Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phellinus linteus (PL) is a fungus mainly found in tropical America, Africa and Asian countries including Korea, Japan and China. PL has been traditionally used for the treatment of arthritis, liver damage and cancer. However, little was known on the biological activity and characterization of Phellinus species in Cambodia. Thus, in the present study, the anti-metastatic mechanism of aqueous extract of Cambodian Phellinus linteus (CPL) was evaluated. Cambodian mushroom was identified as a Phellinus species with 99% homology of Phellinus linteus by DNA sequence analysis and comparison by the National Center for Biotechnology Information. CPL did not exhibit any significant cytotoxicity against B16BL6 cells, invasive melanoma cells at 1 mg/ml. However, CPL inhibited platelet aggregation induced by B16BL6 cells and also disrupted the adhesion to gelatin and invasion of B16BL6 cells in a concentration dependent manner. Similarly, CPL dose-dependently inhibited the pulmonary metastatic colonies in C57BL/6 mice intravenously injected by B16BL6 cells up to 55.5% at a dose of 50 mg/kg compared with untreated control. CPL also down-regulated the expression of urokinase type plasminogen activator (uPA), one of key proteins associated with invasion and metastasis of tumor cells in a concentration dependent fashion, while CPL didn't significantly affect the expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) by reverse transcriptase-polymerase chain reaction (RT-PCR). Taken together, these findings indicate that Cambodian Phellinus linteus may inhibit metastasis at least partly via regulation of uPA associated with tumor cell induced platelet aggregation (TCIPA) and also suggest a further study for isolation of active ingredients and the involvement of adhesion molecule signaling pathway.
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PMID:Cambodian Phellinus linteus inhibits experimental metastasis of melanoma cells in mice via regulation of urokinase type plasminogen activator. 1563 58

The aim of this study is to investigate the expression of matrix metalloproteinase 2 (MMP-2) and the tissue inhibitor of metalloproteinase 2 (TIMP-2) in oral squamous cell carcinoma (OSCC) and adjacent normal tissues, and explore the role of MMP-2 and TIMP-2 in carcinoma metastasis and invasion. Expression of MMP-2 and TIMP-2 was evaluated in 40 cases with semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical techniques. The values of MMP-2/beta-actin and TIMP-2/beta-actin in OSCC were significantly higher than those in adjacent normal tissues 2 cm and > or = 5 cm from carcinoma tissues (p<0.05). The results of immunohistochemical analysis show that the positive expression of MMP-2 and TIMP-2 protein in tumor tissues (60.0 and 52.5%) was higher than that in adjacent normal tissues 2 cm (30.0 and 22.5%) and 5 cm (22.5 and 25.0%) from cancer tissues, and the difference was significant p<0.05). The expression of MMP-2 and TIMP-2 was related to the differentiation degree of tumor cells, metastatic lymph node status and stage of carcinoma, but not related to the age and gender of patients, or location of the carcinoma. Therefore, MMP-2 and TIMP-2 may play important roles in the invasion and metastasis of OSCC.
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PMID:Expression of matrix metalloproteinase 2 and its tissue inhibitor in oral squamous cell carcinoma. 1614 92

Matrix metalloproteinases (MMPs), a class of enzymes responsible for the degradation of extracellular matrix proteins, play important roles in inflammatory and immune responses. In skin, MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are normally inactive but can be expressed during tissue injury. Both degrade collagen IV and other critical components of the basement membrane zone that separates the epidermis from the dermis. The expression of MMP-2 and -9 was studied in sulfur mustard (SM)-exposed ear skin from mice to determine their role in tissue vesicant injury. Punch biopsies of mouse ears were collected between 6 and 168 h after exposure to 97.5 mM (0.08 mg) SM diluted in CH(2)Cl(2). They were examined histologically and assayed for MMP-2 and -9 expression by gelatinase activity assays, real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. A time-related increase in overall gelatinase activity was observed in SM-treated ears. At 168 h after SM exposure, the relative levels of MMP-9 mRNA were increased 27-fold and MMP-9 protein 9-fold when compared with the control (CH(2)Cl(2) treated) ears. In contrast, there were no observable increases in the MMP-2 mRNA or protein levels between treated and control ears. These observations suggest the differential expression of MMP-2 and -9 during the cutaneous response to SM injury and suggest a role for MMP-9 in SM-induced injury.
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PMID:Preferential expression of matrix metalloproteinase-9 in mouse skin after sulfur mustard exposure. 1648 79

Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection, with tumor recurrence in the form of microdisseminated disease. Extracellular matrix (ECM)-related molecules and their receptors predominantly participate in the invasion process, including cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the healthy brain by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 30 invasion-related molecules (twenty-one ECM components, two related receptors, and seven ECM-related enzymes) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM), intracerebral lung adenocarcinoma metastasis, and normal brain were evaluated. Significant differences were established for 24 of the 30 molecules. To confirm our results at the protein level, immunohistochemical analysis of seven molecules was performed (agrin, neurocan, syndecan, versican, matrix metalloproteinase 2 [MMP-2], MMP-9, and hyaluronan). Determining the differences in the levels of invasion-related molecules for tumors of different origins can help to identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas.
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PMID:Expression of invasion-related extracellular matrix molecules in human glioblastoma versus intracerebral lung adenocarcinoma metastasis. 2039 22

Diffuse growth of gliomas is based on enhanced cell migration and remodeling of the extracellular matrix. Up-regulation of matrix metalloproteinases in gliomas is associated with a poor prognosis. The activated leukocyte adhesion molecule is considered to be indispensable for conversion of matrix metalloproteinase 2 into its active form. We therefore investigated the expression of activated leukocyte adhesion molecule in 9 malignant glial cell lines, 105 normal/reactive human brain specimens, 248 astrocytomas/glioblastomas, 98 ependymomas, 35 oligodendrogliomas, 10 neurocytomas, 10 primitive neuroectodermal tumors (PNET), and 36 medulloblastomas by immunohistochemistry and in selected cases by reverse transcriptase polymerase chain reaction. Correlation between activated leukocyte adhesion molecule expression and tumor grades and entities, proliferation activity, matrix metalloproteinase 2 expression, prognostic isocitrate dehydrogenase (IDH)1 mutation (R132H) status, O-6-methylguanine DNA-methyltransferase (MGMT) promoter status, or association with patient survival were analyzed. All oligodendrogliomas were strongly activated leukocyte adhesion molecule positive. Numbers of activated leukocyte adhesion molecule positive tumors were higher in glioblastomas (93%) than in diffuse astrocytomas (83%), but mean expression intensity was significantly reduced. Anaplastic ependymomas (68%) exhibited reduced numbers of activated leukocyte adhesion molecule-positive tumors and staining intensity compared with lower-grade ependymomas (85%). Activated leukocyte adhesion molecule expression in gliomas was independent of proliferative activity, MGMT status, patient survival, and age, whereas gliomas with IDH1 (R132H) mutation had significantly higher activated leukocyte adhesion molecule levels than their wild-type counterparts. Matrix metalloproteinase 2-negative glioblastomas exhibited significantly reduced activated leukocyte adhesion molecule expression levels compared with astrocytomas. In summary, our findings indicate that activated leukocyte adhesion molecule expression levels in gliomas are probably linked to other mechanisms than its supposed role as regulator of matrix metalloproteinase 2.
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PMID:Activated leukocyte cell adhesion molecule is expressed in neuroepithelial neoplasms and decreases with tumor malignancy, matrix metalloproteinase 2 expression, and absence of IDH1R132H mutation. 2230 88


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