环境污染与癌症

1　前言癌症已成为当今世界上危害人类生命健康的一种常见病 ,它和脑血管病、心血管病在人类死亡原因中占前三位。近几十年来 ,人们在同癌症作斗争的过程中 ,不断发现这种过去认为病因不明 ,神秘莫测的凶恶病魔 ,主要不是人们以往所熟悉的细菌、病毒或寄生虫等原因引起 ,而是与人们所生活的环境有很大关系。大量的调查研究结果表明 ,80— 90 %以上的癌症极有可能是由于环境因素引起的。2　环境致癌物的分类环境因素之所以与癌症的发病率相关 ,这是由于环境污染后会使不同的环境中含有不同的致癌物。通常环境致癌物可分为化学的、物理的和生…     

microRNA层面上癌症的公共机制

microRNAs(miRNA)是一类内源性的非编码小RNA。已有研究表明miRNAs的靶基因中有不少癌症的相关基因。为了全面研究miRNA与癌症的关系,作者将19种癌症的相关基因集合分别富集到494个miRNAs靶基因集合上,得到各类癌症所富集的miRNAs。结果发现19种癌症仅集中地富集在144个miRNAs上,由此验证了癌症在miRNAs上的公共机制。在此基础上,作者对癌症富集较多的8个miRNAs做了进一步研究,结果发现这8个miRNAs均为高度保守的miRNAs,且它们的靶基因集合一致富集在基因本体论(gene ontology,GO)的基本生物学过程上,并与转录因子活性以及蛋白激酶活性相关。另一方面,在基于miRNA构建的癌症网络中,前列腺癌与乳腺癌,结肠癌与乳腺癌之间共享较多的miRNAs,表明了这些癌症在miRNA层面上存在密切的关系。     

癌症与可变剪接

可变剪接在发育、分化和癌症等过程中发挥着非常重要的作用。近年来,越来越多的研究表明可变剪接与癌症有着密切的关系,许多癌症相关基因受可变剪接调控。由于癌症特异性的剪接变体具有明显的诊断价值,使得对癌症与可变剪接的研究成为热点。简要概述了癌症相关基因的可变剪接、可变剪接变体的鉴定方法、可变剪接与癌症治疗等研究进展。     

人为制造的“癌威胁”？

科学家在与癌症的长期较量中发现,它不是人们以往所熟悉的细菌、病毒或寄生虫等引起的,而是与人们生活的环境有很大关系。大量的调查研究结果表明,80%～90%以上的癌症极有可能是由于环境因素导致的。不断披露的"癌症村"及环境极度恶化地区癌症患者的高发现象,就是最好的佐证。遗憾的是,如此严峻的问题尚未引起全社会的足够重视。     

疫苗与肿瘤防治

一个多世纪以前,医生们发现一个有趣的巧合;癌症患在受到细菌感染之后,其癌肿有时会萎缩。这就使人们产生了一个想法：用癌症疫苗来调动人体的免疫系统,就像对细菌那样对癌细胞发起进攻,从而达到消灭癌细胞的目的。与人们所熟悉的那种预防麻疹、流感和其他传染病的防疫针不     

基于双聚类挖掘癌症共享的基因功能模块

基因多效性是癌症遗传机制中的普遍现象, 但罕见系统性的分析。文章提出采用双聚类挖掘基因功能模块的新思路探索癌症的共享分子机制和不同癌症间的关系。获取20种癌症的基因表达数据, 应用改良t检验和倍数法筛选出至少在两种癌症中差异表达的基因, 得到10417×20的数据矩阵; 采用双聚类方法获得22个癌症共享的基因簇; 进一步富集分析得到17个基因功能模块(Bonferroni校正后P<0.05), 主要参与有丝分裂染色单体分离的调控、细胞分化、免疫和炎症反应、胶原纤维组织等生物过程; 主要执行ATP结合和微管活动、MHCⅡ类受体活性、肽链内切酶抑制活性等分子功能; 活动区域主要在细胞骨架、染色体、MHCⅡ蛋白质复合体、中间丝蛋白、胶原纤维等。基于模块构建癌症相关网络, 显示胃癌、卵巢腺癌、宫颈鳞癌和间皮瘤等之间相关程度较高, 而两种血液系统癌症(急性髓细胞性白血病与多发性骨髓瘤)分子机制与其他癌症存在较大差异。可见癌症共享的基因功能模块与多种生物机制有关, 癌症之间相似性可能与组织起源、共同的致癌机制等有关。文章提出的基因多效性分析方法有助于解释人类复杂性疾病的共享分子机制。     

慷慨的分飨

肠内细菌可能是一种用来解释营养与癌症风险之间联系的诱人秘密。与许多伟大的政治同盟一样,生物学中的共生关系可能已经开始相伴并对抗,并先于两党达成共识,至少对于一些进化生物学家们来说如此。经常为科学家们所援引的例子是线粒体,它是真核生物细胞的能量供应细胞器,     

癌症相关microRNA与靶基因的生物信息学分析

MicroRNAs(miRNAs)是一类长度约为22nt的内源性非编码RNA,通过与靶基因转录本互补结合调控基因的表达。近年来,研究发现miRNA与癌症发生密切相关,miRNA可以直接充当癌基因或者抑癌基因而影响肿瘤的发生和生长。为更进一步揭示癌症相关miRNA的特征及靶基因的功能,文章通过数据库搜索及文献检索,在人类基因组中发现了475个癌症相关miRNA,系统地比较了癌症相关miRNA与非癌症miRNA以及基因内和基因间区癌症相关miRNA在保守性、SNP位点分布、癌谱及转录调控等特性。研究发现,癌症相关miRNA比非癌症miRNA保守性要强,发生SNP概率比较低,同时发现miRNA所涉及癌症数目与保守性成正相关。基因组定位分析发现,癌症相关miRNA比非癌症miRNA更倾向于成簇存在。进一步对宿主基因、癌症相关miRNA及作用的靶基因与癌症发生进行关联分析,发现一些非癌症miRNA的宿主基因倾向于被癌症miRNA作用。本研究结果为深入理解miRNA与癌症之间的关系,以及进一步为miRNA作为癌症诊断指示物提供理论依据。     

迈向生物医学信息时代

一月份,我在美国国家癌症研究所（NCI）聆听来自剑桥大学的BrucePonder的讲座。讲座中一个有趣的问题引起了我的注意。Ponder阐述了FGFR2基因突变与乳癌之间的关联关系。癌症研究领域的传奇人物Judah Folkman向Ponder提出了这样一个问题：     

拉曼光谱技术在肿瘤检测中的应用

癌症是威胁人类健康和生命的严重疾病之一,早期诊断与及时治疗是提高癌症患者生存率的最有效途径。激光拉曼光谱技术作为一种非侵入性的检测技术,可以无损伤地提供丰富的分子结构特征和物质成分信息,从分子水平上反映癌变组织与正常组织之间的结构差异,从而可用于癌症的早期诊断。综述了激光拉曼光谱技术在皮肤癌、鼻咽癌、肺癌、胃癌、结肠癌、乳腺癌及前列腺癌诊断中的研究进展,并对拉曼光谱技术在癌症诊断中的发展方向和应用前景作了进一步的展望,为癌症的早期检测和诊断技术的应用研究提供参考依据。     

Bioluminescent Bacterial Imaging In Vivo

This video describes the use of whole body bioluminesce imaging (BLI) for the study of bacterial trafficking in live mice, with an emphasis on the use of bacteria in gene and cell therapy for cancer. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumors following systemic administration. Bacteria engineered to express the lux gene cassette permit BLI detection of the bacteria and concurrently tumor sites. The location and levels of bacteria within tumors over time can be readily examined, visualized in two or three dimensions. The method is applicable to a wide range of bacterial species and tumor xenograft types. This article describes the protocol for analysis of bioluminescent bacteria within subcutaneous tumor bearing mice. Visualization of commensal bacteria in the Gastrointestinal tract (GIT) by BLI is also described. This powerful, and cheap, real-time imaging strategy represents an ideal method for the study of bacteria in vivo in the context of cancer research, in particular gene therapy, and infectious disease. This video outlines the procedure for studying lux-tagged E. coli in live mice, demonstrating the spatial and temporal readout achievable utilizing BLI with the IVIS system.     

Ribosome induces transdifferentiation of A549 and H-111-TC cancer cell lines

Previously we reported that, lactic acid bacteria (LAB) can induce human dermal fibroblast (HDF) cells to form multipotent cell clusters which are able to transdifferentiate into three germ layer derived cell lineages. Later on, we confirmed that ribosome is responsible for the LAB-induced transdifferentiation and ribosomes from diverse organisms can mimic the LAB effect on HDF cells. In our present study we have shown that, upon incorporation of ribosomes, non-small cell lung cancer cell line A549 and gastric tubular adenocarcinoma cell line H-111-TC are transformed into spheroid like morphology those can be transdifferentiated into adipocytes and osteoblast. Our qPCR analysis has revealed that, during the formation of ribosome induced cancer cell spheroids, the expression of the cancer cell associated markers and cell cycle/proliferation markers were altered at different time point. Through our investigation, here we report a novel and a non-invasive approach for cancer cell reprogramming by incorporating ribosomes.     

Usage of Aplysia lectin interactions with T antigen and poly-N-acetyllactosamine for screening of E. coli strains which bear glycoforms cross-reacting with cancer-associated antigens

Aplysia gonad lectin (AGL), which strongly agglutinates cancer cells, was found, in the present study, to bind to erythrocyte T antigen, in addition to its affinity to Ii system antigens. These antigens were reported to be overexpressed and to contribute to tumor progression and invasion. In healthy human sera, there are antibodies against them, stimulated by the normal intestinal microflora, which bear similar glycoforms. Since the levels of these antibodies were reported to be lower in most cancer patients' sera, we have examined the applicability of AGL to isolation of enteric commensal Escherichia coli strains which bear glycoforms cross-reacting with the cancer-associated antigens. Among 30 E. coli isolates examined, two were agglutinated by AGL. One of them was also agglutinated by certain related galactophilic lectins, which bind to the T and Tn antigens. The agglutination of the two bacteria by healthy human sera, as a group, was stronger than that displayed by the cancer patients' sera. These results indicate that AGL might be useful for identification of the desired bacteria, which could potentially serve for cancer diagnosis and therapy.     

Glutathione S transferase mu polymorphism and gastric cancer in the Portuguese population

The glutathione S-transferases appear to form part of a protective mechanism against the development of cancer where environmental chemical carcinogens are involved. In humans one member of the mu class gene family (GSTM1) has been shown to be polymorphic and is only expressed in ~50% of individuals. Previous studies have shown a possible link between the null phenotype and susceptibility to cancer but have been equivocal regarding stomach cancer. To evaluate any association in Portuguese gastric cancer individuals with GSTM1 variability, we performed GST M 1 polymorphism by PCR amplification in 148 gastric cancer patients and in 84 healthy control individuals. We found no statistical differences between the gastric cancer and control populations (wild type phenotype: 52%, 48%; null phenotype: 48%, 52%, respectively). A subset analysis into site of tumour also revealed no significant differences between the groups, although we found a slight increase of the wild type phenotype in the samples of the antrum compared with the control population (57% vs 48%, respectively; 2= 1.18; p 0.28) and a slight increase of the null phenotype in the signet ring cells/mucocellular group (2= 1.05; p 0.3). However, in both cases it did not reach statistical significance. A subset analysis of the histological groups following the WHO criteria revealed a statistically significant difference (2= 3.704; p 0.05) between the moderately differentiated gastric adenocarcinoma and the presence of the wild type phenotype. These results do not support the hypothesis that the GSTM1 null phenotype predisposes to gastric cancer in the Portuguese population and the moderately differentiated gastric adenocarcinoma seems to be associated with the presence of the G STM 1 wild type phenotype.     

晚期肿瘤患者下呼吸道感染临床分析

目的：探讨晚期肿瘤患者下呼吸道感染的细菌学分类情况及抗生素耐药性特点。方法：采用回顾性调查107例晚期肿瘤患者并下呼吸道感染痰菌分离的病原菌并分析其特点,药敏试验采用K—B纸片法。结果：137株病原菌,G杆菌67株(48．9％)．G^ 球菌44株(32．1%),真菌26株(19．0％)。主要致病细菌依次为铜绿假单胞菌19．7％．金黄色葡萄球菌13．9％,肺炎克雷伯菌10．9％。万古霉素、新霉素、环丙沙星对G^ 球菌较敏感;环丙沙星、阿米卡星、头孢哌酮对G杆菌作用较强．其他抗菌药物对各种病原菌均呈现不同程度的耐药。结论：晚期恶性肿瘤并下呼吸道感染的病原菌多为条件致病菌,耐药率高。应加强病原菌培养及药敏监测,以指导临床科学使用抗生素。     

恶性肿瘤患者合并感染临床分析

目的：探讨肿瘤患者合并感染常见病原菌的分布及对抗生素的敏感性。方法：回顾性总结分析139例恶性肿瘤患者合并感染的标本细菌培养及药敏情况。结果：112例细菌学检查阳性的患者感染部位以呼吸道最多,占69.6%,153份标本共检出122株细菌,其中真菌48株,占39.3%;G^-杆菌38株,占31.1%;G^ 球菌36株,占29.5%。所检出的葡萄球菌对万古霉素,新霉素较敏感,大肠埃希菌对阿米卡星31.1%;G^ 球菌36株,占29.5%,所检出的葡萄球菌对万古霉素,新霉素较敏感,大肠埃然菌对阿米卡星敏感,铜绿假单胞菌对环丙沙星尚敏感,其余抗生素对病原菌均呈现不同程度的耐药,结论：肿瘤患者合并感染的病原菌主要为条件致病菌,而且有较严重的耐药情况,临床治疗应重视病原学检查,合理使用抗生素,减少耐药菌株的产生和内源性感染。     

MDSCs might be “Achilles heel” for eradicating CSCs

During tumor initiation and progression, the complicated role of immune cells in the tumor immune microenvironment remains a concern. Myeloid-derived suppressor cells (MDSCs) are a group of immune cells that originate from the bone marrow and have immunosuppressive potency in various diseases, including cancer. In recent years, the key role of cancer stemness has received increasing attention in cancer development and therapy. Several studies have demonstrated the important regulatory relationship between MDSCs and cancer stem cells (CSCs). However, there is still no clear understanding regarding the complex interacting regulation of tumor malignancy, and current research progress is limited. In this review, we summarize the complicated role of MDSCs in the modulation of cancer stemness, evaluate the mechanism of the relationship between CSCs and MDSCs, and discuss potential strategies for eradicating CSCs with respect to MDSCs.     

County-level characteristics associated with incidence,late-stage incidence,and mortality from screenable cancers

BackgroundCancer screening differs by rurality and racial residential segregation, but the relationship between these county-level characteristics is understudied. Understanding this relationship and its implications for cancer outcomes could inform interventions to decrease cancer disparities.MethodsWe linked county-level information from national data sources: 2008–2012 cancer incidence, late-stage incidence, and mortality rates (for breast, cervical, and colorectal cancer) from U.S. Cancer Statistics and the National Death Index; metropolitan status from U.S. Department of Agriculture; residential segregation derived from American Community Survey; and prevalence of cancer screening from National Cancer Institute’s Small Area Estimates. We used multivariable, sparse Poisson generalized linear mixed models to assess cancer incidence, late-stage incidence, and mortality rates by county-level characteristics, controlling for density of physicians and median household income.ResultsCancer incidence, late-stage incidence, and mortality rates were 6–18% lower in metropolitan counties for breast and colorectal cancer, and 2–4% lower in more segregated counties for breast and colorectal cancer. Generally, reductions in cancer associated with residential segregation were limited to non-metropolitan counties. Cancer incidence, late-stage incidence, and mortality rates were associated with screening, with rates for corresponding cancers that were 2–9% higher in areas with more breast and colorectal screening, but 2–15% lower in areas with more cervical screening.DiscussionLower cancer burden was observed in counties that were metropolitan and more segregated. Effect modification was observed by metropolitan status and county-level residential segregation, indicating that residential segregation may impact healthcare access differently in different county types. Additional studies are needed to inform interventions to reduce county-level disparities in cancer incidence, late-stage incidence, and mortality.     

内皮抑素与肿瘤治疗

内皮抑素(endostatin)是近年来发现的,天然产生的新血管生成抑制因子。它在体内由胶原ⅩⅧ经酶解产生,可以抑制新血管生成,在肿瘤动物模型中显示出显著的抑瘤活动。通过抑制肿瘤相关的新血管的形成来治疗肿瘤,是目前出现的新疗法,内皮抑素是这种疗法中很有前景的侯选药物之一。在美国已经开始了用内皮抑素治疗肿瘤的Ⅰ期临床试验,关于它的临床前基础实验也在广泛开展。本文综述了内皮抑素在肿瘤治疗中的应用基础研究 。