Development of anti-TRAIL receptor antibod y in combination with chemotherapeutic therapy against advanced genitourinary cancers : expansion of animal model

进行抗TRAIL受体抗体与针对晚期泌尿生殖系统癌症的化疗疗法组合的开发。我们发现：（1）抗TRAIL死亡受体2抗体lexatumumab与临床可达到浓度的阿霉素、顺铂、表阿霉素或吡拉西坦组合具有协同细胞毒性作用;（2）协同细胞毒性被半胱天冬酶抑制剂显著抑制，证明半胱天冬酶级联，尤其是半胱天冬酶-8在协同作用中起重要作用;（3）PCR阵列分析鉴定了26个与凋亡相关的基因。

Development of anti-TRAIL receptor antibody in combination with chemotherapeutic therapy against advanced genitourinary cancers was performed. We found : (1) anti-TRAIL death receptor 2 antibody lexatumumab in combination with clinically achievable concentrations of adriamycin, cisplastin, epirubicin, or pirarubicin had a synergistic cytotoxic effect ; (2) the synergistic cytotoxicity was significantly inhibited by caspase inhibitors demonstrating caspase cascade, especially caspase-8 plays an important role in the synergy ; (3)PCR array analysis identified 26 genes related with apoptosis.