无机纳米材料介导的肿瘤放疗增敏的研究进展

放疗作为一种肿瘤治疗手段,可通过电离辐射对肿瘤细胞造成直接或间接的损伤,但电离辐射对正常组织的损伤和肿瘤的放疗抵抗等问题会影响放疗的疗效。肿瘤放疗增敏是近年来的研究热点,其旨在增强肿瘤对放疗的敏感性,从而克服放疗的缺陷,提高放疗的疗效。无机纳米材料介导的肿瘤放疗增敏主要通过增加细胞内的辐射能量沉积、催化产生活性氧自由基和调控肿瘤微环境等方式提高放疗的疗效。笔者就无机纳米材料介导的肿瘤放疗增敏的研究进展进行综述。     

核受体在肿瘤放疗增敏中作用机制的研究进展

放疗是肿瘤治疗的主要方法之一,但肿瘤存在辐射抗性,且正常组织存在辐射耐受剂量问题,两者严重影响肿瘤的放疗效果。因此,研究辐射增敏新策略以提高肿瘤细胞的辐射敏感性尤其重要。核受体是细胞内含量丰富的一类转录因子超家族,参与机体多种病理生理过程。近年来的研究结果表明,核受体及其相关配体可能参与肿瘤的放疗抵抗,因而核受体可能是肿瘤放疗增敏的新靶点。笔者总结了核受体及相关配体在肿瘤放疗增敏方面的研究进展。     

新型辐射增敏药RRx-001

辐射增敏药可提高射线对肿瘤细胞,尤其是乏氧细胞的杀伤率,增强放疗效果,且其对有氧正常组织危害小,使用方便,因而有望成为放疗中的重要辅助药物。新型二硝基氮杂环丁烷辐射增敏药RRx-001源自航空产业。作为一氧化氮的供体分子,RRx-001可透过红细胞膜,与血红蛋白的β半胱氨酸93结合,并在乏氧环境中大量释放一氧化氮,从而提高乏氧细胞对照射的敏感度。临床实验显示RRx-001具有良好的安全性和耐受性。目前其对胆管癌、结直肠癌等肿瘤的治疗正在进行临床Ⅱ期实验。     

放射增敏剂在肿瘤治疗中的应用

放射治疗是治疗恶性肿瘤的重要手段之一。临床上常因正常组织耐受剂量的限制而不能给予肿瘤足够的照射剂量,而造成治疗失败,因此,如何提高肿瘤对射线的敏感性是临床肿瘤放疗面临的突出问题。放射增敏剂作为一种增强肿瘤放疗敏感性、提高放疗疗效的药物,通过增加辐射诱导的氧自由基及DNA损伤、调控放疗关键分子靶点以达到放射增敏目的。本文结合放射增敏剂在放射治疗中的应用,概述了放射增敏剂的发展现状及相关领域的研究进展,并对多种放射增敏剂的作用机制进行了简要综述,以期为进一步研究放射增敏调控的分子机制、促进放射增敏剂的研发,以及设计新的策略改善放射治疗结果提供帮助。     

组蛋白去乙酰化酶抑制剂用于放疗增敏的分子机制研究进展

放射治疗是目前临床上最常用的治疗癌症的手段之一，但其仍存在辐射剂量高、正常组织不良反应大，以及肿瘤细胞的放疗耐受等缺点。因此，寻求安全有效的放疗增敏剂以提高肿瘤细胞对辐射的敏感性一直是放疗研究的热点。组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitors，HDACIs）是一类表观遗传学修饰剂，除了其固有的抗癌特性外，还能调节肿瘤细胞对电离辐射和紫外线辐射敏感性。本文在查阅文献基础上，重点阐述了HDACIs增强肿瘤细胞辐射敏感性的不同分子机制以及对肿瘤细胞的选择性杀伤作用。     

金纳米簇放射治疗增敏作用的研究进展

目前恶性肿瘤的放射治疗疗效仍欠满意,放疗增敏剂是提高放疗疗效的有效手段。金纳米材料因其高原子序数可有效增加肿瘤细胞的放疗敏感性。金纳米簇因其更小的尺寸有更加优良的放射生物学、放射物理学特性。本文综述了金纳米簇特殊的放射生物学、放射物理学特性,并详细地介绍了其对外照射放疗、放射性核素治疗、X射线诱导的光动力治疗的增敏作用。     

肿瘤辐射增敏机制研究进展

辐射增敏作用机制非常复杂，迄今为止尚无明确的解释。其机制主要包括改变肿瘤微环境、清除自由基和电子、细胞周期同步化、抑制DNA损伤修复、促进细胞凋亡和生物还原作用。辐射增敏作用机制的研究在提高肿瘤放疗效果方面具有重要的理论指导意义。     

放射增敏药物研究的现状及其趋向

放射增敏药物研究的现状及其趋向胡璧肿瘤临床治疗中，放疗是一个非常重要的措施，在总的治疗中占７０％、然而肿瘤放疗效果不尽理想，如果采用正常组织可耐受的照射剂量进行治疗，肿瘤的平均治愈率仅４０％，用放射增敏药，可以提高射线对肿瘤细胞的敏感性。因此，国内外...     

恶性肿瘤基因治疗和放射治疗相互作的机制及联合治疗展望

放疗和基因治疗是恶性肿瘤治疗的两种手段,放疗通过提高基因的转移效率、DNA的重组整合及诱导基因的表达等机制增强基因治疗的效果,基因治疗通过提高辐射敏感性、减少正常组织放疗损伤、修复辐射受损的基因及提高血管的功能等机制提高放疗的效果,两者的联合治疗有协同作用。     

肿瘤放射增敏药物的研究进展

放射治疗是临床肿瘤治疗的重要手段之一.肿瘤细胞的放射敏感性是影响肿瘤放疗疗效的关键因素.放射增敏药物能够增强机体的放射敏感性,通过提高肿瘤细胞的放射敏感性达到降低照射剂量、提高放疗疗效、降低正常组织损伤的目的.现有的放射增敏药物主要分为细胞毒类药物、靶向药物以及中药制剂3大类.该文将对肿瘤放射增敏药物的作用机制、现状及相关研究进展进行综述.     

放射治疗诱发体内旁效应的研究进展

随着肿瘤放疗机制的不断深入研究,人们发现肿瘤放疗时引起的体内旁效应对肿瘤治疗及预后起着至关重要的作用。体内旁效应的产生主要与放疗后引起的氧化应激信号的传递、DNA损伤和免疫系统的激活相关,因此,人们可以通过干预旁效应减少放疗对正常组织损伤并提高肿瘤治疗效果。笔者就近年来放疗引起的体内旁效应及其分子机制的研究进展进行综述。     

纳米金在肿瘤显像与放射治疗中的应用

纳米金因具有良好的表面性质和优异的生物亲和性,使其能被多种基团修饰,从而获得对肿瘤细胞的靶向性;又因其具有表面等离子共振效应等强吸收和发光特性,故可进行肿瘤显像.另外,在肿瘤放疗过程中,纳米金能够将吸收的光能转化为热能进行肿瘤局部加热,起到了放疗增敏的效果,从而减少受照剂量,减轻放疗对正常组织的伤害.该文阐述靶向修饰的...     

Imaging of late complications from mantle field radiation in lymphoma patients

Hodgkin lymphoma is one of the most curable cancers because of its sensitivity to both radiation and several chemotherapy agents. Radical radiotherapy alone provided curative therapy for patients who had Hodgkin lymphoma as early as six decades ago. Yet, the radiation field included normal organs, such as breast tissue, thyroid, and coronary arteries, which were at risk for long-term complications. Dedicated imaging approaches have been developed to evaluate late radiation effects on these structures.     

Milestones in normal tissue radiation biology over the past 50 years: From clonogenic cell survival to cytokine networks and back to stem cell recovery

Purpose: To illustrate the progress in normal tissue radiation biology over the last five decades and its impact on radiotherapy.

Materials and methods: Major milestones over the last 50 years and their consequences for radiation oncology are described: The identification of clonogenic cell survival and the (target) stem cell concept, the dissociation between early and late responding tissues with regard to dose fractionation and development of the linear-quadratic model, characterisation of the effect of overall treatment time, the definition of retreatment tolerance. Current knowledge of mechanisms of radiation pathogenesis is a basis for most recent approaches for amelioration of normal tissue effects.

Results: Advances in radiobiological research in normal tissues in the last 50 years have had a major impact on radiation oncology. This includes the linear-quadratic model to adjust doses in altered fractionation protocols, and quantitation of repopulation processes to avoid toxicities in accelerated regimen. Based on new insights into the pathogenesis of normal tissue radiation effects, promising strategies for their modulation, e.g., with cytokines or by stem cell therapy, have been developed.

Conclusions: Research on radiobiology with relevant in vivo models, and relevant treatment protocols is essential for the further progress in radiation oncology.     

由SABR再论放射敏感性

随着现代放射治疗技术进步,放疗已由过去二维时代进入三维和四维时代,治疗精度大幅度提高,分割模式也发生了深刻变革。从传统放射治疗发展到以三维适形放射治疗（3D-CRT）和调强放射治疗（IMRT）为代表的聚焦照射,提高了肿瘤靶区剂量,减少了正常组织的损伤。同时随着影像引导技术进步,治疗机与影像引导结合,每次治疗前通过影像扫描技术获得肿瘤靶区位置信息,或用4D影像引导技术精确地将射线投射到目标靶点,达到立体定向体部放射治疗（stereotactic body radiation therapy,SBRT）/立体定向消融放疗（stereotactic ablative radiotherapy,SABR）的目的,放射治疗完全进入精准、高效和低毒时代。高剂量、大分割照射已经取得令人信服和可喜的疗效,传统放射生物学理论已无法解释这种照射模式抗肿瘤细胞作用机制。传统放疗认为,肿瘤有敏感与不敏感之分,但是,进入SABR时代,肿瘤对其治疗均反应良好,放射治疗学迫切需要建立新的放射生物学学说和体系,在传统放射生物学理论基础上,更好地阐明新技术原理、作用机制,并建立与传统放射生物学内在联系,为临床普及和推广消融放疗技术奠定理论基础。     

金纳米粒子在肿瘤放疗中的研究进展

放疗在肿瘤的治疗中起着不可替代的作用，但由放疗引起的不良反应以及放疗过程中的肿瘤耐受问题仍未得到根本解决，因此放疗增敏显得尤为重要。金纳米粒子（GNPs）作为新型的纳米类放疗增敏制剂，因其较高的生物相容性受到了专家学者的广泛关注和研究。作为新型的纳米制剂，GNPs的理化性质，包括粒径、表面电荷和组装形态等能够影响体内代谢行为和肿瘤蓄积，因此导致放疗增敏率不同。笔者对近几年GNPs作为放疗增敏制剂的研究进展做进一步的总结和进展性汇报。     

Nuclear medicine meets radiation therapy- the radiooncologist's view

Radiobiological and cell biological knowledge is increasingly used to further improve local tumour control or to reduce normal tissue damage after radiotherapy. Important research areas are evolving which need to be addressed jointly by nuclear medicine and radiation oncology. For this differences of the biological distribution of diagnostic and therapeutic nuclides compared with the more homogenous dose-distribution of external beam radiotherapy have to be taken into consideration. Examples for interdisciplinary biology-based cancer research in radiation oncology and nuclear medicine include bioimaging of radiobiological parameters characterizing radioresistance, bioimage-guided adaptive radiotherapy, and the combination of radiotherapy with molecular targeted drugs.     

Non-small cell lung cancer (NSCLC)

The goal of radiation therapy for non-small cell lung cancer (NSCLC) is to improve the survival rate of patients without increasing treatment-related toxicity and to improve patients' quality of life. Several prospective randomized trials have demonstrated a survival advantage in combined modality treatment over radiotherapy or chemotherapy alone when a cisplatin-based chemotherapy regimen is utilized in the treatment plan. Combined modality treatment of cisplatin-based chemotherapy and radiotherapy is standard treatment for selected patients such as those with better performance status with locally or regionally advanced lung cancer including T3-T4 or N2-N3. Determining the contribution of new agents in combined modality treatment will require carefully designed and conducted clinical trials. High-dose involved field radiation therapy using 3D-conformal radiation therapy potentially enables the use of higher doses than standard radiation therapy, because less normal tissue is irradiated, and may improve local control and survival. The combination of radiotherapy with chemotherapy and dose escalation using 3D-conformal radiation therapy is also a possibility in unresectable NSCLC. In surgery cases, the results of several Phase III trials of cisplatin-based preoperative chemotherapy have suggested survival improvement. But the concept needs to be tested in a larger Phase III trial.