387) GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl) guanine (PMEG) has significant activity as monotherapy in dogs with non-Hodgkin's lymphoma. |
PMID:23672437 DOI:10.1111/vco.12038 |
2015 Veterinary and comparative oncology |
* Novel acyclic nucleotide analogues GS-343074 and GS-424044 demonstrate antiproliferative and pro-apoptotic activity in canine neoplastic cell lines. |
- GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl) guanine (PMEG) has significant activity as monotherapy in dogs with non-Hodgkin's lymphoma. Phase I trials have been initiated in humans based on the encouraging activity observed in canine lymphoma. Two new analogues of GS-9219 (GS-343074 and GS-424044) were recently produced for evaluation as potential novel antineoplastic agents against solid tumours. As a preclinical step, effect of GS-343074 and GS-424044 were evaluated against ten canine cancer cell lines for antiproliferative effect. Both analogues displayed antiproliferative activity against multiple canine cancer cell lines, although GS-343074 was more potent and of broader spectrum compared to GS-424044. Flow cytometric analysis of cells that experienced growth inhibition support apoptotic death as a mechanism of action for both analogues. On the basis of in vitro results described here, GS-343074 and GS-424044 show promise as novel anticancer agents in canine cancer. |
(1)67 differences | (15)5 correlations | (29)3 influence | (44)2 dose-dependent |
(2)40 increase | (16)5 effects | (30)3 negative | (45)2 elevation |
(3)36 difference | (17)5 for | (31)3 number | (46)2 evidence |
(4)28 decrease | (18)5 increases | (32)3 roles | (47)2 factors |
(5)12 reduction | (19)5 risk | (33)2 (P | (48)2 group |
(6)11 predictors | (20)4 effect | (35)2 alterations | (49)2 inhibition |
(7)10 association | (21)4 in | (36)2 and | (50)2 interaction |
(8)9 improvement | (22)4 reductions | (37)2 at | (51)2 morbidity |
(9)8 *null* | (23)4 relationship | (38)2 between-group | (52)2 positive |
(10)7 changes | (24)3 (p | (39)2 blood | (53)2 prediction |
(11)7 predictor | (25)3 alteration | (40)2 challenge | (54)2 proportion |
(12)7 role | (26)3 as | (41)2 contribution | (55)2 source |
(13)6 correlation | (27)3 higher | (42)2 cytotoxic | (56)2 time |
(14)5 associations | (28)3 improvements | (43)2 decreases |
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