血小板内在性ＶＥＧＦ－Ａを分子標的とする新規大腸癌治療の臨床及び分子生物学的研究

正如我们在提案中提出的，我们在离体和体外模型中研究了两种药物（贝伐单抗和Pegaptinib），并且只有贝伐单抗用于人体研究。我们招募了诊断为晚期结直肠癌的患者，并在不同的时间间隔分离血小板。我们观察到贝伐单抗对血小板内VEGF-A浓度的影响令人沮丧。人体研究结果与我们的离体和体外实验一致。与血清和血浆相比，血小板内VEGF-A浓度几乎保持不变。我们还监测了贝伐单抗给药前后患者血小板中VEGF-A不同亚型的动力学。为了增加人体研究的数量，我们最近修改了患者招募方案。

As proposed in our proposal, we have examined two agents in ex vivo and in vitro models (Bevacizumab and Pegaptinib), and only Bevacizumab in human study. We recruited patients diagnosed with advanced colorectal cancer, and isolated the platelets at different interval.We observed a dismal effect of bevacizumab on the concentrations of intra-platelet VEGF-A. The human study results correspond with our ex vivo and in vitro experiments. Compared to serum and plasma, the intra-platelet VEGF-A concentrations remained nearly unchanged. We have also monitored the kinetics of different isoforms of VEGF-A in platelets obtained from the patients before and after Bevacizumab administration. To increase the number in human study, we have recently modified the protocol of patient recruitment.