1.Role of tissue inhibitors of metalloproteinases (TIMPs) in colorectal carcinoma.
Young Eun JOO ; Kang Seok SEO ; Jin KIM ; Hyun Soo KIM ; Jong Sun REW ; Chang Soo PARK ; Sei Jong KIM
Journal of Korean Medical Science 1999;14(4):417-423
Increased production of matrix metalloproteinases (MMPs) has been associated with increases in invasive and metastatic potential in many types of human carcinoma. Tissue inhibitors of metalloproteinase (TIMP)-1 inhibits most interstitial collagenases and MMP-9. TIMP-2 binds specifically and noncovalently to the pro-form of MMP-2 and inhibits its enzyme activity. In this study, we examined TIMP-1 and TIMP-2 expressions in relation to clinicopathological variables in colorectal carcinoma with in situ hybridization and immunohistochemistry. TIMP-1 and TIMP-2 expressions were localized overwhelmingly to pericancer stromal cells, while malignant and normal mucosal cells were weak or negative. Strong stromal TIMP-1 immunoreactivity correlated with Dukes' stage (p=0.022), status of lymph node metastasis (p=0.044) and poor survival (p= 0.005). The degree of immunohistochemical staining of TIMP-2 did not correlate with all clinicopathological variables. The correlation between enhanced TIMP-1 expression and advanced stage and poor survival suggest a growth promoting activity of TIMP-1 in colorectal carcinoma.
Adenocarcinoma/pathology
;
Adenocarcinoma/mortality
;
Adenocarcinoma/enzymology*
;
Adult
;
Aged
;
Aged, 80 and over
;
Antibodies
;
Collagenases/immunology
;
Collagenases/genetics*
;
Collagenases/analysis
;
Colorectal Neoplasms/pathology
;
Colorectal Neoplasms/mortality
;
Colorectal Neoplasms/enzymology*
;
DNA Probes
;
Female
;
Gelatinase A
;
Gelatinase B
;
Gelatinases/immunology
;
Gelatinases/genetics*
;
Gelatinases/analysis
;
Gene Expression Regulation, Enzymologic
;
Gene Expression Regulation, Neoplastic
;
Human
;
In Situ Hybridization
;
Male
;
Metalloendopeptidases/immunology
;
Metalloendopeptidases/genetics*
;
Metalloendopeptidases/analysis
;
Middle Age
;
Predictive Value of Tests
;
RNA, Messenger/analysis
;
Stromal Cells/pathology
;
Stromal Cells/enzymology
;
Survival Analysis
;
Tissue Inhibitor-of Metalloproteinase-2/immunology
;
Tissue Inhibitor-of Metalloproteinase-2/genetics*
;
Tissue Inhibitor-of Metalloproteinase-2/analysis
;
Tissue-Inhibitor of Metalloproteinase-1/immunology
;
Tissue-Inhibitor of Metalloproteinase-1/genetics*
;
Tissue-Inhibitor of Metalloproteinase-1/analysis
2.Expression of MMP-2 and TIMP-1 in renal tissues of patients with chronic active antibody-mediated renal graft rejection.
Bao-yao WANG ; Qiang YAN ; He-qun ZOU ; Wei-guo SUI ; Gui-mian ZUO ; Gui-rong LIANG ; Hao LUO ; Shui-yong XIE ; Huai-zhou CHEN ; Shen-ping XIE
Journal of Southern Medical University 2011;31(12):2048-2051
OBJECTIVETo investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR.
METHODSImmunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed.
RESULTSThe expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05).
CONCLUSIONAbnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.
Adult ; Antibody Formation ; Complement C4b ; metabolism ; Female ; Fibrosis ; etiology ; Graft Rejection ; immunology ; Humans ; Kidney ; metabolism ; Kidney Diseases ; pathology ; Kidney Transplantation ; adverse effects ; immunology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Middle Aged ; Peptide Fragments ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism
3.Effect of TGFbeta1 vaccine on the expression of MMP-2 and TIMP-2 in rats with liver fibrosis.
Ming-qin LU ; Yong-ping CHEN ; Chen-wei PAN ; Xiao-dong WANG
Chinese Journal of Hepatology 2006;14(9):692-694
Animals
;
Liver
;
pathology
;
Liver Cirrhosis, Experimental
;
metabolism
;
pathology
;
therapy
;
Male
;
Matrix Metalloproteinase 2
;
metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Tissue Inhibitor of Metalloproteinase-2
;
metabolism
;
Transforming Growth Factor beta1
;
immunology
;
Vaccines
;
therapeutic use
4.Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasis.
Yun FENG ; Hong-Wei HE ; Bao-Wei LI ; Zheng-Xian ZHANG ; Xi CHEN ; Xiao-Fang LI
Acta Pharmaceutica Sinica 2011;46(12):1462-1465
This study is to investigate the tumor invasion and metastasis inhibition effects of the immunoconjugate composed of lidamycin and anti-type IV collagenase monoclonal antibody Fab' fragment. Boyden chamber assay was used to evaluate the influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was used to measure the change of invasion factor MMP-2 and MMP-9's secretion, and RT-PCR was adopted to determine TIMP-1 mRNA expression level. The immunoconjugate inhibition of tumor in situ metastasis was also tested in nude mice. The Fab'-LDM conjugates had dose-dependent inhibition effect on HT-1080 cells' invasion. At the concentrations of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the invasion by (60 +/- 12) % and (79 +/- 11) % respectively. At the concentration of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the secretion of MMP-2 by (42 +/- 8) % and (54 +/- 6) % and that of MMP-9 by (57 +/- 3) % and (87 +/- 1) %, respectively. RT-PCR indicated that conjugates increased the anti-invasion factor TIMP-1 level. The in vivo experiment showed that, compared with the control group, the tumor inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 +/- 13) %, (86 +/- 26) %, (74 +/- 22) % respectively. In conclusion, Fab'-LDM could inhibit the invasion and metastasis of tumor and it might be a new tumor biotherapy agent.
Aminoglycosides
;
pharmacology
;
Animals
;
Antibiotics, Antineoplastic
;
pharmacology
;
Antibodies, Monoclonal
;
immunology
;
Cell Line, Tumor
;
Enediynes
;
pharmacology
;
Fibrosarcoma
;
metabolism
;
pathology
;
Humans
;
Immunoconjugates
;
pharmacology
;
Immunoglobulin Fab Fragments
;
pharmacology
;
Matrix Metalloproteinase 2
;
immunology
;
secretion
;
Matrix Metalloproteinase 9
;
immunology
;
secretion
;
Mice
;
Mice, Inbred BALB C
;
Mice, Nude
;
Neoplasm Invasiveness
;
Neoplasm Metastasis
;
Neoplasm Transplantation
;
RNA, Messenger
;
metabolism
;
Tissue Inhibitor of Metalloproteinase-1
;
genetics
;
metabolism
;
Tumor Burden
;
drug effects