Cytotoxic Drug Resistance Mechanisms

There is now a range of cytotoxic drugs that have considerable clinical usefulness in producing responses in tumors and even, in a small proportion of cases, cure. However, the acquisition of drug resistance is a major clinical problem and is perhaps the main limiting factor in successful treatment of cancer. Thus, a tumor initially sensitive to chemotherapy will, in the majority of cases, eventually recur as a resistant tumor, which will then progress. Much of our understanding of drug resistance mechanisms comes from the study of tumor cell lines grown in tissue culture. We now understand many of the - lecular mechanisms that can lead to a cell acquiring resistance to antic- cer drugs; however, we still do not know which mechanism(s) are those most relevant to the problem of clinical drug resistance. Indeed, given that many of the cytotoxic anticancer drugs were discovered by random screening, it is - clear what features give a clinically useful anticancer drug a sufficient the- peutic index to be of value. The aim of Cytotoxic Drug Resistance Mechanisms is to provide pro- cols that are appropriate for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumor samples. Tumor cell lines have been enormously useful as experimental models of drug resistance mechanisms, however they have limitations and we need to address the relevance of such mechanisms in patients' tumors. Examining drug resistance in tumors is much more problematic than in cell lines.

Autorentext
Robert Brown, geboren 1957, ist seit über 25 Jahren eines der bekanntesten und anerkanntesten hellsichtigen Medien aus England. Seine besonderen Fähigkeiten wurden bereits als Kind erkannt. Robert Brown, hält weltweit Vorträge, Seminare, Demonstrationen und Einzelberatungen.

Klappentext

Leading clinical and laboratory scientists describe cutting-edge methods for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumors. The protocols contain detailed instructions and extensive troubleshooting tips that allow researchers effectively to study a wide variety of drug resistance mechanisms, including aspects of drug-induced cell death, drug uptake/efflux, drug metabolism, and DNA repair. Each method is designed to help identify the correlation between molecular and biochemical data and the clinical responses of the patient. Cytotoxic Drug Resistance Mechanisms illuminates all the clinically relevant mechanisms used as markers of the biological response to anticancer biotherapeutics today.

Inhalt
Drug Resistance.- Cell Sensitivity Assays.- Cell Sensitivity Assays.- Cell Sensitivity Assays.- Analysis of Apoptosis in Tissue Sections.- Measurement of P-glycoprotein Function.- Measuring MDR-1 by Quantitative RT-PCR.- Microtiter Plate Technique for the Measurement of Glutathione in Fresh and Cryopreserved Lymphoblasts Using the Enzyme Recycling Method.- Measurement of Reduced Glutathione Using High-Pressure Liquid Chromatography.- Topoisomerase I and II Activity Assays.- 5-Fluorouracil Metabolizing Enzymes.- Measuring DNA Adducts by Immunoassay (ELISA).- Measuring Drug-DNA Adducts in Individual Cells.- Measurement of Drug-Induced DNA Interstrand Crosslinking Using the Single-Cell Gel Electrophoresis (Comet) Assay.- PCR Analysis of Microsatellite Instability.- O 6-Alkylguanine-DNA Alkyltransferase Assay.- Analysis of the p53 Status of Tumors.- Bcl-2 Family Immunohistochemistry.- Genetic Analysis of Drug Resistance by Fluorescence In Situ Hybridization.- Genetic Analysis of Drug Resistance by Reverse In Situ Hybridization.