ABCC3 p.Val104Met
| Predicted by SNAP2: | A: D (53%), C: D (53%), D: D (80%), E: D (75%), F: D (63%), G: D (75%), H: D (75%), I: N (72%), K: D (80%), L: N (57%), M: D (71%), N: D (80%), P: D (80%), Q: D (80%), R: D (80%), S: D (63%), T: D (59%), W: D (75%), Y: D (66%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Resistance to antifolates. Oncogene. 2003 Oct 20;22(47):7431-57. Zhao R, Goldman ID
Resistance to antifolates.
Oncogene. 2003 Oct 20;22(47):7431-57., 2003-10-20 [PMID:14576850]
Abstract [show]
The antifolates were the first class of antimetabolites to enter the clinics more than 50 years ago. Over the following decades, a full understanding of their mechanisms of action and chemotherapeutic potential evolved along with the mechanisms by which cells develop resistance to these drugs. These principals served as a basis for the subsequent exploration and understanding of the mechanisms of resistance to a variety of diverse antineoplastics with different cellular targets. This section describes the bases for intrinsic and acquired antifolate resistance within the context of the current understanding of the mechanisms of actions and cytotoxic determinants of these agents. This encompasses impaired drug transport into cells, augmented drug export, impaired activation of antifolates through polyglutamylation, augmented hydrolysis of antifolate polyglutamates, increased expression and mutation of target enzymes, and the augmentation of cellular tetrahydrofolate-cofactor pools in cells. This chapter also describes how these insights are being utilized to develop gene therapy approaches to protect normal bone marrow progenitor cells as a strategy to improve the efficacy of bone marrow transplantation. Finally, clinical studies are reviewed that correlate the cellular pharmacology of methotrexate with the clinical outcome in children with neoplastic diseases treated with this antifolate.
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No. Sentence Comment
402 Likewise, the preservation of DDATHF levels, in contrast to the greater decline in influx observed in a cell line with the V104M mutation (Zhao et al., 2000b) and in CEM/MTX cells (Matherly et al., 1993), may reflect an associated decrease in MRP- mediated drug export that tends to preserve activity.
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ABCC3 p.Val104Met 14576850:402:123
status: NEW