In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression
| Autor: | Doreen Ma, Paolo Paoletti, Steve Hoffmann, Olaf Oberschmidt, Heike Pospisil, Clet Niyikiza, Hartmut M. Hanauske-Abel, Victor J. Chen, Axel-Rainer Hanauske, Ulrike Eismann |
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| Rok vydání: | 2007 |
| Předmět: |
Antimetabolites
Antineoplastic Guanine Pemetrexed In Vitro Techniques Biology Thymidylate synthase Glutamates Neoplasms Gene expression Dihydrofolate reductase Tumor Cells Cultured medicine Humans Pharmacology (medical) RNA Messenger Tumor Stem Cell Assay Phosphoribosylglycinamide Formyltransferase Pharmacology Regulation of gene expression Thymidylate Synthase Molecular biology In vitro Gene Expression Regulation Neoplastic Tetrahydrofolate Dehydrogenase Real-time polymerase chain reaction Oncology Folate receptor Cancer research biology.protein Multidrug Resistance-Associated Proteins medicine.drug |
| Zdroj: | Investigational New Drugs. 25:417-423 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | mRNA expression of genes involved in the mechanism of action of pemetrexed was correlated with in vitro chemosensitivity of freshly explanted human tumor specimens.Chemosensitivity to pemetrexed was studied in soft-agar. Multiplex rtPCR experiments for reduced folate carrier (RFC), folate receptor-alpha (FR-alpha), folylpolyglutamate synthetase (FPGS), thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyl transferase (GARFT), mrp4, and mrp5 were performed in parallel. Correlations, threshold optimization, sensitivity, specificity, and efficiency were analyzed using the appropriate statistical methodologies.In 61 samples, low levels of TS, GARFT, DHFR, and mrp4 gene expression significantly correlated with chemosensitivity to pemetrexed. Optimization analyses demonstrated threshold values of 144 copies for TS and six copies for mrp4 relative to 10(4) copies of beta-actin.These results form a rational basis for the design of clinical trials to evaluate the expression of these enzymes as predictors for treatment outcome. |
| Databáze: | OpenAIRE |
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