肝母细胞瘤组织RECK及膜型基质金属蛋白酶-1的表达及与肿瘤转移抑制关系的探讨

目的:探讨RECK蛋白、膜型基质金属蛋白酶-1(MT1-MMP)在肝母细胞瘤组织中的表达及其在肿瘤转移抑制中的作用。方法:采用第二代通用型二步法监测系统(PV-6000)免疫组织化学方法检测35例肝母细胞瘤组织和15例正常肝脏组织及10例肝脏良性肿瘤组织中RECK、MT1-MMP的表达情况。结果:肝母细胞瘤组织RECK的表达水平明显降低(28.6%);MT1-MMP肝母细胞瘤组织中高表达(54.3%),并随着肿瘤浸润深度的加深、远处转移的发生而增高(p<0.05);二者表达呈负相关(p<0.05)。结论:RECK和MT1-MMP在肝母细胞瘤组织中的表达呈负相关;RECK和MT1-MMP在肝母细胞瘤的进展中起重要作用。     

miR-96通过RECK促进结直肠癌细胞的迁移和侵袭

目的:研究miRNA-96在结直肠癌转移中的作用及其机制。方法:采用Transwell试验分析结直肠癌Lo Vo细胞的迁移和侵袭能力,采用荧光素报告基因及蛋白免疫印迹试验研究结直肠癌中miR-96的作用靶点。结果:miR-96抑制剂处理后下调miR-96的表达并抑制Lo Vo细胞的迁移和侵袭。荧光素报告基因试验显示RECK是miR-96的作用靶点,且RECK沉默能够部分阻碍miR-96抑制剂所导致的Lo Vo细胞迁移和侵袭减少。结论:miRNA-96可通过作用于RECK促进结直肠癌细胞转移,这可能成为治疗结直肠癌转移的新靶点。     

PTEN:抑制肿瘤侵袭及转移的新靶点

侵袭与转移是恶性肿瘤的主要生物学特征之一,并影响肿瘤的疗效及预后.其主要通过肿瘤细胞与血管内皮细胞以及细胞基质之间的相互作用,穿透血管内皮细胞、降解细胞外基质,从而向局部及远处转移.多种信号转导分子参与了肿瘤的侵袭、转移过程.PTEN基因表达的蛋白具有蛋白磷酸酶及脂质磷酸酶双重活性,其作为抑癌基因通过对细胞内多种信号转导通路的调控,参与维持细胞的正常生理活动;负调控肿瘤细胞的生长、细胞周期;诱导肿瘤细胞凋亡;抑制肿瘤细胞的侵袭、浸润及转移.本文就PTEN如何参与抑制肿瘤细胞侵袭及转移做一综述.     

RECK及MMP-9蛋白在皮肤鳞状细胞癌中的表达及临床病理意义（英文）

目的：观察RECK基因及基质金属蛋白酶-9（MMP-9）在皮肤鳞状细胞癌（CSCC）中的表达,探讨其与肿瘤浸润转移的关系。方法：应用免疫组化SP法检测40例CSCC组织、17例癌旁不典型增生组织及14例正常皮肤组织中RECK及MMP-9蛋白的表达。结果：①RECK在CSCC、癌旁不典型增生及正常皮肤中的表达率依次增高（30.0%、47.1%、85.7%）,组间比较差异有统计学意义（P＆lt;0.05）;MMP-9蛋白在CSCC、癌旁不典型增生及正常皮肤中的表达率依次降低（82.5%、76.4%、28.6%）,组间比较差异有统计学意义（P＆lt;0.05）②RECK及MMP-9与CSCC的组织学分级、淋巴结转移密切相关（P均＆lt;0.05）;与CSCC患者的性别、年龄无关（P均＆gt;0.05）③RECK及MMP-9在CSCC中的表达呈负相关（r=-0.475p＆lt;0.01）。结论：RECK和MMP-9与CSCC的浸润转移密切相关,RECK在CSCC中表达减少或缺失可能是通过上调MMP-9的表达从而促进CSCC的侵袭与转移。     

肿瘤酸性微环境的研究进展

研究表明,肿瘤转移是恶性肿瘤的临床治疗失败的根本原因。肿瘤转移不仅取决于肿瘤细胞自身的特性,还涉及其与肿瘤酸性微环境之间的相互作用。肿瘤微环境构成非常复杂,可促进肿瘤的增生、转移、侵袭,以及逃避宿主免疫监视和治疗耐药性。肿瘤细胞的生存依赖于在酸性微环境条件下的适应,肿瘤细胞可以通过一些离子交换体维持酸性微环境,缺氧的肿瘤组织酸化可以释放蛋白酶如纤维蛋白酶及MMPs降解细胞外基质、上调VEGF基因表达促进肿瘤新生血管生成等促进肿瘤侵袭转移。近年来,影响肿瘤微环境的因素已经成为癌症研究领域中的新兴话题。     

nm23-H1调控肿瘤侵袭转移分子机制研究进展

侵袭转移是恶性肿瘤的重要生物学特征,也是导致肿瘤患者治疗失败和死亡的主要原因。研究表明,nm23基因家族与肿瘤的发生、发展及转移密切相关。其中,nm23-H1是被发现的第一个人类nm23基因,与肿瘤侵袭转移关系极为密切。现将nm23-H1基因调控肿瘤侵袭转移分子机制的研究进展作一综述。     

肿瘤转移基因研究进展

肿瘤转移和侵袭的分子调控机制是当前肿瘤分子生物学研究的前沿。肿瘤转移基因ｍｔｓｌ的发现对转移机理的研究具有重要意义。     

上皮间质转化在肿瘤侵袭转移中的研究进展

上皮-间质转化（epithelial-mesenchymal transitions,EMT）是上皮细胞向间质细胞转化的现象,不仅参与胚胎发育和正常生理,还参与许多病理过程。同样EMT也参与肿瘤的发生与发展,尤其在促进肿瘤侵袭转移中发挥着重要作用。研究表明,肿瘤细胞借助EMT方式增强肿瘤细胞迁移和运动能力,促进肿瘤的侵袭与转移。在肿瘤侵袭转移历程中,关于EMT发生的分子调控机制研究已取得了良好的进展,但其详细机制仍然不是十分清楚。本文主要介绍生长因子、转录因子、miRNAs、甲基化及其他调控因子在肿瘤EMT中的调控功能,进一步综述EMT在肿瘤侵袭转移中的作用。     

趋化因子CXCL12及其受体CXCR4与肿瘤的关系

趋化因子是一组具有趋化作用的细胞因子,最近研究发现趋化因子CXCL12及其受体CXCR4与多种肿瘤的侵袭和转移密切相关,该文就CXCL12及CXCR4的生物学特性、在肿瘤侵袭及淋巴结转移中的作用特征及作用机制等方面进行综述,从而为肿瘤转移防治提供依据。     

TRIM29在肿瘤中的研究进展

TRIM29蛋白属于TRIM蛋白家族,是一种E3泛素连接酶,它在肿瘤的增殖、侵袭转移、耐药及肿瘤免疫中都具有十分重要的作用,且其功能具有细胞和组织特异性.TRIM29蛋白可通过与p53的相互作用促进肿瘤细胞的增殖;通过促进肿瘤细胞上皮-间质转化、激活经典的Wnt信号通路等增强肿瘤细胞的侵袭转移能力.高表达的TRIM29...     

On the origin of the Hirudinea and the demise of the Oligochaeta

The phylogenetic relationships of the Clitellata were investigated with a data set of published and new complete 18S rRNA gene sequences of 51 species representing 41 families. Sequences were aligned on the basis of a secondary structure model and analysed with maximum parsimony and maximum likelihood. In contrast to the latter method, parsimony did not recover the monophyly of Clitellata. However, a close scrutiny of the data suggested a spurious attraction between some polychaetes and clitellates. As a rule, molecular trees are closely aligned with morphology-based phylogenies. Acanthobdellida and Euhirudinea were reconciled in their traditional Hirudinea clade and were included in the Oligochaeta with the Branchiobdellida via the Lumbriculidae as a possible link between the two assemblages. While the 18S gene yielded a meaningful historical signal for determining relationships within clitellates, the exact position of Hirudinea and Branchiobdellida within oligochaetes remained unresolved. The lack of phylogenetic signal is interpreted as evidence for a rapid radiation of these taxa. The placement of Clitellata within the Polychaeta remained unresolved. The biological reality of polytomies within annelids is suggested and supports the hypothesis of an extremely ancient radiation of polychaetes and emergence of clitellates.     

On the ontogeny of the haptor and the evolution of the Monogenea

Data on the ontogeny of the posterior haptor of monogeneans were obtained from more than 150 publications and summarised. These data were plotted into diagrams showing evolutionary capacity levels based on the theory of a progressive evolution of marginal hooks, anchors and other attachment components of the posterior haptor in the Monogenea (Malmberg, 1986). 5 + 5 unhinged marginal hooks are assumed to be the most primitive monogenean haptoral condition. Thus the diagrams were founded on a 5 + 5 unhinged marginal hook evolutionary capacity level, and the evolutionary capacity levels of anchors and other haptoral attachement components were arranged according to haptoral ontogenetical sequences. In the final plotting diagram data on hosts, type of spermatozoa, oncomiracidial ciliation, sensilla pattern and protonephridial systems were also included. In this way a number of correlations were revealed. Thus, for example, the number of 5 + 5 marginal hooks correlates with the most primitive monogenean type of spermatozoon and with few sensillae, many ciliated cells and a simple protonephridial system in the oncomiracidium. On the basis of the reviewed data it is concluded that the ancient monogeneans with 5 + 5 unhinged marginal hooks were divided into two main lines, one retaining unhinged marginal hooks and the other evolving hinged marginal hooks. Both main lines have recent representatives at different marginal hook evolutionary capacity levels, i.e. monogeneans retaining a haptor with only marginal hooks. For the main line with hinged marginal hooks the name Articulon-choinea n. subclass is proposed. Members with 8 + 8 hinged marginal hooks only are here called Proanchorea n. superord. Monogeneans with unhinged marginal hooks only are here called Ananchorea n. superord. and three new families are erected for its recent members: Anonchohapteridae n. fam., Acolpentronidae n. fam. and Anacanthoridae n. fam. (with 7 + 7, 8 + 8 and 9 + 9 unhinged marginal hooks, respectively). Except for the families of Articulonchoinea (e.g. Acanthocotylidae, Gyrodactylidae, Tetraonchoididae) Bychowsky's (1957) division of the Monogenea into the Oligonchoinea and Polyonchoinea fits the proposed scheme, i.e. monogeneans with unhinged marginal hooks form one old group, the Oligonchoinea, which have 5 + 5 unhinged marginal hooks, and the other group form the Polyonchoinea, which (with the exception of the Hexabothriidae) has a greater number (7 + 7, 8 + 8 or 9 + 9) of unhinged marginal hooks. It is proposed that both these names, Oligonchoinea (sensu mihi) and Polyonchoinea (sensu mihi), will be retained on one side and Articulonchoinea placed on the other side, which reflects the early monogenean evolution. Except for the members of Ananchorea [Polyonchoinea], all members of the Oligonchoinea and Polyonchoinea have anchors, which imply that they are further evolved, i.e. have passed the 5 + 5 marginal hook evolutionary capacity level (Malmberg, 1986). There are two main types of anchors in the Monogenea: haptoral anchors, with anlages appearing in the haptor, and peduncular anchors, with anlages in the peduncle. There are two types of haptoral anchors: peripheral haptoral anchors, ontogenetically the oldest, and central haptoral anchors. Peduncular anchors, in turn, are ontogenetically younger than peripheral haptoral anchors. There may be two pairs of peduncular anchors: medial peduncular anchors, ontogentically the oldest, and lateral peduncular anchors. Only peduncular (not haptoral) anchors have anchor bars. Monogeneans with haptoral anchors are here called Mediohaptanchorea n. superord. and Laterohaptanchorea n. superord. or haptanchoreans. All oligonchoineans and the oldest polyonchoineans are haptanchoreans. Certain members of Calceostomatidae [Polyonchoinea] are the only monogeneans with both (peripheral) haptoral and peduncular anchors (one pair). These monogeneans are here called Mixanchorea n. superord. Polyonchoineans with peduncular anchors and unhinged marginal hooks are here called the Pedunculanchorea n. superord. The most primitive pedunculanchoreans have only one pair of peduncular anchors with an anchor bar, while the most advanced have both medial and lateral peduncular anchors; each pair having an anchor bar. Certain families of the Articulonchoinea, the Anchorea n. superord., also have peduncular anchors (parallel evolution): only one family, the Sundanonchidae n. fam., has both medial and lateral peduncular anchors, each anchor pair with an anchor bar. Evolutionary lines from different monogenean evolutionary capacity levels are discussed and a new system of classification for the Monogenea is proposed.In agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. EditorIn agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. Editor