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 (> or =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.
Rha
Sun Young
SY
Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul 120-752, Korea.
Jeung
Hei Cheul
HC
Roh
Jae Kyung
JK
Kim
Jin Ju
JJ
Noh
Sung Hoon
SH
Min
Jin Sik
JS
Kim
Byung Soo
BS
Chung
Hyun Cheol
HC
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D016670:Gabexate / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000494:pharmacology; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D015842:Serine Proteinase Inhibitors; D016670:Gabexate; D020782:Matrix Metalloproteinases