ABCC1 p.Thr24Met

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PMID: 9740539 [PubMed] Etievant C et al: "Vinflunine (20',20'-difluoro-3',4'-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro."
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79 The T24 sensitive (T24S) parental and the resistant T24M subline [28] were obtained from Dr R. Kiss, Laboratory of Histology, Université Libre de Bel- gique, ULB (Brussels, Belgium).
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ABCC1 p.Thr24Met 9740539:79:52
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83 The less well-characterized T24M cells, selected for resistance to a cocktail of doxorubicin, NVB and DIAM 3 (an investigational alkylating compound [32]) has been described as expressing an increased level of Pgp [33].
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ABCC1 p.Thr24Met 9740539:83:28
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87 Cell culture conditions Parental and resistant human tumor cell lines were cultured in RPMI 1640 medium (Seromed, Poly- labo, Strasbourg, France) supplemented with 10% heat inactivated fetal calf serum (FCS, GIBCO, Cergy-Pontoise, France), except for T24S and T24M cells which were grown in MEM medium (GIBCO) supplemented with 5% FCS.
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ABCC1 p.Thr24Met 9740539:87:260
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92 Characteristics of the tumor resistant sublines studied in vitro and the culture conditions used Resistance phenotypea Tumor Selecting agent Seeding Resistance index Pgp MRP Topo II Cell line origin [maintenance density to selecting agent over- over- decreased concentration] [cells/ml] expression expression level P388/ADR [24,30] murine doxorubicin 4.0 × 104 66 + ± + leukemia [1 µM] CEM/VBL 1000 [25] human vinblastine 2.0 × 104 135 + nr - leukemia [1 µM] T24M [28,33] human DOX/NVB/DIAM3b 2.5 × 104 6/3600/50 + nr nr bladder ca.b [0.1/1/10 µg/ml] MCF7/200R [27,31] human doxorubicin 5.0 × 104 >222 + - + breast ca.
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ABCC1 p.Thr24Met 9740539:92:484
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185 The well-known Pgp-associated MDR sublines, CEM/VBL1000 and MCF7/200R and the less well-characterized T24M subline, all expressed definite cross-resistance to VFL, as they did to the three other tubulin-interacting agents tested.
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ABCC1 p.Thr24Met 9740539:185:102
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189 Furthermore, whilst the T24M cells showed a comparable high level of resistance to NVB (3600-fold) and to vincristine (3700- fold), these proved less cross resistant to vinblastine (1200-fold) and again were least resistant to VFL (840-fold).
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ABCC1 p.Thr24Met 9740539:189:24
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190 Overall, in this group of Pgp overexpressing human tumor cell lines, the T24M, and especially the MCF7/200R sublines proved consistently less cross-resistant to VFL compared with vinblastine, vin- Figure 4.
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ABCC1 p.Thr24Met 9740539:190:73
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198 Resistance indices for the different resistant cell lines Cell line Resistance Resistance indexa phenotype vinblastine vincristine vinorelbine vinflunine CEM/VBL1000 Pgp-MDR 135 1547 469 184 T24M Pgp-MDR 1200 3700 3600 840 MCF7/200R Pgp-MDR 684 2440 600 188 GLC4/ADR non Pgp-MDR 1 4 1 1 CEM/VM1 non Pgp-MDR 0.5 0.8 0.5 0.5 aResistance index = IC50 resistant cell line/IC50 sensitive cell line.
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ABCC1 p.Thr24Met 9740539:198:191
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