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Targeting mast cells in gastric cancer with special reference to bone metastases

World Journal of Gastroenterology 2015年第37期21卷 10493-10501页

作者： christian leporini Michele Ammendola Ilaria Marech Giuseppe Sammarco Rosario Sacco Cosmo Damiano Gadaleta Caroline Oakley Emilio Russo Giovambattista De Sarro Girolamo Ranieri Department of Health Science Clinical Pharmacologyand Pharmacovigilance Unit and Pharmacovigilance’s Centre Calabria Region University of Catanzaro "Magna Graecia"Medical School Department of Medical and Surgery Sciences Clinical Surgery Unit University of Catanzaro "Magna Graecia" Medical School Diagnostic and Interventional Radiology Unit with Integrated Section of Translational Medical Oncology National Cancer Research Centre

Bone metastases from gastric cancer(GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells(MCs) positive to tryptase(MCPT) in primary gastric tumor angiogenesis. Recently,we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating,peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents,such as MCs tryptase inhibitors(gabexate mesylate,nafamostat mesylate) or c-KitR tyrosine kinase inhibitors(imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patientsaffected by bone metastases.

关键词： Bone metastases Gastric cancer receptor activator

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