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Biological phenotype determination with ex vivo model in gastric cancer for matrix-metalloproteinase inhibitor treatment.

 Sun Young Rha  ;  Hei Cheul Jeung  ;  Jae Kyung Roh  ;  Jin Ju Kim  ;  Sung Hoon Noh  ;  Jin Sik Min  ;  Byung Soo Kim  ;  Hyun Cheol Chung 
 International Journal of Molecular Medicine, Vol.10(3) : 251-256, 2002 
Journal Title
 International Journal of Molecular Medicine 
Issue Date
Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology ; Adenocarcinoma/surgery ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cell Differentiation ; Enzyme Inhibitors/pharmacology* ; Female ; Gabexate/pharmacology ; Humans ; Inhibitory Concentration 50 ; Male ; Matrix Metalloproteinase Inhibitors* ; Matrix Metalloproteinases/pharmacology ; Middle Aged ; Multivariate Analysis ; Phenotype ; Prognosis ; Serine Proteinase Inhibitors/pharmacology ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/pathology* ; Stomach Neoplasms/surgery ; Time Factors ; Treatment Outcome
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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5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
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