Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.     

A human colon cancer cell capable of initiating tumour growth in immunodeficient mice

Colon cancer is one of the best-understood neoplasms from a genetic perspective, yet it remains the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. What has yet to be established is whether every colon cancer cell possesses the potential to initiate and sustain tumour growth, or whether the tumour is hierarchically organized so that only a subset of cells--cancer stem cells--possess such potential. Here we use renal capsule transplantation in immunodeficient NOD/SCID mice to identify a human colon cancer-initiating cell (CC-IC). Purification experiments established that all CC-ICs were CD133+; the CD133- cells that comprised the majority of the tumour were unable to initiate tumour growth. We calculated by limiting dilution analysis that there was one CC-IC in 5.7 x 10(4) unfractionated tumour cells, whereas there was one CC-IC in 262 CD133+ cells, representing >200-fold enrichment. CC-ICs within the CD133+ population were able to maintain themselves as well as differentiate and re-establish tumour heterogeneity upon serial transplantation. The identification of colon cancer stem cells that are distinct from the bulk tumour cells provides strong support for the hierarchical organization of human colon cancer, and their existence suggests that for therapeutic strategies to be effective, they must target the cancer stem cells.     

Ti-M分子筛合成及其性能研究

 以高硅丝光沸石(M分子筛),TiO₂粉和HClO₄为原料,水热晶化法合成Ti-M分子筛.运用FT-IR和UV-vis光谱技术表征合成的Ti-M分子筛样品的物化特性,证明了钛原子进入了M分子筛的骨架位,推测出骨架钛在Ti-M分子筛中的确存在.选择环已酮氨氧化为探针反应,考察了Ti-M对此反应的催化活性,结果表明Ti-M分子筛对环已酮氨氧化具有较好的催化性能.     

直肠灌水后CT增强显像在直肠癌诊断中的应用价值

目的探讨直肠灌水后CT增强显像在直肠癌诊断中的应用价值。方法选择临床高度怀疑直肠癌的病例46例,先用生理盐水进行直肠灌注后,再行盆腔的CT增强扫描,利用三维重建技术对直肠病变进行诊断,并将所得结果与肠镜活检病理或术后病理结果对照,以判断直肠灌水后CT增强显像对直肠癌诊断的准确率,以及评估直肠肿块局部浸润情况与术后病理的符合率。结果46例病例中,CT增强显像阳性为43例,阴性为3例。其中CT显像病变侵犯肌层,但未突破浆膜层25例;突破浆膜层10例;周围组织侵犯8例;病理确诊为直肠癌有42例。CT增强显像假阴性1例,假阳性2例,CT增强融合显像对直肠癌诊断的准确性为93.48%,局部侵犯的符合率为98%。结论直肠灌注后CT增强融合显像在直肠癌的诊断及判断肿瘤局部侵犯情况中具有重要的临床价值。     

Nucleostemin siRNA对结肠癌细胞株HT-29细胞凋亡的影响

利用RNA干扰技术沉默结肠癌细胞株HT-29细胞中Nucleostemin(NS)基因的表达,并分析其对HT-29细胞凋亡的影响,进一步利用半定量RT-PCR和Western blotting技术检测细胞凋亡相关基因caspase-3/9 mRNAs和蛋白的表达.结果表明,NS基因的沉默能明显提高caspase-3/9的活性(P0.05),并诱导细胞发生凋亡,此外,HT-29细胞中NS基因沉默后,caspase-3/9mRNAs和蛋白的表达均明显升高,提示NS基因沉默介导的细胞凋亡与caspase-3/9基因表达的升高密切相关.     

直肠灌水后CT增强显像在直肠癌诊断中的应用价值

目的 探讨直肠灌水后CT增强显像在直肠癌诊断中的应用价值.方法 选择临床高度怀疑直肠癌的病例46例,先用生理盐水进行直肠灌注后,再行盆腔的CT增强扫描,利用三维重建技术对直肠病变进行诊断,并将所得结果与肠镜活检病理或术后病理结果对照,以判断直肠灌水后CT增强显像对直肠癌诊断的准确率,以及评估直肠肿块局部浸润情况与术后病理的符合率.结果 46例病例中,CT增强显像阳性为43例,阴性为3例.其中CT显像病变侵犯肌层,但未突破浆膜层25例;突破浆膜层10例;周围组织侵犯8例;病理确诊为直肠癌有42例.CT增强显像假阴性1例,假阳性2例,CT增强融合显像对直肠癌诊断的准确性为93.48%,局部侵犯的符合率为98%.结论 直肠灌注后CT增强融合显像在直肠癌的诊断及判断肿瘤局部侵犯情况中具有重要的临床价值.     

分子自组装技术及表征方法

自组装单分子膜的研究是近年来倍受关注的研究领域。随着膜的应用领域的拓展,对膜的组装技术和表征方法不断提出新的要求。综述了现阶段分子自组装膜的主要制备方法和基底表面的处理方法;着重从电化学、谱学、显微学等方面综述了近几年来自组装单分子膜的表征方法研究进展,并对其发展前景作了展望。     

MAPO-11分子筛的合成及表征

研究了MAPO 11分子筛的合成工艺,考察了镁铝摩尔比、模板剂、晶化温度以及晶化时间等因素对合成工艺的影响,采用X射线衍射、电镜扫描、热重量差热分析等手段对合成的样品进行了表征。结果表明,在一定的镁铝摩尔比范围内,能合成出结晶度和纯度较高的MAPO 11分子筛,这种分子筛的热稳定性较差。     

MAPO-11分子筛的合成及表征

研究了MAPO-11分子筛的合成工艺，考察了镁-铝摩尔比、模板剂、晶化温度以及晶化时间等因素对合成工艺的影响，采用X射线衍射、电镜扫描、热重量一差热分析等手段对合成的样品进行了表征。结果表明，在一定的镁-铝摩尔比范围内，能合成出结晶度和纯度较高的MAPO-11分子筛，这种分子筛的热稳定性较差。     

JR6对人结肠癌细胞HT-29氧化还原系统影响

探讨新型抗肿瘤药物JR6诱导人结肠癌细胞HT-29凋亡机制.使用噻唑兰比色法(MTT)检测JR6对人结肠癌细胞HT-29的生长抑制作用,并测定HT-29细胞中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)的活性和丙二醛(MDA)浓度.JR6对HT-29细胞生长有明显抑制作用,可以降低HT-29细胞中SOD、GSH-Px、CAT活性,升高MDA浓度.JR6对HT-29细胞有明显的细胞毒作用,其IC50为39.8μg/ml,可能通过影响HT-29细胞中SOD、GSH-Px、CAT活性和MDA浓度,达到诱导HT-29细胞凋亡的目的.     

RNA干扰Nucleostemin基因对人结肠癌细胞株HT-29细胞增殖及细胞周期的影响

将Nucleostemin(NS)siRNA利用脂质体2000转染人结肠癌细胞株HT 29,分别利用CCK-8试剂盒和流式细胞术检测NS siRNA对HT 29细胞增殖和细胞周期的影响,进一步利用Real-time PCR和Western blotting技术检测NS基因和细胞周期相关基因p21 mRNA和蛋白的表达.结果表明,NS siRNA的转入能有效下调NS mRNA和蛋白的表达(P0.05),并能明显抑制人结肠癌细胞株HT 29的细胞增殖(P0.05),并诱导细胞周期静止在G_0/G_1期,转染NS siRNA后,p21 mRNA和蛋白的表达均明显升高,提示细胞增殖抑制和细胞周期静止与p21基因表达的升高密切相关.     

希罗达联合放疗治疗低位直肠癌术前的疗效观察

目的评价术前希罗达联合盆腔放射治疗对低位局部进展期直肠癌的疗效.方法将病症确诊60例低位直肠癌患者随机分为两组:单纯手术组30例,常规进行手术治疗;联合治疗30例,术前联合希罗达和放疗,然后再手术.结果单纯手术组和联合治疗组的手术切除率分别为83.5%和100%,差异有显著性(P<0.05);保肛率分别为30.0%和86.7%,差异有非常显著性(P<0.01);局部复发率分别为16.0%和0,差异有显著性(P<0.05).结论术前希罗述+放疗提高低位直肠癌的手术切除率和保肛率,降低局复发率,是目前较好的新辅助治疗方案。     

Visual characterization of targeted effect of holo-transferrin-tagged dihydroartemisinin on human breast cancer cells

Targeted drugs could significantly reduce cytotoxic effect and increase therapeutic activity. Dihydroartemisinin (DHA) has been shown to be effective in killing cancer cells. However, it exhibits non-targeted property. Holo-transferrin (TF) is a suitable drug-carrier to target cancer cells, because cancer cells need iron uptake by the TF-mediated mechanism to maintain their uncon- trolled growth. Furthermore, TF receptors (TF-R) are highly expressed on cancer cell surfaces. In this paper, 3-(4,5-dimethylthi- azol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the different killing effect of 4-(12-Dihydroart- emisininoxy) Benzoic Acid Hydrozide-transferrin (DBAH-TF) on human breast cancer cells (MCF-7) cells and human normal breast (HNB) cells, and atomic force microscopy (AFM) was used to visually observe the targeted effect of DBAH-TF on MCF-7 cells. MTT results show that DBAH-TF is 172 times more potent than DHA in killing MCF-7 cells, while the cytotoxic effect of DBAH-TF on HNB cells is merely 1/33 to DHA. Also, the killing effect of DBAH-TF on MCF-7 cells is 286 times that on HNB cells, showing targeted effect. Moreover, there are distinct differences in ultrastructures of cellular surfaces after DBAH-TF and DHA treatment. Through AFM imaging, many characteristic holes were observed on the cancer cell surface after being effected by DBAH-TF, which differ from the holes with irregular shapes affected by DHA. These results visually show that the DBAH-TF targeted drug has more potent killing effect on MCF-7 cells compared with DHA.     

六方中孔硅分子筛的合成与表征

以十二胺(DDA)为模板剂,采用溶胶凝胶法室温下合成了六方中孔硅分子筛原粉(HMS-DDA),分析了焙烧法与有机溶剂抽提法,特别是溶剂、抽提时间等因素对合成六方中孔硅分子筛(HMS)中孔结构的影响,利用XRD、FT-IR、HRTEM、XPS及TG-DTA等分析手段对其进行了表征。结果表明:焙烧温度、抽提溶剂及抽提时间对HMS-DDA的脱模及HMS材料的晶格重组、结构有序度及骨架稳定性有显著影响,其中以丙酮为溶剂抽提样品9 h,材料具有良好的中孔有序度和最稳定的中孔结构。同时证实了在HMS-DDA合成过程中,荷电为零的无机硅物种(I°)与中性伯胺分子(S°)之间依靠非静电力协同完成S°I°分子自组装。     

MCM-41介孔分子筛的修饰与表征

分别以γ—氨基丙基三乙氧基奎烷（γ-aminopropyltriethoxy silane,NH2(CH2)3Si(OC2H5)3,APTES和γ-环氧丙氧基丙基三甲氧基硅烷（γ-glycidoxypropyltrimethoxy silane,CH2OCHCH2O(CH2)3Si(OCH3)3,GPTES）为偶联剂，成功地将氨基和醚基官能团搂枝于MCM-41介孔分子筛孔道中，制备了无机-有机复合介孔材料NH2（CH2）3-MCM-41和CH2OCHCH2O（CH2）3-MCM-41。用XRD、N2吸附-脱附、元素分析和FT-IR对复合材料进行了表征。结果表明，氨基和醚基有机基团不仅进入了MCM-41孔道，修饰了孔壁，而且使MCM-41保持了有序的孔道结构。     

The search for the causes of breast and colon cancer

Epidemiological studies of breast and colon cancers implicate diet as a causative factor but the evidence is stronger for colon cancer, the occurrence of which may be reduced by diets with less animal fat and more fruit and vegetables.     

蜂胶黄酮Pinobanksin-3-acetate对结肠癌HCT-116细胞增殖及凋亡的影响

 为探讨蜂胶黄酮(Pinobanksin-3-acetate, PB3A)对结肠癌HCT-116 细胞增殖及细胞凋亡的影响, 采用四甲基偶氮唑盐(MTT)比色法, 检测不同浓度、不同时间PB3A、5-氟尿嘧啶(5-FU)及两种药物联合作用对HCT-116 细胞生长所产生的影响, 倒置显微镜观察细胞的形态学变化特点, Annexin V-FITC/PI 双染色、流式细胞仪检测药物作用24 h 后的细胞凋亡率。结果显示, PB3A 对HCT-116 细胞增殖有明显的抑制作用, 并呈浓度和时间依赖性。其抑制活性与5-FU 几乎没有显著性差异, 联合用药具有协同效应; 在一定剂量范围内, 可见凋亡细胞明显增多。流式细胞仪分析结果表明, 细胞凋亡率明显上升, 呈剂量依赖性。PB3A 对HCT-116 细胞具有明显的增殖抑制和诱导细胞凋亡作用。     

H2-calponin对结肠癌细胞增殖的抑制作用

摘要：目的：探讨H2-calponin在结肠癌发生发展中所发挥的作用。方法：Western blot检测H2-calpinin在结肠癌组织和细胞系中的表达;构建H2-calpinin特异性小干扰RNA,稳定转染结肠癌SW480细胞系,同时将转染随机序列的SW480细胞作为对照,通过MTT实验、FACS细胞周期检测等方法研究H2-calponin下调对结肠癌细胞恶性生物行为的影响。结果：H2-calponin的表达与结肠癌的增殖能力具有相关性,下调H2-calponin的表达能够促进结肠癌细胞的增殖=。结论：本实验率先验证了H2-calponin能够抑制结肠癌细胞的增殖。     

高纯相X型分子筛的水热合成与表征

目的 合成高纯相X型分子筛,并对其进行了相关表征.方法 在不引入有机胺模板剂的条件下,通过水热法合成了X型分子筛;考察了反应温度、反应时间对合成X型分子筛的影响,并利用XRD,SEM等技术对所得产物进行了相关表征.结果与结论 优化了X型分子筛的合成条件,最终在100℃下晶化4h,得到了相应产物;通过XRD,SEM等技术对其进行了相关表征,证明所得产物为高结晶度、高纯相的X型分子筛.该分子筛具有明显的异向生长的特点,呈现出大面积暴露（111）晶面的正八面体结构.