Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases (MMPs) are members of an enzyme family that require a zinc ion in their active site for catalytic activity. MMPs are critical for maintaining tissue allostasis. MMPs are active at neutral pH and can therefore catalyze the normal turnover of extracellular matrix (ECM) macromolecules such as the interstitial and basement membrane collagens, proteoglycans such as aggrecan, decorin, biglycan, fibromodulin and versican as well as accessory ECM proteins such as fibronectin. Members of the MMP family include the "classical" MMPs, the membrane-bound MMPs (MT-MMPs) the ADAMs (a disintegrin and metalloproteinase; adamlysins) and the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif). There are more than 20 members in the MMP and ADAMTS family including the collagenases, gelatinases, stromelysins, some elastases and aggrecanases. Adamlysins are membrane-bound MMPs that also degrade aggrecan, but more importantly, one ADAM family member (i.e.ADAM-17) is a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE) that activates pro-TNF-alpha. Most of the MMPs are synthesized as inactive latent enzymes. Conversion to the active enzyme is generally mediated by activator systems that include plasminogen activator or the pro-hormone convertase, furin. MMP activity is regulated by a group of endogenous proteins, called, tissue inhibitor of metalloproteinases (TIMPs) that bind to active and alternative sites of the activated MMP. Significant advances have occurred in the understanding of the regulation of MMPs, ADAMs and ADAMTSs gene expression. In addition, development of MMP inhibitors to study MMP structure/function relationships spawned many studies to determine the effectiveness of MMP inhibitors in regulating abnormal connective tissue turnover. In addition, development of MMP null mice carrying specific MMP deletions has provided an opportunity to explore the role of MMPs in normal development as well as in such diverse conditions and diseases as skeletal dysplasias, coronary artery and heart disease, arthritis, cancer, and brain disorders.
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PMID:Matrix metalloproteinases (MMPs) in health and disease: an overview. 1636 48

A 83-year-old man was admitted to our hospital with a large hepatic tumor located in lateral segment. Alpha-fetoprotein was 7ng/ml, and protein induced by vitamin K deficiency and antagonist-II (PIVKA-II) was 50792mAU/ml. The tumor was diagnosed as hepatocellular carcinoma (HCC) by angiographically assisted CT. No ascites was detected and major serological findings were T-Bil 0.7mg/dl, Alb 4.2g/dl, and PT 129%. Because of advanced age and a history of heart disease, he was treated with transarterial chemoembolization using cisplatin (Lip-TACE). The total dose was 128mg of cisplatin and 15ml of lipiodol. No adverse effects appeared. After the third session of Lip-TACE, the levels of PIVKA-II became negative and continued within the normal range for 26 months. We confirmed a decrease of HCC with lipiodol accumulation by abdominal CT, and the response rate was PR. He has been well for 3 years since the first Lip-TACE procedure.
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PMID:[Large hepatocellular carcinoma successfully treated with transarterial chemoembolization using cisplatin]. 1965 67