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肝癌是最常见的人类恶性肿瘤之一.肝癌的发生是一个多因素交互作用逐级发生的过程.包括乙肝、丙肝病毒感染、酗酒、肝硬化等都可能导致肝癌.研究表明,胰岛素样生长因子 (IGF)系统由IGF1、IGF2及其受体(IGF1R、IGF2R)和胰岛素样生长因子结合蛋白(IGFBP)组成,在正常以及恶性肝细胞的增殖、分化和转移过程中起重要作用.本综述回顾近年来胰岛素样生长因子系统与肝癌发生发展的机理研究,及其在肝癌治疗中可能的临床应用前景的研究进展,并对目前该研究领域存在的主要问题和未来的研究展望提出了看法. 相似文献
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为研究胰岛素样生长因子 1(IGF1)及其突变体与IGF结合蛋白 3(IGFBP3)的相互作用 ,针对IGF1的第 3、4、15、16位氨基酸残基 ,采用定点突变的方法构建了 [Y15L16 ]IGF1和 [Q3A4Y15L16 ]IGF1。然后分别将IGF1/IGF1突变体和IGFBP3cDNA克隆至酵母表达载体pGBT9和pACT2中 ,利用酵母双杂交技术检测IGF1/IGF1突变体和IGFBP3之间的相互作用。结果表明用酵母双杂交系统检测IGF1与其结合蛋白的结合力是可行的 ,构建的这两个IGF1突变体与IGFBP3的结合力 ,与天然IGF1相比 ,结合力大大减小 相似文献
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目的观察姜黄素对阿尔茨海默病(Alzheimer'sdisease,AD)模型APP/PS1双转基因小鼠胰岛素受体(insulinreceptor,InR)和胰岛素样生长因子1受体(insulin·likegrowthfactor1receptor,IGF1R)表达的影响。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、阳性罗格列酮对照组(每日10ms/kg)、姜黄素大(每日400mg/kg)、中(每日200mg/kg)、小剂量组(100mg/kg),正常组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Westernblot方法进行检测。结果InR和IGF1R免疫组化染色,模型组小鼠大脑海马CA1区较正常对照组InR阳性细胞明显增加(P〈0.01),姜黄素干预组有所恢复;而模型组小鼠大脑海马CA1区较正常对照组IGF1R阳性细胞明显减少(P〈0.01),姜黄素干预组有所恢复。Western blot检测海马InR和IGF1R的蛋白表达结果与免疫组织化学检测结果一致。结论姜黄素可以使APP/PS1双转基因小鼠海马增加的InR和减少的IGF1R得以恢复,改善APP/PS1双转基因小鼠胰岛素信号转导。 相似文献
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IGF-Ⅰ及其受体、IGF结合蛋白-2和LH受体mRNA在卵泡中的表达 总被引:2,自引:0,他引:2
利用原位杂交和原位DNA-3’末端标记的方法研究了胰岛素样生长因子河(IG-I)、IGF-I受体、IGF结合蛋白-2、和促性腺激素受体的信使核糖核酸(mRNA)在不同生长与闭锁阶段的大鼠卵巢卵泡中表达的变化。结果表明:IGF-I主要在正常生长的初级卵泡、窦前卵泡和小窦状卵泡中表达。在各生长与成熟阶段的卵泡中都检测到IGF-I受体mRNA,闭锁卵泡的IGF-I受体表达降低。窦前与窦状的生长和闭锁卵泡均表达IGFBP-2。促卵泡激素(FSH)受体在窦前和小窦状卵泡的表达水平比其在大卵泡中的高。窦前与小窦状卵泡仅在膜细胞中表达黄体生成素(LH)受体mRNA,大卵泡的膜细胞与颗粒细胞均表达LH受体,在闭锁卵泡中仅在膜细胞中观察到LH受体的信号。综上结果,提示IGF-I,IGF-I受体和FSH受体在窦前和小窦状卵泡中的协同表达对卵泡的早期发育有重要作用。LH受体mRNA特异地在大卵泡的颗粒细胞中表达可能与优势卵泡选择相关。 相似文献
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胰岛素受体家族的结构与功能研究 总被引:2,自引:0,他引:2
胰岛素(insulin)与胰岛素样生长因子-1(IGF-1)分别是由胰岛β细胞和肝细胞分泌的 多肽类激素.它们通过结合并激活位于细胞膜上的受体酪氨酸激酶(RTKs),发挥重要的生理作用. 作为起始信号传导的第一步,胰岛素与IGF-1是如何与各自受体的膜外区域(ectodomain) 结合并进一步激活受体的细胞膜内酪氨酸激酶活性一直属于科学研究的关键基础问题.本文 概述了胰岛素受体家族(IR和IGF-1R)及其配体的结构与功能的特点和关系,并重点介绍 了近年来国内外在胰岛素受体家族复合体结构和功能上的研究手段和取得的突破性进展. 相似文献
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为了深入研究胰岛素和胰岛素样生长因子1(IGF-1)的起源和进化以及结构与功能的关系。表达了胰岛素和IGF-1的祖先分子--文昌鱼胰岛素样肽(ILP)。重组单链ILP的基因用化学方法合成(从cDNA推测的ILPB结构域的C端和A结构域的N端用Ala-Ala-Lys三肽连接起来,并钭B28Arg突变为Lys),克隆到表达载体pVT102-U中,ILP在酿酒酵母中得到有效表达。发酵液经4步分离纯化,得到均一的单链ILP,经质谱测定分子量和氨基酸组成分析证明表达产物正确。通过Lys-C蛋白内切酶处理将重组单链ILP转化成双链形式。虽然双链ILP与人胰岛素受体没有结合活力。但圆二色性光谱显示它与胰岛素的结构非常相似,用表达的单链ILP免疫新西兰大白兔,获得了高滴度的多克隆抗体。 相似文献
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类胰岛素生长因子信号途径及其对脊椎动物生长和发育的调控作用:以斑马鱼为模式动物的新进展 总被引:7,自引:0,他引:7
CunmingDUAN JunDING PeterJ.SCHLUETER YunLI JunbinZHANG TriciaL.ROYER 《动物学报》2003,49(4):421-431
类胰岛素生长因子(包括IGF-I和IGF-Ⅱ)是进化上保守性很强的多肽。IGFs对脊椎动物的生长和早期发育有极其重要的调控作用。IGF的生理作用是由IGF受体中介并受几个分泌性的IGF结合蛋白调节。本文主要介绍了以斑马鱼为模式动物,用基因敲除、转基因动物和培养细胞系等现代实验方法对IGF信号途径的最新研究进展,综述了IGF配体、受体和结合蛋白的结构特点、基因表达和调节和生物学功能。此外,也对斑马鱼作为模式动物的许多优点进行了探讨。 相似文献
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胰岛素样生长因子 I(IGF I)是一种多功能性的细胞营养因子 ,在中枢神经系统的发育过程中发挥着重要的作用。近年来 ,针对IGF I在中枢神经系统 (CNS)中的生物学作用开展了大量的研究。综述了利用IGF I及其所属蛋白家族部分成员的转基因动物模型研究它们在中枢神经系统中的分布和对中枢神经系统各组成部分生长发育的影响及其临床学上的应用。 相似文献
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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. 相似文献
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RICHARD E. NORRIS 《Botanical journal of the Linnean Society. Linnean Society of London》1991,106(1):1-40
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. 相似文献
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JOAN VALUÈS MONTSERRAT TORRELL NÚRIA GARCIA JACAS 《Botanical journal of the Linnean Society. Linnean Society of London》2001,137(4):399-407
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. 相似文献
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肝癌中HBV和HCV基因和抗原的分布及意义 总被引:1,自引:0,他引:1
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 相似文献
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H.-R. GREGORIUS 《Biological journal of the Linnean Society. Linnean Society of London》1984,23(2-3):157-165
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. 相似文献
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. 相似文献