核仁素表达下调对阿霉素所致乳腺癌细胞增殖抑制和凋亡的影响

乳腺癌是女性最常见的恶性肿瘤,我国的乳腺癌发病率呈急剧上升的趋势.核仁素是真核生物核仁中最主要的一种磷酸蛋白质,具有多种生物学功能,包括调控核糖体的合成与成熟,调控细胞的增殖、生长、胚胎发生、胞质分裂、染色体复制和核仁发生等过程.我们探讨了下调核仁素表达对乳腺癌细胞增殖抑制和凋亡的影响,现将结果报告如下.     

c-Myc在肿瘤中的表达及功能

原癌蛋白c-Myc在多种组织和细胞中均有表达,其功能的异常与淋巴瘤、前列腺癌、乳腺癌、胰腺癌等多种肿瘤的发生和预后密切相关.随着对c-Myc在肿瘤中的表达及功能研究的不断深入,通过靶向c-Myc治疗肿瘤取得了较大进展.     

促红细胞生成素及其受体在肿瘤发生发展中的作用

研究发现,促红细胞生成素(EPO)及EPO受体(EPOR)在多种恶性肿瘤组织中表达,且EPO能促进肿瘤微血管形成,刺激肿瘤细胞增殖,抑制凋亡,还调节肿瘤细胞对放化疔治疗的敏感性.另有研究表明,EPO的应用不利于肿瘤的控制和预后.EPO对肿瘤患者的疾病进展和生存期的影响仍需进一步研究.     

核仁素在胃癌组织芯片中的表达及其意义

目的:探讨核仁素在胃癌组织的表达及其临床意义。方法:采用组织芯片检测胃癌、癌旁良性组织及正常组织中核仁素及细胞核增殖抗原Ki-67的表达。分析胃癌与非癌组织中核仁素的表达定量和定位的差异,统计学分析其与临床病例参数之间的关系及与Ki-67蛋白表达的相关性。结果:胃癌组织和非癌组织中均有核仁素及Ki-67阳性表达于细胞核,但核仁素在胃癌组织的部分细胞的胞膜和/或胞质中亦有阳性表达。核仁素和Ki-67蛋白在胃癌组织阳性表达率明显高于癌旁良性组织及正常组织(P<0.01)。两者在癌旁良性组织及正常组织中的表达无统计学差异。核仁素蛋白在胃癌组织中的表达与肿瘤分化程度、临床病理分期有关(P<0.05)。核仁素与Ki-67的蛋白表达呈显著正相关(P<0.05,r=0.292)。结论:胃癌组织中核仁素的表达增高,检测核仁素的表达可作为临床判断胃癌恶性程度及预后的重要参考指标。     

微RNA与肿瘤

微RNA（miRNA）是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

微RNA与肿瘤

微RNA(miRNA)是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

微RNA与肿瘤

微RNA(miRNA)是一类非编码的小RNA分子,通过直接抑制基因转录或蛋白质的表达而在器官发育,细胞增殖、分化和凋亡等多种生理过程中发挥关键作用.miRNA异常表达往往导致包括肿瘤在内的多种疾病.研究发现,miRNA在肿瘤发生发展、侵袭转移及肿瘤的诊治中起着重要作用.     

Survivin与恶性肿瘤生物学行为的关系

生存素(Survivin)与多种恶性肿瘤关系密切,研究Survivin在肿瘤中表达及作用机制,在寻找新的肿瘤标记物、判断预后、探讨并逆转肿瘤恶性生物学行为等方面都取得了显著成果.     

中介素与肿瘤

中介素可通过多种信号通路促进肿瘤血管生成,并受肿瘤细胞缺氧影响表达增加.近年来,国内外出现多项中介素与肿瘤发生、发展、侵袭之间相互关系及作用机制的研究,有望为肿瘤治疗提供新靶点.     

肾上腺髓质素与肺癌关系的研究进展

目的:总结国内外对肾上腺髓质素与肺癌的研究进展.方法:应用PubMed及CHKD期刊全文数据库,以"肽、肾上腺髓质素、肺、肿瘤"等为关键词,检索1993-01-2009-09相关文献40篇.纳入标准:1)肾上腺髓质素在肺部肿瘤中的表达.2)肾上腺髓质素对肺部肿瘤细胞的作用.3)肾上腺髓质素对血管生成的影响.4)肾上腺髓质素的作用机制研究.根据纳入标准符合分析的文献21篇.结果:肾上腺髓质素(ADM)在多种肿瘤组织和肿瘤细胞中表达,肺癌细胞是ADM的重要靶细胞.ADM通过诱导c-fos、c-jun和egr-1等不同早期反应基因、癌基因和与癌周细胞交互作用而调控肺癌细胞的活动.缺氧是肿瘤生长微环境的基本特征之一,缺氧通过缺氧诱导因子-1(HIF-1)调控肺癌细胞ADM的表达.ADM受体抗体AMRs能够抑制肺肿瘤血管生成和肿瘤的生长.结论:ADM可能参与肺癌的发生、发展,阻断ADM的作用通路可部分或全部阻断ADM对肿瘤的作用,ADM有可能成为肺癌治疗新的靶点.     

Nucleolin antisense oligodeoxynucleotides induce apoptosis and may be used as a potential drug for nasopharyngeal carcinoma therapy

Nucleolin (C23, NCL) mRNA was up-regulated in nasopharyngeal carcinoma (NPC) cells compared to that of normal nasomucosal (NNM) cells using a cDNA microarray approach. The level of nucleolin protein was also up-regulated in 13 NPC cell lines, 30 biopsy specimens and nine other cancer cell lines compared to five NNM cells or normal stromal cells, which were analyzed using immunoblotting or immunohistochemistry. We transfected nucleolin antisense oligodeoxynucleotides (phosphorothioate-modified oligodeoxynucleotides; S-ODNs) into NPC-TW01 cells to knockdown nucleolin expression to evaluate the function of nucleolin in cancer cells. Nucleolin knockdown induced NPC cells but not NNM cells to undergo apoptosis. Furthermore, treatment of NPC-TW01 xenograft tumors with nucleolin antisense oligodeoxynucleotides suppressed the growth of xenograft tumors without obvious side effects. Therefore, we suggest that nucleolin may be a potential cancer therapeutic target and that nucleolin antisense oligodeoxynucleotides may be used as a potential drug for therapy in NPC.     

Nucleolin inhibits Hdm2 by multiple pathways leading to p53 stabilization

Nucleolin is a c-Myc-induced gene product with defined roles in ribosomal RNA processing and the inhibition of chromosomal DNA replication following stress. Here we find that changes in nucleolin protein levels in unstressed cells cause parallel changes in the amount of p53 protein. Alterations in p53 levels arise from nucleolin binding to the p53 antagonist Hdm2, resulting in the inhibition of both p53 ubiquitination and Hdm2 auto-ubiquitination. Nucleolin does not alter p53 ubiquitination by human papillomavirus E6, indicating that the effect is specific for Hdm2. Although the inhibition of ligase activity would be expected to stabilize Hdm2, we instead find that nucleolin also reduces Hdm2 protein levels, demonstrating that nucleolin inhibits Hdm2 using multiple mechanisms. Increases in nucleolin levels in unstressed cells led to higher expression of p21(cip1/waf1), a reduced rate of cellular proliferation, and an increase in apoptosis. Thus, nucleolin has a number of properties in common with the tumor suppressor ARF (alternate reading frame). We propose that nucleolin, like ARF, responds to hyperproliferative signals by upregulation of p53 through Hdm2 inhibition.     

Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori

TNF-α-inducing protein (Tipα) is a unique carcinogenic factor of Helicobacter pylori, which is secreted into culture broth. The biological activities of Tipα and deletion mutant were studied. Tipα protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-α and chemokine gene expressions are induced by NF-κB activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between Tipα and cell-surface nucleolin causes a cancer-oriented microenvironment that increases the risk of gastric cancer. This paper discusses a new mechanism of gastric cancer development with H. pylori and provides a new preventive strategy.     

2008年版"世界卫生组织造血及淋巴组织肿瘤分类"指要

 2008年第4版"世界卫生组织造血及淋巴组织肿瘤分类"把该类肿瘤分列为12个项目,对分子生物学进展结合较多,基因、染色体改变均加入分类中。慢性骨髓增生性疾病改为骨髓增生性肿瘤,并将肥大细胞增多症（mastocytosis）归于此栏中。新增了伴有嗜酸细胞增多的髓系及淋巴细胞系恶性肿瘤及异常的PDDFRA、PDDFRB或FGFR1基因一栏。在骨髓增生异常综合征／骨髓增生性肿瘤（MDS／MPN）一栏中增加了伴环形铁粒幼细胞再生障碍性贫血并显著的血小板增多（RARS-T）（可能为一单独性疾病）。在骨髓增生异常综合征（MDS）一栏中分为一系或多系增生异常伴有一系或多系血细胞减少,并增添了儿童MDS。在急性髓系白血病及其有关前体细胞恶性肿瘤中,把髓系肉瘤（myeloid sarcoma）单独分类;新增加了唐氏综合征（Down syndrome）伴有的髓系增生疾病;新增加了母细胞性浆细胞样树突细胞肿瘤（blastic plasmacytoid dendretic cell neoplasm）。把系列不明的白血病（acute leukemia of ambiguous lineage）单列为一个项目,含6种白血病。在前体淋巴系肿瘤中分为B系及T系,淋巴母细胞性白血病／淋巴母细胞性淋巴瘤,其区别点在于骨髓中淋巴母细胞＞25 %,则诊断为淋巴细胞白血病[和急性髓系白血病（AML）不同,不设下限为20 %]。成熟B淋巴细胞系肿瘤分为39种,包括慢性淋巴细胞白血病、骨髓瘤、重链病、Burkitt淋巴瘤等,但不包括移植后淋巴细胞增生性疾病（PTLD）。成熟T淋巴细胞系和NK细胞系肿瘤栏目下列举了22种成熟T淋巴细胞系和NK细胞系恶性肿瘤。霍奇金淋巴瘤栏目下列举了6种霍奇金淋巴瘤。组织细胞和树突状细胞恶性肿瘤包括7种恶性肿瘤及播散性幼年型黄肉芽肿。移植后淋巴细胞增生性疾病（PTLD）被单独分类在一个栏目中,又分为５种类型。     

Quantitation of differences between spontaneous and induced liver tumors in mice with an automated image analyzer

Spontaneous hepatocellular neoplasms of B6C3F1 mice (basophilic neoplasms) as well as those induced with the herbicide Nitrofen (eosinophilic neoplasms) were observed with an image analyzing computer to determine if quantifiable morphologic differences existed between them. Several morphologic parameters were measured on 5 liver sections from each of the following groups: (a) unexposed control liver; (b) non-trabecular basophilic neoplasms; (c) trabecular basophilic neoplasms; (d) small well circumscribed eosinophilic neoplasms; and large irregular eosinophilic neoplasms without (e) and with (f) pulmonary metastases. The total number of hepatocytes per unit area was significantly smaller in the eosinophilic neoplasms than in the basophilic neoplasms or the controls. This was the result of a greatly increased cell cross-sectional area in the eosinophilic neoplasms, caused predominantly by a larger cytoplasmic cross-sectional area. Nuclear cytoplasmic ratios of cells in eosinophilic neoplasms were lower than in the other groups for this reason. This demonstrates that quantitative morphologic differences exist between the spontaneous and induced neoplasms, which supports the conclusion that Nitrofen is a true carcinogen, and not a promoting agent.     

微小RNA与肿瘤

近年来微小RNA（miRNA）逐渐成为肿瘤研究的热点。越来越多的研究表明,miRNA已涉及到肿瘤的发生和发展,miRNA的表达与肿瘤的病理进程具有相关性,大约有数百个miRNA在肿瘤中异常表达,miRNA在不同肿瘤中具有时空特异性的表达谱。     

微小RNA与肿瘤

近年来微小RNA(miRNA)逐渐成为肿瘤研究的热点.越来越多的研究表明,miRNA已涉及到肿瘤的发生和发展,miRNA的表达与肿瘤的病理进程具有相关性,大约有数百个miRNA在肿瘤中异常表达,miRNA在不同肿瘤中具有时空特异性的表达谱.     

胃泌素和微小RNA与大肠癌的发生发展

已证实某些大肠癌中胃泌素能高表达并通过其受体介导的信号转导通路促进细胞增殖且抑制凋亡。微小RNA（miRNA）参与大肠癌相关基因表达调控,研究表明miRNA在大肠癌中的调控网络与胃泌素促大肠癌增殖信号通路存在多个交叉点,提示在胃泌素促大肠癌细胞增殖过程中可能存在一类新的胃泌素-miRNA信号通路,有望为大肠癌的诊断和分子靶向治疗寻找到一个新的切人途径。