RhoE促进胃癌转移及其分子机制

摘要：目的 探讨RhoE对胃癌转移的影响及可能的机制。方法 Western Blot(WB)和免疫组织化学检测RhoE蛋白在胃癌组织中的表达;WB,半定量PCR检测RhoE 蛋白和mRNA在转移潜能不同的胃癌细胞系中的表达;利用RhoE的正义表达载体稳定转染胃癌细胞系SGC7901,通过迁移实验、侵袭实验检测其对胃癌细胞体外迁移、侵袭能力的影响。WB检测改变胃癌细胞中RhoE表达后基质金属蛋白酶（MMP）表达变化。结果 RhoE蛋白在胃癌组织和细胞系中的表达与胃癌转移相关联;上调RhoE表达能促进胃癌细胞的体外迁移能力和侵袭能力MMP9表达也随之上调。结论 本实验率先证实RhoE能够促进胃癌转移,这一作用可能是通过上调MMP9实现的。     

应用基因表达谱芯片研究人肺鳞癌相关基因

应用基因表达谱芯片检测人肺鳞癌与正常肺组织间差异表达基因,并对其进行初步分析。提取5例人肺鳞组织及其癌旁正常肺组织的RNA,混合后分别逆转录合成标记有荧光分子的cDNA探针,与联合基因BiostarH-1×1型基因芯片杂交。计算机分析扫描芯片荧光信号图像,比较两种组织中差异表达基因,对筛选的肿瘤相关基因进行初步分析。结果:两种组织间存在大量差异表达基因,其中113条基因在肺癌组织中较正常肺组织表达上调,112条基因在肺癌组织中较正常肺组织表达下调。分析这些差异表达基因发现,肺鳞组织及其癌旁正常肺组织的基因表达谱差异主要集中在原癌基因和抑癌基因、免疫相关基因、代谢相关基因、蛋白翻译合成相关基因、细胞信号和传递蛋白、细胞凋亡相关基因等方面;而在细胞周期蛋白、细胞骨架和运动、细胞受体、DNA合成和修复及结合和转录等方面则关联甚少。说明基因芯片在筛选疾病相关基因的改变时,具有快速、高效、高灵敏度等特点,人肺鳞癌基因差异表达谱的分析为阐明肺癌的发病分子机制提供了新线索。     

鄂西北食管癌高发区食管癌患者头发中微量元素的测定和比较研究

鄂西北食管癌高发区食管癌患者头发中微量元素的测定和比较研究龙际银,汪福意,卢汉兵,赵兰华,屈永年,冯安华（１）同济医科大学郧阳医学院２）华中师范大学分析测试中心３）丹江口市第一人民医院）关键词头发,微量元素,食管瘤,ＩＣＰ－ＡＥＳ中国分类号Ｏ５６７·...     

顺铂与丝裂霉素对体外人胃癌细胞的影响

进行了顺铂(DDP)、丝裂霉素(MMC)合用对人胃癌细胞影响的实验研究.用MTT法观察其对体外培养的人胃癌细胞SGC7901,在DDP与MMC合并用药前后对细胞存活率的影响,并通过流式细胞仪检测细胞周期变化,透射电镜观察细胞超微结构变化.DDP与MMC合用与单独应用化疗药相比细胞存活率明显下降,其增效倍数为单独用药的2.52～4.36倍(P＜0.01),细胞生长停止在S期,S期数分数为0.49,抑制细胞有丝分裂及DNA合成,细胞超微结构显示细胞核固缩、空泡形成、微绒毛减少、线粒体及内质网肿胀.结果显示,顺铂与小剂量化疗药物合用,可获得化疗药物单独用药相同疗效,丝裂霉素增加化疗药对肿瘤细胞的细胞毒作用,增加敏感性,减少药物副作用.     

前列腺穿刺活检术的研究进展

前列腺癌(Prostate Cancer, PCa)是一种对中老年男性危害巨大的恶性疾病。近年来,前列腺癌在我国的发病率及死亡率显著升高。以往,系统性6针穿刺活检法是临床上应用最多的前列腺癌诊断方法,但此方法并不能明显提高前列腺癌的检出率。随着影像学技术如单光子计算机断层扫描(ECT)、多排螺旋CT (MDCT)、经直肠超声(TRUS)和多参数磁共振成像(mpMRI)等技术的发展,以及多种融合技术在实际操作中的应用,前列腺穿刺变得精准化、可视化,病理诊断阳性率有所提高,同时穿刺针数减少,并发症的发生降低。本文就近年来前列腺穿刺活检术的新进展进行综述。     

女贞子-黄芪治疗转移性去势抵抗性前列腺癌的网络药理学机制

本研究利用数据挖掘和网络药理学探讨女贞子(Ligustrum lucidum)-黄芪(Astragalus membranaceus)治疗转移性去势抵抗性前列腺癌(Metastatic Castration-Resistant Prostate Cancer,mCRPC)的作用机制。利用中药系统药理学(Traditional Chinese Medicine Systems Pharmacology,TCMSP) 数据库与分析平台检索女贞子-黄芪的有效成分和作用靶点;利用R语言对芯片数据集GSE77930进行分析,筛选差异表达的基因;利用Cytoscape 3.8.0软件构建有效成分-靶点网络及蛋白互作网络;利用R语言对核心靶点进行GO富集分析和KEGG分析;采用Cytoscape 3.8.0软件构建女贞子-黄芪活性成分-靶点通路关系网络。结果表明女贞子-黄芪的关键活性成分共33个,包括槲皮素(Quercetin)、山奈酚(Kaempferol)、木犀草素(Luteolin)、异鼠李素(Isorhamnetin)、芒柄花黄素(Formononetin)等;核心作用靶点18个,其中AR、VCAM1、PCNA、NTRK1、TP53、EGFR和FBXO6等靶点可能是女贞子-黄芪治疗mCRPC的重要靶点。KEGG分析发现,女贞子-黄芪主要通过乙型肝炎(Hepatitis B)、前列腺癌(Prostate Cancer,PCa)、细胞周期(Cell cycle)、Vascular Endothelial Growth Factor (VEGF)信号通路(VEGF signaling pathway)和细胞衰老(Cellular senescence)等通路发挥抗mCRPC的作用。本研究结果可为mCRPC的临床治疗提供参考。     

妊娠相关性鼻咽癌预后研究进展

妊娠相关性鼻咽癌(Pregnancy-Associated Nasopharyngeal Cancer, PANPC)是一种更为罕见的、特殊类型的鼻咽癌(Nasopharyngeal Cancer, NPC),其治疗模式通常参照非妊娠相关的成人鼻咽癌治疗指南。妊娠期间体内代谢状态复杂,常规治疗模式下,妊娠相关性鼻咽癌患者的预后是否有别于非妊娠相关性鼻咽癌患者,其治疗策略是否应有所不同,目前关于妊娠相关性鼻咽癌患者预后的研究报道不多且结论不一,本文就此作归纳总结,以供临床参考。     

中医药与肿瘤免疫治疗

中医理论认为阴阳失衡、正虚邪盛是肿瘤发生发展的关键原因。调整阴阳、扶正祛邪是肿瘤治疗的重点。中医强调通过调整阴阳、扶助正气达到阴平阳秘、正气充足的机体平衡状态,从而实现控制肿瘤生长、改善患者临床症状、提高患者生活质量等目的。这与现代医学肿瘤免疫治疗时,通过打破免疫耐受、逆转免疫逃逸从而重建机体正常免疫功能、增强抗肿瘤能力的基本治疗思路契合一致,两者具有异曲同工之妙。中医的调整阴阳、扶正抗癌思想对肿瘤免疫治疗具有重要的指导意义。中医药扶正抗癌的疗效机制可能主要与肿瘤免疫相关。     

Epigenetic mechanisms in the context of complex diseases

Complex diseases arise from a combination of heritable and environmental factors. The contribution made by environmental factors may be mediated through epigenetics. Epigenetics is the study of changes in gene expression that occur without a change in DNA sequence and are meiotically or mitotically heritable. Such changes in gene expression are achieved through the methylation of DNA, the post-translational modifications of histone proteins, and RNA-based silencing. Epigenetics has been implicated in complex diseases such as cancer, schizophrenia, bipolar disorder, autism and systemic lupus erythematosus. The prevalence and severity of these diseases may be influenced by factors that affect the epigenotype, such as ageing, folate status, in vitro fertilization and our ancestors’ lifestyles. Although our understanding of the role played by epigenetics in complex diseases remains in its infancy, it has already led to the development of novel diagnostic methods and treatments, which augurs well for its future health benefits. Received 6 December 2006; received after revision 29 January 2007; accepted 15 March 2007     

Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis

The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G₀/G₁ phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin. Received 14 February 2007; received after revision 26 March 2007; accepted 3 April 2007