UMLS:C0019204 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies were raised against seven major matrix metalloproteinases: stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11), interstitial collagenase (MMP-1), M(r) 72,000 type IV collagenase (72 kDa type IV collagenase, MMP-2), M(r) 92,000 type IV collagenase (92 kDa type IV collagenase, MMP-9) and matrilysin (PUMP, MMP-7) as well as against prolyl 4-hydroxylase, to study the expression of these collagenolytic enzymes in normal liver in relation to the activity of collagen synthesis. Tissue samples of four normal human livers, three hepatocellular carcinomas and one cholangiocellular carcinoma were analysed. In normal liver we found expression of stromelysin-1, stromelysin-3, interstitial collagenase, M(r) 72,000 and M(r) 92,000 type IV collagenases and varying expression of prolyl 4-hydroxylase. Stromelysin-2 was inconsistently detectable; matrilysin was not found. In hepatocellular carcinoma the expression pattern of matrix metalloproteinases showed only minor changes compared with the normal tissue; stronger signals than in normal tissue were seen for stromelysin-1, and stromelysin-2 was also strongly positive. M(r) 72,000 and M(r) 92,000 type IV collagenases and interstitial collagenase were less strongly expressed; stromelysin-3 was unchanged. Expression of prolyl 4-hydroxylase was also increased compared with normal liver. Matrilysin was only seen in cholangiocellular carcinoma, which showed a completely different pattern of matrix metalloproteinase expression. Our results show that metalloproteinases are expressed in human liver with much greater abundance than previously described. Their expression pattern is not changed fundamentally in hepatocellular carcinoma but is completely different from that of other tumour tissues such as cholangiocellular carcinoma.
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PMID:Expression pattern of matrix metalloproteinases in human liver. 763 22

Studies of tissue inhibitors of metalloproteinases (TIMPs) suggest that one of their main functions is to inhibit metalloproteinase (MMP) activity and thus prevent tumor invasion by preserving extracellular matrix (ECM) integrity. In the present study we examined the distribution of transcripts for TIMP-1, MMP-2 and MMP-9 in monkey hepatocellular carcinoma tissues. In situ hybridization demonstrated elevated levels of TIMP-1 transcripts in fibrous tissue septa, tumor inflammatory infiltrate, tumor blood vessels and in expanded portal areas. However, elevated transcripts for MMP-2 and MMP-9 were found only in tumor inflammatory infiltrate. In lung metastasis high levels of TIMP-1 transcripts were found in the stromal cells surrounding necrotic tumor nodules, in tumor blood vessels, and in mesothelial cells. MMP-9 transcripts were elevated at the periphery of the necrotic tumor nodules. These findings suggest that TIMP-1 and type IV collagenases/gelatinases can be independently regulated in vivo and that TIMP-1 may have functions in ECM remodeling which are unrelated to inhibition of MMP activity.
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PMID:Localization of messenger RNA for tissue inhibitor of metalloproteinases-1 and type IV collagenases/gelatinases in monkey hepatocellular carcinomas. 764 22

A one-step sandwich enzyme immunoassay (EIA) for human matrix metalloproteinase 2 (MMP-2, 72-kDa gelatinase/type IV collagenase, EC 3.4.24.24) was established with a pair of monoclonal antibodies prepared against the precursor form of MMP-2 (proMMP-2) purified from the conditioned medium of human skin fibroblasts or against a synthetic peptide corresponding to the N-terminal domain of proMMP-2. ProMMP-2 in samples was allowed to simultaneously react with both solid-phase and peroxidase-labeled antibodies. Sensitivity of this EIA system was 2.4 pg/assay (0.24 microgram/l) and linearity was obtained between 10 and 5,000 pg/assay (1.0-500 micrograms/l). The EIA system recognized both the free form of proMMP-2 and its complex form with TIMP-2 with the same degree of immunoreactivity. ProMMP-2 levels in human sera from patients in various disease states were analyzed. In sera from patients with hyperthyroidism (12), primary biliary cirrhosis (8) and hepatocellular carcinoma (11), 749 +/- 166, 716 +/- 135 and 686 +/- 236 micrograms/l of proMMP-2 were detected, respectively and these were significantly higher than that observed in 213 normal human sera (570 +/- 118 micrograms/l). In contrast, the levels in sera from 33 patients with osteoarthritis (449 +/- 72 micrograms/l), 45 with rheumatoid arthritis (408 +/- 139 micrograms/l), 13 with stomach cancer (427 +/- 103 micrograms/l) and 10 with pancreatic cancer (422 +/- 130 micrograms/l) were significantly lower than that found in normal sera. Immunoblot and gel filtration analyses showed that human sera contain several MMP-2 species in addition to proMMP-2 which exist in a complex form with TIMP-2.
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PMID:A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72-kDa gelatinase/type IV collagenase) using monoclonal antibodies. 814 45

A one-step sandwich enzyme immunoassay system was developed with a pair of monoclonal antibodies against two individual oligopeptides prepared from the amino acid sequence of the human tissue inhibitor of metalloproteinases-2 (TIMP-2). The assay system consisting of two simultaneous immunoreactions used a solid phase monoclonal antibody and a horse-radish peroxidase-labeled monoclonal antibody. The system detected a free form of TIMP-2 and that complexed with active forms of matrix metalloproteinases (MMPs) giving a different sensitivity for each MMP but not TIMP-2 complexed with the precursor of 72 kDa gelatinase/type IV collagenase (MMP-2). The sensitivity of the system was 1.6 microgram/l (16 pg/assay) and linearity was obtained between 6.3 and 50 micrograms/l (63-500 pg/assay). TIMP-2 levels in the sera of 20 patients with rheumatoid arthritis (68 +/- 25 micrograms/l, mean +/- S.D.) and 13 patients with hepatocellular carcinoma (76 +/- 46 micrograms/l) were significantly higher (P < 0.05) than those of 18 normal subjects (5.6 +/- 7.4 micrograms/l). In contrast, the levels in the sera of 10 patients with gastric cancer (45 +/- 18 micrograms/l) and 7 patients with cancer of the uterus (36 +/- 13 micrograms/l) were significantly lower (P < 0.05 or P < 0.01) than those of normal subjects. Immunoreactivity analyses suggested that the precursor of MMP-2 in normal sera exists in a complexed form with TIMP-2 by interacting with the C-terminal domain of TIMP-2.
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PMID:A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases-2 using monoclonal antibodies. 828 59

Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion by degrading extracellular matrix proteins. However, little is known about the in situ expression of MMP in human normal livers and primary liver tumors. In this study, we therefore examined the in situ expression of immunoreactive MMP and tissue inhibitors of MMP (TIMP) in 10 normal livers, 11 surgically resected intrahepatic cholangiocarcinomas (CCs), and 6 surgically resected hepatocellular carcinomas (HCCs). In normal livers, MMP and TIMP were infrequently and faintly expressed in bile ducts, but were not expressed in hepatocytes. In the 11 CCs, MMP-1, MMP-2, MMP3, MMP-9, TIMP-1, and TIMP-2 were expressed in tumor cells and/or tumor stroma in 11 (100%), 5 (45%), 8 (73%), 3 (27%), 9 (82%), and 9 (82%), respectively. The expression of MMP and TIMP in tumor cells was located in the cytoplasm with a diffuse or granular pattern; that in the tumor stroma was situated in fibroblasts, leukocytes, and extracellular matrix. Their expression was stronger in CC cases with severe invasion than in CC cases with mild invasion. In contrast, MMP and TIMP were not expressed in any cases of HCC. These results show that intrahepatic bile duct cells may neoexpress or overexpress MMP and TIMP after malignant transformation but that hepatocytes do not, and suggest that MMP and TIMP play an important role in CC cell invasion by degrading extracellular matrix proteins.
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PMID:Expression of immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human normal livers and primary liver tumors. 867 49

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.
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PMID:Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential. 869 Mar 99

The effects of dibutyryl cyclic AMP (DBcAMP) on tissue inhibitor metalloproteinase (TIMP) expression were studied in the human hepatoma cell line PLC/PRF/5 with relation to the invasive activity of the cells. Messenger RNA expression levels of metalloproteinases (MMP)-2 and 9, and TIMP-1, 2 and 3 in the cells were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-9 and TIMP-2 mRNA expression were not detectable in the cells with or without DBcAMP treatment. Relative MMP-2 and TIMP-1 mRNA expression levels in the cells were not affected by DBcAMP, whereas TIMP-3 mRNA expression was enhanced by DBcAMP. This stimulatory effect of DBcAMP on TIMP-3 expression was confirmed at the mRNA and intracellular protein levels by Northern and Western blotting, respectively. Invasive activity of PLC/PRF/5 cells was determined using the in vitro Matrigel (extracellular matrix extract) invasion model. DBcAMP inhibited the invasive activity of the cells, and this effect was eliminated by addition of an antisense oligonucleotides corresponding to TIMP-3 mRNA. These results suggested that TIMP-3 expression is enhanced by DBcAMP and may play a role in inhibition of the invasive activity of hepatoma cells.
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PMID:Dibutyryl cyclic AMP-induced enhancement of tissue inhibitor of metalloproteinases-3 expression and its possible relation to the invasive activity of the human hepatoma cell line PLC/PRF/5. 1069 30

To examine the possible involvement of MMP-9 and -2 in the development of liver diseases caused by HCV or HBV infection, serum activities of both enzymes were studied by zymograph. Eight groups of subjects (60 for each) were examined in the study: healthy control, patients with hepatoma, liver cirrhosis, chronic hepatitis B or chronic hepatitis C, and carriers positive for HBsAg, both HBsAg and HBeAg, or anti-HCV. The results showed significant changes in the MMP-9 and -2 activities in the carriers. The presence of HBeAg was accompanied by a highest activity of MMP-2 and an inversely correlated (r=-0.578, P=<0.001), lowest activity of MMP-9 among all groups. For those with active liver diseases, MMPs activities were fluctuated at each stage of pathological symptoms. Chronic hepatitis B and C patients had significant different serum MMP-2 and -9 activities. These findings imply an influence on the balance of MMPs system by the existence of virus that might influence the following progression of liver disease, and a distinction between the pathological mechanisms of HCV and HBV. Since the serum MMPs activities were significantly varied between each stage of liver disease, an individual profile of these parameters might serve as an easy accessing serum marker to monitor the progression of liver disease.
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PMID:Significant differences in serum activities of matrix metalloproteinase-2 and -9 between HCV- and HBV-infected patients and carriers. 1072 81

The antitumor activity of cinnamamide (CNM), an agent acting on matrix metalloproteinase (MMP), was investigated in the present study. CNM displayed low cytotoxicity. By the MTT assay the IC50 (50% inhibitory concentration) values of CNM on cell proliferation ranged from 1.29 to 1.94 mM in human oral epidermoid carcinoma KB cells, human hepatoma BEL-7402 cells and human fibrosarcoma HT-1080 cells. Moreover, the IC50 for human fetal lung 2BS cells reached 4.33 mM. The administration of CNM in the range of 50-150 mg/kg (i.p. or p.o.) showed moderate antitumor effects in mice. When administered i.p. or p.o., CNM (150 mg/kg) inhibited the growth of transplanted hepatoma 22 by 48.8 or 40.5%, respectively. At the dose of 100 mg/kg, CNM inhibited the growth of colon 26 carcinoma by 39.0% and that of Lewis lung carcinoma by 53.9%. In the Lewis lung carcinoma model, CNM at the dose of 100 mg/kg (i.p.) also reduced the lung metastasis by 59.1%. Gelatine zymography revealed that CNM was able to decrease the level of MMP-2 in conditioned medium of HT-1080 tumor cells in a concentration-dependent manner. These results indicate that CNM is an antitumor agent with low cytotoxicity acting on MMP and may serve as a lead compound in the development of antitumor drugs.
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PMID:Cinnamamide, an antitumor agent with low cytotoxicity acting on matrix metalloproteinase. 1075 63

Matrix metalloproteinases (MMP) play an important role in tumor cell invasion and metastasis. We examined the expression of MMPs in hepatocellular carcinoma (HCC) to determine whether they may help indicate the progression of HCC and patient outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP were determined in 37 pairs of HCC and adjacent non-tumor tissue specimens by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The tumor to non-tumor (T/N) ratios for mRNA expression of each MMP were compared with the clinicopathological findings and two-year disease-free survival rates. Immunohistochemical analysis for MMP-1 and -9 was performed in 30 specimens. MMP-1 and -9 expression was significantly higher in tumor tissue than in non-tumor tissue (p=0.001 and 0.0078, respectively). By contrast, the expression of MMP-2 and -7 was significantly lower in tumor tissue than in non-tumor tissue (p=0. 003 and 0.03, respectively). A higher MMP-9 T/N ratio was significantly associated with small HCCs (</=2 cm) and higher serum AFP values (>/=20 ng/ml) (p=0.013 and 0.028, respectively). Immunohistochemical analysis suggested that well differentiated HCC showed stronger immunoreactivity for MMP-9 than moderately differentiated HCC. MMP T/N ratio was not significantly associated with the disease-free survival rates. Overexpression of MMP-9 mRNA (T/N ratio >/=2) may be associated with the progression of small HCC (</=2 cm).
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PMID:Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma. 1089 30

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