首次发现细菌DNA转移到人的细胞中——F1000上一篇14分的文章 一般说来，细菌介导DNA进入真核生物的例子就只有根瘤农杆菌，也就是农杆菌通过侵染植物伤口进入细胞后，可将T-DNA插入到植物基因组中，并且可以通过减数分裂稳定的遗传给后代。这是唯一的例子吗？来自瑞士巴塞尔大学(University of Basel)的一个小组近期发现一类革兰阴性的兼性厌氧菌——汉赛巴尔通体(Bartonella henselae)能通过第四分泌系统（ type IV secretion system ）将DNA转移到人的细胞中去，此项研究发表在 PNAS 上，题为 Conjugative DNA transfer into human cells by the VirB/VirD4 type IV secretion system of the bacterial pathogen Bartonella henselae 。在著名的F1000网站上，此文被评了14分，是相当高的一个分数，足见其影响力，来自纽约州立大学石溪分校（State University of New York at Stony Brook）的Benot Lacroix和 Vitaly Citovsky评价道：“ This seminal paper reports the first case of DNA transfer from a human bacterial pathogen, Bartonella henselae, to the host human cell. Furthermore, B. henselae becomes the second known bacterium, after Agrobacterium tumefaciens, that can transfer genetic material into eukaryotic cells. Agrobacterium, that genetically transforms plants, has been considered to represent the only known naturally occurring case of trans-kingdom DNA transfer from bacteria to eukaryotes . This study broke this dogma , demonstrating that a human pathogen, B. henselae, is capable of genetically transforming its host cell. In fact, this discovery was not entirely unexpected as Agrobacterium can, under laboratory conditions, transform non-host organisms, such as fungi and animal cells, indicating that the mechanism for DNA transfer is evolutionarily conserved ”，来自华盛顿大学（University of Washington）的Gene Nester也评价道：“ This article is interesting because it demonstrates that the bacterial pathogen Bartonella henselae can transfer DNA into human cells by a type IV secretion system. This is the only known case of such DNA transfer into human cells, except for the transfer by the plant pathogen Agrobacterium under laboratory conditions . The authors have presented convincing evidence that a cryptic plasmid in B. henselae can be transferred at a low frequency into a human endothelial cell line. Transfer is increased 100-fold if a secretion signal is fused to the C-terminus of the Mob protein of the plasmid. Various regions of the plasmid are shown to be integrated into the human chromosome, a process that appears to depend on cell division. The authors suggest that Bartonella might serve as a vector for gene delivery systems for DNA vaccinations and gene therapy”，足见此项研究具有十分重要的意义，并在构建相关基因工程载体和基因治疗方面提供了一项策略 。 PNAS全文详见附件，F1000上的链接 http://f1000.com/12877956 。 首次发现外来基因转入人体Conjugative DNA transfer into human cells by the VirBVir.pdf
http://portal.elseviermed.cn/tabid/97/ID/2582/Default.aspx trpc6通道是G2/M期转移和人胶质瘤形成的必要因素 Essential role of trpc6 channels in G2/M phase transition and development of human glioma Ding X, He Z, Zhou K, Cheng J, Yao H, Lu D, Cai R, Jin Y, Dong B, Xu Y, Wang Y 2010/8/19 16:31:00 向好友发送电子邮件 收件人： （请填写电子邮箱地址，如果有多个邮箱请用逗号,分开。） 发件人：（电子邮箱地址） 内容：（可选） 最多填写200字。 Journal of the National Cancer Institute, 2010, Volume202, Issue14 相关研究文献分析 http://www.gopubmed.org/web/gopubmed/1?WEB0v101iftwxbaqIqI11I00h001000j100500001002000001200301011000606 window.setTimeout(function() {var param1 = '1?WEB0v101iftwxbaqItI11I00h001000j10040001';var param2 = '5969940102028124860';var param3 = 1;if (replaceFromServerUrl(param1+'&rl',param2,param3)) {window.location=param1;} ;}, 20); 136 documents semantically analyzed Top Years Publications 2010 41 2009 18 2008 17 2006 12 2007 11 2005 10 2004 5 2003 4 1997 3 2002 3 2001 3 1999 3 1998 2 2000 2 1992 1 1994 1 Top Countries Publications USA 68 China 31 Japan 9 Germany 8 Taiwan 3 France 2 United Kingdom 2 Hong Kong 1 Canada 1 India 1 South Korea 1 Sweden 1 Italy 1 Israel 1 Iran 1 Netherlands 1 Turkey 1 Poland 1 Switzerland 1 Russia 1 1 2 3 4 Top Cities Publications Houston 13 Shanghai, China 7 Bethesda 4 Wuhan 4 Suzhou 3 Detroit 3 Xi'an 3 San Diego 3 Boston 3 Tbingen 3 Baltimore 3 Phoenix 3 Los Angeles 3 Tokyo 2 Rochester, MN, USA 2 Tokushima, Japan 2 San Francisco 2 Seattle 2 Chongqing, China 2 Philadelphia 2 1 2 3 4 1 2 3 4 Top Journals Publications J Natl Cancer Inst 18 Cancer Res 13 J Biol Chem 8 J Neurosurg 6 Int J Cancer 5 Bmc Cancer 4 J Neurooncol 4 Neuro Oncol 4 Ai Zheng 4 Clin Cancer Res 3 Expert Opin Ther Targets 2 Lab Invest 2 Neurosurgery 2 Proc Natl Acad Sci U S A 2 Cancer Sci 2 Endocrinology 2 Zhonghua Bing Li Xue Za Zhi 2 Oncogene 2 Plos One 2 Gut 1 1 2 3 4 1 2 3 ... 48 Top Authors Publications Yung W 6 Lang F 4 Sawaya R 3 Gmez Manzano C 3 Fueyo J 3 Kondo Y 2 Wang J 2 Gong W 2 Steck P 2 Liu T 2 Jiang H 2 Fine H 2 Pastorino S 2 Mari? D 2 Aldape K 2 Yuan J 2 Yu Y 2 Platoshyn O 2 Landsberg J 2 Rao J 2 1 2 3 ... 48 1 2 3 ... 113 Top Terms Publications Humans 111 Neoplasms 98 Proteins 89 Glioma 89 Cell Line 80 Animals 77 Brain Neoplasms 74 Mice 73 RNA, Messenger 68 Cell Line, Tumor 67 Genes 65 Gene Expression Regulation, Neoplastic 54 Cell Proliferation 53 Reverse Transcriptase Polymerase Chain Reaction 53 Cell Cycle 52 cell cycle 48 Glioblastoma 46 Blotting, Western 45 Tissues 44 RNA 44 1 2 3 ... 113
http://www.gopubmed.org/web/gopubmed/1?WEB0zwzydl07ik4gIlI1I00f01000j10040001rl Snail or Twist or Slug andmetastasis 12 documents semantically analyzed Top Years Publications 2009 7 2007 3 2006 1 2005 1 Top Countries Publications USA 4 Taiwan 2 Japan 2 Germany 2 France 1 United Kingdom 1 Top Cities Publications Taipei 2 Boston 1 Los Angeles 1 Sagamihara 1 Baltimore 1 Durham 1 Berlin 1 Munich 1 Lyon 1 Cardiff 1 Top Journals Publications J Pathol 2 Cancer Res 2 Hepatology 1 Crit Rev Immunol 1 Int J Oncol 1 Mol Biol Rep 1 Cancer Biol Ther 1 Clin Cancer Res 1 J Cell Biol 1 Ann Surg Oncol 1 1 2 3 4 Top Authors Publications Wu J 1 Yang M 1 Chen C 1 Chau G 1 Chiou S 1 Su C 1 Chou T 1 Peng W 1 Lai H 1 Liu C 1 Chao T 1 Su P 1 Lee H 1 Shih Y 1 Su H 1 Chu T 1 Yu M 1 Lin Y 1 Kuperwasser C 1 Dimeo T 1 1 2 3 4 1 2 3 ... 16 Top Terms Publications Neoplasm Metastasis 12 epithelial to mesenchymal transition 11 slug 11 Neoplasms 10 Humans 9 Cadherins 8 Transcription Factors 8 Genes 8 e-cadherin 7 Mesoderm 7 Down-Regulation 6 Mice 6 Tissues 6 Epithelial Cells 6 Animals 5 Prognosis 4 Carcinoma 4 signal transduction 4 Breast Neoplasms 4 Twist Transcription Factor 4 1 2 3 ... 16 http://www.sciencenet.cn/htmlpaper/20091141054205247697.shtm 科学家们鉴定出引发肝癌转移特定分子标记物 肝细胞性肝癌（HCC）或原发性肝癌由肝脏的上皮组织恶化而来，通常由乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染导致。美国国立癌症研究所估计美国国内每年有15,000名男性和6,000名女性被诊断为HCC。据世界卫生组织（World Health Organization，WHO）2004年的报道，全球有632,000例HCC患者，其中发病率最高的地区是西太平洋地区和非洲。 台北退伍军人总医院的研究者调查了HCC的分子机制，而由于HBV的高流行率（15-20%），HCC是台湾最常见的肿瘤之一。这项研究第一次提供了多个上皮至间充质转化（EMT）分子标记物的综合概况，并发现在HCC中Snail和Twist蛋白是EMT的主要诱因，而Slug蛋白则不起主要作用。这项研究由国家科学委员会部分资助，发表在十一月号的《肝脏学》杂志，此杂志由美国肝脏疾病研究协会承办。 上皮至间充质转化（EMT）是人肿瘤侵袭和转移发展过程中的关键步骤，描述了上皮细胞不再彼此黏附，而转变为具有成纤维细胞特性的一个过程。EMT过程始于主要的EMT调节因子（包括Snail，Twist和Slug蛋白）对上皮钙粘蛋白（E-cadherin）功能的抑制。 上皮钙粘蛋白（钙依赖的黏附分子）是一类存在于上皮细胞中帮助组织细胞粘结的蛋白。当上皮钙粘蛋白不存在了，癌症细胞就可以转移移动。 吴家成（音）教授和同事们收集了123例原发HCC病人的肝癌和癌旁组织的样品，这些病人于1990年至2002年间在台北退伍军人总医院接受了肝癌切除手术。在60.2%病人中发现了上皮钙粘蛋白功能的减弱。吴教授解释：我们发现在上皮钙粘蛋白功能减弱的患者中，无肿瘤的时间和总的存活都有一个统计学显著的减少。上皮钙粘蛋白表达降低也常与肿瘤体积较大和多发性肿瘤相关联。 结果显示，Snail和Twist蛋白（控制基因何时开关的转录因子和蛋白）的共表达指示了最糟糕的HCC病人预后。吴教授认为：我们的研究第一次证明了这两个蛋白（Snail和Twist）虽然独立工作，却共同促进EMT。 根据这个研究，Twist蛋白的过表达与HCV相关的HCC有相关性，这部分解释了这种肝癌的高度转移性和次中肝癌患者的不良预后。吴教授认为：我们的结果提供了必须的信息，可用来决定HCC病人的预后，为将来发现新的HCC的治疗方法提供了基础。 更多阅读 《肝脏学》发表论文摘要（英文） http://www3.interscience.wiley.com/journal/122542499/abstract?CRETRY=1SRETRY=0 Hepatobiliary Malignancies Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma Muh-Hwa Yang 1 2 3 , Chih-Li Chen 4 , Gar-Yang Chau 5 6 , Shih-Hwa Chiou 1 7 , Chien-Wei Su 1 8 , Teh-Ying Chou 1 9 , Wei-Li Peng 7 , Jaw-Ching Wu 1 3 7 * 1 Institutes of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 2 Division of Hematology-Oncology, Taipei Veterans General Hospital, Taipei, Taiwan 3 Genomic Medicine Research Center, Taipei Veterans General Hospital, Taipei, Taiwan 4 School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan 5 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan 6 Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 8 Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 9 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan email: Jaw-Ching Wu ( jcwu@vghtpe.gov.tw ) * Correspondence to Jaw-Ching Wu, Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan Potential conflict of interest: Nothing to report. These authors contribute equally to this study. fax: 886-2-28745074 setDOI("ADOI=10.1002/hep.23221") Funded by: National Science Council; Grant Number: NSC93-2321-B-010-012, 94-2321-B-010-010, 95-2321-B-010-005, 98-3112-B-010-017 Ministry of Education, Aim for the Top University Plan; Grant Number: 96A-D-T304, 97A-C-T501 Taipei Veterans General Hospital; Grant Number: V97ER2-016, V98ER2-017 Fu-Jen Catholic University, Taipei, Taiwan; Grant Number: 109531030990-3, 109631030990-3 Abstract The epithelial-mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC). Reduced E-cadherin and nonmembranous -catenin expression, the hallmarks of EMT, were shown in 60.2% and 51.5% of primary HCC samples, respectively. Overexpression of Snail, Twist, or Slug, the major regulators of EMT, was identified in 56.9%, 43.1%, and 51.4% of primary HCCs, respectively. Statistical analysis determined that Snail and Twist, but not Slug, are major EMT inducers in HCC: overexpression of Snail and/or Twist correlated with down-regulation of E-cadherin, nonmembranous expression of -catenin, and a worse prognosis. In contrast, there were no such significant differences in samples that overexpressed Slug. Coexpression of Snail and Twist correlated with the worst prognosis of HCC. Hepatitis C-associated HCC was significantly correlated with Twist overexpression. HCC cell lines with increased Snail and Twist expression (e.g., Mahlavu) exhibited a greater capacity for invasiveness/metastasis than cells with low endogenous Twist/Snail expression (e.g., Huh-7). Overexpression of Snail or/and Twist in Huh-7 induced EMT and invasiveness/metastasis, whereas knockdown of Twist or Snail in Mahlavu reversed EMT and inhibited invasiveness/metastasis. Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E-cadherin transcription. Conclusion: Our study provides a comprehensive profile of EMT markers in HCC, and the independent and collaborative effects of Snail and Twist on HCC metastasis were confirmed through different assays. (H EPATOLOGY 2009.) Received: 30 March 2009; Accepted: 9 July 2009
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