癌基因和抑癌基因研究进展

癌基因和抑癌基因的发现和研究是肿瘤研究史上的一个里程碑,标志着肿瘤研究进入了分子时代,从而在更深层次上为阐明基因的结构、表达、调控、功能的改变与肿瘤形成的关系提供了科学依据和可能性,具有重要的理论和实际意义。本文概述了癌基因和抑癌基因的最新研究进展。     

骨肉瘤相关基因的研究

骨肉瘤为最常见的恶性骨肿瘤,多发于10-25岁青少年,恶性程度高,复发率,转移率,死亡率高。虽然骨肉瘤化学治疗的开展明显提高了骨肉瘤患者的生存率,但效果并不很令人满意。近些年来,随着分子生物学、分子遗传学的发展,人们已经越来越多的认识到,骨肉瘤的发生、发展及预后往往涉及多个基因的改变,包括致癌基因的表达及活化,抑癌基因的丢失及失活。本文通过查询近年大量国内外关于骨肉瘤癌基因方面的文献,分析与骨肉瘤发生、发展及预后密切相关的致癌基因及抑癌基因。希望通过对这些基因深入的探讨,为骨肉瘤的治疗寻找新的方向及新的潜在的治疗新靶点奠定理论基础。     

肿瘤发生的遗传机理

本文从癌基因和抑癌基因两方面综述了肿瘤发生的遗传机理 ,旨在使人们培养“防重于治”的健康理念。     

MicroRNA-17-92与肿瘤

microRNA是一类在生物体中广泛表达的、非编码调节性小分子RNA(约22～24nt).它们一经问世,即被发现参与多种疾病的发生.miR-17-92及其旁系同源序列就是其中之一,它们已被证实在肺、心脏及免疫系统的正常发育及肿瘤形成中均起到重要作用.本文从miR-17-92及其旁系同源序列在不同肿瘤组织中的表达及其在肿瘤发生中的分子机制,对这一基因簇与肿瘤发生的关系进行综述.     

肿瘤发生的遗传机理

本从癌基因和抑癌基因两方面综述了肿瘤发生的遗传机理,旨在使人们培养“防重于治”的健康理念。     

喉癌的比较基因组杂交研究

寻找与喉癌发生进展的相关基因,应用比较基因组杂交技术分析了18例喉癌患者。结果显示,每例喉癌细胞染色体均有不同程度的变化,包括染色体全部或部分的扩增或丢失。平均每例有12．9处异常区域,丢失多于扩增,分别为每例7．2处和5．7处。主要为3q(78％,)、5p(61％)、11q(56％)、1q(50％,)、8p(44％)、8q(39％)和15q(39％)的扩增;3p(70％)、5q(78％)、90(67%)、13q(50％)、1p(44％)和14q(39％)的丢失。有多条染色体区带上出现特异的扩增或丢失,特别是1p13-21(8／18)、3p21-23(14／18)、5p21-22(14／18)、9p12-pter(10／18)和13q21-31(8／18)的拷贝数增加明显,而1q11-2l(11／18)、3q15-21(12／18)、8p22-24(6／18)、11q12-13(8／18)、15q21-23(7／18)和18p11(8／18)区域的丢失为喉癌的特征性变化,说明这些区域中存在与喉癌发生发展密切相关的癌基因、抑癌基因或其他相关基因。     

SAS癌基因的发现和研究进展

ＳＡＳ癌基因最初是从恶性纤维组织细胞瘤中分离出来的，最近已得到克隆并定位于１２ｑ１３－１４，并发现其在人的一些软组织肉瘤中明显扩增，且与肿瘤的生长及转移有关，其编码的蛋白质为ＴＭ４ＳＦ家族的一员，可能具有细胞信号传导的作用，但其具体的作用机制尚有待进一步探讨。     

与肿瘤转移有关的基因的研究进展

与肿瘤转移有关的基因的研究进展姚旻,周信达（上海医科大学肝癌研究所,上海２０００３２）关键词癌基因,抑癌基因,肿瘤转移相关基因肿瘤转移过程复杂,包括①肿瘤细胞通过表面受体和细胞外基质发生特异性粘附;②肿瘤细胞本身或局部微生态系统（ｍｉｃｒｏｅｃｏｓｙ...     

蛋白激酶Cα过表达导致正常人胚肺成纤维细胞生长失调的研究

采用自行构建的过表达ＰＫＣα亚类的正常人胚肺细胞模型,观察到细胞生长加速,血清依赖性明显下降,细胞形态发生变化,单层培养丧失接触抑制性,出现岛状生长,与对照组细胞相比,贴壁依赖性下降,在软琼脂中能形成小集落,细胞中微丝发生部分解聚,进一步检测观察到细胞中与转化密切相关的ｒａｓ癌基因表达明显增强,抑癌基因ｐ５３表达下降。首次表明在正常人胚肺细胞中ＰＫＣα的过表达直接导致细胞增殖加速,并可诱导出现部分     

BRCA1、PTEN、Rb、C-myc和C-myb在乳腺癌中的异常表达及临床意义探讨

目的 探讨BRCA1、PTEN、Rb、C-myc、C-myb蛋白异常表达在乳腺癌发生、发展中的作用及其临床意义.方法应用免疫组织化学S-P法检测150例乳腺癌、20例不典型增生和30例良性增生性病变组织中BRCA1、PTEN、Rb、C-myc、C-myb蛋白的表达;结合临床病理指标进行分析.结果 乳腺癌组织和不典型增生组织中 BRCA1、PTEN、Rb、C-myc、C-myb蛋白表达与良性增生性病变组织中表达均具有显著性差异(P<0.05).BRCA1蛋白失表达率随乳腺癌组织学分级的增高而增高,在年龄<50岁和ER(雌激素受体)阴性时BRCA1蛋白失表达率增高.PTEN蛋白的失表达与淋巴结转移、ER失表达有关(P<0.05).Rb蛋白在乳腺癌Ⅲ级中失表达率较高,但无统计学差异(P＞0.05).C-myc蛋白的过表达与组织学分级、淋巴结转移及病理类型有关(P<0.05).C-myb蛋白的过表达与乳腺癌组织学分级有关(P<0.05).结论 BRCA1、PTEN、Rb、C-myc、C-myb蛋白异常表达均在乳腺癌的发生过程中起作用;PTEN、C-myc、C-myb 蛋白的异常表达参与了乳腺癌的浸润和转移.     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Phylogenetic definitions and taxonomic philosophy

An examination of the post-Darwinian history of biological taxonomy reveals an implicit assumption that the definitions of taxon names consist of lists of organismal traits. That assumption represents a failure to grant the concept of evolution a central role in taxonomy, and it causes conflicts between traditional methods of defining taxon names and evolutionary concepts of taxa. Phylogenetic definitions of taxon names (de Queiroz and Gauthier 1990) grant the concept of common ancestry a central role in the definitions of taxon names and thus constitute an important step in the development of phylogenetic taxonomy. By treating phylogenetic relationships rather than organismal traits as necessary and sufficient properties, phylogenetic definitions remove conflicts between the definitions of taxon names and evolutionary concepts of taxa. The general method of definition represented by phylogenetic definitions of clade names can be applied to the names of other kinds of composite wholes, including populations and biological species. That the names of individuals (composite wholes) can be defined in terms of necessary and sufficient properties provides the foundation for a synthesis of seemingly incompatible positions held by contemporary individualists and essentialists concerning the nature of taxa and the definitions of taxon names.     

Chronological Events Associated with the Antagonistic Properties of Trichoderma harzianum against Botrytis cinerea: Indirect Evidence for Sequential Role of Antibiosis and Parasitism

Chronological events associated with the degradation of Botrytis cinerea by a strain of Trichoderma harzianum selected for superior biocontrol ability were studied using ultrastructure and cytochemical investigations in an attempt to define the relative roles of antibiosis and parasitism in the antagonistic process. The first ultrastructural changes were observed 12 h before contact between the organisms, and were characterized by punctuated invaginations of the Botrytis plasmalemma. These reactions were followed by a gradual retraction of the plasmalemma, disorganization of the cytoplasm, loss of turgor pressure and cell death within 48 h of contact between hyphae of the interacting fungi. The first evidence of penetration of B. cinerea by T. harzianum was recorded 72 h after contact. This penetration was apparently mediated by either mechanical pressure or localized wall digestion at points of entry, as there was no clear evidence of chitinolytic degradation of the B. cinerea cell wall, as determined by cytochemical labelling of chitin with a lectin-gold conjugate. However, after 10 days there was clear indication of chitin degradation, based on the random and reduced presence of gold particles over the cell wall of B. cinerea. These results suggest that the strain of T. harzianum antagonized first and foremost by antibiosis, leading to cell death, followed by degradation of the cell by means of chitinolytic enzymes. The production of antibiotics may, therefore, be more important than that of chitinolytic enzymes in conferring superior biocontrol properties to T. harzianum.     

From the creation of the Veterinary Schools to the evolution of the notion of contagion in the 19th and 20th centuries

The creation of the Veterinary Schools in the 18th century would reveal a plethora of scientists, some of whom would be the precursors of Pasteur, some rivals, others followers collaborators or friends of the Master. Among the precursors let us name Chabbert, Huzard, Girard, Delafond, Renault, Toussaint, Galtier ; among the rivals: Chauveau, Arloing, Cornevin and Thomas; among the followers, collaborators or friends of Pasteur: Bouley, at first a resolute spontaneist, then the most fervent in defense of Pasteur (President of the Academy of Medicine and of the Academy of Sciences) and Nocard, Director of the School in Alfort, an important collaborator of Pasteur. Later, there was Leclainche, who created the International Office of Epizootics, and who was President of the Academy of Sciences; Guérin, who with Calmette developed the BCG vaccination; Ramon, the father of anatoxins (vaccines against diphtheria, and tetanus, combined vaccines, adjuvants to immunity). Thus, the creation of the Veterinary Schools contributed not only to the evolution of the notion of contagion, to the amelioration of animal health and the economics of agricultural production, but also to serious advances in human care, and to the protection of public health.     

Evolution of pupation site and interspecific competitive ability in Drosophila hydei

A competition experiment conducted over a period of 50 weeks resulted in stable coexistence of Drosophila hydei and D. melanogaster. In a repeat of this experiment the results for the first 25 weeks were similar to the results of the earlier experiment, but after this time the state of coexistence collapsed and a fairly rapid trend towards competitive exclusion was observed. Extinctions of D. melanogaster occurred in 11 of the 12 experimental cages before termination of the experiment at 50 weeks. At about the same time as the competitive ability of D. hydei increased, an alteration in the range of pupation sites utilized by this species was noted. The change in pupation site was demonstrated to be at least partially heritable, and it appears to be responsible for D. hydei's increased competitive ability. This experiment provides an example of natural selection within a competing population acting against the stability of the overall two-species system.     

Chromatic adaptation in a mutant of Fremyella diplosiphon incapable of phycoerythrin synthesis

A mutant of the chromatically adapting cyanobacterium Fremyella diplosiphon, incapable of phycoerythrin synthesis but responding to wavelength modulation of its biliprotein content, was isolated. The biliprotein composition of the mutant and of the wild type were identical after growth in red light, but green light induced, in the mutant, the synthesis of a biliviolin-type chromophore bound to some of the alpha subunits of its phycocyanin. Implications of the results on the regulation and possible pathways of biliprotein biosynthesis are discussed.     

Crystallographic orientations of structural elements in skeletons of Syringoporicae (tabulate corals,Carboniferous): implications for biomineralization processes in Palaeozoic corals

The crystallographic orientation of structural elements in skeletons of representatives of Carboniferous Syringoporicae (Auloporida) has been analysed by scanning electron microscopy (SEM), petrographic microscopy and electron backscatter diffraction (EBSD) on specimens from the Iberian Peninsula. The skeletons of the tabulate corals of the Syringoporicae consist of biogenic calcite crystals, and their microstructure is composed of lamellae, fibres and granules, or of a combination of these. Independent of the microstructure, the c‐axis is oriented towards the lumen, quasi‐perpendicular to the growth direction of the skeleton (perpendicular to the morphological axis lamellae, parallel to fibres). Most phaceloid taxa have a turbostratic distribution, as a biogenic response to prevent the cleavage of crystals. Cerioid and some phaceloid corals, whose microstructure is conditioned by wall elements, do not exhibit turbostratic distribution. Wall elements are determined by the biology of each taxon. Holacanth septal spines are composed of fibres arranged in a cone‐shape structure, sometimes clamped to the external part of the corallite and show a complex crystallography. Monacanth septal spines are spindle shaped and composed of bundles of fibres. Tabulae are composed of lamellae. Their development and crystallographic orientation depends on the position of the epithelium in each case. Shared walls are formed by a combination of the walls of two independent corallites with a median lamina, composed of granules; these have a crystallographic orientation between that of the two corallites. The growth of the microstructure is derived by a coordinated stepping mode of growth, similar to other groups of organisms such as molluscs and scleractinians. The nucleation and formation of packages of co‐oriented microcrystals suggest a growth mode similar to mineral bridges with a competitive growth mode between each crystal. The growth pattern of corallites suggests that the growth direction is divided into two main components: a horizontal growth direction towards the lumen and a vertical direction towards the top.     

Échinodermes de l'Ordovicien supérieur (Ashgill) de Sardaigne et d'Algérie

Research on the influence of sea level variations on the benthic faunas have been carried out in the Upper Ordovician of Sardinia. Study of the depositional facies and sequence analysis of the upper part (Lower Ashgill) of the Portixeddu Formation led to the identification of the sedimentary environments. Cystoids and crinoids are associated to bryozoans and brachiopods in most levels. The numerical analysis of associations and megaguilds shows that crinoids and cystoids have a higher frequency in the proximal and median facies of the upper offshore. The columnal association characterized by Conspectocrinus celticus and the coronoid Mespilocystites tregarvanicus has been discovered in the upper part of the formation. This material and complementary samples from Upper Ordovician of Sardinia and Kabylia (Algeria) bring additional data on the systematic and show the wide distribution of this fauna outside of the Ibero-armorican domain. The distribution of this echinoderm association supports a palaeogeographical position of the Ibero-armorican domain and Sardinia within the north gondwanan margin during the Lower Palaeozoic.     

Morphology of the regiones ethmoidalis and orbitotemporalis in Galea musteloides Meyen 1832 and Kerodon rupestris (Wied-Neuwied 1820) (Rodentia: Caviidae) with comments on the phylogenetic systematics of the Caviidae

The present study describes the fetal regions ethmoidalis and orbitotemporalis of the cranium of Galea musteloides and Kerodon rupestris and compares them with Galea spixii and Cavia porcellus . The fetal crania of these representatives of the Caviinae were serially sectioned and 3D plate reconstructions were built. For a broader scope, serially sectioned heads of the caviomorph taxa Hydrochaeris hydrochaeris and Dasyprocta leporina were also examined. The ethmoidal and orbitotemporal regions of the cranium provides characters that are pertinent to the discussion of systematics of the Caviinae. Nine cranial characters were identified as being significant and discussed phylogenetically. Taking the monophyly of the Cavioidea as given, two characters are autapomorphic for the genus Galea: the reduction of the crista semicircularis and the lacrimale forming the 'arco antorbitario' (Kraglievich 1930). Cavia is the sister group of Galea; synapomorphic characters are the extent of the processus palatinus medialis of the praemaxillare and the presence lamina pterygoidea of the alisphenoid. There were no apomorphic characters of the structural complexes examined that could support the Caviinae. The reduced and nonperforated alisphenoid is an autapomorphic feature of the Caviidae. The division of the nasoturbinale is evidence for a sistergroup relationship of the Hydrochaeridae and the Caviidae. Autapomorphic characters for the Cavioidea include the ventrolateral opening of the organon vomeronasale and the lateral prolongation of the lacrimale.     

Le passage vers l’Atlantique : le processus de néolithisation en Algarve (sud du Portugal)

The late beginning of the research on the neolithisation in the Algarve (southern Portugal) has been providing, as a paradox, excellent conditions for the establishment of interdisciplinary research and the test of working hypotheses. The systematic projects put forward by the University of Algarve permit us today to conclude on a preliminary basis for the formation of a Neolithic enclave at ca. 5500 cal BC, centred in the coastal territories of the region. This enclave is fully Neolithic in economic terms and it is the westernmost extension of the Mediterranean Cardial. However, some specific features of these first Neolithic groups’ artefactual items (such as pottery morphology and style and some technological aspects of chipped stone production) indicate the existence of phenomena of partial reformulation of their material cultures. According to the presently available data, this complex process seems to have occurred in similar traits also in Andalucia and coastal Morocco, that is, at the moment of the passage to the Atlantic. This individualization within the Neolithic of Cardial tradition is the equivalent to the same general cultural phenomena that have been responsible for the formation, for example, of the so-called “Franco-Iberian Cardial” or “Tirrenic Cardial” at the time of settling of the Neolithic groups in these regions.