Synergistic effect of vincristine with tacrolimus or sirolimus in prevention of acute heart allograft rejection in the rat.

The application of multiple immunosuppressive therapy for organ transplantation could enhance therapeutic efficacy, while minimizing the toxicity of individual drugs used in the regimen. In this study, the effect of the combined therapy of vincristine (VCR) with tacrolimus (FK506) or sirolimus (rapamycin, RAPA) was tested in prevention of acute heart allograft rejection in the rat. A Brown Norway (BN, RT 1(n)) to Lewis (LEW, RT 1(1)) rat combination was used in a heart allografting model. VCR was administered intraperitoneally once daily, while FK506 and RAPA were given by gavage once daily for 14 days after transplantation. There were dose-related prolongations of mean survival time (MST) to monotherapy of VCR, FK506, or RAPA. The MST in combination therapy indicated that a synergistic interaction was produced when compared with the respective monotherapies: VCR 0.05 mg/kg/day + FK506 0.5 mg/kg/day (16.00 +/- 1.79 days, P = 0.001; combination index (CI) = 0.557); VCR 0.05 mg/kg/day + FK506 1.0 mg/kg/day (29.00 +/- 10.54 days, P = 0.001; CI = 0.598); VCR 0.05 mg/kg/day + RAPA 0.2 mg/kg/day (17.33 +/- 1.97 days, P = 0.001; CI = 0.500); and VCR 0.05 mg/kg/day + RAPA 0.4 mg/kg/day (21.17 +/- 3.19 days, P = 0.001; CI = 0.838). Combination therapy of VCR and FK506 or RAPA produced synergistic effects in prevention of acute heart allograft rejection in the rat.

Jiang W ，Jiang J ，Xu D ，Wang X ，Qi S ，Ouyang J ，Ma A ，Vu MD ，Bilolo KK ，Chen H ... -  《MICROSURGERY》

Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat.

Bilolo KK ，Ouyang J ，Wang X ，Zhu S ，Jiang W ，Qi S ，Xu D ，Hebert MJ ，Bekersky I ，Fitzsimmons WE ，Chen H ... -  《TRANSPLANTATION》

Is the malononitrilamide FK778 better for the prevention of acute or chronic rejection?

Deuse T ，Schrepfer S ，Pelletier MP ，Fischbein MP ，Robbins RC ，Reichenspurner H ... -  《TRANSPLANTATION PROCEEDINGS》

Synergistic effects of mycophenolate mofetil and sirolimus in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat.

Vu MD ，Qi S ，Xu D ，Wu J ，Peng J ，Daloze P ，Sehgal S ，Leduc B ，Chen H ... -  《TRANSPLANTATION》

Effect of Baohuoside-1 aglycone and tacrolimus monotherapy and combination therapy on prevention of acute heart allograft rejection in the rat.

Qi S ，Zhao H ，Ma A ，Liu L ，Wang X ，Xu D ，Lin G ，Tamura K ，Jiang H ，Daloze P ，Chen H ... -  《MICROSURGERY》