominent role in hepatocyte death during HBV infection. Here we report that HBc mediates resistance of hepatoma cells to agonistic anti-Fas antibody (CH11)-induced apoptosis. When HBc was introduced into human hepatoma cells, the cells became resistant to CH11 cytotoxicity in a p53-dependent manner. HBc significantly down-regulated the expression of p53, total Fas, and membrane-bound Fas at the mRNA and protein levels and reduced FasL mRNA expression. In contrast, HBc up-regulated the expression of soluble forms of Fas by increasing Fas alternative mRNA splicing. Mechanistically, HBc-mediated Fas alternative mRNA splicing was associated with up-regulation of polypyrimidine tract-binding protein 1 and down-regulation of Fas-activated serine/threonine kinase. These results indicated that HBc may prevent hepatocytes from Fas-induced apoptosis by the dual effects of reducing the expression of the proapoptotic form of Fas and enhancing the expression of the antiapoptotic form of the receptor, which may contribute to the survival and persistence of infected hepatocytes during chronic infection.
 ...
PMID:Hepatitis B virus core protein inhibits Fas-mediated apoptosis of hepatoma cells via regulation of mFas/FasL and sFas expression. 2546 93