Words similar to vinca
Example sentences for: vinca
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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.
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.
Because of the high catalytic efficiency and broad substrate specificity, β-lactamases have been extensively used in the ADEPT approach to activate prodrugs of vinca alkaloids [ 27 ] , nitrogen mustard [ 28 29 30 31 32 ] , doxorubicin [ 33 34 35 36 ] and others [ 37 ] . To take advantage of the potent antitumor activity of the CC-1065 class of compounds and the ADEPT approach, we have synthesized β-lactam prodrugs.
In support of this hypothesis, tubulin mutations consistent with altered assembly properties have been identified in paclitaxel-resistant and vinca alkaloid-resistant cells [ 33 66 69 ] .
It was demonstrated that one group of antimitotic agents, vinca alkaloids, bind with similar affinity to all β-tubulin isotypes [ 12 ] , thus suggesting for therapy with vinorelbine, vinblas-tine, or vincristine that tubulin isotype levels are incidental for efficacy.
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