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P Twentyman

Publications and source records attributed to P Twentyman.

11 recordsLinked to original sources
PubMed1998

The influence of glutathione metabolism on multidrug resistance in MRP-overexpressing cells.

The multidrug resistance (+associated) protein (MRP) is one of two ATP-dependent transport molecules which have been shown to be a cause of multidrug resistance in mammalian cells. The protein is ubiquitously expressed in human tissues and in a range of tumor types. In addition to a range of neutral or cationic cytotoxic drugs, MRP also transports heavy metals and organic anions including glutathione (GSH)-conjugates and glucuronate conjugates. In cells depleted of GSH, the activity of MRP towards cationic drugs is abrogated whereas activity towards organic anions is preserved. Possible mechanisms involved in this differential action and strategies for its exploitation in clinical chemotherapy are discussed.

Journal Article↗
PubMed1988

Use of a colorimetric microtiter (MTT) assay in determining the radiosensitivity of cells from murine solid tumors.

We assessed the use of a colorimetric assay for determination of radiosensitivity for cells taken directly from murine solid tumors. The assay uses microtier plates and measures the ability of viable cells to reduce a tetrazolium salt (MTT) to an insoluble form, a formazan salt. We established the dependency of the assay on the cell number and time of assay for two murine tumors (EMT-6 and RIF-1). We compared the MTT assay to the standard clonogenic assay and had good agreement of surviving fraction after radiation doses of 2 and 4 Gy. It is possible, therefore, to adapt the MTT assay for use with cell suspensions prepared directly from fresh murine tumors. This may provide a methodology for the determination of the clinical radiosensitivity of tumors including fresh clinical tumor specimens.

Animals↗
PubMed1986

Identification of a novel calcium-binding protein (CP22) in multidrug-resistant murine and hamster cells.

Analysis of cytoplasmic extracts of multidrug-resistant murine and hamster cells by SDS gel and 2D gel electrophoresis showed that they expressed an abundant 22 kDa protein which was absent from the drug-sensitive parent lines. SDS gel electrophoresis in the presence of EGTA and direct binding tests with 45Ca2+ showed that the resistance-associated protein is a specific calcium-binding protein. Thus the development of multidrug resistance in both colchicine-selected hamster cells and adriamycin-selected murine cells is associated with a major change in calcium metabolism. These observations provide the first molecular basis for the hypothesis that Ca2+ plays a central role in the development of the multidrug resistance phenomenon.

Animals↗
PubMed1982

Effect of misonidazole or metronidazole pretreatment on the response of the RIF-1 mouse sarcoma to melphalan, cyclophosphamide, chlorambucil and CCNU.

The effect has been studied of adding either misonidazole (MISO) or metronidazole (METRO) to cytotoxic drug treatment of C3H mice bearing the RIF-1 sarcoma. The nitroimidazoles were injected 30 min before the cytotoxic drugs at a dose of 2 . 5 mmol/kg. Both clonogenic-cell survival and growth delay were measured as indicators of tumour response and depression in WBC count and acute lethality were used to indicate normal-tissue response. For melphalan, neither pretreatment agent produced any change in tumor response. For cyclophosphamide, no change was produced by METRO but a minimal increase in tumour response occurred with MISO. An enhancement of cell killing by CCNU was seen with MISO pretreatment, but there was no increase in tumour growth delay. METRO, however, did not enhance tumour response by either endpoint. WBC depression by CCNU was not enhanced by MISO pretreatment, and there was no significant reduction in the acute LD50. This indicates a therapeutic advantage from the addition of MISO to CCNU in this model system. For chlorambucil, considerable enhancement of tumour response followed either MISO or METRO pretreatment (dose-modifying factors of 2 . 0 and 1 . 4 respectively). However, the modification by MISO of normal-tissue response to chlorambucil was also enhanced by about a factor of 2, with no therapeutic gain.

Animals↗