多発性骨髄腫における血管新生とCOX-2発現の免疫組織学的検討

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Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid to prostaglandins. Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors. In multiple myeloma (MM), recent studies have demonstrated that COX-2 overexpression is associated with reduced survival. Moreover, several studies have shown a relation between angiogenesis and COX-2 expression. Bone marrow angiogenesis plays an important role in the pathogenesis and progression of MM. The aim of this study was to determine the relationship between COX-2 and tumor angiogenesis in multiple myeloma. Eighty newly diagnosed patients with MM were included in the study. Immunohistochemical stain was used for detecting the expression of COX-2 in paraffin-embedded bone marrow biopsy specimens. The monoclonal antibody against Von Willebrand Factor was used for displaying vascular endothelial cells, and microvascular density (MVD) was detected by counting of Von Willebrand Factor factor -positive vascular endothelial cells. There were 4, 33, and 43 bone marrow biopsy specimens with negative, weak-moderate, and strong COX-2 immunostaining, respectively. Kaplan-Meier overall survival estimate of those patients with negative or weakmoderate COX-2 immunoreactivity in myeloma cells was significantly better than that of patients with strong COX-2 immunoreactivity (P=0.02) . COX-2 overexpression was associated with reduced survival. Kaplan-Meier overall survival estimate of those patients with low MVD (≤24) was significantly better than that of patients with high MVD (24<) . Moreover, both COX-2 and MVD correlated with the stage (Dune salmon), serum β-2 microglobulin, bone marrow plasma cells, and bone lesion. The expression of COX-2 in myeloma cells correlated significantly with tumor angiogenesis and may become a new therapeutic target for anti-COX-2 in multiple myeloma.
学校法人昭和大学・昭和医学会の論文

多発性骨髄腫における血管新生とCOX-2発現の免疫組織学的検討

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