靶向CCL21/CCR7轴治疗肿瘤转移的研究进展

转移是肿瘤患者死亡最常见的原因,而淋巴转移是大多数肿瘤转移的主要途径之一。近年来,CC趋化因子配体21 (CC chemokine ligand 21,CCL21)及其受体CC趋化因子受体7型(CC chemokine receptor type 7,CCR7)在淋巴转移中的作用逐渐受到关注。CCL21主要由淋巴内皮细胞产生,其与树突状细胞(Dendritic cells,DCs)和T细胞等表面CCR7的相互作用是免疫细胞淋巴迁移及淋巴结归巢的主要决定因素。然而,表达CCR7的肿瘤细胞也可以利用类似的机制进入淋巴管进行淋巴转移。如何靶向CCL21/CCR7轴,既能抑制淋巴转移,又不影响抗肿瘤免疫反应已成为肿瘤免疫治疗研究的重要议题。文中将对CCL21/CCR7轴在淋巴转移中的作用及其作为靶点治疗肿瘤转移的临床前和临床试验研究进行综述,为靶向CCL21/CCR7信号轴治疗肿瘤转移的相关研究提供参考。     

CCL20及其受体CCR6在肝细胞肝癌中的作用

肝细胞肝癌(hepatocellular carcinoma,HCC)(简称肝癌)是常见的血管侵袭性高、耐药性强的恶性肿瘤之一.CC趋化因子配体20(CC chemokine ligand 20,CCL20)作为一种炎症介质能够诱导肿瘤细胞定向迁移,与其唯一受体趋化因子受体6(chemokine receptor 6,...     

人趋化因子受体CCR3与β-arrestin相互作用研究

G蛋白偶联受体(G protein-coupled receptors,GPCRs)主要负责介导细胞内外跨膜信号转导功能,是重要的药物靶点.β-arrestin作为GPCRs行使功能的重要途径之一,其对调节GPCRs信号转导过程有重要意义.但目前对于β-arrestin如何与GPCRs相互作用并调控其信号转导功能尚不十分清楚.本文以趋化因子受体3 (CC chemokine receptor 3,CCR3)为研究对象,构建了β-arrestin与CCR3的共表达体系,利用激光共聚焦荧光成像与荧光共振能量转移(fluorescence resonance energy transfer,FRET)技术研究了β-arrestin与CCR3在活细胞水平的相互作用,利用RNAi和趋化实验考察了β-arrestin对CCR3稳转细胞趋化行为的调控作用,并在体外利用石英晶体微天平(quartz crystal microbalance,QCM)技术测定了β-arrestin突变体(R169E)与CCR3之间结合常数.结果显示,趋化因子CCL11 (chemokine C-C motif ligan...     

CC趋化因子与心肌梗死的研究进展

CC类趋化因子亚家族是趋化因子家族中成员最多、研究最广泛的一大类细胞因子,其主要功能是参与炎症细胞激活、迁移、黏附等病理生理过程.大量研究表明,CC类趋化因子亚家族成员参与了心肌梗死后病理过程的各个阶段.其中研究最为深入的是单核细胞趋化蛋白1 (monocyte chemoattractant protein-1,MCP-1)及其受体CC趋化因子受体2 (CC chemokine receptor 2,CCR2). MCP-1和CCR2在心肌梗死后炎症期、增殖期及疤痕愈合期都发挥了重要作用从而影响梗死后心室重构.近年来,CC类趋化因子亚家族其他成员亦被逐渐揭示参与了心肌梗死的发展.本文结合以往大量文献,就CC类趋化因子亚家族在心肌梗死各个阶段中的作用,尤其是梗死后各期对于心室重构的影响进行综述,以期为今后的CC趋化因子研究提供方向,为相关疾病的预防和治疗研究提示潜在的药物靶点.     

CC趋化因子配体2与肝疾病

近年来CC趋化因子配体2(chemokine(C-C motif)ligand 2,CCL2)在肝脏疾病发病机制中的作用越来越受到重视.大量研究表明,CCL2在各种肝损伤中表达上调.CCL2是炎症反应的主要调节因子,通过与其受体CCR2相互作用,使血液中的单核细胞穿过血管内皮向炎症部位迁移.白色脂肪组织分泌的CCL2能直接诱导肝细胞的脂肪聚集,与非酒精性肝病的发病机理密切相关.肝实质细胞分泌的CCL2能激活并募集肝星形细胞,参与肝纤维化甚至肝硬化的形成.CCL2能介导肝癌细胞的转移和浸润,刺激肿瘤血管生成,其与肿瘤的关系也成为研究的热点.本文将阐述CCL2与病毒性肝炎、酒精性肝炎、非酒精性脂肪性肝炎、肝纤维化、肝硬化和肝癌的研究进展.     

趋化因子CCL28在炎症与肿瘤中作用的研究进展

CCL28,又称为粘膜相关上皮趋化因子(mucosae-associated epithelia chemokine,MEC),是在2000年发现的一种CC家族趋化性细胞因子。CCL28在基因定位、蛋白质序列上有其独特性,其相应的受体为CCR3和CCR10。CCL28最初在粘膜组织中被发现,与Ig A抗体的分泌有关,被认为其参与了机体的粘膜免疫作用。目前对于CCL28的研究非常有限,主要集中于其在炎症组织微环境中的作用,近来也有文献报道提示其与肿瘤的关系密切。本文就趋化因子CCL28在炎症与肿瘤中的研究进展作一综述。     

芍药苷对哮喘模型小鼠气道炎症趋化因子及受体的干预作用

目的观察芍药苷给药后对小鼠哮喘模型气道炎症趋化因子及受体的影响。方法用卵蛋白(OVA)致敏和激发建立小鼠哮喘模型;ELISA法检测血清IL-6、TNF-α水平及支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中卵蛋白特异性Ig E(OVA-Ig E)和趋化因子CCL19、CCL21水平;RT-PCR法检测肺组织中趋化因子受体CCR7mRNA表达;Western blot检测肺组织CCR7及核转录因子-κB(nuclear factor-κB,NF-κB)蛋白表达。结果芍药苷干预组小鼠血清IL-6、TNF-α水平显著下降;BALF中OVA-Ig E和CCL19、CCL21水平显著降低;肺组织CCR7mRNA、CCR7及NF-κB蛋白表达明显减少。结论芍药苷对哮喘模型小鼠气道炎症趋化因子CCL19/CCL21及其受体CCR7具有显著的抑制作用。     

CCL27及其受体在抗病毒免疫中的作用

趋化因子是一类结构相关、对白细胞具有趋化活性、相对分子质量为(8～10)×103的小分子蛋白质,在炎症和免疫反应中可诱导白细胞和淋巴细胞迁移.CCL27是一种CC型趋化因子,其配体为CCR10.CCL27与接触性软疣病毒编码产生的蛋白质MC148有较高的同源性,但却与人疱疹病毒8型编码产生病毒巨噬细胞炎症蛋白-Ⅱ竞争结合受体CCR10.     

CC类趋化因子亚家族与心肌梗死的研究进展

CC类趋化因子亚家族是趋化因子家族中成员最多、研究最广泛的一大类细胞因子,其主要功能参与炎症细胞激活、迁移、粘附等病理生理过程。大量研究表明,CC类趋化因子亚家族成员参与了心肌梗死后病理过程的各个阶段。其中研究最为深入的为单核细胞趋化蛋白-1（monocyte chemoattractant protein-1,MCP-1）及其受体CC趋化因子受体2（CC chemokine receptor 2,CCR2）,在心肌梗死后炎症期、增殖期及疤痕愈合期都发挥了重要作用从而影响梗死后心室重构。近年来,CC类趋化因子亚家族其他成员亦被逐渐揭示参与了心肌梗死的发展。本文结合以往大量文献将对CC类趋化因子亚家族在心肌梗死各个阶段中尤其是梗死后各期对于心室重构的影响进行综述,以期为今后的实验研究提供方向及疾病的预防和治疗提供药物靶点。     

CCL8相关通路与过敏性疾病

CC趋化因子配体8(CC chemokine ligand 8, CCL8)与细胞表面受体结合后可调控与细胞增殖、分化、凋亡及炎症等相关的信号通路,在包括过敏性鼻炎、过敏性皮炎、过敏性哮喘等多种过敏性疾病的发病机制中发挥重要作用。本文介绍了与CCL8相关的JAK-STAT信号通路、p38 MAPK信号通路、NF-κB信号通路和STAT3信号通路通过影响辅助性T淋巴细胞分化、白细胞介素水平以及活性氧的产生等方面参与过敏性疾病发病的机制,期望针对CCL8及相关通路的研究为过敏性疾病的诊断与治疗提供参考。     

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.