Drug transporters have been implicated in resistance of solid and non-solid tumors to a variety of chemotherapeutic agents. Higher expression of the ABCB1 drug transporter is often observed in drug-resistant tumor cells, although the precise mechanism remains unclear. During selection of MCF-7 cells for survival in increasing concentrations of docetaxel (MCF-7TXT cells), we observed in this study a temporal correlation between the acquisition of docetaxel resistance at selection dose 9 and the increased expression of ABCB1.
View Article and Find Full Text PDFBackground: Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters.
View Article and Find Full Text PDFExpression of bovine PKCalpha in Saccharomyces cerevisiae results in growth inhibition, which is strongly augmented upon addition of phorbol esters. To investigate the nature of this PKC-induced inhibition of cell growth, wildtype and bovine PKCalpha-expressing yeast cells were examined by flow cytometry and by fluorescence microscopy after staining with propidium iodide. Upon expression and activation of the mammalian PKC isoform, cells accumulated in the G2/M phase of the cell cycle and exhibited impaired chromsome segregation.
View Article and Find Full Text PDFGenome profiling approaches such as cDNA microarray analysis and quantitative reverse transcription polymerase chain reaction are playing ever-increasing roles in the classification of human cancers and in the discovery of biomarkers for the prediction of prognosis in cancer patients. Increasing research efforts are also being directed at identifying set of genes whose expression can be correlated with response to specific drugs or drug combinations. Such genes hold the prospect of tailoring chemotherapy regimens to the individual patient, based on tumour or host gene expression profiles.
View Article and Find Full Text PDFcDNA microarray analysis is a highly useful tool for the classification of tumors and for prediction of patient prognosis to specific cancers based on this classification. However, to date, there is little evidence that microarray approaches can be used to reliably predict patient response to specific chemotherapy drugs or regimens. This is likely due to an inability to differentiate between genes affecting patient prognosis and genes that play a role in response to specific drugs.
View Article and Find Full Text PDFcDNA microarray analysis is highly useful for monitoring genome-wide changes in gene expression that occur in biological processes. Current standards require that microarray observations be verified by quantitative (Q)-PCR or other techniques. Few studies have optimized Q-PCR for verification of microarray findings.
View Article and Find Full Text PDFWith the advent of DNA microarray analysis, it is now possible to examine the response of virtually the entire human genome to cellular drug exposure and to uncover a wide variety of genes correlating with the establishment of drug resistance. This relatively new field of "pharmacogenomics" is likely to vastly increase our understanding of the mechanisms of drug action and how cells respond and adapt to drug exposure. However, DNA microarray studies typically result in the identification of hundreds of genes that may or may not be of relevance in vivo-particularly when large, genetically diverse study populations are used.
View Article and Find Full Text PDFLess than half of breast cancer patients respond to second-line chemotherapy with paclitaxel after failing treatment with anthracyclines such as doxorubicin. A recent clinical trial by Paridaens et al. [J.
View Article and Find Full Text PDFDrug resistance is a major impediment to the successful treatment of breast cancer using chemotherapy. The photoactivatable drug calphostin C has shown promise in killing select drug-resistant tumor cells lines in vitro. To assess the effectiveness of this agent in killing doxorubicin- or paclitaxel-resistant breast tumor cells and to explore its mode of action, MCF-7 cells were exposed to increasing concentrations of either doxorubicin or paclitaxel until maximum resistance was obtained.
View Article and Find Full Text PDF