Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. We previously described that a nitrosourea, chlorozotocin (CZT), increased in vivo the pulmonary metastatic dissemination of a rat rhabdomyosarcoma and enhanced in vitro the cloning efficiency (CE) of the same tumor cell line. The selection procedure for chlorozotocin-selected cell lines (R1 to R9 lines), by in vitro CZT-treatment and cloning assay, indicated that 2.5% of the parental cell line was a CZT-resistant subpopulation. This subset acquired, in the course of the selection steps in semi solid medium, a multidrug-resistant phenotype. In a stem cell assay, the resistance of the R9 line was increased 10-fold for adriamycin (ADR) and up to 2 fold for cisplatinum. In comparison, C8 control line sensitivity to ADR did not change significantly. This resistance did not affect the non clonogenic population, as shown in a monolayer proliferation assay. Re-exposure of R (R1-R9) lines to CZT or initial CZT contact with C lines transiently but consistently increased the CE; however, clonogenicity remained stable, and this was also observed when deticene, another alkylating drug, was used instead of CZT. Moreover, the CZT-selected R9 line easily proliferated in serum-free medium in the presence of transferrin and insulin, whereas serum was necessary to maintain the growth of the parental cell line or C lines. Finally, we show that in vitro selection of variants, by both resistance to CZT and cloning, led to the isolation of a multi-drug resistant subpopulation, serum independent for its proliferation - two properties associated with progressive malignancy.
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PMID:Chlorozotocin-induced selection of autocrine and multidrug resistant variants from a rat rhabdomyosarcoma. 296 63

The ability of high-density lipoprotein (HDL) to support the growth of an established tumor cell line exposed to defined medium supplemented with transferrin has been examined. Low-density A-431 carcinoma cells maintained on extracellular matrix- or fibronectin-coated dishes proliferated actively when exposed to a synthetic medium supplemented with HDL, 500 micrograms protein per ml. Epidermal growth factor added at concentrations above 0.5 ng/ml inhibited cell growth, while at concentrations above 5 ng/ml it was cytotoxic. Among the various substrata tested for their ability to support the active proliferation of low-density A-431 cells when exposed to transferrin and HDL, plastic was the least efficient. On fibronectin-coated dishes, cells ceased to proliferate after 8 population doublings, while on extracellular matrix-coated dishes cells could be passaged for 50 population doublings. In the case of colon carcinoma, rhabdomyosarcoma, and Ewing's sarcoma cells exposed to medium supplemented with transferrin, the addition to the cultures of HDL alone resulted in a growth rate and final cell density which were similar to those observed when cells were exposed to serum-supplemented medium. In the case of the mammary carcinoma cell lines MCF-7 and ZR-75-1, HDL also supported cell growth, although to a lesser extent than did serum. The present study therefore indicates that HDL is capable of supporting, either totally or partially, the in vitro proliferation of tumor cells.
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PMID:High-density lipoproteins and the proliferation of human tumor cells maintained on extracellular matrix-coated dishes and exposed to defined medium. 704 62

HRV89, a major-group rhinovirus, uses intercellular adhesion molecule 1 (ICAM-1) for cell entry, while minor-group HRV2 uses the LDL receptor for clathrin-mediated endocytosis. Entry of HRV89 into HeLa epithelial cells was found to be inefficient, and infectious virus was still detected on the plasma membrane after 3 h of incubation with the cells. Endocytosis, and consequently infection, of HRV89 but not of HRV2, was almost completely blocked by the actin-polymerization inhibitor cytochalasin D, while the phosphatidylinositol 3-kinase inhibitor LY294002 had no effect on infection with either virus. Cytochalasin D also inhibited major-group HRV infection of rhabdomyosarcoma cells expressing ICAM-1 when the time available for uncoating was limited to 30 min. Although cholesterol depletion strongly inhibited HRV89 infection of HeLa cells, it only slightly affected HRV89 endocytosis, indicating that a lipid raft environment was not essential for virus uptake. The sodium-proton exchange inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) significantly reduced cell entry and infection by HRV89 only at a concentration that also inhibited HRV2 infection and Alexa 488-transferrin entry. These data rule out classical macropinocytosis as an infectious entry pathway of HRV89 in HeLa cells. Notably, the proton ATPase inhibitor bafilomycin strongly affected cell entry of both viruses, suggesting a role for submembraneous pH in rhinovirus endocytosis.
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PMID:Entry of human rhinovirus 89 via ICAM-1 into HeLa epithelial cells is inhibited by actin skeleton disruption and by bafilomycin. 2391 88