中村祐輔 （ Yusuke Nakamura ）及其高引论文 诸平 中村 祐輔 是日本的顶尖科学家之一，曾领导了日本一些最大的科研项目。此外，他还是一位成功的生物技术企业家，创立了肿瘤治疗科学株式会社（ OncoTherapy Science Inc. ）。由于 中村 祐輔 的努力，日本在国际 HapMap 项目中大约完成了四分之一的工作。根据谷歌学术搜索结果，中村祐辅的论著累计被引近11.7万次，2009年以来被引约4.8万次；H指数为152，2009年以来的H指数为95。被引频次最多的论文是与他人合作1988年发表于 “ New England Journal of Medicine ” 的论文—— B Vogelstein, ER Fearon, SR Hamilton, SE Kern, AC Preisinger,.... Genetic alterations during colorectal-tumor development . New England Journal of Medicine，1988，319 (9)：525-532.累计被引5768次；其次是2005年发表于 Nature的论文—— International HapMap Consortium. A haplotype map of the human genome . Nature，2005，437(7063)：1299-1320.累计被引4000余次，被引频次在1000次以上的论著有10篇，现将被引次数在500次以上的论著摘引如下，供大家参考。 Title 1–100 Cited by Year Genetic alterations during colorectal-tumor development B Vogelstein, ER Fearon, SR Hamilton, SE Kern, AC Preisinger, ... New England Journal of Medicine 319 (9), 525-532 , 1988 5768 1988 A haplotype map of the human genome International HapMap Consortium Nature 437 (7063), 1299-1320 , 2005 4042 * 2005 The international HapMap project RA Gibbs, JW Belmont, P Hardenbol, TD Willis, F Yu, H Yang, LY Ch'ang, ... Nature 426 (6968), 789-796, 2003 3205 2003 A second generation human haplotype map of over 3.1 million SNPs KA Frazer, DG Ballinger, DR Cox, DA Hinds, LL Stuve, RA Gibbs, ... Nature 449 (7164), 851-861, 2007 3148 2007 Identification of FAP locus genes from chromosome 5q21 KW Kinzler, MC Nilbert, LK Su, B Vogelstein, TM Bryan, DB Levy, ... Science 253 (5020), 661-665, 1991 2065 1991 Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas SJ Baker, ER Fearon, JM Nigro, AC Preisinger, JM Jessup, DH Ledbetter, ... Science 244 (4901), 217-221, 1989 1818 1989 Variable number of tandem repeat (VNTR) markers for human gene mapping Y Nakamura, M Leppert, P O'Connell, R Wolff, T Holm, M Culver, C Martin, ... Science 235 (4796), 1616-1622, 1987 1741 1987 Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients I Nishisho, Y Nakamura, Y Miyoshi, Y Miki, H Ando, A Horii, K Koyama, ... Science 253 (5020), 665-669, 1991 1574 1991 Allelotype of colorectal carcinomas B Vogelstein, ER Fearon, SE Kern, AC Preisinger, Y Nakamura, R White Science 244 (4901), 207-211, 1989 1348 1989 i p53AIP1/i, a Potential Mediator of p53-Dependent Apoptosis, and Its Regulation by Ser-46-Phosphorylated p53 K Oda, H Arakawa, T Tanaka, K Matsuda, C Tanikawa, T Mori, ... Cell 102 (6), 849-862, 2000 1046 2000 Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma C Larsson, B Skogseid, K Öberg, Y Nakamura, M Nordenskjöld Nature Publishing Group 332 (6159), 85-87, 1988 919 1988 Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis A Suzuki, R Yamada, X Chang, S Tokuhiro, T Sawada, M Suzuki, ... Nature genetics 34 (4), 395-402, 2003 862 2003 Estimation of the warfarin dose with clinical and pharmacogenetic data. TE Klein, RB Altman, N Eriksson, BF Gage, SE Kimmel, MT Lee, NA Limdi, ... The New England journal of medicine 360 (8), 753-764, 2009 845 2009 AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1 S Satoh, Y Daigo, Y Furukawa, T Kato, N Miwa, T Nishiwaki, T Kawasoe, ... Nature genetics 24 (3), 245-250, 2000 828 2000 Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene Y Mori, H Nagse, H Ando, A Horii, S Ichii, S Nakatsuru, T Aoki, Y Miki, ... Human molecular genetics 1 (4), 229-233, 1992 819 1992 Functional SNPs in the lymphotoxin-α gene that are associated with susceptibility to myocardial infarction K Ozaki, Y Ohnishi, A Iida, A Sekine, R Yamada, T Tsunoda, H Sato, ... Nature genetics 32 (4), 650-654, 2002 736 2002 Genome-wide detection and characterization of positive selection in human populations PC Sabeti, P Varilly, B Fry, J Lohmueller, E Hostetter, C Cotsapas, X Xie, ... Nature 449 (7164), 913-918, 2007 721 2007 A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage H Tanaka, H Arakawa, T Yamaguchi, K Shiraishi, S Fukuda, K Matsui, ... Nature 404 (6773), 42-49, 2000 710 2000 Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers KW Kinzler, MC Nilbert, B Vogelstein, TM Bryan, DB Levy, KJ Smith, ... Science 251 (4999), 1366-1370, 1991 674 1991 Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17 D Barker, E Wright, K Nguyen, L Cannon, P Fain, D Goldgar, DT Bishop, ... Science 236 (4805), 1100-1102, 1987 670 1987 An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy K Kobayashi, Y Nakahori, M Miyake, K Matsumura, E Kondo-Iida, ... Nature 394 (6691), 388-392, 1998 619 1998 The gene for familial polyposis coli maps to the long arm of chromosome 5 M Leppert, M Dobbs, P Scambler, P O'connell, Y Nakamura, D Stauffer, ... Science 238 (4832), 1411-1413, 1987 617 1987 Complete sequencing and characterization of 21,243 full-length human cDNAs T Ota, Y Suzuki, T Nishikawa, T Otsuki, T Sugiyama, R Irie, A Wakamatsu, ... Nature genetics 36 (1), 40-45, 2003 587 2003 Localization of an ataxia-telangiectasia gene to chromosome 11q22–23 RA Gatti, I Berkel, E Boder, G Braedt, P Charmley, P Concannon, F Ersoy, ... Nature Publishing Group 336 (6199), 577-580, 1988 585 1988 Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease W Satake, Y Nakabayashi, I Mizuta, Y Hirota, C Ito, M Kubo, T Kawaguchi, ... Nature genetics 41 (12), 1303-1307, 2009 557 2009 International network of cancer genome projects TJ Hudson, W Anderson, A Aretz, AD Barker, C Bell, RR Bernabé, ... Nature 464 (7291), 993-998, 2010 543 2010 Genome-wide Analysis of Gene Expression in Human Hepatocellular Carcinomas Using cDNA Microarray Identification of Genes Involved in Viral Carcinogenesis and Tumor Progression H Okabe, S Satoh, T Kato, O Kitahara, R Yanagawa, Y Yamaoka, ... Cancer research 61 (5), 2129-2137, 2001 542 2001 Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer T Sato, A Tanigami, K Yamakawa, F Akiyama, F Kasumi, G Sakamoto, ... Cancer research 50 (22), 7184-7189, 1990 527 1990 Genetic instability in pancreatic cancer and poorly differentiated type of gastric cancer HJ Han, A Yanagisawa, Y Kato, JG Park, Y Nakamura Cancer research 53 (21), 5087-5089, 1993 510 1993
抗癌新药 OTS964 诸平 据《科学转化医学》（ Science Translational Medicine ） 杂志网站 2014 年 10 月 22 日 报道，日本川崎市的肿瘤治疗科学株式会社（ オンコセラピー・サイエンス株式会社 ，或 Onco Therapy Science Inc., Kawasaki, Japan ）和美国芝加哥大学医学系（ Department of Medicine, The University of Chicago ）的研究人员合作研发出了一种名为 OTS964 的新型抗癌 药。 OTS964 的化学名称为 ( R )-9-(4-(1-( 二甲氨基 ) 丙烷 -2- 基 ) 苯基 )-8- 羟基 -6- 甲基噻吩 喹啉 -4(5 H )- 酮 { ( R )-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno quinolin-4(5 H )-one } ），这种药物被证明能消除移植在小鼠体内的侵袭性人肺癌组织。研究人员指出，其作用机理在于 OTS964 能抑制一种蛋白的活性，这种蛋白在包括肺癌和乳腺癌在内的多种癌症中过量表达，在健康成人组织中却鲜有表达。下图解释了脂质OTS964进入癌细胞之后，可以抑制 TOPK 酶，防止癌细胞最后阶段分裂。口服时药物耐受性很好， 毒性 有限。而将OTS964用脂质作为载体制成的一种通过静脉注射剂,使药效不会受到任何影响，但是副作用会更小一些。OTS964目标就是 TOPK酶，这是 一种 由多种人类癌细胞所产生的 蛋白质,它被认为是促进肿瘤的生长。TOPK 高 表达与乳腺癌和肺癌患者的预后不良有关。 这一研究成果 2014 年 10 月 22 日 在《科学转化医学》（ Science Translational Medicine ）杂志网站发表—— Yo Matsuo , Jae-Hyun Park , Takashi Miyamoto 1 , Shinji Yamamoto 1 , Shoji Hisada 1 , Houda Alachkar and Yusuke Nakamura . TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis . Science Translational Medicine 22 October 2014: Vol. 6, Issue 259, p. 259ra145. DOI: 10.1126/scitranslmed.3010277. 7 位作者中芝加哥大学医学教授 中村祐輔 （ Yusuke Nakamura ）博士是通讯作者，他原来在日本东京大学人类基因组中心工作过，是一位日本遗传学领域的杰出科学家，曾领导和组织过日本一些最大的科研项目，同时他还创建了肿瘤治疗科学株式会社。这位日本顶尖的遗传学家、原东京大学人类基因组中心的 中村 祐輔 （ Yusuke Nakamura ）教授在 2012 年上半年加入了芝加哥大学。 中村 祐輔 表示，他离开日本是因为对基因组学研究的支持缺乏，而他在 2011 年 1 月担任医药创新局（ Office of Medical Innovation ）的秘书长后，也感到无能为力。他在接受《自然》(NATURE)杂志采访时表示：“创新局不起任何作用。我无事可做。” 中村 祐輔 是日本的顶尖科学家之一，曾领导了日本一些最大的科研项目。此外，他还是一位成功的生物技术企业家，创立了肿瘤治疗科学株式会社（ OncoTherapy Science Inc. ）。由于 中村 祐輔 的努力，日本在国际 HapMap 项目中大约完成了四分之一的工作。但从那之后，日本基因组学研究的经费开始枯竭。政府转向支持后基因组学研究，启动大规模项目来研究蛋白结构等。 中村 祐輔 教授说，“十年前，我们就发现了这种药物的分子靶标，但却花费了近十年的时间才找到抑制它的有效方法。我们最初筛选出了 30 万种化合物，然后合成了其中的 1000 多种，再从中找到了一些在人体内发挥作用的化合物。最后我们定位在最有效的一种化合物，我认为现在我们终于找到了非常有前景的东西。” OTS964 可以口服，也可以注射入人体，其一大特点就是毒性低，采用注射的方式比口服方式的毒性还可以再降低一些，因为口服药物是包裹在一种脂质体之中的。无论是口服还是注射，实验结果都表明这两种方法均能完全消除移植的肿瘤。更多信息请浏览原文。 Sci Transl Med 22 October 2014: Vol. 6, Issue 259, p. 259ra145 Sci. Transl. Med. DOI: 10.1126/scitranslmed.3010277 RESEARCH ARTICLE CANCER TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis Yo Matsuo 1 , * , Jae-Hyun Park 2 , * , Takashi Miyamoto 1 , Shinji Yamamoto 1 , Shoji Hisada 1 , Houda Alachkar 2 and Yusuke Nakamura 2 , † ↵ * These authors contributed equally to this work. ↵ † Corresponding author. E-mail: ynakamura@bsd.uchicago.edu Abstract TOPK (T–lymphokine-activated killer cell–originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. We report the development of a potent TOPK inhibitor, OTS964 {( R )-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno quinolin-4(5 H )-one}, which inhibits TOPK kinase activity with high affinity and selectivity. Similar to the knockdown effect of TOPK small interfering RNAs (siRNAs), this inhibitor causes a cytokinesis defect and the subsequent apoptosis of cancer cells in vitro as well as in xenograft models of human lung cancer. Although administration of the free compound induced hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively caused complete regression of transplanted tumors without showing any adverse reactions in mice. Our results suggest that the inhibition of TOPK activity may be a viable therapeutic option for the treatment of various human cancers.
标签: Nakamura）
