胰腺癌发展中的关键信号通路及其作用

胰腺癌是常见的消化道恶性肿瘤之一,起病隐匿、恶性程度高、预后差。胰腺癌发生受多种因素调节,发病机制不清,具有复杂分子发病机。而且,胰腺癌细胞内在的基因异常表达、表观遗传基因突变等因素对胰腺癌发生发展起重要作用。目前研究显示,胰腺癌发生过程与多种信号通路的交互作用密切相关,这些信号通路的研发都体现了临床分子靶向治疗的潜在前景。本文对近年研究的一些与胰腺癌发生相关的信号通路做了总结,这些通路主要包括Wnt信号通路、MAPK信号通路、PI3K/AKT/m TOR信号通路、Hedgehog信号通路等。主要瞄准这些通路在胰腺癌发生、发展过程中的作用,它们的变化特征以及异常变化所导致的结果等方面的最新研究进展,以期为胰腺癌的早诊早治、个体化诊疗等的基础、临床研究提供前言资料。     

Wnt通路中β-catenin在恶性肿瘤中的异常表达

在肿瘤生物学的研究中,Wnt信号通路具有举足轻重的作用.Wnt家族基因编码一组糖蛋白信号分子,这些糖蛋白分子激活的信号通路在人类不同肿瘤中的作用是相互交织的.Wnt信号通路有三种模式,而经典的信号通路与癌症的发生有着十分密切的联系,β-catenin是Wnt经典信号通路正向调节重要效应物,其在胞质内降解及在核内积累可激活一系列靶基因的转录导致肿瘤的发生.了解这条通路在肿瘤发生过程中具体的分子机制有助于为临床诊断提供依据,为早期干预治疗提供方法.     

靶向Wnt/β-catenin信号通路抑制剂研究进展

Wnt/β-catenin信号通路高度复杂,与Notch通路、Hedgehog通路等都有密切联系,参与机体胚胎发育、调控生物体细胞增殖、代谢等多个方面.研究发现,该信号通路的异常激活与肿瘤密切相关.据汤森路透数据库统计发现,截至2014-04-24,共报道Wnt信号通路抑制剂228个,主要分为受体抑制剂和胞内小分子抑制剂等.本文综述了Wnt/β-catenin信号通路抑制剂及其调控机制,旨在为肿瘤预防与治疗提供新素材.     

Wnt/β-catenin信号通路对舌味觉乳头发育及舌癌的调控作用

Wnt经典信号通路(Wnt/β-catenin信号通路)在小鼠舌味觉乳头的早期发育以及味蕾再生过程中具有重要的调控作用,该信号通路的关键因子的缺失或者过表达可导致舌味觉乳头发育缺陷以及味蕾功能异常.此外,Wnt/β-catenin信号通路在成体舌的异常还与舌癌的发生有关.     

肌营养不良蛋白dys参与调控Hippo信号通路

Hippo信号通路最早在黑腹果蝇中发现,现已被证明在哺乳动物中也是保守的.Hippo通路在器官发育和组织稳态中起着重要作用,Hippo信号通路异常与许多癌症的发生相关.Hippo信号通路依赖于核心激酶级联反应,磷酸化转录共激活因子Yorkie(Yki)进而调控下游靶基因的转录.尽管Wts是Hippo通路的关键激酶组分,...     

环二鸟苷酸对细菌运动调控的研究进展

细菌中的第二信使环二鸟苷酸(c-di-GMP)对细菌的运动性有调节作用.c-di-GMP调控鞭毛的生物合成、菌毛形成和菌毛蛋白的组成,以及其他一些与运动相关的蛋白的合成.细菌的运动性与其毒力、致病性、粘附性、趋化性、生物膜组成等密切相关.在革兰氏阴性细菌中,关于c-di-GMP的信号通路的研究较为清晰,而在革兰氏阳性细菌中,关于该信号转导通路的研究较少.此外,有关c-di-GMP的信号通路的研究主要集中在病原菌.该文主要综述了一些常见病原菌中c-di-GMP对其运动性的调控机制,为研究其他细菌c-di-GMP信号通路提供思路.     

绿茶提取物EGCG治疗乳腺癌分子机制的生物信息学分析

在PubChem数据库中查找绿茶提取物茶多酚(EGCG)活性靶蛋白,从Gene数据库中查找乳腺癌相关基因,运用Ingenuity Pathway Analysis(IPA)软件,构建二者信号通路和分子网络并进行分析.结果显示:二者共同作用的通路有235条,排在前面的主要是癌症分子机制通路、炎症反应通路、糖皮质激素受体信号通路、NF-κB信号通路;共同的分子网络有5个,也主要体现在"转录后修饰与调控,细胞生长、发育,DNA的复制、重组、修复,细胞死亡与生存"等生物学功能上.     

胃癌芯片数据中异常转录因子推断与信号通路分析

用一种新的转录因子介导的信号通路分析方法分析肿瘤芯片数据,从中推断异常的转录因子和信号通路.先通过统计目标基因的表达推断转录因子的活性,然后将那些活性异常的转录因子映射到KEGG信号通路上.此方法整合了基因表达调控的实验数据和信号通路信息.利用此方法,对斯坦福芯片数据库中的162个人类胃癌数据进行分析,结果发现,大部分芯片中的TGF-beta,JAK-STAT,NF-kappaB和Notch信号通路被异常激活.进一步对这些通路进行研究,将有助于探究胃癌的发生、发展机理和进行合理的药物设计.     

ROCK1 与CD40相互作用的质谱分析及在CD40信号通路中功能的初探

为鉴定和验证ROCK1和CD40的相互作用,探索ROCK1在CD40通路中可能发挥的作用,应用HD质谱分析ROCK1和CD40的相互作用,用免疫共沉淀实验验证其相互作用, 用ROCK1抑制剂研究ROCK1对CD40通路的影响. 结果ROCK1与CD40存在相互作用;并参与CD40介导的信号通路.说明ROCK1能与CD40发生相互作用,为CD40信号通路的研究提供了新的线索.     

多泛素链延伸酶E4B对TLR信号通路的调节作用

研究多泛素链延伸酶E4B对TLR信号通路的影响.在HEK293T细胞中,通过双荧光报告系统检测E4B对TLR信号通路的影响,并且用免疫共沉淀的方法鉴定E4B的相互作用蛋白质.发现多泛素链延伸酶E4B能够抑制TLR通路的下游转录因子NF-κB和IRFs的转录活性,并且能与TRAF6发生相互作用.提示多泛素链延伸酶E4B可能参与TLR信号通路的调控,为TLR信号通路的研究提供新的线索.     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Features of Women's language

Language is a means of verbal communication. People use language to communicate with each other. In the society, no two speakers are exactly alike in the way of speaking. Some differences are due to age, gender, statue and personality. Above all, gender is one of the obvious reasons. The writer of this paper tries to describe the features of women＇s language from these perspectives： pronunciation, intonation, diction, subjects, grammar and discourse. From the discussion of the features of women＇s language, more attention should be paid to language use in social context. What＇s more, the linguistic phenomena in a speaking community can be understood more thoroughly.     

An Analysis of Catherine＇s Character——Wuthering Heights

Wuthering Heights, Emily Bronte＇s only novel, was published in December of 1847 under the pseudonym Ellis Bell. The book did not gain immediate success, but it is now thought one of the finest novels in the English language. Catherine is the key character of this masterpiece, because everybody and everything center on her though she had a short life. We can understand this masterpiece better if we know Catherine well.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower Ordovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as "oil families", although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any "oil family". Despite their close stratigraphic proximity, it is evident that the oils of the Lower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new "oil family" within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

Design and analysis of generic LBS application developing platform

Location based services is promising due to its novel working style and contents.A software platform is proposed to provide application programs of typical location based services and support new applications developing efficiently. The analysis shows that this scheme is easy implemented, low cost and adapt to all kinds of mobile nework system.     

Achieving Unusual States of Matter Under High Pressure

正The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry,rooted in the atomic shell structure.Within compounds,Group I elements,for example,invariably assume the+1 oxidation state,and their chemical properties differ completely from those of the p-block elements.These general rules govern our understanding of chemical structures and reactions.Using first principles calcula-     

Exchange-Correlation and Electronic Excitation Energies from Pairing Matrix Fluctuations

We have developed an adiabatic connection to formulate the ground-state exchange-correlation energy in terms of pairing matrix linear fluctuations.This formulation of the exchange-correlation energy opens a new channel for density functional approximations based on the many-body perturbation theory.We illustrate the potential of such approaches with an approximation based on the particle-particle Random Phase Approximation(pp-RPA).This re-     

Density Functional Theory for the Response of Periodic Systems to Electric Fields Based on the Vector Potential Approach

正The electronic and nuclear(structural/vibrational)response of 1D-3D nanoscale systems to electric fields gives rise to a host of optical,mechanical,spectral,etc.properties that are of high theoretical and applied interest.Due to the computational difficulty of treating such large systems it is convenient to model them as infinite and periodic(at least,in first approximation).The fundamental theoretical/computational problem in doing so is that