Words similar to paclitaxel
Example sentences for: paclitaxel
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Furthermore, whereas some of these data suggest a role for tubulin isotypes in drug resistance, cell growth, and differentiation, other work indicates that isotype-independent factors affecting micro-tubule polymer formation are more important than changes in isotype levels [ 32 33 34 35 ] . For example, a decrease in total polymer concentrations causes resistance to microtubule-stabilizing agents such as paclitaxel [ 34 35 ] .
For example, total amounts of polymerizable tubulin are decreased in paclitaxel-resistant cells, whereas col-cemid-resistant tubulin or vinca alkaloid-resistant cells have increased levels of assembled tubulin [ 34 66 67 ] . Furthermore, when cells were transfected with β-tubulin class III, weak resistance to paclitaxel was found, and this resistance was associated with decreased microtubule stability [ 68 ] . This is consistent with the different modes of action of these drugs: paclitaxel stabilizes microtubules and colcemid inhibits tubulin assembly.
Over the past decade paclitaxel and docetaxel have become important chemotherapeutic agents for both ovarian and breast cancers [ 1 2 ] . Considerable interest has focused on the target receptor - tubulin - and mechanisms underlying efficacy, toxicity, and drug resistance [ 7 8 23 24 27 28 ] . Whether tubulin isotype levels might determine cellular responses to antimitotic agents remains controversial.
The expression of genes encoding α-tubulin and β-tubulin seems to be developmentally regulated [ 19 ] . For example, tubulin isotype expression patterns change during the development and maturation of neurons [ 14 20 ] . Studies with paclitaxel or other antimitotic agents, such as colchicine or estramustine, indicate that drug interactions with tubulin isotypes differ [ 21 22 23 24 25 ] and might contribute to cell resistance to antimitotics [ 26 27 28 29 30 31 ] . However, one group of antimitotic agents, the vinca alkaloids, was shown to bind with similar affinity to all tubulin isotypes [ 12 ] , suggesting that alterations in drug binding affinity is unlikely to be the cause of drug resistance.
Furthermore, transfection of CHO cells with β-tubulin classes I, II, or IVb did not produce resistance to paclitaxel [ 32 ] . The alternative hypothesis, derived from the work of Cabral and colleagues, is that rather than the tubulin isotype levels, the amount of polymerized tubulin is the critical factor that regulates response to antimitotic drugs.
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