最新一期《国际热疗学报》(International Journal of Hyperthermia)以封面文章形式发表了肿瘤全身热疗机制的研究成果。此项工作由刘静研究员领导的中科院理化技术研究所低温生物与医学研究室与清华大学医学院生物医学工程系医学微系统技术实验室的联合小组完成,合作者中还有来自清华大学医学院基础医学系的师生。
临床上,许多肿瘤发现时已接近中晚期,传统疗法往往无能为力。针对这类具有转移特性的中晚期癌症,全身热疗是一种极具发展前景的系统疗法,具有安全性高、副作用低等优势,但以往缺乏足够的研究以及相应高性能治疗装备,因而在很大程度上制约了这一重要方法的大规模临床应用。通过对全身热疗各种生物效应和机理的深入研究,弄清其中最关键的治疗因素,可将手术风险降至最低,从而建立标准化的治疗程序,也为正在推进中的免疫疗法和化疗提供新的思路。
在这篇题为“Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia”(发热样全身热疗对小鼠B16黑色素肺转移的抑制及其免疫增强作用)的文章中,作者们建立了一种微波诱导发热样全身热疗范式,并通过对小鼠黑色素瘤肺转移的疗效评估以及免疫标志蛋白的检测,系统探索了全身热疗的作用通路。结果显示,无论是单独实施还是与化疗药物联合使用,这种范式下特定剂量的全身热疗均可明显抑制小鼠B16-F10肺转移黑色素瘤的生长。治疗14天后的生物标记物检测表明,在多条通路(特别是免疫应答增强、肿瘤细胞增殖速率下降、肿瘤细胞凋亡增强以及抑制新生血管等因素)的共同作用下,肿瘤生长被显著抑制。全身热疗可通过增加肿瘤部位细胞间粘附分子和纤维的生成来抑制肿瘤细胞的转移和扩散,它也可通过降低外周CD4+ T细胞的同时增加CD8+ T细胞数量,以此增强细胞免疫功能。
长期以来,理化所和清华大学医学院联合小组在肿瘤热疗领域已开展了大量研究,曾先后提出系列全新的高温消融与全身热疗方法,并出版了系统总结热疗学定量基础理论与应用技术的前沿性学术专著《肿瘤热疗物理学》,推动了相关学科的发展;所发明并研制成功的血管介入式全身热疗设备,性能上优于国外已有技术,有望带来良好的经济和社会效益。(生物谷Bioon.com)
生物谷推荐原文出处:
International journal of hyperthermia DOI: 10.3109/02656736.2011.559613
Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia.
Jia Dewei D,Rao Wei W,Wang Chao C,Jin Chao C,Wang Suqiong S,Chen Dongwei D,Zhang Minghui M,Guo Junwei J,Chang Zhijie Z,Liu Jing J
PURPOSE: Whole body hyperthermia (WBH) has been regarded as a promising alternative therapy to cure late stage cancer with metastasis. As the final biological and therapeutic effects are dependent on the specific protocol, the potential of using a microwave-based WBH approach for metastasis inhibition is established and its typical results are discussed. MATERIALS AND METHODS: The effectiveness of a 30-min whole body hyperthermia (WH) on animals, raised to a rectal temperature of 40.2°?±?0.3°C for 30? min followed by 84 h observation by 2450?MHz microwave irradiation, were evaluated. In an experimental lung metastasis model by injection of B16-F10 melanoma, lungs were removed from sacrificed mice 16 days after tumour implantation, and the expression of heat shock protein, inter-cellular adhesion molecule 1 (ICAM-1), proliferating cell nuclear antigen (PCNA) and cyclin D(1) was examined. CD4(+), CD8(+) and NK cell subpopulation in peripheral blood were measured by flow cytometry before and after the last treatment. RESULTS: The best therapeutic effect was obtained when the mice were treated with WBH in combination with the initial chemotherapy with cis-diaminodichloroplatinum (CDDP) and dacarbazine (DTIC) (p?<?0.05). The WBH alone has an advantage of reduced toxicity and lower cost. Heat shock protein (HSP) expression increased in the hyperthermia groups. Reduction of PCNA and cyclin D(1) was observed in the mice treated with WH alone or in combination with chemotherapy. In the hyperthermia groups, CD4(+)/CD8(+) decreased while the NK increased slightly. CONCLUSIONS: The whole body hyperthermia protocol described in this work inhibits B16 tumour metastasis by inhibiting cell proliferation, neovascularisation and stimulating favourable immune responses. It demonstrated that WBH treatment benefits therapy of metastasis cancers.