Biomarkers ; Humans ; Matrix Metalloproteinases ; Myocardial Infarction ; Prognosis ; Reperfusion ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinases

PURPOSE: Matrix metalloproteinases (MMPs) have been associated with tumor cell invasion and metastasis by mediating the degradation of extracellular matrix components. A tissue inhibitor of metalloproteinases (TIMPs) has been reported to inhibit tumor invasion by means of an inactivation of matrix metalloproteinases. An imbalance between MMPs and the associated TIMPs may play a significant role in the invasive phenotype of malignant tumors. Therefore, MMPs and their inhibitors constitute promising agents for developing anticancer therapies. In the present study, the authors investigated the correlation between the expressions of TIMP-1 and MMPs, and the clinical outcome. MATERIALS AND METHODS: Immunohistochemical staining of MMP-2, -3 and -9, and TIMP-1 was performed on paraffin-embedded tissue sections of 38 early gastric carcinomas and 61 advanced gastric carcinomas. RESULTS: MMP-2 and -9 were found mainly in tumors of the intestinal type and less frequently in those of diffuse type. There were positive correlations between the presence of MMP-2 and -9 and lymph node status. There were inverse correlations between the TIMP-1 expression and tumor invasiveness. CONCLUSION: These results suggests that clinical outcomes such as the depth of invasion or metastasis are closely related to the expression of TIMP-1, MMP-2 and MMP-9.
Adenocarcinoma* ; Extracellular Matrix ; Lymph Nodes ; Matrix Metalloproteinases* ; Negotiating ; Neoplasm Metastasis ; Phenotype ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinases

PURPOSE: The metalloproteinases (MMP) and their inhibitors (TIMP) have been suggested to play a role in tumor invasion and metastasis. There have been some dispute on the exact role of TIMP and MMP in tumor progression. The purpose of this study is to prove TIMP expression in relation with prevention of tumor progression including invasion or metastasis with MMP expression. MATERIALS AND METHODS: We have performed immunohistochemical staining of MMP-2, MMP-9 and TIMP-2 on 15 cases of benign prostatic hyperoplasia (BPH), and 30 cases of prostatic carcinomas which were classified as angio or neural invasion positive (PC-2) and negative group (PC-1). RESULTS: MMP-2, MMP-9, and TIMP-2 were not detected in BPH. PC-2 pateints had higher levels of collagenases than BPH, while PC-1 patients had higher levels of TIMP-2 and lower levels of MMP-2, MMP-9 than PC-2. Expression of TIMP-2 were inversely proportional to collagenases. CONCLUSION: We conclude that highly invasive prostatic carcinoma (PC-2) contained relatively high levels of MMP-2, MMP-9 and low amounts of TIMP-2. These results are discussed with respect to the possible role of MMPs and TIMP in prostatic tumor progression.
Adenocarcinoma* ; Collagenases ; Dissent and Disputes ; Humans ; Matrix Metalloproteinases ; Metalloproteases ; Neoplasm Metastasis ; Tissue Inhibitor of Metalloproteinase-2 ; Tissue Inhibitor of Metalloproteinases*

No abstract available.
Matrix Metalloproteinases* ; Stomach Neoplasms ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

With the effects of the mechanics and biological factors, the imbalance between the degradation and synthesis of chondrocyte, extracelluar matrix and subchondral bone leads to the osteoarthritis. The imbalance between MMPs and TIMPs caused by biomechanical abnormality is the key factor of osteoarthritis. This review will focus on the stress and their roles in the metabolism of the cartilage matrix.
Cartilage ; metabolism ; Humans ; Matrix Metalloproteinases ; metabolism ; Osteoarthritis ; metabolism ; Stress, Mechanical ; Tissue Inhibitor of Metalloproteinases ; metabolism

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix. The balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumors. Although MMP and TIMP are believed to play an important role in invasion and metastasis in malignant solid tumors, little is known about their involvement in malignant lymphoma. Immunohistochemical stains for MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were performed using 56 paraffin blocks of the malignant lymphoma and the results were analyzed by using the tumor grade by Working Formulation. The expression of MMP-9 was noted in 45.5% of low grade, 86.1% of intermediate grade, and 100% of high grade malignant lymphoma. The incidence of MMP-9 expression in tumor cells was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphomas, the incidence of the MMP-9 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.008). The incidence of TIMP-1 expression in the tumor cells and fibroblasts was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphoma, the incidence of the TIMP-1 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.009). The incidences of the MMP-1, MMP-2, and TIMP-2 expression in malignant lymphoma were neither increased in the malignant lymphoma with extracapsular tumor invasion nor correlated with the grade by working formulation. There was no significant difference in the expression rate of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in nodal- and extra-nodal malignant lymphoma. The above results suggest that the expressions of MMP-9 and TIMP-1 are positively correlated with the grade and the presence of extranodal tumor invasion in malignant lymphomas.
Coloring Agents ; Extracellular Matrix ; Fibroblasts ; Incidence ; Lymphoma* ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Paraffin ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. METHOD: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2 ,-9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. RESULTS: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. CONCLUSIONS: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be? important factors in the irreversible fibrosis of the lung parenchyme.
Fibroblasts ; Fibrosis ; Gelatin ; Gelatinases ; Humans ; Immunohistochemistry ; Lung ; Lung Neoplasms ; Matrix Metalloproteinases* ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively. METHODS: We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder. RESULTS: The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis. The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas. CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.
Adenocarcinoma* ; Collagen Type IV ; Connective Tissue ; Gallbladder Neoplasms ; Gallbladder* ; Immunohistochemistry ; Lymph Nodes ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Serous Membrane ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2* ; Tissue Inhibitor of Metalloproteinases

OBJECTIVE: This study was performed to investigate the role of matrix-metalloproteinases(MMP-2,9) and tissue inhibitor of matrix-metalloproteinase(TIMP-2) in tumor metastasis and to correlate the expression of MMP-2,9 and TIMP-2 in cervical carcinomas. METHODS: We have performed immunohistochemical staining of MMP-2,9 and TIMP-2 on 35 patients of cervical carcinomas who were treated by radical hysterectomy between 1995.1.-1996.12. using paraffin-embeded tissue specimens. RESULTS: The lymph node metastasis and lymphvascular invasion groups showed a significantly higher rate of MMP-2 (50.7% vs 37.1%, 51.2% vs 37.5%) (p<0.05). And the lymphvascular invasion group showed a significantly higher rate of expression of MMP-9 (46.6% vs 29.8%) (p<0.05). But, the lymph node metastasis and lymphvascular invasion groups showed a significantly lower rate of expression of TIMP-2 (14.2% vs 36.5%, 11.2% vs 37.3%) (p<0.05). CONCLUSION: Lymph node metastasis and/or lymphvascular invasion of cervical carcinoma were related high percentages of MMP-2,9 and low percentages of TIMP-2 expression. These data suggest that the expression of MMPs and TIMPs are closely correlated with the progression of cervical carcinoma. To determine the ratio of cells expressing MMPs and TIMPs are strongly correlated with clinical outcome requires further study.
Humans ; Hysterectomy ; Lymph Nodes ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Tissue Inhibitor of Metalloproteinase-2

Cell Line, Tumor ; Choriocarcinoma ; metabolism ; Chorionic Gonadotropin ; pharmacology ; Female ; Humans ; Tissue Inhibitor of Metalloproteinases ; metabolism