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Jacobson I.M.,Cornell University | Davis G.L.,Baylor Regional Transplant Institute | El-Serag H.,Baylor College of Medicine | Negro F.,University of Geneva | Trepo C.,Service de Gastro enterologie
Clinical Gastroenterology and Hepatology | Year: 2010

Hepatitis C virus (HCV) infections pose a growing challenge to health care systems. Although chronic HCV infection begins as an asymptomatic condition with few short-term effects, it can progress to cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and death. The rate of new HCV infections is decreasing, yet the number of infected people with complications of the disease is increasing. In the United States, people born between 1945 and 1964 (baby boomers) are developing more complications of infection. Men and African Americans have a higher prevalence of HCV infection. Progression of fibrosis can be accelerated by factors such as older age, duration of HCV infection, sex, and alcohol intake. Furthermore, insulin resistance can cause hepatic steatosis and is associated with fibrosis progression and inflammation. If more effective therapies are not adopted for HCV, more than 1 million patients could develop HCV-related cirrhosis, hepatic decompensation, or HCC by 2020, which will impact the US health care system. It is important to recognize the impact of HCV on liver disease progression and apply new therapeutic strategies. © 2010 AGA Institute.

Louis R.,Service de pneumologie | Schleich F.,Service de pneumologie | Corhay J.-L.,Service de pneumologie | Louis E.,Service de Gastro enterologie
Revue Medicale de Liege | Year: 2012

Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype.

Hamoudi R.A.,University of Cambridge | Appert A.,University of Cambridge | Ye H.,University of Cambridge | Ruskone-Fourmestraux A.,Service de Gastro enterologie | And 11 more authors.
Leukemia | Year: 2010

Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-B pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-B target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-B target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/lymphoma (BCL)2, while translocation-negative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and-negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-B activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors. © 2010 Macmillan Publishers Limited All rights reserved.

Uzzan B.,Laboratoire Of Pharmacologie | Benamouzig R.,Service de Gastro enterologie
Current Colorectal Cancer Reports | Year: 2016

Curcumin is the main component of the Indian spice curcuma (Indian saffron), originating from its rhizome. Curcumin is consumed as food, anywhere in the world and almost daily in India. It has also been used as a drug in Ayurvedic medicine for centuries. This polyphenol substance has pleiotropic effects, interfering with many signaling molecules: pro-inflammatory molecules, transcription factors, enzymes, protein kinases, transport proteins, proteins involved in cell survival, adhesion molecules, growth factors, receptors, proteins regulating cell cycle, chemokines, nucleic acids…. Oral bioavailability of traditional forms of curcumin is low, making it particularly suitable for therapy of diseases of the intestinal tract. Curcumin has anti-inflammatory, anti-oxidant, anti-proliferative, and pro-apoptotic properties, making it an excellent candidate as a chemopreventive agent in colorectal cancer. Contrasting with many in vitro studies devoted to curcumin and a lot of in vivo studies on animal models, curcumin has rarely been assessed in clinical studies dealing with digestive oncology. However, several clinical trials are in progress in this domain. Until now, curcumin has no official medical indication. © 2016 Springer Science+Business Media New York

Chaillon A.,Service de Bacteriologie Virologie | Chaillon A.,University of Tours | Sirinelli A.,Service de Chirurgie Cardiaque | De Muret A.,Laboratoire dAnatomie et Cytologie Pathologiques | And 4 more authors.
Journal of Heart and Lung Transplantation | Year: 2011

Hepatitis E virus (HEV) is an emerging problem amongst transplant recipients. We report a patient with chronic HEV hepatitis after a heart transplant. The patient received a 3-month course of oral ribavirin (17 mg/kg/day). HEV RNA became undetectable in the serum after 1 month of treatment and remained undetectable in serum and stool samples until the last follow-up, 2 months after completion of ribavirin therapy. The values of liver function indicators returned to normal reference ranges. The main ribavirin-induced side effect was a significant but well-tolerated anemia. We confirmed that ribavirin may induce a sustained virologic response (4 months after ribavirin cessation) in heart transplant patients with chronic HEV infection. Liver cytolysis is rather common in patients after heart transplantation. Rapid evolution to liver fibrosis lesions and available anti-viral therapy highlight the need to look for HEV infection in heart transplant recipients with unexplained hepatitis. © 2011 International Society for Heart and Lung Transplantation. All rights reserved.

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