Mono-(adenosine 5'-diphosphate) (ADP)-ribosylation, which transfers an ADP-ribose from nicotinamide adenine dinucleotide (NAD) to an acceptor protein, is an important post-translational modification of cellular proteins. Several bacterial toxins are known to possess the mono-ADP-ribosyltransferase activity to catalyze this reaction as a possible pathogenic factor. Therefore, the aim of this study was to examine whether H. pylori may also induce mono-ADP-ribosylation in a human gastric mucosal protein in association with gastric cancer development. Tumorous and adjacent non-tumorous mucosal tissue specimens were obtained from the surgically removed stomachs of 5 patients with gastric adenocarcinoma, and then were homogenized into cytosolic and membranous fractions. Each homogenate or an H. pylori extract was assayed for mono-ADP-ribosylation with [adenylate-(32)P]-NAD and 3-aminobenzamide, a potent inhibitor of poly-ADP-ribosylation. The radiolabeled proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by radio-image analysis. In the extracts from H. pylori, a strain-dependent, endogenous radiolabeling of 70-kDa protein was detected. An assay of the membranous fractions from 5 gastric adenocarcinomas with the extract of OMH4, a clinical H. pylori isolate, revealed notable radiolabelings of 55- and 45-kDa proteins, which were not found without the OMH4 extract. In contrast, the radiolabelings were minimal in the membranous fractions from respective non-tumorous mucosae, and they were not detected in any of the examined cytosolic fractions. All three radiolabelings of 70-, 55-, and 45-kDa proteins were dependent on NAD, but not on ADP-ribose. Snake venom phosphodiesterase digestion of the 3 radiolabeled proteins released only AMP. We thus found that H. pylori had an enzymatic mono-ADP-ribosyltransferase activity which enabled it to modify the 55- and 45-kDa membranous proteins of human gastric adenocarcinoma, as well as the 70-kDa protein of H. pylori itself. The possible roles underlying our observations on carcinogenesis or development of human gastric carcinoma are yet to be elucidated.
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Eur J Nucl Med Mol Imaging
January 2025
Departments of Radiology and Medical Physics, University of Wisconsin - Madison, Madison, WI, 53705, USA.
Purpose: Trophoblast cell-surface antigen 2 (Trop2) is overexpressed in various solid tumors and contributes to tumor progression, while its expression remains low in normal tissues. Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan-hziy (Trodelvy), has shown efficacy in targeting this antigen. Leveraging the enhanced specificity of ADCs, we conducted the first immunoPET imaging study of Trop2 expression in gastric cancer (GC) and triple-negative breast cancer (TNBC) models using Zr-labeled Trodelvy ([Zr]Zr-DFO-Trodelvy).
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Department of Surgery, University of California San Diego, La Jolla, CA, USA.
Background: Gastric cancer poses a major diagnostic and therapeutic challenge. Improved visualization of tumor margins and lymph node metastases with tumor-specific fluorescent markers could improve outcomes.
Methods: To establish orthotopic models of gastric cancer, one million cells of the human gastric cancer cell line, MKN45, were suspended in 50 μl of equal parts PBS and Matrigel and injected into the nude mouse stomach with a 29-gauge needle.
Aim: Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX and CA XII have been studied for their role in cancer diseases, motivating the design of inhibitors of these isoforms.
Material And Method: Here, we used the tail approach to design a new series of monoaryl () and bicyclic () benzensulfonamide derivatives CA IX and CA XII inhibitors.
Eur J Clin Invest
January 2025
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
Background: Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus.
Materials And Methods: Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans.
World J Gastroenterol
January 2025
Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510151, Guangdong Province, China.
Background: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for managing complications of portal hypertension, particularly acute variceal bleeding (AVB). While effective in reducing portal pressure and preventing rebleeding, TIPS is associated with a considerable risk of overt hepatic encephalopathy (OHE), a complication that significantly elevates mortality rates.
Aim: To develop a machine learning (ML) model to predict OHE occurrence post-TIPS in patients with AVB using a 5-year dataset.
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