Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two monoclonal antibodies of F (ab')2 form, MRK 16 and MRK 20 that recognize P-glycoprotein and P85 kD protein respectively, were useful to detect multidrug resistant cells in human lymphoma, leukemia and gastrointestinal cancer cell lines. They were classified into 4 groups: Group I (4 cell lines) was insensitive to vinca alkaloids, anthracyclines, etoposide (VP-16) and actinomycin-D (ACT-D), and reactive to MRK 16 and MRL 20. Group II (2 cell lines) was insensitive to vincristine (VCR), but not reactive to both antibodies. Group III (3 cell lines) was insensitive to anthracyclines and VP-16, but sensitive to vinca alkaloids and ACT-D, and reactive to MRK 20 but not to MRK 16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. MRK 16 detects P-glycoprotein-associated multidrug resistance (MDR), while MRK 20 detects P 85kd-associated novel MDR. These monoclonal antibodies were useful for detection of MDR cells in clinical samples.
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PMID:[Detection of multidrug resistant cells in human malignant diseases by monoclonal antibodies and strategy to eradicate resistant malignant cells]. 256 3

Primary and acquired resistance of tumor cells to antineoplastic drugs is a major cause of the limited efficiency of chemotherapy. Gastrointestinal (GI) tumors have proven to express cytostatic drug resistance at an unusually high rate. One major reason for this is the multidrug resistant (MDR) phenotype which is often found in carcinomas of the stomach, bile duct, pancreas, liver, and colon. MDR is due to the overexpression of a membrane-bound glycoprotein, the so called P-glycoprotein. However, this is not the only resistance mechanisms of GI tumor cells, but the intracellular compartmentalization of drugs with subsequent release to the microenvironment represents an additional potent mechanism of drug resistance. This is independent of P-glycoprotein and as yet cannot be reversed. Alterations of glutathione-S-transferase (GST) and topoisomerase I and II may be involved either. Analyses of cell lines for cross resistance against a battery of cytostatic drugs suggest even more mechanisms which may contribute to the marked resistance of gastrointestinal cancer. Only a detailed investigation of all different types of drug insensitivity, if ever possible, might offer a chance to fully understand this multifactorial orchestra of events and to develop complex strategies for overcoming drug resistance.
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PMID:Molecular mechanisms and possibilities of overcoming drug resistance in gastrointestinal tumors. 889 37

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.
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PMID:P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer. 1045 34