0000000000331374
AUTHOR
Jean Charles Dagorn
Nupr1-Aurora Kinase A Pathway Provides Protection against Metabolic Stress-Mediated Autophagic-Associated Cell Death
Abstract Purpose: The limited supply of oxygen and nutrients is thought to result in rigorous selection of cells that will eventually form the tumor. Experimental Design: Nupr1 expression pattern was analyzed in human tissue microarray (TMA) and correlated with survival time of the patient. Microarray analysis was conducted on MiaPaCa2 cells subjected to metabolic stress in Nupr1-silenced conditions. DNA repair and cell cycle–associated gene expression was confirmed by real-time quantitative PCR (qRT-PCR). Nupr1 and AURKA protective role were analyzed using RNA interference (RNAi) silencing or overexpression. DNA damage and autophagy were analyzed by Western blot analysis and immunofluoresc…
NUPR1 works against the metabolic stress-induced autophagy-associated cell death in pancreatic cancer cells.
The incidence of pancreatic adenocarcinoma is increasing with more than 43,000 predicted new cases in the US and 65,000 in Europe this year. Pancreatic cancer patients have a short life expectancy with less than 3–4% 5-y survival, which results in an equivalent incidence and mortality rate. One of the major challenges in pancreatic cancer is the identification of pharmacological approaches that overcome the resistance of this cancer to therapy. Intensive research in the past decades has led to the classification of pancreatic cancers and the identification of the driver key genetic events. Despite the advances in understanding the molecular mechanisms responsible for pancreatic cancer patho…
Pancreatitis-associated protein in patients with celiac disease: Serum levels and immunocytochemical localization in small intestine
Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (12…
Clinical evaluation of pancreatitis-associated protein as a serum marker of hepatocellular carcinoma: Comparison with α-fetoprotein
This study evaluated the significance of serum pancreatitis-associated protein (PAP) assay, as a marker of hepatocellular carcinoma (HCC), in comparison and combined with α-fetoprotein (AFP) assay. Sixty-five patients with HCC, 59 with liver cirrhosis (LC) and 68 asymptomatic controls (C) were studied. PAP and AFP values significantly increased from C to LC and HCC group (p < 0.0001). The area under receiver-operating characteristic (ROC) curve for the two markers was not statistically different. At 100% specificity, ROC analysis gave a cut-off level for AFP of 166 IU/l with 40% sensitivity, and a cut-off level of 240 µg/l for PAP with 23% sensitivity. Diagnostic accuracy of combined AFP…
Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?
Abstract: Objective: The vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA. Patients and methods: DNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a s…