BACKGROUND: We investigated the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in malignant fibrous histiocytoma (MFH), and determined whether these could be useful as prognostic factors. METHODS: Among patients treated from 1993 to 2007, 30 cases of MFH were evaluated. Immunohistochemical staining was performed for MMP-2, MMP-9, TIMP-1, and TIMP-2 using paraffin wax-embedded blocks of MFH tissues. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot and zymography were performed using fresh tissues obtained from 17 of the 30 cases. The levels of MMP and TIMP expression were compared between the MFH and normal control groups, and between non-metastatic and metastatic MFH groups. RESULTS: Expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were higher in the MFH group than the control group by RT-PCR, Western blotting, and zymography. Immunohistochemical staining revealed that MMP-2 and MMP-9 protein expression was higher in the metastatic than in the non-metastatic group. The expression levels of MMP-2 and TIMP-1 were significantly higher in the metastatic than in the non-metastatic group (p < 0.05) by RT-PCR. By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with the non-metastatic group (p > 0.05). Finally, gelatin zymography analysis showed that the expression levels of the pro- and active forms of MMP-2 were significantly higher in the metastatic group (p < 0.05), but the expression of the pro- and active forms of MMP-9 showed a slight decrease in the metastatic group (p > 0.05). CONCLUSIONS: These results suggest that MMP-2, MMP-9, TIMP-1, and TIMP-2 may have important roles in the development and progression of MFH, and that the degree of expression of these metalloproteinases and their inhibitors, especially MMP-2, could be useful as prognostic factors related to metastasis in MFH.
Adult ; Aged ; Aged, 80 and over ; Female ; Histiocytoma, Malignant Fibrous/*metabolism ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2/*biosynthesis ; Matrix Metalloproteinase 9/*biosynthesis ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Tissue Inhibitor of Metalloproteinase-1/*biosynthesis ; Tissue Inhibitor of Metalloproteinase-2/*biosynthesis

Actins ; biosynthesis ; genetics ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; enzymology ; virology ; Male ; Matrix Metalloproteinase 1 ; biosynthesis ; genetics ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; blood ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Urokinase-Type Plasminogen Activator ; blood

OBJECTIVETo observe the expression patterns of matrix metalloproteinase-3 and its inhibitor, tissue inhibitor metalloproteinases (TIMP)-1, in remodeling phase of mandibular distraction osteogenesis.

METHODSBilateral mandibular osteotomies were performed in 8 mature rabbits. The mandibles were lengthened 6 mm using a custom-made distractor with a rate of 1 mm/d. All animals were killed in 4 weeks after completion of distraction. The distracted calluses were harvested and processed for histology and immunohistochemistry of MMP-3 and TIMP-1.

RESULTSElevated expression of both MMP-3 and TIMP-1 was found in the distracted calluses resulting from mandibular lengthening. Positive staining for MMP-3 was seen in the osteoblasts and osteocytes, and TIMP-1 was mainly localized in osteoblasts.

CONCLUSIONMMP-3 and TIMP-1 appear to play important roles in the remodeling of new bone created by mandibular distraction osteogenesis.

Animals ; Bone Regeneration ; Bone Remodeling ; Female ; Male ; Mandible ; cytology ; metabolism ; surgery ; Matrix Metalloproteinase 3 ; biosynthesis ; Osteoblasts ; metabolism ; Osteogenesis, Distraction ; Rabbits ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis

OBJECTIVETo compare the effects of matrix metalloproteinase (MMP) inhibitor doxycycline, losartan, and their combination on the expression of MMP-8, 13, tissue inhibitor of MMP-1, 2 (TIMP-1, 2), and collagen remodeling in the noninfarcted myocardium after acute myocardial infarction (AMI) in rats.

METHODSTwo hundred and fifty-four AMI rats, induced by left coronary ligation, were randomly assigned to the following groups: (1) AMI controls group (n = 64); (2) doxycycline group (30 mg x kg(-1) x d(-1), n = 63); (3) losartan group (10 mg x kg(-1) x d(-1), n = 62); (4) concomitant doxycycline and losartan group (30 and 10 mg x kg(-1) x d(-1) respectively, n = 65); and (5) Sham-operated rats (n = 30), which were randomly selected to serve as noninfarction controls. Each group was further divided into three subgroups of 1, 2, and 4 weeks that received treatment. After the completion of treatment, the rats were killed. The mRNA and protein expression of MMPs and TIMPs in the noninfarcted myocardium were quantified by RT-PCR and Western blot, respectively. The type I and type III collagen volume fraction (CVF) of the noninfarced myocardium were assessed immunohistochemically.

RESULTSNo significant difference existed in myocardial infarction sizes among the 12 subgroups of AMI controls and the three treatment groups (42%-48%, all P > 0.05). Compared with sham operated rats, the mRNA and protein expression of MMP-8 and 13 significantly increased by 39%-183% in all three subgroups of AMI controls (all P < 0.05), except both of their mRNA expressions in 2-week subgroups; the mRNA and protein levels of TIMP-1 increased only in 1-week subgroup of AMI controls by 104% and 67%, respectively (both P < 0.05); the mRNA of TIMP-2 increased in all 1, 2, and 4-week subgroups by 144%-232% (all P < 0.05), but its protein expression lagged and only enhanced in 2 and 4-week subgroups of AMI controls by 231% and 332%, respectively (both P < 0.05). Meanwhile, both type I and type III CVF of noninfarcted myocardium significantly increased in all three subgroups of AMI controls (type I CVF: 3.01%-5.64% vs 1.53%-1.67%, P < 0.01-0.001; type III CVF: 2.19%-4.42% vs 1.46%-1.59%, P < 0.05-0.001), with type I CVF being higher in 4-week than in 1 and 2-week subgroups (5.64% vs 3.01% and 3.02% respectively, all P < 0.05). Compared with AMI controls, all three kinds of treatment significantly reduced the increased mRNA and protein expressions of MMP-8, 13 and TIMP-1, 2 after AMI by 14%-60% (all P < 0.05), as well as type I/III CVF in their 2 and 4-week subgroups (type I CVF: 1.56%-2.38% vs 3.02%-5.64%, P < 0.05-0.001; type III CVF: 1.92%-2.65% vs 4.19%-4.42%, P < 0.05-0.01), except for doxycycline's effect on type III CVF in any of its three subgroups (all P > 0.05). Among the three treatment groups, significant differences existed in the above mentioned indicators only at some subgroup levels (all P < 0.05).

CONCLUSIONSLike losartan, doxycycline can also suppress the enhanced mRNA and protein expression of MMP-8, 13 and TIMP-1, 2, and reduce type I collagen deposition in the noninfarcted myocardium after AMI in rats. However, it has no effect on type III collagen deposition.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Collagen Type I ; biosynthesis ; genetics ; Collagenases ; biosynthesis ; genetics ; Doxycycline ; pharmacology ; Drug Synergism ; Female ; Losartan ; pharmacology ; Matrix Metalloproteinase 13 ; Matrix Metalloproteinase 8 ; biosynthesis ; genetics ; Matrix Metalloproteinase Inhibitors ; Myocardial Infarction ; metabolism ; Myocardium ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinases ; biosynthesis ; genetics

Animals ; Liver Cirrhosis ; enzymology ; Male ; Matrix Metalloproteinases, Secreted ; biosynthesis ; genetics ; Mice ; RNA, Messenger ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

OBJECTIVETo observe the in vitro effect of compound 861 (Cpd 861) on tissue inhibitor of metalloprotenase 1 (TIMP1) mRNA levels of HSC-T6 cell.

METHODSHSC-T6 cells were exposed in different concentrations of Cpd 861 (0.25~1.0 mg/ml) for 48 hours. The TIMP1 level was measured by the quantitative reverse-transcription polymerase chain reaction (RT-PCR).

RESULTSThe TIMP1 mRNA levels of HSC-T6 cells at different concentrations of Cpd 861 were lower (2.50 0.71, 0.50 0.01, 0.11 0.03) than those of the normal control (3.78 0.67, P<0.05 or P<0.01).

CONCLUSIONSThe antifibrotic mechanism of Cpd 861 is partly due to its downregulation on TIMP1 mRNA levels of HSC-T6 cells.

Animals ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression ; drug effects ; RNA, Messenger ; biosynthesis ; drug effects ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

OBJECTIVETo investigate the effect of Yangjing Zhongyu decoction (YZD) on metalloproteinase-9 (MMP-9) and its inhibitor-1 (TIMP-1) expression and sex hormone regulation in mid-luteal phase endometrium of women with cryptogenic infertility.

METHODSIn situ hybridization and reverse transcription-polymerase chain reaction method was used to detect MMP-9 and TIMP-1 mRNA, and radioimmunoassay was used to determine levels of serum estradiol (E2) and progesterone (P) synchronously, of 22 infertile women during mid-luteal phase.

RESULTSAfter treatment, the mid-luteal serum E2 and P level was 451.501 +/- 226.342 pmol/L and 46.502 +/- 19.948 nmol/L respectively, significantly higher than that before treatment (304.656 +/- 135.853 pmol/L and 33.782 +/- 15.459 nmol/L respectively), the difference was significant (P < 0.01). Staining of MMP-9 mRNA positive granules in cytoplasm and nuclei of adeno-epithelial cell mid-luteal phase endometrium deepened significantly, but the change in mesenchym was insignificant. The MMP-9 mRNA expression after treatment was 0.617 +/- 0.186 (grey level), significantly higher than the level before treatment (0.490 +/- 0.370), comparison between them showed significant difference (P < 0.05). Change of TIMP-1 mRNA expression in adeno-epithelial and mesenchym before and after treatment was insignificant (0.588 +/- 0.191 vs 0.621 +/- 0.146, P < 0.05). Correlation analysis showed that the quantitative difference of P value before and after treatment was positively correlated with the difference of MMP-9 mRNA before and after treatment (r = 0.682, P < 0.01).

CONCLUSIONYZD could soothen Gan and nourish Shen, raise the level of mid-luteal phase serum P, and further promote MMP-9 gene expression in endometrium to benefit the degradation of extracellular matrix of endometrium, and facilitate for blastocyst implantation.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Endometrium ; metabolism ; Estradiol ; blood ; Female ; Humans ; Infertility, Female ; drug therapy ; metabolism ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Phytotherapy ; Progesterone ; blood ; RNA, Messenger ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics

OBJECTIVE: To investigate the expression and significance of matrix metalloproteinase-3 (MMP-3), osteopontin (OPN) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human lens epithelial cells (LECs) of cataract. METHODS: The MMP-3, OPN, and TIMP-1 expressions in LECs of anterior subcapsular cataract (31 cases), nuclear cataract (28 cases) and normal lens (12 cases) were detected by immunohistochemistry, respectively. RESULTS: The MMP-3 expression in anterior subcapsular cataract was significantly higher than that in nuclear cataract and normal lens (chi2=31.49, 34.479; P=0.000); but there was no statistic significance between nuclear cataract and normal lens (chi2=2.449, P=0.118). The OPN expression in anterior subcapsular cataract was also significantly higher than that in nuclear cataract and normal lens (chi2=29.450, 15.889; P=0.000). There was no significant difference in the TIMP-1 expression among the 3 groups (P>0.05). Positive correlation was found between MMP-3 and OPN in LECs of anterior subcapsular cataract (r=0.381, P=0.035). But no significant correlation was found among MMP-3, OPN, and TIMP-1 (r=0.121, -0.289; P=0.516, 0.114). CONCLUSION Increased expression of MMP-3 and OPN and the expression imbalance between MMP-3 and TIMP-1 may play a critical role in the pathogenesis of anterior subcapsular cataract.
Adult ; Aged ; Aged, 80 and over ; Cataract ; classification ; etiology ; metabolism ; Epithelial Cells ; metabolism ; Female ; Humans ; Lens, Crystalline ; metabolism ; Male ; Matrix Metalloproteinase 3 ; biosynthesis ; Middle Aged ; Osteopontin ; biosynthesis ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis

OBJECTIVESTo study the effects of c9,t11-conjugated linoleic acid (c9,t11-CLA) on invasive ability of human gastric carcinoma cell line (SGC-7901) and to explore its possible mechanism.

METHODSReconstituted basement membrane invasion assay was used to evaluate invasive ability of cancer cells. Expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR) in SGC-7901 cells.

RESULTSAt the concentrations of 200 micromol/L, 100 micromol/L and 50 micromol/L, c9,t11-CLA suppressed their reconstituted basement membrane invasion of SGC-7901 by 53.7%, 40.9% and 29.3%, respectively. c9,t11-CLA could induce the expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA in SGC-7901 cells.

CONCLUSIONSThe invasion of SGC-7901 cells could be inhibited by c9,t11-CLA through reconstituted basement membrane. Anti-invasion action of c9,t11-CLA might be associated with induction of expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA in tumor cells.

Adenocarcinoma ; pathology ; Gene Expression ; drug effects ; Humans ; Linoleic Acid ; pharmacology ; therapeutic use ; Monomeric GTP-Binding Proteins ; biosynthesis ; genetics ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Invasiveness ; prevention & control ; Nucleoside-Diphosphate Kinase ; RNA, Messenger ; biosynthesis ; drug effects ; Stomach Neoplasms ; pathology ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Tumor Cells, Cultured

OBJECTIVETo investigate the expression and clinical implication of tissue inhibitor of metalloproteinase-1 (TIMP-1) in colorectal carcinoma.

METHODSTIMP-1 expression in 54 colorectal carcinoma was observed by SP immunohistochemical method, and the results were analyzed in relation to the clinical data of patients.

RESULTSTIMP-1 was localized on the membrane and in the cytoplasm of the enteric epithelial cells, and its expression rate was 100% in normal tissue but only 59.6% (31/52) in colorectal carcinoma tissues. In addition, the expression rate of TIMP-1 was higher in the tumor tissues without lymph node metastasis than in tissues with lymph node metastasis (P<0.05).

CONCLUSIONThe expression of TIMP-1 is inversely correlated to lymph node metastasis of colorectal carcinoma, and decreased TIMP-1 expression may play a role in the progression of colorectal carcinoma.

Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; Epithelial Cells ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis