Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human lung carcinoma cell line DLKP was exposed to sequential pulses of 10 commonly used chemotherapeutic drugs (VP-16, vincristine, taxotere, mitoxantrone, 5-fluorouracil, methotrexate, CCNU, BCNU, cisplatin and chlorambucil); resulting cell lines exhibited resistance to the selecting agents (ranging approx. 1.5- to 36-fold) and, in some cases, cross-resistance to methotrexate (approx. 1.4- to 22-fold), vincristine (1.6- to 262-fold), doxorubicin (Adriamycin, approx. 1.1- to 33-fold) and taxotere (approx. 1.1- to 36-fold). Several of the variants displayed collateral sensitivity to cisplatin. A marked increase in in vitro invasiveness and motility was observed with variants pulsed with mitoxantrone, 5-fluorouracil, methotrexate, BCNU, cisplatin and chlorambucil. There was no significant change in invasiveness of cells pulsed with VP-16, vincristine, taxotere or CCNU. All of the pulse-selected variants showed elevated levels of MDR-1/P-gp protein by Western blot analysis, although mdr-1 mRNA levels were not increased (except for DLKP-taxotere). In DLKP-taxotere, MRP1 protein levels were also greatly elevated, but mrp1 mRNA levels remained unchanged. BCRP was upregulated in DLKP-mitoxantrone at both the mRNA and protein levels. Gelatin zymography, Western blot and RT-PCR showed that DLKP and its variants secreted MMPs 2, 9 and 13. MMP inhibition assays suggested that MMP-2 plays a more important role than MMPs 9 and 13 in cell invasion of these DLKP drug-resistant variants in vitro. These results indicate that drug exposure may induce not only resistance but also invasiveness in cancer cells.
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PMID:Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. 1523 24

The neural precursor surface marker CD133 is thought to be enriched in brain cancer stem cells and in radioresistant DAOY medulloblastoma-derived tumor cells. Given that membrane type-1 matrix metalloproteinase (MT1-MMP) expression is a hallmark of highly invasive, radioresistant, and hypoxic brain tumor cells, we sought to determine whether MT1-MMP and other MMPs could regulate the invasive phenotype of CD133(+) DAOY cells. We found that when DAOY medulloblastoma or U87 glioblastoma cells were implanted in nude mice, only those cells specifically implanted in the brain environment generated CD133(+) brain tumors. Vascular endothelial growth factor and basic fibroblast growth factor gene expression increases in correlation with CD133 expression in those tumors. When DAOY cultures were induced to generate in vitro neurosphere-like cells, gene expression of CD133, MT1-MMP, MMP-9, and MDR-1 was induced and correlated with an increase in neurosphere invasiveness. Specific small interfering RNA gene silencing of either MT1-MMP or MMP-9 reduced the capacity of the DAOY monolayers to generate neurospheres and concomitantly abrogated their invasive capacity. On the other hand, overexpression of MT1-MMP in DAOY triggered neurosphere-like formation which was further amplified when cells were cultured in neurosphere medium. Collectively, we show that both MT1-MMP and MMP-9 contribute to the invasive phenotype during CD133(+) neurosphere-like formation in medulloblastoma cells. Increases in MMP-9 may contribute to the opening of the blood-brain barrier, whereas increased MT1-MMP would promote brain tumor infiltration. Our study suggests that MMP-9 or MT1-MMP targeting may reduce the formation of brain tumor stem cells.
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PMID:Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. 1856 95

Multidrug-resistant tuberculosis (MDR-TB) is a form of TB caused by Mycobacterium tuberculosis (M. tuberculosis) that do not respond to, at least, isoniazid and rifampicin, the two most powerful, first-line (or standard) anti-TB drugs. Novel intervention strategies for eliminating this disease were based on finding proteins that can be used for designing new drugs or new and reliable kits for diagnosis. The aim of this study was to compare the protein profiles of MDR-TB with sensitive isolates. Proteomic analysis of M. tuberculosis MDR-TB and sensitive isolates was obtained with ion exchange chromatography coupled with MALDI-TOF-TOF (matrix-assisted laser desorption/ionization) in order to identify individual proteins that have different expression in MDR-TB to be used as a drug target or diagnostic marker for designing valuable TB vaccines or TB rapid tests. We identified eight proteins in MDR-TB isolates, and analyses showed that these proteins are absent in M. tuberculosis-sensitive isolates: (Rv2140c, Rv0009, Rv1932, Rv0251c, Rv2558, Rv1284, Rv3699 and MMP major membrane proteins). These data will provide valuable clues in further investigation for suitable TB rapid tests or drug targets against drug-resistant and sensitive M. tuberculosis isolates.
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PMID:Proteomic analysis of drug-resistant Mycobacterium tuberculosis by one-dimensional gel electrophoresis and charge chromatography. 2741 16