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

We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy.
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PMID:Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications. 168 Feb 3

We assessed the expression of P-glycoprotein, the product of the multidrug resistance gene, in 107 specimens from patients with transitional cell carcinoma of the upper urinary tract, using an immunohistochemical method with a polyclonal antibody. P-glycoprotein was expressed in 28 of 107 (26%) specimens. While P-glycoprotein expression was not related to the grade or stage of these tumors, the incidence of P-glycoprotein in specimens with tumors which coexisted in renal pelvic and ureter is significantly higher than those with either renal pelvic or ureter tumor alone. In the patients with advanced upper urinary tract tumor who had adjuvant chemotherapy including at least one P-glycoprotein-transported drug (mdr regimen), overall survival of patients with P-glycoprotein-positive tumor was significantly shorter than that of patients with negative tumor. This pilot study demonstrates that P-glycoprotein can be expressed in one fourth of transitional cell carcinomas of the upper urinary tract and that P-glycoprotein expression serves as a prognostic indicator in patients with these tumors who are treated with mdr regimens.
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PMID:Expression of multidrug resistance gene product (P-glycoprotein) in transitional cell carcinomas of the upper urinary tract. 771 32

Expression of the MRP gene has been demonstrated in vitro to be a casual factor in non-P-glycoprotein-mediated multidrug resistance, and is implicated in resistance to a number of the chemotherapeutic agents currently used in the treatment of high-grade transitional cell carcinoma (TCC) of the bladder (doxorubicin, epirubicin and vinblastine). Using a sensitive RT-PCR-based technique, we have quantified MRP mRNA levels in a series of untreated TCC (n=24), normal bladder (n=5) and control tissue and cell line samples. MRP mRNA was widely expressed and detectable in all samples analysed, with considerable (up to 190-fold) variation observed between individual tumour samples. MRP mRNA levels found in TCC samples were lower than those determined for normal peripheral mononucleocyte (2.3-fold) and testis (4.1-fold) samples, previously reported to be high-expressing tissues, and varied over a similar range to that observed in normal bladder samples. Results indicate that MRP mRNA levels in a greater proportion of high-grade (G3) bladder tumours (55%, 6/11) are significantly reduced (P=0.018) compared with low- and moderate-grade (G1/2) bladder tumours (8%, 1/13), and suggest that MRP mRNA levels frequently become reduced as a consequence of tumour progression to advanced, poorly differentiated disease. No correlation was apparent between MRP and MDR1 mRNA levels, thus providing no evidence to suggest common regulation of the two genes. In a limited number of patients, no evidence was found to support a role for MRP mRNA levels as a determinant of response to chemotherapy in patients being uniformly treated with either cisplatin-methotrexate-vinblastine (n=6) or epirubicin-cisplatin-methotrexate (n=4) regimens. Similarly, no overall pattern of altered MRP mRNA expression was observed following chemotherapy in four patients from whom post chemotherapy biopsies were taken. This study provides a useful pilot investigation regarding the level, variation and pattern of MRP mRNA expression in TCC of the bladder, and suggests that further studies to establish the clinical significance of these variations are required.
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PMID:Alterations in expression of the multidrug resistance-associated protein (MRP) gene in high-grade transitional cell carcinoma of the bladder. 860 4

Two cell lines, SNK57 and NKB1, were established from human bladder cancer: SNK57 from a transitional cell carcinoma (TCC) in a 73-year-old female and NKB1 from a residual TCC following MEC (methotrexate, farmorubicin and cisplatin) chemotherapy in a 64-year-old female. Doubling time of SNK57 and NKB1 cells was 24 hours and 45 hours, respectively. The chromosome number of both cell lines was 100 percent anueploid with a mode of 43 chromosomes for SNK57 and 107 for NKK1. Both SNK57 and NKK1 induced tumors at the site of subcutaneous injection of nude mice. Histology of the tumors closely resembled that of the original ones from which they were derived. Although NKB1 was 4 times more resistant to doxorubicin (ADM) as compared to SNK57, overexpression of MDR1 gene product, P-glycoprotein was not evident in NKB1 as well as SNK57. These two new cell lines with different chemosensitivity to ADM may be a useful model for developing new chemotherapeutic strategies for human bladder cancer.
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PMID:Establishment and characterization of two human bladder cancer cell lines. 918 30

Medical records and biopsy specimens were retrospectively reviewed from 25 dogs diagnosed with unresectable urinary bladder carcinoma and treated with chemotherapy. Our intention was to identify clinical, histologic, and immunohistochemical indicators of prognosis. Immunohistochemical stains for P-glycoprotein, glutathione-S-transferase pi, and factor VIII-related antigen were applied to archived tissue. There were more spayed female dogs than castrated male dogs (76% versus 24%). Transitional cell carcinoma was the most common tumor (88%, n = 22), followed by undifferentiated carcinoma (8%, n = 2) and squamous cell carcinoma (4%, n = 1). Overall median survival was 251 days. Histologic diagnosis and immunohistochemical characteristics did not correlate with prognosis. Spayed females survived significantly longer than castrated males (358 days versus 145 days, P = .042). Dogs that received either doxorubicin or mitoxantrone in addition to a platinum-based chemotherapeutic (either cisplatin or carboplatin) lived significantly longer than those that received only a platinum compound (358 days versus 132 days, P = .042).
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PMID:Prognostic factors in dogs with urinary bladder carcinoma. 1101 9

The expression of multidrug resistant proteins in bladder cancer and clinical implication was studied. Expression of multidrug-associated protein (MRP), P-glycoprotein (P-gp), P53 and Bcl-2 proteins were detected by using immunohistochemical method in 40 specimens of bladder transitional cell carcinoma. The results showed that the positive rate of MRP, P-gp, P53 and Bcl-2 was 52.5%, 57.5%, 47.5% and 62.5% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in the grade I, II and III of tumors was 46.3%, 38.5%, 38.5%, 23.1%; 52.9%, 39.8%, 47.1%, 76.4%; 60.0%, 80.0%, 60.0%, 90.0% respectively. The positive rate of MRP, P-gp, P53 and Bcl-2 in 24 primary tumor specimens was 37.5%, 41.7%, 33.3%, 45.8% and that in 16 cases in recurrent specimens receiving chemotherapy 75.0%, 81.3%, 68.8%, 87.5% respectively. It was suggested the positive rate of MRP, P-gp, P53 and Bcl-2 was increased with the advance of tumor grade. The positive rate of four proteins in all recurrent cases was significantly increased (P < 0.05). The expression of MRP, P-gp, P53 and Bcl-2 proteins might be the important factors for chemotherapy failure.
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PMID:Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2 proteins in bladder cancer and clinical implication. 1152 49

Cyclooxygenase-2 (COX-2), P-glycoprotein (P-gp) and multi-drug resistance-associated protein (MRP) are considered important tumor-associated proteins in humans and dogs. In the present study, we immunohistochemically evaluated the expression of these proteins in canine patients with transitional cell carcinoma (TCC). Of 52 cases, 30 (57.7%) were positive for COX-2, 40 (76.9%) for P-gp, and only 10 (19.2%) for MRP. In addition, 27 samples (27/52, 51.9%) were positive for two markers, while 3 (5.7%) and 5 (9.6%) cases were positive and negative, respectively, for all three markers. No significant correlations were seen for COX-2 and P-gp on Fisher's exact test and Mann-Whitney's test, but a significance was seen on Spearman's rank correlation analysis using the IHC scoring system (P=0.043). These results suggest that P-gp expression is induced by overexpression of COX-2 in canine patients with TCC.
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PMID:Expression of cyclooxygenase-2, P-glycoprotein and multi-drug resistance-associated protein in canine transitional cell carcinoma. 1731 22

Urinary bladder cancer is one of the most common cancers worldwide. Human transitional cell carcinoma (TCC) cells are epithelial-like adherent cells originally established from a primary bladder carcinoma. Studies have shown that TCC cells are resistant to some chemotherapeutic agents such as vincristine (VCR). In the present study, the effect of feselol, a sesquiterpene coumarin isolated from the fruits of Ferula badrakema, was investigated on VCR effectiveness. Our results demonstrated that feselol itself did not have any cytotoxic effect on TCC cells. In order to check its combinatorial effects, TCC cells were exposed to various combined concentrations of feselol and VCR. Then, morphological changes were monitored and cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay for three consequent days. Results showed that the combination of 40 microg/ml VCR with 16 microg/ml feselol increased the cytotoxicity of VCR by 28.32% after 48 h. This effect might be due to inhibition of P-glycoprotein in TCC cells by feselol.
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PMID:The enhancement of vincristine cytotoxicity by combination with feselol. 2062 35