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

被引:0
|
作者
Rha, SY
Jeung, HC
Roh, JK
Kim, JJ
Noh, SH
Min, JS
Kim, BS
Chung, HC
机构
[1] Yonsei Univ, Coll Med, Canc Metastasis Res Ctr, Yonsei Canc Ctr, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea
[3] Yonsei Univ, Coll Med, Dept Gen Surg, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea
[5] Inha Univ, Sch Med, Dept Clin Pathol, Sungnam, South Korea
关键词
MMPI; ex vivo model; gastric cancer;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 (greater than or equal to5 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.
引用
收藏
页码:251 / 256
页数:6
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