TNF相关的凋亡诱导配体及其受体研究进展

TNF相关的凋亡诱导配体（TNF-related apoptosis-induicing ligand,TRAIL),属于TNF超家族成员,与Apo-1L(FasL)有较高的同源性,又称为Apo-2L。TRAIL有两类受体,一类是死亡受体,如DR4和DR5,TRAIL与DR4或DR5结合可以诱导细胞凋亡;另一类是“诱骗”受体,如DcR1、DcR2,可以竞争性地与TRAIL结合,逃避或抑制TRAIL诱导的正常细胞损伤。TRAIL及其受体的发现为肿瘤的治疗提供了一个新的方向。     

鳜肿瘤坏死因子相关的凋亡诱导配体Trail基因的原核表达

肿瘤坏死因子相关的凋亡诱导配体(Tumor related apoptosis inducing ligand,TRAIL),亦称Apo-2L,是由Wiley,et al.在1995年搜索EST数据库时首次发现并成功克隆的,是继TNF和FasL之后发现的第三个TNF家族的凋亡分子[1].     

肿瘤细胞抗TRAIL凋亡诱导的分子机制

肿瘤坏死因子相关的凋亡诱导配体(tumornecrosisfactor-relatedapoptosis-inducingligand,TRAIL)是肿瘤坏死因子(tumornecrosisfactor,TNF)超家族的成员之一,它能选择性诱导肿瘤细胞凋亡,对大多数正常细胞无杀伤作用。研究表明,某些恶性肿瘤抵抗TRAIL诱导的凋亡,且TRAIL重复作用使一些TRAIL敏感的细胞产生获得性抗性,这是TRAIL应用于肿瘤治疗的重大障碍。现对与TRAIL凋亡诱导通路直接相关的抗TRAIL机制及由Akt等途径介导的抗性分子机制进行综述。     

死亡受体5介导细胞凋亡的研究及应用

死亡受体DR5(death receptor 5)属于肿瘤坏死因子受体(tumor necrosis factor receptor,TNFR)超家族的成员,其胞质区部分含有死亡结构域(death domain,DD),广泛分布于各种肿瘤细胞和正常组织细胞的膜上.配体TRAIL与肿瘤细胞表面的DR5结合,可诱导大多数肿瘤凋亡,而对正常的组织几乎没有作用.近年来死亡受体DR5与细胞凋亡的关系已成为研究热点之一,对DR5介导细胞凋亡的机制和应用进展作一综述.     

胃癌细胞TRAIL受体的表达与其对TRAIL敏感性的关系

目的:探讨胃癌细胞表面TRAIL受体表达水平及其与TRAIL敏感性的关系.方法:PI染色、流式细胞仪检测TRAIL诱导BGC-823及SGC-7901细胞的凋亡率,流式细胞仪检测细胞膜表面四种TRAIL受体-R1、R2、R3、R4的表达情况.结果:TRAIL诱导胃癌细胞凋亡具有剂量和时间依赖性,BGC-823较SGC-7901对TRAIL诱导的凋亡更敏感,TRAIL(100μg·L-1)作用24h的细胞凋亡率分别是59.9%、24.3%.死亡受体TRAIL-R1/DR4、TRAIL-R2/DR5在BGC-823细胞膜表面表达的阳性率高达97.87%和99.42%,而在SGC-7901分别为7.03%和95-31%,诱骗受体TRAIL-R3/DcR1、TRAIL-R4/DcR2在两株细胞膜表面极少表达.结论:胃癌细胞对TRAIL诱导凋亡的敏感性差异可能与细胞膜表面死亡受体有关,尤其与DR4的表达有关.     

重组人凋亡素2 配体对放射线诱导肺腺癌A549 细胞凋亡作用的研究

目的:研究凋亡素2配体(Apo-2 ligand,Apo-2L),或称肿瘤坏死因子相关凋亡诱导配体(TNF-related apoptosis-inducing lig-and,TRAIL)在体外对人肺腺癌A549细胞系的放射增敏作用的研究。方法:MTT法检测Apo-2L单药或与放射线联合对腺癌A549细胞的抑制率,将细胞分为4组,对照组、Apo-2L组、Apo-2L+放射照射组、单纯照射组,200ng/ml、286 ng/ml的Apo-2L作用24小时后给予放射照射,照射剂量分别为:(1Gy、1.4 Gy、1.8Gy、2 Gy、3 Gy),然后进行流式细胞仪分析照射后24h各组细胞凋亡率变化。结果:MTT结果显示,腺癌A549细胞的抑制率与Apo-2L的浓度成正相关,凋亡素2配体作用24h后IC50为286ng/ml.流式细胞仪分析显示286ng/ml的Apo-2L处理24h后,细胞凋亡率从(6.68)%上升至(50)%,照射后24h Apo-2L+照射组凋亡率明显升高,为72.790%,对照组0.1185%,Apo-2L组50%,单纯照射组51.5067%。结论:Apo-2L在体外对腺癌A549细胞有抑制增殖和促进凋亡作用,并且Apo-2L联合放射线可以明显提高腺癌A549细胞的凋亡率。     

以TRAIL为靶点的肿瘤治疗研究进展

肿瘤坏死因子相关凋亡配体（tumor necrosis factor-related apoptosis-inducing ligand,TRAIL）是肿瘤坏死因子（tumor necrosis factor,TNF）超家族成员。TRAIL与其受体结合后启动凋亡信号转导,选择性地诱导肿瘤细胞凋亡,而对正常组织细胞没有明显的伤害,而且一些药物和细胞因子可协同TRAIL诱导肿瘤细胞凋亡。本文就TRAIL及其受体、TRAIL诱导凋亡的机制以及影响凋亡的因素和途径,以TRAIL为靶点的肿瘤治疗的研究现状作一综述。     

补骨脂酚通过激活ROS强化TRAIL的抗肝细胞癌HepG2细胞作用的机制研究

目的:探究补骨脂酚(Bakuchiol,Bak)对肿瘤坏死因子相关凋亡诱导配体(Tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)抗HepG2细胞作用的影响及内在机制。方法:常规培养HepG2细胞,给予梯度浓度的Bak处理,检测细胞活力。联合应用Bak与TRAIL处理,检测细胞活力。Western blot检测Bak处理后氧化应激水平、死亡受体4(Death Receptor 4,DR4)、DR5的表达变化。联合应用Bak与TRAIL检测凋亡情况。进而引入ROS清除剂NAC,联合NAC处理后,检测ROS、DR4、DR5以及凋亡情况。结果:Bak剂量依赖地抑制了HepG2细胞的活力,联合应用Bak+TRAIL对细胞活力的抑制作用优于单独用药。Bak处理后氧化应激水平升高,体现在ROS增加,GSH水平下降;Western blot检测发现Bak处理后DR4、DR5表达增加。联合应用Bak+TRAIL显著增加了细胞凋亡蛋白Bax的表达,抑制了抗凋亡蛋白Bcl2的表达。引入ROS阻断剂NAC处理后,与Bak+TRAIL组相比,ROS水平下降,DR4、DR5表达减少。凋亡检测发现NAC处理降低了Bak+TRAIL引起的细胞凋亡。结论:Bak可以显著增强TRAIL引起的HepG2细胞凋亡,该作用可能与Bak激活氧化应激进而上调DR4、DR5表达有关。     

抑制PI3K信号通路促进TRAIL诱导人乳腺癌MCF-7细胞凋亡

肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)对癌细胞有独特的细胞毒性作用,而对正常细胞没有影响.但乳腺癌细胞耐受TRAIL诱导凋亡.本研究探索磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)信号通路对人乳腺癌MCF-7细胞耐受TRAIL的影响.采用MTT法、显微照相以及DAPI染色观察TRAIL对MCF-7细胞生长的抑制作用以及诱导细胞凋亡状况;流式细胞分析细胞凋亡的情况;激光共聚焦显微镜观察多聚ADP核糖多聚酶-1(poly(ADP-ribose)polymerase-1,PARP-1)的迁移和定位;Western印迹分析死亡受体、caspase-3/8、磷酸化的AKT[pAKT(Ser473)]、Src和PARP-1等蛋白质表达.结果显示,小剂量TRAIL(80 nmol/L)和Ly294002(40μmol/L)对MCF-7细胞生长没有显著的抑制作用,但是大剂量TRAIL(160 nmol/L)和Ly294002(80μmol/L)则能抑制MCF-7细胞生长;低剂量Ly294002协同TRAIL抑制MCF-7细胞生长,并诱导细胞凋亡;Ly294002和TRAIL共同作用能促进PARP-1从胞浆进入细胞核;蛋白质表达分析显示,MCF-7细胞均表达死亡受体DR4、DR5、诱骗受体DcR1和DcR2、以及caspase-8,但是不表达caspase-3;Ly294002和TRAIL共同作用也能抑制pAKT(Ser473)和Src的表达,并且导致PARP-1断裂.本研究结果提示,抑制PI3K信号可增加MCF-7细胞对TRAIL诱导的敏感性;MCF-7细胞通过PI3K/AKT途径促进Src的表达耐受TRAIL的细胞毒性作用;Ly294002联合TRAIL是一种新的药物组合方式治疗乳腺癌.     

肿瘤坏死因子相关凋亡诱导配体（TRAIL）及抗肿瘤作用

肿瘤坏死因子相关凋亡诱导配体（TRAIL）是肿瘤坏死因子（TNF）超家族成员之一,能选择性的诱导肿瘤细胞、转化细胞凋亡,而对正常组织无毒性,有望成为肿瘤治疗的新方法,备受人们的关注。本文从TRAIL的结构、受体、诱导肿瘤细胞凋亡机制及在肿瘤治疗中的应用等方面作了介绍,以期为TRAIL临床应用提供参考。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.