TY - JOUR
T1 - Effectiveness of 2',2'difluorodeoxycytidine (Gemcitabine) combined with hyperthermia in rat R-1 rhabdomyosarcoma in vitro and in vivo
AU - van Bree, C.
AU - Beumer, C.
AU - Rodermond, H. M.
AU - Haveman, J.
AU - Bakker, P. J.
PY - 1999
Y1 - 1999
N2 - To investigate the schedule-dependency of 2',2'difluorodeoxycytidine (dFdC, Gemcitabine) combined with hyperthermia (HT), in vitro as well as in vivo. Rat R-1 rhabdomyosarcoma cells were treated with various concentrations of dFdC for 70 min, 4 h and 24 h. After various time intervals HT (60 min at 43 degrees C) was applied. Cell survival was determined by clonogenic assays. Female Wag/Rij rats bearing R-1 tumours on the hind limbs were treated with dFdC (20 mg/kg), with locally applied HT (60 min at 43 degrees C) or with a combined treatment using different time intervals (0, 24 and 48 h). Tumour growth delay (TGD) and normal tissue toxicity were assessed. With dFdC alone, significant cytotoxicity was observed after a 24 h-exposure. Except for the 24 h-exposure, HT reduced the cytotoxicity of dFdC in simultaneous applications. An enhanced cytotoxic effect was found when HT was applied 20 h after a 4 h-incubation with dFdC. In vivo, HT applied 48 h after dFdC-administration resulted in potentiation of the effect of dFdC with respect to TGD without an increase in toxicity. The efficacy of dFdC combined with HT is schedule-dependent both in vitro and in vivo. The addition of HT enhances the effectiveness of dFdC in the R-1 tumour model
AB - To investigate the schedule-dependency of 2',2'difluorodeoxycytidine (dFdC, Gemcitabine) combined with hyperthermia (HT), in vitro as well as in vivo. Rat R-1 rhabdomyosarcoma cells were treated with various concentrations of dFdC for 70 min, 4 h and 24 h. After various time intervals HT (60 min at 43 degrees C) was applied. Cell survival was determined by clonogenic assays. Female Wag/Rij rats bearing R-1 tumours on the hind limbs were treated with dFdC (20 mg/kg), with locally applied HT (60 min at 43 degrees C) or with a combined treatment using different time intervals (0, 24 and 48 h). Tumour growth delay (TGD) and normal tissue toxicity were assessed. With dFdC alone, significant cytotoxicity was observed after a 24 h-exposure. Except for the 24 h-exposure, HT reduced the cytotoxicity of dFdC in simultaneous applications. An enhanced cytotoxic effect was found when HT was applied 20 h after a 4 h-incubation with dFdC. In vivo, HT applied 48 h after dFdC-administration resulted in potentiation of the effect of dFdC with respect to TGD without an increase in toxicity. The efficacy of dFdC combined with HT is schedule-dependent both in vitro and in vivo. The addition of HT enhances the effectiveness of dFdC in the R-1 tumour model
U2 - https://doi.org/10.1080/026567399285530
DO - https://doi.org/10.1080/026567399285530
M3 - Article
C2 - 10598951
SN - 0265-6736
VL - 15
SP - 549
EP - 556
JO - International journal of hyperthermia
JF - International journal of hyperthermia
IS - 6
ER -