类器官在放射治疗中应用的研究进展

随着核能在军事、科研和医学各个领域的广泛应用,放射医学已成为一门重要的学科。迄今为止,放射医学的研究大多使用细胞模型和动物模型,然而这两种模型都有其局限性,类器官模型的出现填补了这些传统模型留下的空白。类器官是源自组织干细胞的3D体外培养系统,类器官因其具有与原始组织相似的结构、功能和遗传特征而被广泛应用于放射医学、疾病研究、药物开发和癌症建模等领域。本综述按放射治疗部位介绍了各种类器官模型在放射治疗中的研究应用,并对类器官模型目前的局限性及未来前景进行相关论述。     

肿瘤放射治疗学新进展与发展设想

目的综述国内外肿瘤放射治疗学研究现状和发展动态,提出未来我军放射治疗专业发展的目标、方向和重点。方法检索近10年来国内外放射治疗领域的相关论文、综述和会议资料,分析该学科领域的新进展。结果20世纪80年代以来,放射治疗全面进入三维立体精确定位、精确计划、精确治疗的新时代,充分显示了最大限度杀伤肿瘤、提高肿瘤控制率,最大限度保护肿瘤周围正常器官、降低严重并发症发生率的技术优势。图像引导的放射治疗作为精确放疗的技术保证,其研究与发展已成为当前的热点。结论未来肿瘤放射治疗将在全面推进精确放疗发展进程的基础上,更加注重与新技术相伴随的放射物理学及放射生物学的研究进展。同时,精确放疗与化疗、热疗、介入治疗、分子靶向治疗等相结合的综合治疗模式以及重离子治疗癌症等新技术的开展,将使癌症患者显著受益于医学科学技术的进步。     

PET—CT在肿瘤放射治疗中的价值

目的探讨PET／CT在放射治疗中的临床应用价值。方法对病理和临床综合检查确诊的178例恶性肿瘤患孝行^18F—FDGPET／CT全身或局部显像,其中头颈部肿瘤15例,肺癌59例,恶性淋巴瘤21例,骨转移瘤55例,脑瘤4例,结、直肠癌4例,转移性淋巴结20例;分析其PET／CT表现,测量兴趣区标准化摄取最大值（SUVmax）,勾画生物靶区,评价肿瘤放疗疗效。结果178例恶性肿瘤患者中新发现淋巴结转移37例;淋巴结伴远处器官转移25例;调整肿瘤的分期62例;勾画生物靶区68例;评估肿瘤放疗后疗效45例：判断放疗后肿瘤残留或复发32例。结论PET／CT在放射治疗应用中具有定性分期准确、勾画生物靶区、判断肿瘤残留、复发和评价疗效等独特优势。     

兔VX2肿瘤放射治疗后早期DWI及~1H-MRS的评价作用

肿瘤放射治疗是局部恶性肿瘤综合治疗的重要组成部分,它对肿瘤局部控制或手术前缩小瘤灶发挥着重要的作用。但临床上肿瘤外放射治疗后不会进行肿瘤病理检测,无法获得病理与影像的对照资料。因此,利用兔VX2肿瘤放射治疗模型来评价肿瘤放射治疗早期DWI和~1H-MRS的表现,可为肿瘤放射治疗前后病理和影像学的变化提供动物实验模型依据。本文对VX2肿瘤放射治疗后功能磁共振的影像学评估现状和前景进行综述。     

肿瘤干细胞在肿瘤放射治疗学中的研究进展

肿瘤细胞的放射敏感性是决定放射治疗能否成功的重要因素之一.研究表明,临床上肿瘤的放射敏感性主要取决于肿瘤的组织来源、分化程度、遗传背景、大体类型以及患者的一般状况,如是否存在严重贫血和糖尿病等.而放射生物学研究提示肿瘤细胞的内在敏感性、细胞周期、增殖情况以及肿瘤细胞所处的微环境,如乏氧等是影响肿瘤放射敏感性的重要因素.随着肿瘤基础研究的深入,现在认为恶性肿瘤是一种干细胞疾病,即肿瘤来源于肿瘤干细胞(cancer stemcell,CSC)[1].近年来,先后在脑胶质瘤、乳腺癌、肺癌、黑色素瘤和前列腺癌等多种实体瘤中克隆到了肿瘤干细胞.这类细胞虽然仅占整个肿瘤细胞的一小部分,但是它们具有自我更新能力和多向分化潜能,可能是形成不同分化程度肿瘤和肿瘤不断生长的根源,是肿瘤发生、扩散和复发等过程中的"起始细胞",也可能是肿瘤治疗失败的根源所在[1-2].肿瘤干细胞概念的提出,给传统肿瘤放射治疗学带来了新进展,也带来了新的挑战.为此,本文拟对肿瘤干细胞在肿瘤放射治疗中的研究进展作一综述.     

应用剂量体积直方图分析恶性胸腺肿瘤放疗对心脏的毒性影响

放射治疗是恶性肿瘤治疗的重要手段之一。放射治疗中 ,肿瘤周围的正常组织和重要器官不可避免地要接受一定的照射剂量 ,在一定程度上造成这些组织和器官的损伤 ,影响患者的生存质量。随着适形和调强技术及三维治疗计划系统在放射治疗临床上的应用 ,可以更好地保护重要器官免受高剂量照射 ,并且通过治疗计划系统可以给出正常组织和器官所接受的剂量及其剂量分布。借助于一定的数学模型 ,由其剂量分布可获得正常组织并发症出现的概率 (ＮＴＣＰ)。这种模型必须能适用于正常组织和器官受到非均匀照射 ,并能反映出对组织类型的依赖性和较好地解…     

机体的内在放射敏感性与放射治疗

放射治疗是目前临床卜常用的医疗手段。决定放射治疗效果的因素很多，但靶组织的放射敏感性是其中关键的因素之一，尤其是肿瘤组织与正常组织间的放射敏感性差异更具有重要意义“’。研究患者对放射治疗的敏感性对于实施放射治疗，以期达到最佳效果，更具临床实用价值。本文就临床工作中涉及最多的细胞或组织的放射敏感性及其在放射治疗巾的预测作用作一综述。1组织或细胞的放射敏感性测定方法以实验手段测定组织或细胞的放射敏感性是继放射治疗学后出现的新的研究领域，其H的在于应用正常或肿瘤组织细胞进行体外放射敏感性试验，为判断、…     

放射增敏剂的作用机制及临床研究进展

放射治疗是治疗恶性肿瘤的主要手段之一，但是临床上多数肿瘤的放射治疗疗效较低，因此如何增加肿瘤的放射敏感性一直是肿瘤放射治疗领域中受关注的问题。已有为数不多的放射增敏剂应用于临床或正在进行临床试验，各种放射增敏剂的作用方式及效果各有差别，本文作者从几个方面综述如下。     

台湾地区干细胞治疗的研究方向及新进展

由于具有疗效良好、不良反应小、个性化等优势,细胞治疗在临床治疗领域中扮演着日益重要的角色。由生物谷主办的2014细胞治疗国际研讨会于6月20—21日在上海召开,会议以转化医学为切入点,将基础研究与临床应用相结合,邀请了国内外顶尖的细胞治疗基础研究和临床专家,针对细胞治疗伦理、细胞制品质量控制、T细胞过继免疫治疗、干细胞移植治疗、基因修饰化细胞治疗等热门议题进行讨论。干细胞治疗更成为各个国家和地区医疗机构与药厂关注的重点。针对台湾地区干细胞治疗领域的进展与政策,台湾国立阳明大学干细胞研究中心主任李光申教授接受了生物谷的采访。     

骨髓间质干细胞治疗放射损伤的研究进展

随着放射治疗技术的发展、设备的不断完善,放射治疗在肿瘤治疗中得到广泛应用^[1]。与手术治疗相比,放射治疗具有非侵入性、可以保留器官、在时间及空间上可以精确调控等优势,在很多情况下能有效地消除肿块。但放射治疗在杀灭肿瘤细胞的同时,不可避免地对周围正常组织造成一定程度的损伤。     

利用3D打印颅脑辐射等效体模进行个性化适形放疗的剂量验证

目的 建立利用3D打印颅脑辐射等效体模对患者进行个性化放疗剂量验证的方法,为三维适形放射治疗安全提供一种可靠的剂量保证手段。方法 采集两例患者（患者1和患者2）的CT图像数据,基于患者1的图像数据,重建其颅骨与脑组织,制作颅脑体模,验证颅骨与脑组织的等效材料。基于患者2的图像数据,根据3D图像重建并选用组织等效材料重建完全的头颅结构,采用3D打印技术制作全头颅体模。通过对目标区域插入电离室剂量仪并行放射治疗方案,获得头颅体模病灶部的剂量,验证和校准实际放疗计划的安全性。结果 对所获两个体模分别进行DR、CT成像,颅脑体模的等效骨骼与患者1骨骼的X射线灰度值差异为13 721,颅脑体模的等效脑组织与患者1的脑组织的CT值差异为35~40 HU,全头颅体模等效颞肌与患者2的颞肌组织的CT值差异为18~28 HU,影像数据表明体模材质的辐射等效性与人体组织近似,并且等效剂量分布符合常规治疗范围,体模的剂量验证可以有效验证放疗计划系统的准确性。结论 基于3D打印和组织等效技术所设计的个性化放疗体模,可应用于个性化放射治疗验证。体模制作方法简单快速,个性化程度高,为三维适形放射治疗安全提供一种可靠的剂量保证手段。     

3D打印技术在放疗中的应用与进展

随着3D打印技术的发展和成熟,其在医学领域被广泛应用,尤其在骨科、口腔颌面外科等方面取得了突破性进展。而在肿瘤的放疗领域,创新性地将3D打印技术与放疗技术相结合并应用于临床,可大大提高放疗的精确度和临床疗效,为肿瘤的精确放疗提供有力保障。     

Repair of Potentially Lethal Damage in Rat Mammary Clonogens Following Irradiation in Organoid Culture

Summary

In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4–24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2–4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A new four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4–24 h after exposure.     

Real-time dosimetry in external beam radiation therapy

With growing complexity in radiotherapy treatment delivery, it has become mandatory to check each and every treatment plan before implementing clinically. This process is currently administered by an independent secondary check of all treatment parameters and as a pre-treatment quality assurance (QA) check for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy treatment plans. Although pre-treatment IMRT QA is aimed to ensure the correct dose is delivered to the patient, it does not necessarily predict the clinically relevant patient dose errors. During radiotherapy, treatment uncertainties can affect tumor control and may increase complications to surrounding normal tissues. To combat this, image guided radiotherapy is employed to help ensure the plan conditions are mimicked on the treatment machine. However, it does not provide information on actual delivered dose to the tumor volume. Knowledge of actual dose delivered during treatment aid in confirming the prescribed dose and also to replan/reassess the treatment in situations where the planned dose is not delivered as expected by the treating physician. Major accidents in radiotherapy would have been averted if real time dosimetry is incorporated as part of the routine radiotherapy procedure. Of late real-time dosimetry is becoming popular with complex treatments in radiotherapy. Real-time dosimetry can be either in the form of point doses or planar doses or projected on to a 3D image dataset to obtain volumetric dose. They either provide entrance dose or exit dose or dose inside the natural cavities of a patient. In external beam radiotherapy, there are four different established platforms whereby the delivered dose information can be obtained: (1) Collimator; (2) Patient; (3) Couch; and (4) Electronic Portal Imaging Device. Current real-time dosimetric techniques available in radiotherapy have their own advantages and disadvantages and a combination of one or more of these methods provide vital information about the actual dose delivered to radiotherapy patients.     

2016年度福建省放射治疗应用基本情况调查分析

目的 掌握2016年度福建省放射治疗应用基本情况。方法 采用统一设计的调查表,通过普查的方法搜集全省放射治疗单位的放射治疗及其配套设备的种类与数量、放射治疗工作人员数以及放射治疗质量控制工作开展情况,统计26家医院的放射治疗患者和门诊量等数据。通过相关性和多重线性回归分析建立模型来估算全省的放射治疗患者总数。结果 2016年福建省有32家放射治疗单位,放射治疗设备62台（套）,模拟定位机33台,放射治疗计划系统（TPS）57套,放射治疗工作人员762名,可搜集到的26家医院的放射治疗患者共计15 156人。根据多元线性回归模型得到医用电子加速器的应用频度与门急诊和住院量,放射治疗工作人员数,加速器设备数呈正相关（r=0.311、0.893、0.956,P<0.05）;后装治疗的应用频度与门急诊和住院量、放射治疗工作人员数、后装设备数呈正相关（r=0.307、0.966、0.988,P<0.05）。通过估算得到福建省2016年度放射治疗应用频度为0.54例/千人口。经调查各单位基本都能按照规定开展加速器输出剂量校准,但晨检仪、井型电离室等放射治疗质控设备的配置明显不足。结论 近几年福建省的放射治疗发展较快,规范、加强应用过程中的质量控制和监督应当作为将来放射治疗管理的关注重点。     

CXCR4 as biomarker for radioresistant cancer stem cells

Abstract

Purpose: Radioresistance of cancer cells remains a fundamental barrier for maximum efficient radiotherapy. Tumor heterogeneity and the existence of distinct cell subpopulations exhibiting different genotypes and biological behaviors raise difficulties to eradicate all tumorigenic cells. Recent evidence indicates that a distinct population of tumor cells, called cancer stem cells (CSC), is involved in tumor initiation and recurrence and is a putative cause of tumor radioresistance. There is an urgent need to identify the intrinsic molecular mechanisms regulating the generation and maintenance of resistance to radiotherapy, especially within the CSC subset. The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. The interaction of CXCR4 with its ligand, the chemokine C-X-C motif ligand 12 (CXCL12), plays an important role in modulating the tumor microenvironment, angiogenesis and CSC niche. Moreover, the therapeutic inhibition of the CXCR4/CXCL12 signaling pathway is sensitizing the malignant cells to conventional anti-cancer therapy.

Content: Within this review we are summarizing the role of the CXCR4/CXCL12 axis in the modulation of CSC properties, the regulation of the tumor microenvironment in response to irradiation, therapy resistance and tumor relapse.

Conclusion: In light of recent findings, the inhibition of the CXCR4/CXCL12 signaling pathway is a promising therapeutic option to refine radiotherapy.     

靶向DNA损伤应答关键分子在肿瘤放疗增敏中的应用

放射治疗是临床肿瘤治疗的重要手段,主要通过破坏DNA双链对肿瘤细胞造成严重损伤。然而,其作为单一的治疗手段,治疗效果受肿瘤细胞固有DNA损伤修复能力的影响。多项研究表明,靶向调节DNA损伤响应关键分子可以有效抑制DNA损伤修复,协同增强放化疗敏感性。本文对一些关键的DNA损伤响应抑制剂联合放疗、化疗在多种肿瘤治疗中的应用进行了总结,并阐述了联合治疗诱导由环鸟嘌呤核苷酸腺嘌呤核苷酸合成酶-干扰素基因刺激因子介导的免疫反应。最后总结和展望了联合治疗存在的挑战和发展前景。     

Repair of potentially lethal damage in rat mammary clonogens following irradiation in organoid culture.

In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4-24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2-4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A near four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4-24 h after exposure.     

A graphical user interface for automatic image registration software designed for radiotherapy treatment planning

Medical imaging forms a vital component of radiotherapy treatment planning and its evaluation. The integration of the useful data obtained from multiple imaging modalities for radiotherapy planning is achieved by image registration softwares. In radiotherapy planning systems, normally the computed tomography (CT) slices are kept as a standard upon which other modality images (magnetic resonance imaging [MRI], single photon emission computed tomography [SPECT], positron emission tomography [PET], etc.) are aligned—automatically or interactively. Following validation of successful registration, they are resampled and reformatted, as per the requirements. This paper defines the minimum requirements of automatic image registration software for 3-dimensional (3D) radiotherapy planning and describes the implementation of a suitable graphical user interface developed in Visual Basic (version 5). The automatic image registration (AIR) routines freely available from Dr. Roger P. Woods, UCLA, (USA) were used in this software. This software could be easily implemented and was easy to use for image processing suitable for radiotherapy planning systems.