采用在体流式细胞仪对放射诱导乳腺癌转移的早期预警及治疗监测的研究

Radiotherapy is one of the important treatment of the breast cancer, distant metastasis is an important cause of the breast cancer treatment failure. So, early warning and monitoring of therapeutic efficacy of metastasis is conducive to the implementation of individualized treatment. Circulating tumor cells (CTC) were closely correlated with outcome of breast cancer patients, and positively correlated with frequency of distant metastasis. Therefore, CTC is expected for early warning of breast cancer metastasis and prognosis. Currently, CTC detection mainly dependent on the in vitro detection, there were some drawback, such as poor sensitivity, not quantitative real-time, and can not be dynamic monitoring the change of CTCs. Our group developed in vivo flow cytometry, which can real-time monitoring presence of CTC in vivo, is expected to overcome the bottlenecks encountered by the CTC in vitro detection. Meanwhile, our previous work suggested that dual targeted EGFR and PI3K enhanced radiosensitivity of breast cancer, co-inhibition of EGFR and PI3K was expected to inhibit radiation-induced breast cancer metastasis. In summary, in vivo flow cytometry is expected qualitative / quantitative analysis of circulating tumor cells of breast cancer, and to provide the technology platform and the theoretical basis to provide early warning and monitoring of therapeutic efficacy for radiation-induced breast cancer distant metastasis.

放射治疗是乳腺癌重要治疗手段之一，远处转移是乳腺癌治疗失败的主要原因，远处转移的早期预警与治疗监测有利于临床乳腺癌个体化治疗的实施。循环肿瘤细胞(CTC)和乳腺癌患者疗效具有密切的相关性，同时与乳腺癌远处转移频率呈正相关。因此，CTC有望用于乳腺癌转移的早期监测及预后判断。目前CTC的检测手段主要依赖于离体检测，存在灵敏度较差，不能实时定量，无法动态监测，具有创伤性等瓶颈。本课题组团队自主研发在体流式细胞仪，能够实时监测在体CTC的存在，有望克服CTC离体技术检测所遇到的瓶颈问题。同时，我们前期工作提示:双靶点阻断EGFR和PI3K可增加乳腺癌放射敏感性，采用EGFR和PI3K双靶点阻断有望抑制放射诱导的乳腺癌转移，因此，采用在体流式细胞仪有望定性/定量分析乳腺癌循环肿瘤细胞，为放射诱导的乳腺癌远处转移提供早期预警与治疗监测提供技术平台及理论依据。

放射治疗是乳腺癌重要治疗手段之一，远处转移是乳腺癌治疗失败的主要原因，远处转移的早期预警与治疗监测有利于临床乳腺癌个体化治疗的实施。本课题采用自主研发在体流式细胞仪实时、动态、无创的评估放射诱导乳腺癌细胞转移的发生及早期预警，同时监测通过靶向阻断EGFR和PI3K，及构建偶联整合素αvβ3特异性结合肽RGD及血管内皮生长因子受体（VEGFR）特异性抑制剂TKI-258双基因靶点的多功能金纳米棒颗粒（TKI-258-pGNRs@mSiO2-RGD）观察多靶点阻断对乳腺癌放射敏感性和转移的影响。研究结果显示：8Gy X线照射48小时后肿瘤细胞的侵袭性显著增加，且肿瘤细胞侵袭性的变化与MMP-2分泌及活性变化一致。采用多靶点阻断能够显著增加肿瘤细胞的放射敏感性，提高肿瘤细胞的杀伤效能。同时，在此基础上，我们采用PSMA作为前列腺癌特异性分子标记物，特异性识别外周血前列腺癌循环肿瘤细胞，同时应用阴性富集联合iFISH法提高了前列腺癌外周血循环肿瘤细胞的捕获效能。该检测手段已经申请1项发明专利，为前列腺癌CTC的捕获和鉴定提高了新的检测手段。因此，采用在体流式细胞仪有望定性/定量分析乳腺癌循环肿瘤细胞，为放射诱导的乳腺癌远处转移提供早期预警与治疗监测提供技术平台及理论依据。