凋亡素诱导的肿瘤细胞凋亡

细胞凋亡是机体维持自身稳定的一种基本生理机制 ,并贯穿于整个生命活动。细胞凋亡异常可导致一些疾病的发生 ,如肿瘤的发生。同时 ,细胞凋亡的可诱导性也为肿瘤治疗提供了新的思路。凋亡素是来源于鸡贫血病毒的一个小分子蛋白。它能够选择性地诱导肿瘤细胞的凋亡 ,而对正常二倍体的细胞无任何毒副作用 ,并且正常细胞对凋亡素具有耐受性。凋亡素诱导肿瘤细胞凋亡既不需要依赖 p53 ,也不会被bcl-2的过表达所抑制。凋亡素还能诱导人成骨肉瘤细胞多药耐药株 R-OS-73 2的细胞凋亡。这些特点使凋亡素成为一种新型的候选抗肿瘤制剂。     

端粒酶催化亚基启动子介导的靶向性肿瘤基因治疗的研究进展

近年来,端粒酶是肿瘤研究领域的热点之一,是一种核糖核酸蛋白体复合物,在绝大多数恶性肿瘤细胞中呈阳性表达,而在正常体细胞中则一般为阴性。端粒酶的活性主要是受人端粒酶催化亚单位基因的转录调控,而人端粒酶催化亚单位基因的转录主要受其启动子的调控。因此,人端粒酶催化亚单位启动子介导的使抗肿瘤基因在肿瘤细胞内靶向表达的基因治疗是肿瘤基因治疗的热点。本文对此进行了综述,旨在为肿瘤的基因治疗提供新思路。     

“肿瘤消”诱导肿瘤细胞凋亡的作用研究

研究“肿瘤消”的抗肿瘤活性和作用,为临床用药提供依据。通过 MTT 法检测“肿瘤消”对多种肿瘤细胞株和正常细胞存活率的影响;采用 Hoechst 染色法和 DNA 片段化分析对“肿瘤消”诱导 MDCC-MSBl 细胞凋亡的作用进行检测;Western blot 检测“肿瘤消”诱导 MDCC-MSBl 细胞凋亡相关蛋白因子表达情况。MTT 法检测结果显示,“肿瘤消”对 MDCC-MSBl、C6、SP2／0和 A549细胞的增殖具有明显抑制作用,对293A 细胞增殖无显著影响;Hoechst 染色和 DNA 片段化分析均证实“肿瘤消”能诱导 MDCC-MSBl细胞凋亡;Western blot 检测发现“肿瘤消”诱导 MDCC-MSBl 细胞凋亡与凋亡因子 caspase 3、caspase 8和caspase 9的活化有关。证实“肿瘤消”具有诱导肿瘤细胞凋亡的作用。     

中药诱导肿瘤细胞凋亡机制研究进展

中药及其生物活性成分具有毒副作用小、无残留、药理作用独特等特点,在抗肿瘤研究方面,已经成为抗肿瘤药物或其辅助药物,目前研究的热点是中药治疗肿瘤作用机制的研究。论文从单味中药及其有效成分、中药复方诱导肿瘤细胞凋亡机制等方面对中药诱导细胞凋亡在肿瘤的发生、发展和转归中所起的作用进行了综述。中药可以诱导肿瘤细胞凋亡,其可能的作用机制是通过调控原癌基因和抑癌基因的表达、影响细胞凋亡通路的信号传导及阻滞肿瘤细胞增殖周期等抑制肿瘤细胞的永生化。     

大蒜素诱导肿瘤细胞凋亡研究进展

近年来许多体外研究表明大蒜素能够诱导包括白血病、肝癌、卵巢癌、胃癌等多种肿瘤细胞的凋亡,并取得了很好的效果,其诱导肿瘤细胞凋亡的途径可能是通过影响细胞生长周期、相关凋亡基因、caspase蛋白表达、细胞端粒酶活性等方式来实现的。大蒜素作为大蒜的主要活性成分,其抗癌效果备受人们的关注。大蒜素诱导肿瘤细胞凋亡是一个比较复杂的生物学过程,论文对大蒜等诱导肿瘤细胞凋亡的作用机制进行了综述。     

血小板凝血酶蛋白1对犬乳腺肿瘤细胞体外生物学特性的影响分析

本研究旨在深入探讨血小板凝血酶蛋白1(THBS1)对犬乳腺肿瘤细胞CHMp的影响,并阐明其影响犬乳腺肿瘤发生发展的作用机制。通过构建THBS1慢病毒稳定过表达和THBS1沉默表达的犬乳腺肿瘤细胞CHMp细胞系,采用CCK-8试验、划痕试验、Transwell试验、原位荧光检测和流式细胞术检测THBS1对CHMp细胞增殖、迁移、侵袭、细胞凋亡和细胞周期情况的影响;通过qRT-PCR和Western blot检测THBS1对CHMp细胞凋亡相关因子(p53、Bcl-2、Bax)表达情况的影响,验证THBS1对CHMp细胞凋亡通路的影响。结果显示,过表达THBS1能有效增强犬乳腺肿瘤细胞CHMp的增殖、迁移和侵袭能力,并且减少CHMp细胞的凋亡数量,而沉默THBS1后结果与之相反;流式细胞术得出THBS1能够影响CHMp细胞的细胞周期分布;经qRT-PCR和Western blot检测发现,在THBS1过表达后,p53和Bcl-2的表达量均明显增高,Bax的表达量明显减少,在沉默THBS1后结果与之相反。结果表明,THBS1的异常表达能够影响犬乳腺肿瘤细胞CHMp的增殖、迁移、侵袭以及细胞周期;此外,THBS1能够通过影响细胞凋亡因子p53、Bcl-2和Bax的表达来影响CHMp细胞凋亡相关通路,进而影响犬乳腺肿瘤的发生发展。     

端粒酶与肿瘤相关性研究进展

端粒是一段存在于真核细胞染色体末端,随着细胞分裂而缩短的特殊结构。端粒酶可延长端粒,但在正常人体细胞内活性较低或无活性。大多数肿瘤细胞通过激活端粒酶活性,延伸端粒达到细胞无限增殖的可能。端粒酶的活性与肿瘤的发生密切相关。本文以近年来临床常见的恶性肿瘤为出发点,综述了其与端粒酶活性关系及端粒酶抑制剂的最新研究。     

中药抑制肿瘤细胞端粒酶活性的研究进展

肿瘤严重威胁着人类健康,近年来癌症患者不断增多且死亡率逐年上升。中药以其安全性高、价格低、毒副作用小等优点成为抗肿瘤的首选药物。研究证实,肿瘤细胞与端粒酶之间存在相互激发的关系,肿瘤细胞缺乏端粒酶调节机制,一旦端粒酶活性被激活,肿瘤细胞将会有无限增殖的能力。因此,抑制肿瘤细胞端粒酶活性可作为治疗肿瘤的方法之一。文章将从中药的几种有效成分及复方中药对肿瘤细胞端粒酶活性的抑制作用作一综述,探讨中药抑制肿瘤细胞端粒酶活性的研究进展及其应用前景。     

马立克病肿瘤组织内HSP60表达及生物学作用初步研究

本试验旨在研究HSP60与马立克病肿瘤发生、发展之间的相关性。通过人工感染,建立鸡马立克病肿瘤模型,定期剖杀,利用病理组织学和免疫组织化学方法,检测HSP60与肿瘤细胞定位之间的相关性;设计HSP60 RNA干扰序列,构建重组慢病毒,转染MSB-1细胞,利用流式细胞技术,探索降低HSP60转录表达对MSB-1细胞凋亡水平的影响。结果显示：HSP60在肿瘤细胞的细胞质内强表达;成功构建了HSP60 RNA干扰慢病毒,且5147序列干扰效果最佳;5147序列慢病毒转染48 h时,与对照序列组和空白对照组相比,HSP60转录、表达水平极显著降低（P<0.01）,MSB-1细胞凋亡水平极显著升高（P<0.01）。在马立克病肿瘤发生、发展过程中,HSP60组织细胞定位与肿瘤细胞具有明显的相关性,降低HSP60表达水平能够导致MSB-1细胞凋亡升高,说明HSP60对肿瘤细胞的存活具有重要的生物学作用。     

肿瘤坏死因子诱导凋亡配体TRAIL的研究进展

肿瘤坏死因子诱导凋亡配体TRAIL作为肿瘤坏死因子超家族成员之一,其能和死亡受体相结合从而选择性诱导肿瘤细胞凋亡,却不会影响正常细胞,其正逐渐成为临床上新型抗肿瘤制剂。本文从肿瘤坏死因子诱导凋亡配体TRAIL何受体诱导凋亡机制入手,探讨其在临床方面的应用。     

Inhibition of telomerase in canine cancer cells following telomestatin treatment

Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase‐based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase‐positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 μM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase‐positive cancer cells. These effects were not seen in telomerase‐negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase‐based therapies.     

Measurement of telomerase activity in dog tumors

Telomeres are specific structures present at the end of liner chromosomes. DNA polymerase can not synthesize the end of liner DNA and, as a result, the telomeres become progressively shortened by successive cell divisions. To overcome the end replication problem, telomerase adds new telomeric sequences to the end of chromosomal DNA. The enzyme activity is undetectable in most normal human adult somatic cells, in which shortening of the telomere is thought to limit the somatic-cell life span. In contrast to normal somatic cells, many human tumors possess telomerase activity. The present study looked at whether telomerase activity might serve as a marker for canine tumors. Telomerase activity was measured using the telomeric repeat amplification protocol assay. Normal dog somatic tissues showed little or no telomerase activity, while normal testis exhibited a high level of telomerase activity. We measured telomerase activity in tumor samples from 45 dogs; 21 mammary gland tumors, 16 tumors developed in the skin and oral cavity, 7 vascular tumors and 1 Sertoli cell tumor. Greater than 95% of the tumor samples contained telomerase activity (3-924 U/2 micrograms protein). The results obtained in this study indicated that telomerase should be a useful diagnostic marker for a variety of dog tumors, and it may serve as a target for antitumor chemotherapy.     

端粒酶的活性及其调控机制

端粒酶由RNA模板、调节蛋白和催化亚等组成，对端粒细胞的稳定起着重要作用。本文介绍端粒酶的结构，端粒酶与体细胞，细胞衰老及肿瘤分子等之间的生物学意义，以及端粒酶的基因表达与转录，分子之间的相互作用等分子调控机制。     

Induction of telomerase activity in avian lymphoblastoid cell line transformed by Marek's disease virus, MDCC-MSB1

Telomerase has been studied extensively in human and murine tumors, but little is known about the role of telomerase in the tumor biology of other vertebrate species such as the chicken. We studied the telomerase activity of the lymphoblastoid cell line derived from lymphomas induced by Marek's disease virus (MDCC-MSB1) compared with another avian cell line (PA5) and peripheral blood lymphocytes (PBL) using the telomeric repeat amplification protocol (TRAP) Assay. Telomerase activity in MDCC-MSB1 was 4.5 times greater than in the PA5 cell line and normal avian lymphocytes. These results demonstrate for the first time that telomerase is more intense in one transformed cell line than in normal cells, suggesting a potential role for telomerase in carcinogenesis induced by an avian virus.     

端粒酶活性抑制研究进展

端粒酶是一种核糖蛋白,包括端粒酶RNA、端粒酶相关蛋白和端粒酶催化亚基三个主要组成部分,端粒和端粒酶具有特殊结构和功能,是近年来分子生物学研究的热点。端粒酶在85%～95%的恶性肿瘤中呈阳性,而正常体细胞则呈阴性,因此是一类潜在的高选择性的抗肿瘤药物,抑制剂的开发研究为恶性肿瘤的早期诊断,预后估计和基因治疗开辟了新的道路。     

Bovine herpesvirus type 1 (BHV-1) up-regulates telomerase activity in MDBK cells

The proliferative capacity of mammalian cells is regulated by telomerase, an enzyme uniquely specialised for telomeric DNA synthesis. The critical role of telomerase activation in tumor progression and maintenance has been well established in studies of cancer and of oncogenic transformation in cell culture. Experimental data suggest that telomerase activation has an important role in normal somatic cells, and that failure to activate sufficient telomerase also promotes disease. Evidence regarding the role of telomerase in the pathogenesis of several viruses including human immunodeficiency virus has led to an increased interest in the role of telomerase activity in other virus infections. In this research we evaluated the telomerase modulating activity of Bovine herpesvirus 1 (BHV-1) in MDBK cells. MDBK cells were infected at different multiplicity of infection with BHV-1 Cooper strain and telomerase activity at different times post-infection was measured by the TRAP assay. Our data indicate that BHV-1 significantly up-regulates telomerase activity at 3 and 6h post-infection decreasing after the 24h post-infection. Our data, showed that the effect was mediated by an immediate-early or early viral gene, and use of the protein translation inhibitor cycloheximide confirmed that an immediate early gene is primarily responsible.