苦参碱和氧化苦参碱抗肿瘤作用的研究进展

苦参碱和氧化苦参碱是一类生物碱,具有多方面的药理活性,其中的抗肿瘤作用,近年来受到了极大的关注.目前国内外关于苦参碱和氧化苦参碱抗肿瘤作用的研究显示,苦参碱和氧化苦参碱通过抑制肿瘤细胞DNA的合成、抑制相关酶活性、影响肿瘤细胞的正常周期来抑制肿瘤细胞增殖;通过控制相关因子的表达来抑制肿瘤的转移;通过影响了与肿瘤相关基因的表达、影响端粒酶的活性等途径,来诱发细胞发生凋亡,诱导肿瘤细胞向正常细胞分化.     

放射增敏剂的研究进展

文内综述了化学增敏剂的实验研究进展,由于放射增敏剂能提高肿瘤的治愈率,因此得到国内外有关学者的广泛研究     

Cloning of a novel gene associated with human nasopharyngeal carcinoma

One EST N27741 with high expression in normal adult nasopharynx tissues but low expression in adult poorly differentiated squamous nasopharyngeal carcinoma has been selected out by the high-density cDNA array expression profiling technique. The differential expression has been confirmed by RT-PCR. One novel gene of 1096 bp has been cloned based on this EST. Bioinformatics analysis found that the new gene sequence contains a whole reading frame encoding 256 amino acids. There is a stop codon TAA in front of the 5′ end start codon, and a tailing signal AATAAA and poly A tail at the 3′ end. There is no homologous known gene found after searching by blasting this sequence to non-redundancy nucleotide database. Therefore it is considered a novel gene related to nasopharyngeal carcinoma.     

基于Oracle 10G的桌面网格平台构建

在实际应用中,网格技术由于研究平台、工具等的限制,目前基于多应用的网格平台还没有得到很好的发展。利用Oracle 10G的网格组件,结合Web Service技术构建Windows下的网格平台GPBO,打破以往网格平台应用的限制,以获取高稳定性和高可用性。提出了GPBO平台的模型和GPBO平台工作的具体机制,对故障切换和任务传送的Web Service方法做了具体介绍,并由实验数据的加速比标准说明GPBO可获得的高性能和GPBO与其他网格平台的不同之处。     

双极化圆柱介质谐振器天线设计与实验研究

全极化数字相控阵天线具有波束扫描灵活、抗干扰能力强的优点,已成为以飞行器为载体的雷达天线领域的发展趋势之一。考虑到安装平台的限制,天线单元是相控阵天线的关键部件,研制适合工程应用的双极化天线单元具有重要意义。提出以双极化介质谐振器天线为全极化数字相控阵天线单元的设计方案;该方案具有辐射效率高、结构简单、易于馈电、体积小、极化端口隔离特性好等性能。设计了一种带有金属反射板的双极化圆柱形介质谐振器天线单元,采用全波电磁仿真软件对天线单元进行设计和优化,开展了天线单元的加工和性能测试工作。在4.95~5.05 GHz的带宽内,驻波比均小于2;天线的极化端口隔离度约为-20 d B;测试的天线波束宽度约大于80°,增益约大于6 d B,交叉极化电平约为-20 d B。天线的性能达到预期的指标要求,适合于实际工程应用。     

AW915115参与大鼠再生肝星形细胞的Notch信号转导

为了解新基因AW915115在Notch信号通路中的作用及与大鼠肝再生的相关性,用Percoll密度梯度离心结合免疫磁珠分选方法分离大鼠再生肝的8种细胞,用Rat Genome 230 2.0芯片等检测上述细胞的Notch信号通路基因在大鼠肝再生中的表达变化,用BLAST、Microsoft Excel等软件分别分析新基因与已知基因的序列同源性和共表达关系,用生物信息学和系统生物学等方法分析上述基因参与的生理活动.结果表明,AW915115与活化Notch受体的N-乙酰葡糖基转移酶基因lfng同源,并且在2 h和12 h再生肝星形细胞中表达下调.根据上述基因的同源性和共表达关系推测,新基因AW915115参与大鼠再生肝星形细胞的Notch信号转导.     

Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene

Several groups have shown that the malignant phenotype can be transferred to NIH/3T3 fibroblasts by incorporation of DNA isolated from tumour cell lines. These studies have demonstrated that the transforming activity of DNA isolated from human bladder, lung and colon carcinoma cell lines is related to an alteration of the cellular homologues of the ras genes of Harvey or Kirsten murine sarcoma viruses. It is, however, unclear what relevance these observations have to the multi-stage nature of tumorigenesis in vivo, in which several independent events are required in both humans and experimental animals. The activation of a cellular oncogene in a defined experimental system for the progressive induction of solid tumours has not yet been demonstrated. We report here that high molecular weight DNA from transplanted squamous cell carcinomas induced by sequential treatment of mouse skin with initiators and promoters of carcinogenesis causes morphological transformation of NIH/3T3 fibroblasts at high frequency. The transforming properties are due to the transfer of an activated cellular homologue of the Harvey-ras (rasH) oncogene.     

Functional genomics reveal that the serine synthesis pathway is essential in breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.     

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Macrophages, which are abundant in the tumour microenvironment, enhance malignancy. At metastatic sites, a distinct population of metastasis-associated macrophages promotes the extravasation, seeding and persistent growth of tumour cells. Here we define the origin of these macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumours in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (the receptor for chemokine CCL2), as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumour cells, is dependent on CCL2 synthesized by both the tumour and the stroma. Inhibition of CCL2-CCR2 signalling blocks the recruitment of inflammatory monocytes, inhibits metastasis in vivo and prolongs the survival of tumour-bearing mice. Depletion of tumour-cell-derived CCL2 also inhibits metastatic seeding. Inflammatory monocytes promote the extravasation of tumour cells in a process that requires monocyte-derived vascular endothelial growth factor. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Our data provide the mechanistic link between these two clinical associations and indicate new therapeutic targets for treating metastatic breast cancer.     

乳酸菌抗癌作用的研究进展

乳酸菌特别是双歧杆菌的“三抗”用早已为人们所认识,目前我国对抗感染的机理研究已取得了很大进展,但对抗肿瘤和抗衰老的研究还停留在动物实验阶段,本文通过对国内外在动物实验、流行病学调查及临床研究的结果的总结,概述了乳酸菌预防和治疗肿瘤的作用机理,以期人们能对乳酸菌制品的医用价值有更加深入的认识和了解。     

Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity?

Variability in the phenotype of cells comprising individual tumours is a striking feature of animal and human cancer and is generally referred to as tumour heterogeneity. Studies of clonally derived cell populations from tumours that originated presumably from a single transformed cell have shown that tumours are made up of cells that differ in a variety of traits, including drug resistance, antigen expression and metastatic potential. The origin and maintenance of tumour heterogeneity are unclear, but mutational and epigenetic mechanisms are thought to be involved. Here we report the results of a search for transforming genes in human melanoma which have raised the possibility that ras gene activation follows the same variable pattern as other traits involved in tumour heterogeneity. DNA from 4 of 30 melanoma cell lines yielded transforming ras genes in the NIH/3T3 assay. Of five cell lines originating from separate metastatic deposits of a single patient, only one contained activated ras, indicating heterogeneity in ras activation in this case and suggesting that ras activation was not involved in tumour initiation or maintenance in this patient.     

LKB1 modulates lung cancer differentiation and metastasis

Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis.     

Systematic identification of genomic markers of drug sensitivity in cancer cells

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.     

Chfr defines a mitotic stress checkpoint that delays entry into metaphase

Chemicals that target microtubules induce mitotic stress by affecting several processes that occur during mitosis. These processes include separation of the centrosomes in prophase, alignment of the chromosomes on the spindle in metaphase and sister-chromatid separation in anaphase. Many human cancers are sensitive to mitotic stress. This sensitivity is being exploited for therapy and implies checkpoint defects. The known mitotic checkpoint genes, which prevent entry into anaphase when the chromosomes are not properly aligned on the mitotic spindle, are, however, rarely inactivated in human cancer. Here we describe the chfr gene, which is inactivated owing to lack of expression or by mutation in four out of eight human cancer cell lines examined. Normal primary cells and tumour cell lines that express wild-type chfr exhibited delayed entry into metaphase when centrosome separation was inhibited by mitotic stress. In contrast, the tumour cell lines that had lost chfr function entered metaphase without delay. Ectopic expression of wild-type chfr restored the cell cycle delay and increased the ability of the cells to survive mitotic stress. Thus, chfr defines a checkpoint that delays entry into metaphase in response to mitotic stress.