Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug resistance is a major obstacle to successful chemotherapy for cancer. When it occurs, resistance to a wide range of agents is noted. Factors that rule this resistance can be defined as pharmacologic and cellular. Pharmacologic factors are those that prevent an adequate degree of tumor cell exposure and include considerations of dose and schedule of drugs. Cellular factors are those that imply the tumor cell itself and it is probable that multiple mechanisms co-exists: 1) the drug transport across the tumor cell membrane and the duration of the drug exposure, 2) the drug metabolism (activation, inactivation), 3) the cellular targets and the DNA repair processes. The pleiotropic multidrug resistance (mdr, mrp, lrp), alterations of a target enzyme (topoisomerase II, protein kinase C, glutathione S transferase, O6 alkylguanine-DNA alkyltransferase) and the protein modifications (heat shock protein, metallothioneins) are the principal mechanisms involved. Several methods have been established for the determination of the presence of these drug resistance mechanisms but variations in the results are observed with the different methods used. Therefore, the value and the relative importance of these mechanisms in human tumor resistance is not yet established. In the mean-time, strategies to prevent and to overcome this resistance are developed.
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PMID:[Resistance to antineoplastic treatments: mechanisms, clinical value]. 895 96

DNA topoisomerases are major defined targets for a large variety of clinically important anticancer agents, including etoposide, adriamycin, and mitoxantrone. Mutations at amino acids 439, 450 and 803 of DNA topoisomerase II were examined in multiple anticancer drug-resistant anaplastic thyroid carcinomas (ten cell lines and three cancerous tissues) by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent DNA sequencing. No mutation was found in these cell lines and tissues, but mdr1, mrp and/or lrp mRNA were expressed to a varying degree, and there was no significant difference in DNA topoisomerase IIalpha content among the cell lines and tissues as evaluated by Western blotting. Our experimental data indicate that overexpression of multidrug resistance-related mRNA is sufficient to confer drug resistance.
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PMID:Lack of a point mutation of human DNA topoisomerase II in multidrug-resistant anaplastic thyroid carcinoma cell lines. 917 55