Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

The Production of High Affinity Monoclonal Antibodies to Human Chorionic Gonadotropin and Their Application to Immunoradiometric Assay

Abstract

Production of monoclonal antibodies against hCG has been studied using hCG as the antigen. This study reports the successful isolation of hybrid clones secreting monoclonal antibodies specific for hCG with an affinity constant higher than 10¹⁰M^?l. Of 23 fusions, only 17 fusions have produced positive clones which secrete antibodies giving high levels of binding with ^l25I-labelled hCG in the supernatant. Finally, 6 different monoclonal antibodies have been isolated; 4 of them, specific for the β-subunit, with a Ka approximately 1.1–4.0 ± 10¹¹M^?1 and 2 others, specific for the α-subunit, presenting an affinity of 2.5 ± 10¹⁰M^?l. When the antibodies specific for the β-subunit are used, specific and highly sensitive radioim-munoassays are obtained after only 3 hrs of incubation. Using iodinated monoclonal antibodies specific for the α-subunit and tubes coated with antibodies against the β-subunit, we have developped sensitive immunoradiometric assays.