To study the effect of Trastuzumab in combination with IFN α-2b on HER2 and MRP1 of ACHN in vitro, ACHN cell line of RCC was cultured by employing cell culture. The tetrazolium-based colorimetric assay was used to ev...To study the effect of Trastuzumab in combination with IFN α-2b on HER2 and MRP1 of ACHN in vitro, ACHN cell line of RCC was cultured by employing cell culture. The tetrazolium-based colorimetric assay was used to evaluate the growth-inhibiting effect of Trastuzumab with IFN α-2b. SP method was utilized to determine the expression of HER2 and MRP1 of the cells. Our results showed that Trastuzumab had inhibitory effect on the growth of renal tumor cells and reversing effect on the multi-drug-resistance (MDR) in RCC in a time- and dose-dependent manner. Treated with Trastuzumab with or without IFN α-2b, the expression of HER2 and MRP1 genes of RCC was decreased significantly (P<0.05). It was concluded that Trastuzumab with IFN α-2b could inhibit the proliferation of RCC and the expression of HER2 and MRP1 of ACHN and to some extent, reverse the MDR of the tumor cells.展开更多
Pegylated interferon (PEG-IFN) has become standard therapy for hepatitis C virus (HCV) infection. We evaluated whether PEG-IFN pharmacodynamics and pharmacokinetics account for differences in treatment outcome and whe...Pegylated interferon (PEG-IFN) has become standard therapy for hepatitis C virus (HCV) infection. We evaluated whether PEG-IFN pharmacodynamics and pharmacokinetics account for differences in treatment outcome and whether these parameters might be predictors of therapeutic outcome. Twenty-four IFN-nave, HCV/human immunodeficiency virus-coinfected patients received PEG-IFN α-2b (1.5 μg/kg) once weekly plus daily ribavirin (1,000 or 1,200 mg) for up to 48 weeks. HCV RNA and PEG-IFN αconcentrations were obtained from samples collected frequently after the first 3 PEG-IFN doses. We modeled HCV kinetics incorporating pharmacokinetic and pharmacodynamic parameters. Although PEG-IFN concentrations and pharmacokinetic parameters were similar in sustained virological responders (SVRs) and nonresponders (NRs), the PEG-IFN α-2b concentration that decreases HCV production by 50%(EC50) was lower in SVRs compared with NRs (0.04 vs. 0.45 μg/L [P = .014]). Additionally, the median therapeutic quotient (i.e., the ratio between average PEG-IFN concentration and EC50 [ ˉC/EC50]), and the PEG-IFN concentration at day 7 divided by EC50 (C(7)/EC50) were significantly increased in SVRs compared with NRs after the first (10.1 vs. 1.0 [P = .012], 2.8 vs. 0.3 [P = .007], respectively) and second (14.0 vs. 1.1 [P = .016], 5.4 vs. 0.4 [P = .02], respectively) PEG-IFN doses. All 3 parameters may be used to identify NRs. In conclusion, PEG-IFN concentrations and pharmacokinetic parameters do not differ between SVRs and NRs. In contrast, pharmacodynamic measurements-namely EC50, the therapeutic quotient, and C(7)/EC50-are different in coinfected SVRs and NRs. These parameters might be useful predictors of treatment outcome during the first month of therapy.展开更多
文摘To study the effect of Trastuzumab in combination with IFN α-2b on HER2 and MRP1 of ACHN in vitro, ACHN cell line of RCC was cultured by employing cell culture. The tetrazolium-based colorimetric assay was used to evaluate the growth-inhibiting effect of Trastuzumab with IFN α-2b. SP method was utilized to determine the expression of HER2 and MRP1 of the cells. Our results showed that Trastuzumab had inhibitory effect on the growth of renal tumor cells and reversing effect on the multi-drug-resistance (MDR) in RCC in a time- and dose-dependent manner. Treated with Trastuzumab with or without IFN α-2b, the expression of HER2 and MRP1 genes of RCC was decreased significantly (P<0.05). It was concluded that Trastuzumab with IFN α-2b could inhibit the proliferation of RCC and the expression of HER2 and MRP1 of ACHN and to some extent, reverse the MDR of the tumor cells.
文摘Pegylated interferon (PEG-IFN) has become standard therapy for hepatitis C virus (HCV) infection. We evaluated whether PEG-IFN pharmacodynamics and pharmacokinetics account for differences in treatment outcome and whether these parameters might be predictors of therapeutic outcome. Twenty-four IFN-nave, HCV/human immunodeficiency virus-coinfected patients received PEG-IFN α-2b (1.5 μg/kg) once weekly plus daily ribavirin (1,000 or 1,200 mg) for up to 48 weeks. HCV RNA and PEG-IFN αconcentrations were obtained from samples collected frequently after the first 3 PEG-IFN doses. We modeled HCV kinetics incorporating pharmacokinetic and pharmacodynamic parameters. Although PEG-IFN concentrations and pharmacokinetic parameters were similar in sustained virological responders (SVRs) and nonresponders (NRs), the PEG-IFN α-2b concentration that decreases HCV production by 50%(EC50) was lower in SVRs compared with NRs (0.04 vs. 0.45 μg/L [P = .014]). Additionally, the median therapeutic quotient (i.e., the ratio between average PEG-IFN concentration and EC50 [ ˉC/EC50]), and the PEG-IFN concentration at day 7 divided by EC50 (C(7)/EC50) were significantly increased in SVRs compared with NRs after the first (10.1 vs. 1.0 [P = .012], 2.8 vs. 0.3 [P = .007], respectively) and second (14.0 vs. 1.1 [P = .016], 5.4 vs. 0.4 [P = .02], respectively) PEG-IFN doses. All 3 parameters may be used to identify NRs. In conclusion, PEG-IFN concentrations and pharmacokinetic parameters do not differ between SVRs and NRs. In contrast, pharmacodynamic measurements-namely EC50, the therapeutic quotient, and C(7)/EC50-are different in coinfected SVRs and NRs. These parameters might be useful predictors of treatment outcome during the first month of therapy.
