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

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Our project is 1) to examine the kinetics of intra-platelet VEGF-A in bevacizumab (Avastin) treated colorectal cancer (CRC) patients, and 2) to study dynamics of various intra-platelet growth factor in patients with Hepatocellular carcinoma (HCC). We also conducted in vitro and ex vivo experiments to investigate the bearing of bevacizumab on the intra-platelet VEGF-A. Following four major results were obtained from this grant.1. We observed a perioperative exhaustion (depletion) of intra-platelet serotonin concentrations in patients who developed early HCC recurrence and this was able to independently predict HCC recurrence [Aryal et. al, Journal of Cancer (2017)].2. Platelet-derived growth factor-BB (PDGF-BB) was significantly diminished in patients with cancer recurrence. [Aryal B, et al. Journal of Oncology (2019); article id 1925315].3. We observed a significant elevation of intra-platelet vWF during liver regeneration; moreover, patients who could not achieve marked rise in post-resection intra-platelet vWF concentration were found to have increased incidence of post-resection liver dysfunction [Aryal B, et al. Under Review (2019)].4. We performed experiments using an ex vivo and in vitro models to examine the effect of bevacizumab and pegaptanib on IP VEGF-A neutralization, suggesting that the intra-platelet VEGF-A could influence the impact of bevacizumab treatment, as platelets represent a major reservoir of VEGF.I appreciated this funding and would like to proceed more to accomplish this series of the project.