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)

A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed chromosomal alterations. One of the marker chromosomes showed characteristics of a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation using specific probes to the Y chromosome. The cells stained with fluorescent antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin but not with desmin. The presence of epithelial membrane antigen, human milk fat globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase and oestrogen receptor-related antigen was demonstrated by indirect immunoperoxidase staining, but no CA-125 antigen could be detected. The cells showed positive reaction with antibodies to P-glycoprotein. The function of the P-glycoprotein transport system was demonstrated by the rhodamine-123 release test. The cells were initially responsive to doxorubicin, and to high concentrations of cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced by the addition of verapamil or tamoxifen. This was shown by the soft agar clonogenic assay, by direct cell counting and by the MTT reducing test. Our results show that combination between drug and sensitivity modulators may be of potential clinical value in ovarian cancer.
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PMID:A cell line with unusual characteristics from an ovarian carcinoma patient: modulation of sensitivity to antitumour drugs. 134 52

The emergence of drug-resistant tumor cells remains a major problem in cancer chemotherapy. Resistance to multiple unrelated antineoplastic drugs may be related, in part, to expression of the P-glycoprotein. The cell line RD, derived from an embryonic rhabdomyosarcoma tumor, was used as an in vitro model to examine the development of drug resistance. A cell line resistant to actinomycin D (RD-DAC) was developed by growing RD in increasing concentrations of the drug. The ID50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant line to actinomycin D was more than 15 times that of the parental line. The resistant line was cross-resistant to vincristine and doxorubicin. Resistance to actinomycin D resulted in increased P-glycoprotein expression, which was associated with a change in desmin and vimentin expression. These results suggest that exposure to chemotherapeutic drugs can induce not only classical multidrug resistance, but also a process of cellular differentiation in rhabdomyosarcoma cells.
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PMID:Actinomycin D causes multidrug resistance and differentiation in a human rhabdomyosarcoma cell line. 791 94

Classical cytotoxic treatment of rhabdomyosarcoma (RMS) is accompanied often by significant morbidity and poor response. The use of cytotoxic agents may induce a multidrug resistance phenotype, which plays an important role in the sensitivity of tumoral cells to drugs. Using actinomycin D, a drug of choice in the treatment of RMS, we induced resistance in the TE.32.7 human RMS cell line. The TE.32.7-DAC-resistant cell line exhibited cross-resistance to vincristine and doxorubicin and showed mdr1/P-glycoprotein over-expression, suggesting that this mechanism was involved in the reduction in intracellular drug concentration and may be responsible for the failure of treatment of RMS with classical cycles of cytotoxics. Furthermore, this resistant cell line showed increased expression of the muscle differentiation markers desmin and alpha-actinin and ultrastructural changes which clearly indicated myogenic differentiation. Our findings suggest that, although this tumor is probably arrested along the normal myogenic pathway to maturation, induction of cell differentiation with anti-neoplastic drugs may be an alternative therapeutic approach. However, the failure of TE.32.7-DAC cells to completely re-enter the program of myogenic differentiation supports the hypothesis that multidrug resistance is a major obstacle in differentiation therapy for RMS.
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PMID:Therapeutic differentiation in a human rhabdomyosarcoma cell line selected for resistance to actinomycin D. 945 97

Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.
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PMID:Biological characteristics and chemosensitivity profile of four human anaplastic thyroid carcinoma cell lines. 1168 81

From an undifferentiated soft tissue sarcoma (STS) a cell line designated US8-93 has been established. At subcloning the cell line US8-93 three different lines (US8-93A, B and C) could be set up. In a subsequent study characteristics for ultrastructure, growth, cell cycle distribution, karyotype, protein overexpression detected by immunohistochemistry (IHC) and p53 mutational status were determined. The cell line US8-93 as well as subclones contain mainly bipolar spindle-shaped cells and additionally some polygonal and multinucleated cells. Cells possess the characteristics of primitive mesenchymal cells based on their positive reactions with anti-vimentin and negative reactions for desmin, cytokeratin, myoglobin, S100, and NSE, implying a classification as an undifferentiated STS. Cytogenetic analysis revealed nearly diploid cells with several structural and numerical aberrations for chromosomes 1, 3, 4, 6, 9, 10, 12, 13, 15 and 18. IHC positivity was found for the tumor suppressor proteins p53 and Rb, the oncogene products Bcl-2, K-ras, N-ras, P-glycoprotein Mdr-1 and MDM-2. In the p53 gene a nonsense mutation in exon 4 was detected, that was confirmed in the original primary tumor and in three derivative clonal lines. The described STS cell line represents a valuable supplementation to the relatively small number of human STS cell lines currently available and may also provide a good in vitro model for studies of STS tumorigenesis in respect to a mutated p53 gene.
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PMID:Morphological and molecular characterization of an undifferentiated soft tissue sarcoma cell line and derivative clones. 2152 41