用共聚焦显微镜研究plk1在秋水仙胺和长春新碱抗肿瘤效应中的作用

目的：研究plk1在秋水仙胺和长春新碱抗肿瘤效应中的作用。方法：采用Western blotting和共聚焦显微镜检测秋水仙胺、长春新碱及plk1 反义寡核苷酸（Asodn）处理对K562细胞plk1及γ微管蛋白表达的影响。结果：Western blotting 检测结果提示秋水仙胺和长春新碱不影响plk1和γ微管蛋白的表达量，但共聚焦显微镜观察发现秋水仙胺和长春新碱影响plk1在分裂期聚集和中心体形成。plk1 Asodn处理不仅可明显降低plk1蛋白表达，而且影响γ微管蛋白聚合形成中心体。结论:秋水仙胺和长春新碱抗肿瘤效应可能是通过plk1介导的抑制γ微管蛋白聚合形成中心体来实现的,plk1具有作为肿瘤治疗靶点的可能性。     

Polo样激酶1在大鼠心肌细胞分化过程中的表达

目的通过检测polo样激酶1(plk1)在大鼠生后不同发育阶段心肌组织中的表达,探讨心肌细胞退出细胞周期的相关机制。方法生后0d、3d、7d、10d、2周和成年健康Wistar大鼠各5只,采用针对横纹肌肌动蛋白和磷酸化组蛋白H3的免疫荧光双标方法,测定各组大鼠心肌细胞有丝分裂指数;用RT-PCR和免疫印迹技术,检测心肌组织plk1 mRNA和蛋白表达的改变。结果大鼠生后0d心肌细胞有丝分裂指数[(0.905±0.087)%]是生后2周[(0.372±0.094)%]的2.4倍(P<0.01);plk1基因和蛋白在大鼠生后表达明显下调,2周后未检测到表达。结论plk1基因的表达下调与大鼠心肌细胞增殖停滞密切相关,在大鼠心肌细胞退出细胞周期的调控机制中发挥重要作用。     

长链非编码RNA LOXL1-AS1在人类恶性肿瘤中的作用及其分子调控机制

长链非编码RNA(lncRNA)广泛参与生物体的各种生理与病理过程。lncRNA作为肿瘤致癌因子或抑癌因子参与恶性肿瘤的多种生物过程，与恶性肿瘤的发生、发展密切相关。赖氨酰氧化酶样蛋白1-反义RNA1(LOXL1-AS1)是近年来发现的一种lncRNA,其在多种恶性肿瘤中表达上调，并与肿瘤大小、TNM分期、淋巴结转移、患者预后等病理特征相关。LOXL1-AS1通过与多种微小RNA竞争性结合，调节下游靶基因的表达及调控相关信号通路发挥促癌作用。该文通过总结LOXL1-AS1参与多种人类恶性肿瘤的生物学过程，不同的分子调控机制影响肿瘤细胞增殖、转移、侵袭和凋亡等恶性生物学行为，探讨潜在的临床意义和应用前景，以期为恶性肿瘤的临床诊断、治疗和筛选预后标志物提供理论基础和参考依据。     

肝癌相关抗原HAg18-1ELISA诊断药盒对肿瘤病人血清学诊断的临床意义

本文报告用HAg18-1 ELISA诊断药盒测定肝细胞肝癌病人,胃、肠、肺、乳腺等多种恶性肿瘤病人血清及对肿瘤组织浸液的HAg18-1阳性率,其数值分别为80.0％～86.1％、44.2％～76.2％和62.0％。肝细胞肝癌的阳性率最高,在多种恶性肿瘤病人中广泛交叉存在、且血清阳性的6个病例手术探查肝脏正常。但HAg18-1在术后临床无病阶段的多种恶性肿瘤病人及非肿瘤对照者阳性率很低,分别为4.2％及7.5％。HAg18-1与肝细胞肝癌的关系,十分有助于肝细胞肝癌的诊断及治疗,其与肝细胞肝癌以外的多种恶性肿瘤关系,使其具备对这类肿瘤病人的随访监护治疗效应的价值。     

结直肠癌中MCL-1基因的研究进展

髓样细胞白血病-1(myeloid cell leukemia-1, MCL-1)广泛表达于人类正常组织中,在细胞分化和凋亡中起重要作用,主要功能是维持线粒体膜稳定,抑制细胞色素C释放,从而阻止凋亡发生,促进细胞生存。MCL-1在一些恶性肿瘤中高表达,促进肿瘤发生、发展并诱导肿瘤细胞对化疗药物产生抵抗作用。MCL-1在结直肠癌(colorectal cancer, CRC)中的表达高于正常肠黏膜和腺瘤组织,抑制肿瘤细胞凋亡和促进血管生成,并与CRC的预后和远处转移等相关。多种抗肿瘤药物通过调节MCL-1的表达,影响其疗效及耐药性。     

TRIB1的研究进展

TRIB1属于人类TRIB家族，是促分裂原活化蛋白激酶（mitogen·activatedproteinkinase，MAPK）途径级联控制的调节蛋白，在多种组织中表达，与骨髓恶性肿瘤、卵巢癌、动脉粥样硬化及组织移植密切相关。此文就TRIB1的起源、家族、结构、功能、参与的信号途径及相关疾病作一综述。     

Clusterin蛋白在乳腺癌中作用的研究进展

Clusterin是近年新发现的一种凋亡相关蛋白,在多种恶性肿瘤中上调表达,与多种恶性肿瘤的发生和进展有关.在人体细胞中有两种Clusterin的异构体.一种是核型,其功能是促凋亡,另一种是分泌型,其功能是促生存.研究结果表明在乳腺癌中,Clusterin在蛋白质和RNA水平上的表达与乳腺大小,雌激素受体,孕激素受体状态,以及从原发癌向淋巴结转移的进展有关,Clusterin可能在乳腺癌形成和进展中发挥作用.针对Clusterin的反义寡核苷酸治疗可以提高乳腺癌细胞对部分化疗药物的治疗敏感性,从而有望成为乳腺癌治疗的新靶点.     

TRIB1的研究进展

TRIB1属于人类TRIB家族,是促分裂原活化蛋白激酶(mitogen - activated protein kinase,MAPK)途径级联控制的调节蛋白,在多种组织中表达,与骨髓恶性肿瘤、卵巢癌、动脉粥样硬化及组织移植密切相关.此文就TRIB1的起源、家族、结构、功能、参与的信号途径及相关疾病作一综述.     

HE4在妇科盆腔恶性肿瘤中表达的意义研究进展

目的:探讨人附睾蛋白4(HE4)在妇科盆腔恶性肿瘤中的表达及临床意义.方法:查阅国内外相关文献,综合分析在妇科盆腔恶性肿瘤中,HE4的表达情况.结果:HE4在多种妇科盆腔恶性肿瘤中高表达,与众多肿瘤的发生发展密切相关.结论:作为新的妇科盆腔恶性肿瘤的标志物,HE4有着广阔的临床应用前景,其价值有待进一步深入研究.     

低氧诱导因子-1α在非小细胞肺癌中表达增强

低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)是由HIF-1α及HIF-1β两个亚基组成的异源性二聚体,近年来发现HIF-1α在多种恶性肿瘤中均表达,并与肿瘤的发生、发展、转移及预后等密切相关[1]。本研究检测了55例非小细胞肺癌的组织标本中HIF-1α和CD105的表达,探讨其与临床病理特征之间的关系。     

STK15的研究进展

丝氨酸/苏氨酸激酶15(serine/threon ine k inase15,STK15)是一类广泛存在于真核细胞中的丝氨酸/苏氨酸激酶,参与细胞的DNA合成后期/有丝分裂期转换(G2/M),通过微管晶核因子的募集促进中心体成熟及微管晶核形成,确保双极分裂纺锤体的生成及维持,保证染色体平均分配至2个子细胞。STK15在多种恶性肿瘤中存在过表达,导致中心体异常扩增、异倍体形成以及细胞恶性转化,并与肿瘤的生物学行为有关,阻断STK15表达可抑制肿瘤细胞的生长,STK15有望成为肿瘤治疗的又一候选靶点。     

In vivo tumor imaging using polo-box domain of polo-like kinase 1 targeted peptide

Polo-like kinase 1 (Plk1) is a regulator of cell cycle progression during mitosis; it is overexpressed in many different tumors and has been implicated as a potential antimitotic target. Plks are characterized by the presence of a highly conserved C-terminal polo-box domain (PBD) that is involved in regulating kinase activity. The phosphopeptide Pro-Leu-His-Ser-p-Thr (PLHSpT) is a potent selective inhibitor of the PBD of human plk1 that acts by inducing mitotic arrest and apoptotic cell death in cancer cells. We synthesized cRGDyK-S-S-CPLHSpT to exploit the drug delivery and molecular imaging using positron emission tomography (PET). The peptide was blocked dramatically proliferation of tumor in?vitro and in?vivo. It was attempted to develop and show a tumor PET image with the radiolabeled-peptide. Here we showed the peptide is promising not only as an anticancer drug, but also as a radioligand for tumor diagnosis with PET. We expect that our contribution will provide new insights into the design of Plk1 peptide inhibitors and have significant implications for anticancer therapy and tumor diagnosis.     

人细胞增殖相关激酶plk3基因逆转录病毒载体的构建及对细胞增殖的影响

目的构建人细胞增殖相关激酶基因plk3的逆转录病毒载体(RV),观察该基因对细胞增殖和细胞周期的影响。方法将plk3基因亚克隆至pMSCV-puroR载体中,经酶切和测序鉴定,制备高滴度的RV,以流动感染法高效感染,半固体集落培养法测定基因导入率。用嘌呤霉素筛选后,获得K562-plk3-puroR和HL60-plk3-puroR细胞。以野生型细胞和导入空载体的K562-puroR和HL60-puroR细胞作为对照,用PCR鉴定基因的导入,并测定细胞周期及凋亡率等,研究plk3基因导入对细胞的影响。结果获得pMSCV-plk3-puroR质粒并经酶切和测序证实。对K562和HL60细胞的基因导入率,分别达82.3%±3.70%和62.9%±4.94%(n=3)。经嘌呤霉素筛选后,转基因细胞的阳性率>99%。K562-plk3-pu-roR和HL-60-plk3-puroR转基因细胞的增殖曲线比对照细胞降低(P<0.01);而导入空载体的K562-puroR和HL60-puroR细胞的增殖曲线与野生型细胞相比较无显著差异。与K562细胞相比较,常规培养时,处于G0~G1期的K562-plk3-puroR细胞增多[(49.7±3.38)%vs(43.9±2.34)%,P=0.03]。以无血清培养基培养10h后,进入S期的K562-plk3-puroR细胞减少[(43.6±3.74)%vs(54.5±1.52)%,P=0.02],凋亡率降低[(1.3±0.31)%vs(3.4±0.37)%,P=0.01]。结论构建了plk3基因的逆转录病毒载体,发现plk3基因的导入可延缓细胞增殖,并抑制细胞进入增殖周期。     

Chromosome mechanisms and INI1 inactivation in human and mouse rhabdoid tumors

The human rhabdoid tumorigenesis orchestrated by INI1 inactivation is associated with specific rearrangements of chromosome 22 that correlate with preferential anatomic tumor locations. A literature review revealed significant correlations between an apparently normal karyotype and kidney tumors, monosomy 22 and cerebral tumors, and chromosome 22 translocations and tumors at other anatomic sites. In the mouse rhabdoid tumor model, specifically in the four tumors that we tested for loss of heterozygosity, neither partial deletion nor monosomy of chromosome 10 could be detected. In contrast to the human data, the only chromosome mechanism involved in the 18 mouse tumors studied appears to be a mitotic recombination or a nondisjunction-duplication. Additionally, and despite mouse tumor incidence across a variety of sites, no rhabdoid tumor could be observed in the mouse kidney. These data suggest that the chromosome mechanisms for INI1 inactivation and the selective cell survival pressure differ in human and mouse.     

Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded astrocytomas and compared with tumor grade and overall patient survival. Moreover, double immunofluorescence stainings were performed with LAMP-1 and the astrocytic marker GFAP and the putative stem cell marker CD133 on ten glioblastomas. Most tumors expressed the LAMP-1 protein in the cytoplasm of the tumor cells, while the blood vessels were positive in all tumors. The percentage of LAMP-1 positive tumor cells and staining intensities increased with tumor grade but variations in tumors of the same grade were also found. No association was found between LAMP-1 expression and patient overall survival in the individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem cells. Targeting of lysosomes may be a promising novel therapeutic strategy against this highly malignant neoplasm.     

Genetic mapping of a putative tumor suppressor locus that influences tumorigenesis and metastasis in mice

The tumor suppressor TP53 is mutated in approximately 70% of Li-Fraumeni syndrome (LFS) families; however, other genes may lead to the predisposition to tumors in other families. We developed a mouse model to search for other tumor suppressors that may be involved in the syndrome. Inbred CE/J mice, which succumb to multiple types of tumors similar to those found in LFS, were crossed with the Trp53-null 129-Trp53tm1Tyj mouse. We monitored the tumor onset and type and found a significant earlier tumor onset in the CE/J:129-Trp53tm1Tyj mice compared with 129-Trp53tm1Tyj mice with a Trp53-null allele. Additionally, in CE/J:129-Trp53tm1Tyj-Trp53+/- mice, the tumors metastasize, which does not occur in other strains of mice. Using simple-sequence length polymorphism analysis for loss of heterozygosity in tumors, we identified a putative tumor suppressor locus within 1 cM on mouse chromosome 11, which encompasses 12 mapped genes.     

Primary intracranial tumors as cause of death in the fetus and infant

Clinical and pathomorphological findings in 2 stillborn and 15 lifeborn children with primary intracranial tumors are reported. All infants died within the first year of life and the tumors were confirmed histologically. In 6 children the tumors (3 intracranial teratomas, 1 glioblastoma, 1 hemangioblastoma, 1 choroid plexus papilloma) were present at birth. All 6 were born with pathologically enlarged heads. Another child exhibited symptoms of brain tumor at the age of three weeks. The tumor was probably present at birth as well. In the remaining infants the signs and symptoms of tumor development became evident some months after birth. These tumors might have occurred postnatally. In a girl aged 9 months, a nephroblastoma of the right kidney and a malignant cerebral tumor, probably a glioma, were present. An incidental coexistence of both tumors is considered, however, a common etiology cannot be excluded. 8 of the 17 intracranial tumors were supratentorially situated. This supports the view that the proportion of supratentorial tumors is higher in early life than in older children.