Search results for " GAS"
showing 10 items of 4643 documents
Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma
2019
Background & Aims Alterations of individual genes variably affect the development of hepatocellular carcinoma (HCC). Thus, we aimed to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRNs). Methods Using data from The Cancer Genome Atlas, from the LIRI-JP (Liver Cancer – RIKEN, JP project), and from our transcriptomic, transfection and mouse transgenic experiments, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of β-catenin (CTNNB1). We further generated and validated a quantitative mathematical model of the GRN using human cell lines and in vivo expression data. Results We found that LIN28B and C…
Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice.
2017
Background Amylase-trypsin inhibitors (ATIs) in wheat and related cereals are potent activators of myeloid innate immune cells via engagement of TLR4. Furthermore, ATIs have been shown to serve as adjuvants in experimental intestinal inflammatory diseases. Objective The aim of this study was to analyze whether ATIs are also modifiers of allergic inflammation. Methods Therefore, CD4 + T cells from donors sensitized to grass or birch pollen were stimulated with autologous allergen-pulsed dendritic cells in the presence or absence of ATIs or the control storage protein zein from corn. To analyze allergen-induced gut and lung inflammation, immunodeficient mice were engrafted with PBMCs from the…
Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer
2016
Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the auto…
A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?
2021
Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved. Genetic studies have so far highlighted a major role of gene variants promoting fat deposition in the liver (PNPLA3 rs738409
Identification of clinical phenotypes and related survival in patients with large hccs
2021
Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin >
The calm before the storm: a report from the International Liver Cancer Association Congress 2015 – part 2
2016
International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.
VESTIGE: Adjuvant Immunotherapy in Patients With Resected Esophageal, Gastroesophageal Junction and Gastric Cancer Following Preoperative Chemotherap…
2020
Background: Perioperative chemotherapy plus surgery is one recommended standard treatment for patients with resectable gastric and esophageal cancer. Even with a multimodality treatment more than half of patients will relapse following surgical resection. Patients who have a poor response to neoadjuvant chemotherapy and have an incomplete (R1) resection or have metastatic lymph nodes in the resection specimen (N+) are especially at risk of recurrence. Current clinical practice is to continue with the same chemotherapy in the adjuvant setting as before surgery. In the phase II randomized EORTC VESTIGE trial (NCT03443856), patients with high risk resected gastric or esophageal adenocarcinoma …
Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis.
2018
Abstract BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickne…
Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses
2016
Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver…
Prevention of endpoints in primary biliary cholangitis with ursodeoxycholic acid: quantifying the benefit
2020
Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with an established benefit for patients suffering from primary biliary cholangitis (PBC). It was first introduced in the 60s and took until the late 90s to demonstrate a survival benefit in large meta-cohort studies.1 Since then, UDCA is the established first-line therapy according to current guidelines.2 The benefit of UDCA is multidimensional, and patients receiving UDCA experience increased transplant-free survival, a decreased risk of hepatocellular carcinoma and potentially improved quality of life.3–5 The survival benefit is predicted by a number biochemical markers that reflect cholestasis and that are accepted surrogates of the…