Anti-apoptotic Bcl-2 proteins: structure,function and relevance for radiation biology

Purpose : Bcl-2 family members mediate anti-apoptotic signals in a wide variety of human cell systems. Despite its proven antiapoptotic function, several results indicate that overexpression of Bcl-2 is not clearly associated with increased radiation resistance in vitro or in vivo. The reasons for this obvious contradiction are not understood. Materials and methods : Current data on the function of Bcl-2 as an anti-apoptotic protein, its role for the modulation of radiation sensitivity in vitro and its value as prognostic marker in vivo are reviewed. Results : Bcl-2 and related proteins are currently perceived to be the most important anti-apoptotic proteins. Their function is related to their ability to interfere with mitochondrial apoptosis pathways. Contradictory data have been published on the relevance of Bcl-2 and related family members for in vitro and in vivo tumour response. The value of Bcl-2 as a prognostic marker thus remains unclear. Conclusions : Although Bcl-2-related proteins are currently the most relevant anti-apoptotic modulators, their relevance for radiation responses in vivo or in vitro remain undefined. Furthermore, their determination in a routine clinical setting does not appear to be justified.     

A primer on molecular biology for imagers: III. Proteins: structure and function

This article along with the first 2 in this series (4,12) completes the discussion on the key molecules and process inside the cell namely, DNA, RNA, and proteins. These 3 articles provide a very basic foundation for understanding molecular biology concepts and summarize some of the work of numerous scientists over the past century. We understand these processes far better now than we did in the past, but clearly this knowledge is by no means complete and a number of basic scientists are working hard to elucidate and understand the fundamental mechanisms that operate within a cell. Genes and gene products work with each other in complex, interconnected pathways, and in perfect harmony to make a functional cell, tissue, and an organism as a whole. There is a lot of cross-talk that happens between different proteins that interact with various other proteins, DNA, and RNA to establish pathways, networks, and molecular systems as a team working to perfection. The past 15 years have seen the rapid development of systems biology approaches. We live in an era that emphasizes multi-disciplinary, cross-functional teams to perform science rather than individual researchers working on the bench on a very specific problem. Global approaches have become more common and the amount of data generated must be managed by trained bioinformatics personnel and large computers. In our subsequent articles, we will discuss these global approaches and the areas of genomics, functional genomics, and proteomics that have revolutionized the way we perform science.     

Bcl-2家族蛋白与肺型氧中毒

近30年来,研究人员对肺型氧中毒进行了广泛而深入的研究,但是其发病机制仍不完全清楚.过去的研究主要围绕活性氧(reactive oxygen species,ROS)的作用展开,并且得到了广泛的实验支持.近年来,细胞因子和细胞凋亡过程在肺型氧中毒中的作用引起了研究人员越来越浓厚的兴趣.     

Radiation-induced lung damage: a challenge for radiation biology,experimental and clinical radiotherapy

Summary

The induction of pyrimidine dimers in E. coli DNA by secondary ultraviolet light associated with 6 MVp X-rays in the dose range 20–90 Gy has been demonstrated using T₄ endonuclease V. Under the experimental conditions used in these experiments the major component of this secondary U.V. light is Cerenkov emission.     

Fundamentals of molecular imaging: rationale and applications with relevance for radiation oncology

Molecular imaging allows for the visualization and quantification biologic processes at cellular levels. This article focuses on positron emission tomography as one readily available tool for clinical molecular imaging. To prove its clinical utility in oncology, molecular imaging will ultimately have to provide valuable information in the following 4 pertinent areas: staging; assessment of extent of disease; target delineation for radiation therapy planning; response prediction and assessment and differentiation between treatment sequelae and recurrent disease. These issues are addressed in other contributions in this issue of Seminars in Nuclear Medicine. In contrast, this article will focus on the biochemical principles of cancer metabolism that provide the rationale for positron emission tomography imaging in radiation oncology.     

Fibrinogen: structure, function, and surface interactions

Fibrinogen plays a central role in the mechanism of coagulation and thrombosis and is partially involved in the development of postintervention restenosis. Because of therapeutic implications, it is convenient for the vascular interventionalist to revisit its structure, function, and relationships within the vascular environment. This review focuses on the molecular structure, mechanisms of polymerization and lysis, and fibrinogen interaction with the platelet alpha(IIb)beta(3) [corrected] integrin. It also addresses the less understood interaction of fibrinogen with artificial surfaces. Glycoprotein IIb-IIIa blockers, targeted to interfere with fibrinogen-platelet interactions, widely used in clinical practice, are discussed, and trials of new drugs are also summarized.     

喉癌放疗敏感性与 p53和Bcl-2基因综合表达的关系

目的 根据喉癌细胞自身生物学特性,探讨Ｂｃｌ－２和Ｐ５３基因综合表达与放射治疗敏感性的相互关系。方法 应用抗Ｂｃｌ－２和Ｐ５３基因蛋白单克隆抗体,采用ＤＡＣＯ ＣＳＡ Ｓｙｓｔｅｍ法染色技术,对两组共７０例喉鳞癌组织标本进行了免疫组织化学染色分析,将Ｂｃｌ－２和Ｐ５３基因表达分子个级别,诮Ｇｒａｍｅｒ修正）列胶系数（Ｃ）进行检验,探讨各自及综合表达强度与喉癌放疗敏感性的基因表达强度与放射敏感性之间     

Basic review of radiation biology and terminology

OBJECTIVE: The purpose of this paper is to review basic radiation biology and associated terminology to impart a better understanding of the importance of basic concepts of ionizing radiation interactions with living tissue. As health care workers in a field that utilizes ionizing radiation, nuclear medicine technologists are concerned about the possible acute and chronic effects of occupational radiation exposure. Technologists should have a clear understanding of what they are exposed to and how their safety could be affected. Furthermore, technologists should be knowledgeable about radiation effects so that they can adequately assuage possible patient fears about undergoing a nuclear medicine procedure. After reading this article, the nuclear medicine technologist will be familiar with: (a) basic radiation biology concepts; (b) types of interactions of radiation with living tissue, and possible effects from that exposure; (c) theoretical dose-response curves and how they are used in radiation biology; (d) stochastic versus nonstochastic effects of radiation exposure, and what these terms mean in relation to both high- and low-dose radiation exposure; and (e) possible acute and chronic radiation exposure effects.     

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Diagnostic and therapeutic radiation technology has developed dramatically in recent years, and its use has increased significantly, bringing clinical benefit. The use of diagnostic radiology has become widespread in modern society, particularly in paediatrics where the clinical benefit needs to be balanced with the risk of leukaemia and brain cancer increasing after exposure to low doses of radiation. With improving long-term survival rates of radiotherapy patients and the ever-increasing use of diagnostic and interventional radiology procedures, concern has risen over the long-term risks and side effects from such treatments. Biomarker development in radiology and radiotherapy has progressed significantly in recent years to investigate the effects of such use and optimise treatment. Recent biomarker development has focused on improving the limitations of established techniques by the use of automation, increasing sensitivity and developing novel biomarkers capable of quicker results. The effect of low-dose exposure (0–100 mGy) used in radiology, which is increasingly linked to cancer incidences, is being investigated, as some recent research challenges the linear-no-threshold model. Radiotherapy biomarkers are focused on identifying radiosensitive patients, determining the treatment-associated risk and allowing for a tailored and more successful treatment of cancer patients. For biomarkers in any of these areas to be successfully developed, stringent criteria must be applied in techniques and analysis of data to reduce variation among reports and allow data sets to be accurately compared. Newly developed biomarkers can then be used in combination with the established techniques to better understand and quantify the individual biological response to exposures associated with radiology tests and to personalise treatment plans for patients.Research into the identification of biomarkers of radiation exposure is an emerging and developing area with multiple possible benefits for patients, doctors and the general public. A radiation biomarker is a biological entity that changes after exposure to radiation, allowing exposed individuals to be identified and, with some biomarkers, a dose to be estimated. There are different types of biomarkers, including chromosome aberrations, protein expression or gene expression. Some can measure accurately the dose received, while others can only indicate if a dose was received. Biomarkers can help clinicians manage treatment for a patient exposed accidentally to the wrong radiation dose or on purpose through radiotherapy. They may be able to predict the treatment response of a tumour and estimate the risk of acute or late effects in normal tissues. Biomarkers can also identify the dose received by the patient in a full or partial body exposure. Such information can help inform the necessary medical treatment plan for the patient, and it may also identify patients with a high likelihood of developing cancer in the future so that regular monitoring can be set up.     

KGF对电离辐射后十二指肠中CTGF和Bcl-2基因表达的影响

目的 观察角质细胞生长因子（KGF）对电离辐射后十二指肠结缔组织生长因子（CTGF）、凋亡相关基因Bcl-2表达的影响,初步探讨KGF在肠道损伤中的分子机制。 方法 将昆明小鼠按随机数表法分为对照组、照射组、治疗组,每组10只。对照组不给予照射,照射组与治疗组给予剂量率为0.678 Gy/min、吸收剂量8 Gy的腹腔γ射线照射;治疗组在照射前2 d及照射后3 d均腹腔注射KGF,给药量为6 mg/kg。照射后第15天处死小鼠,取十二指肠组织做病理切片并观察病理表现;采用荧光定量PCR方法检测十二指肠组织中KGF、CTGF及Bcl-2基因的表达水平。计量资料以x±s表示;两组间差异采用独立样本t检验,P < 0.05表示差异有统计学意义。 结果 对照组十二指肠肠绒毛、隐窝结构完整,排列整齐;照射组十二指肠出现绒毛萎缩、变短或脱落,部分腺窝和绒毛处可见少量凋亡细胞;治疗组肠绒毛组织结构完整,腺窝可见少量凋亡细胞。照射组十二指肠组织中KGF、CTGF、Bcl-2基因表达量上调,与对照组相比差异具有统计学意义（t=-125.55、-6.55、-6.69,均P < 0.05）。与照射组相比,治疗组CTGF基因表达量显著下调、Bcl-2基因表达量显著上调,差异均有统计学意义（t=4.89,-20.96,均P < 0.05）。 结论 KGF可能通过下调CTGF基因修复电离辐射造成的损伤,并且可能通过调节Bcl-2凋亡相关基因的表达水平来降低细胞凋亡。     

大鼠急性心肌缺血再灌注心肌细胞凋亡与Bcl—2／Bax蛋白的表达

目的：为了证实急性心肌缺血再灌注过程中存在着不同程度的心肌细胞凋亡现象,初步研究心肌细胞凋亡与Bcl-2/Bax蛋白表达的关系。方法：电镜观察心肌细胞的超微结构变化,抽提心肌组织DNA琼脂糖凝胶电泳,TUNEL法原位标记凋亡的心肌细胞,免疫组化技术和图像分析技术检测心肌细胞内Bcl-2/Bax蛋白表达。结果：缺血及再灌注组电镜观察心肌细胞出现典型凋亡超微结构特征,TUNEL染色可见不同程度的心肌细胞凋亡阳性反应,DNA电泳显示在缺血再灌注2h组出现明显的DNA ladder,再灌注较在缺血组心肌细胞中Bcl-2表达明显降低（P＜0．05）,而Bax表达明显增高＊（P＜0．05）,结论：急性心肌缺血及再灌注能诱导不同程度的心肌细胞凋亡,Bcl-2/Bax基因对心肌细胞凋亡的发生有着重要的调控作用。     

Aging of human muscle: structure, function and adaptability

With increasing age, human skeletal muscles gradually decrease in volume, mainly due to a reduced number of motor units and muscle fibers, and a reduced size of type 2 fibers. As a result, progressive weakening and impaired mobility occur. High-resistance strength training is beneficial, even in the very old, and could possibly reverse some of the detrimental effects of age-related weakness. The importance of exercise for older people affords an excellent opportunity for the medicine community as a major source of information and promotion of physical activity for this rapidly growing segment of the population. In this review, we summarize the current knowledge of the effects of aging on the human neuromuscular system, describe some of the major underlying mechanisms of the aging atrophy and focus on the importance of strength training to improve muscle function in older people.     

放疗前后喉癌组织中Bcl-2及Bax蛋白表达及其临床意义

目的　探讨放疗对喉癌组织中Bcl 2和Bax基因蛋白表达的影响及放疗后喉癌复发原因。方法　通过采用免疫组化SP法 ,测定 2 7例患者放疗前、放疗后和复发后喉癌组织中Bcl 2和Bax蛋白的表达。结果　与放疗前相比 ,放疗后喉癌组织中Bcl 2蛋白表达明显减少 (P <0 0 1) ,Bax蛋白表达明显增多 (P <0 0 5 )。喉癌放疗后局部组织中Bax蛋白表达与复发的时间长短有关 (P <0 0 5 )。结论　喉癌组织内Bcl 2和Bax蛋白表达参与了放疗引起的细胞凋亡过程 ,局部组织内Bax蛋白的表达水平与喉癌复发时间有关