Biological phenotype determination with ex vivo model in gastric cancer for matrix-metalloproteinase inhibitor treatment
Among the many biological characteristics of cancer, matrix-metalloproteinases (MMPs) are essential for tumor invasion and metastasis. To test the possibility of ex vivo model as a therapeutic guideline for MMP inhibitor (MMPI) treatment, we evaluated IC50 of the gabexate mesylate against MMP-9. Thirty-four paired normal and gastric cancer tissues were tested to measure the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography. Both MMP-9 expression (p=0.04) and IC50 (p=0.02) were higher in cancer than normal tissues. IC50 of the cancer tissues was higher than paired normal tissues especially in cases with large tumor (≥5 cm) (p=0.03), higher T-stage (p=0.04), lymph node metastasis (p=0.04) and advanced stage (p=0.04). In cancers extending beyond submucosa or in diffuse/mixed type, a tendency of higher IC50 was observed than tumors confined to submucosa or intestinal type cancer despite similar MMP-9 activity between the groups. Patients with high IC50 showed poorer prognosis than patients with low IC50 in curatively-resected group. In multivariate analysis, high IC50 was suggested as an independent prognostic factor. We were able to differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who may benefit from MMPI treatment.
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Document Type: Research Article
Affiliations: Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul 120-752, Korea;
Publication date: January 1, 2002
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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