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核黄素光动力疗法对循环 HCT116 肿瘤细胞失活的实验研究。

An experimental study on riboflavin photosensitization treatment for inactivation of circulating HCT116 tumor cells.

机构信息

Medical School of Chinese PLA, Beijing, PR China; Blood Transfusion Department, the First Medical Center of Chinese PLA General Hospital, Beijing, PR China.

Blood Transfusion Department, the First Medical Center of Chinese PLA General Hospital, Beijing, PR China.

出版信息

J Photochem Photobiol B. 2019 Jul;196:111496. doi: 10.1016/j.jphotobiol.2019.04.005. Epub 2019 Apr 16.

Abstract

Surgical resection is one of the most common radical treatments for cancers. However, tumors may be compressed or the local intravascular pressure may be increased during surgical manipulation, causing the shedding and entry of tumor cells into the blood circulation and hence distant recurrence and metastasis of tumors. We have preliminarily established a method of riboflavin photosensitization treatment (RPT) for inactivation of circulating tumor cells. This technology promises to solve the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. In the present study, apoptosis detection and tumorigenicity experiment in immunodeficient mice were conducted to evaluate the effect of RPT for inactivation of circulating tumor cells respectively. Next, functional evaluation was carried out for the immune cells through detecting apoptosis rate and cytokine secretion of lymphocyte. Finally, thromboelastography (TEG) and free hemoglobin were detected to assess peripheral blood coagulation and red blood cell damage. The results showed that RPT (50 μmol/L riboflavin, 10.8 J/cm UV) could effectively make tumor cell lose the ability of proliferation in the peripheral blood. In the meantime, the damage caused to peripheral blood coagulation, immune cell function and red blood cells was generally acceptable. The results of the study showed that RPT had huge potential in addressing the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. This therapy is expected to be an auxiliary and supportive method to reduce the risk of hematogenous metastasis and recurrence of cancers, and to increase the surgical success rate of malignant solid tumors.

摘要

手术切除是癌症最常见的根治性治疗方法之一。然而,在手术操作过程中,肿瘤可能会受到压迫或局部血管内压升高,导致肿瘤细胞脱落并进入血液循环,从而导致肿瘤的远处复发和转移。我们已经初步建立了一种核黄素光动力治疗(RPT)用于灭活循环肿瘤细胞的方法。该技术有望解决手术操作前实体瘤细胞脱落和进入血液循环的问题,以及手术切除过程中几乎不可避免的肿瘤细胞血行播散问题。在本研究中,通过凋亡检测和免疫缺陷小鼠肿瘤形成实验分别评价了 RPT 对循环肿瘤细胞灭活的效果。然后,通过检测淋巴细胞凋亡率和细胞因子分泌来对免疫细胞进行功能评价。最后,通过血栓弹力图(TEG)和游离血红蛋白检测来评估外周血凝血和红细胞损伤情况。结果表明,RPT(50μmol/L 核黄素,10.8J/cm UV)可有效使外周血中的肿瘤细胞失去增殖能力。同时,对外周血凝血、免疫细胞功能和红细胞造成的损伤一般是可以接受的。研究结果表明,RPT 有望解决手术操作前实体瘤细胞脱落和进入血液循环的问题,以及手术切除过程中几乎不可避免的肿瘤细胞血行播散问题。该疗法有望成为降低癌症血行转移和复发风险、提高恶性实体瘤手术成功率的辅助和支持方法。

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