Patients with cirrhosis and bare‐stent TIPS may have increased risk of hepatocellular carcinoma

Rafael Bañares, Oscar Núñez, María Escudero, Cristina Fernández, Javier Vaquero, Inmaculada Beceiro, Antonio Echenagusía, Gerardo Clemente, Leandro Santos – 22 February 2005 – A trend toward a higher incidence of hepatocelullar carcinoma (HCC) in patients with cirrhosis treated with bare‐stent transjugular intrahepatic portosystemic shunt (TIPS) has been observed in previous studies. To assess the influence of TIPS as a risk factor for developing HCC, we have compared the incidence of HCC in two retrospective cohorts of patients.

Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis

Yoshitaka Kamegaya, Yoichi Hiasa, Lawrence Zukerberg, Nina Fowler, Jason T. Blackard, Wenyu Lin, Won H. Choe, Emmett V. Schmidt, Raymond T. Chung – 22 February 2005 – We developed hepatitis C virus (HCV) core‐E1‐E2 and HCV core transgenic mice on a common genetic background to assess the contribution of HCV structural proteins to hepatocarcinogenesis. Eight‐week‐old core‐E1‐E2, core, and nontransgenic mice inbred on the FVB×C57Bl/6 background were treated with diethylnitrosamine (DEN) and sacrificed at 32 weeks old. Proliferation and apoptosis were assessed by immunohistochemistry.

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites

Joan Clària, Jeffrey D. Kent, Marta López‐Parra, Ginés Escolar, Luís Ruiz‐del‐Arbol, Pere Ginès, Wladimiro Jiménez, Boris Vucelic, Vicente Arroyo – 22 February 2005 – Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti‐inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX‐2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis.

Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice

Adrien Croquelois, Alex Blindenbacher, Luigi Terracciano, Xueya Wang, Igor Langer, Freddy Radtke, Markus H. Heim – 22 February 2005 – The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype.

Interplay among cardiotrophin‐1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration

Naiara Beraza, Juan Martín Marqués, Eduardo Martínez‐Ansó, María Iñiguez, Jesús Prieto, Matilde Bustos – 22 February 2005 – Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase‐2 (COX‐2). Cardiotrophin‐1 (CT‐1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined.

Keratin mutation primes mouse liver to oxidative injury

Qin Zhou, Xuhuai Ji, Lixin Chen, Harry B. Greenberg, Shelly C. Lu, M. Bishr Omary – 22 February 2005 – Mutation of the cytoskeletal intermediate filament proteins keratin 8 and keratin 18 (K8/K18) is associated with cirrhosis in humans, whereas transgenic mice that overexpress K18 Arg89→Cys (R89C) have significant predisposition to liver injury. To study the mechanism of keratin‐associated predisposition to liver injury, we used mouse microarrays to examine genetic changes associated with hepatocyte keratin mutation and assessed the consequences of such changes.

Small ubiquitin‐related modifiers: A novel and independent class of autoantigens in primary biliary cirrhosis

Caroline Janka, Carlo Selmi, M. Eric Gershwin, Hans Will, Thomas Sternsdorf – 22 February 2005 – Serum autoantibodies against components of nuclear dots (anti‐NDs), namely PML and Sp100, are specifically detected in 20% to 30% of patients with primary biliary cirrhosis (PBC). Although anti‐ND antibodies are nonpathogenic, the mechanisms that lead to this unique reactivity are critical to understanding the loss of immune tolerance in PBC. Importantly, Sp100 and PML are both covalently linked to small ubiquitin‐related modifiers (SUMOs).

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