... Japan Search for more papers by this author Kenzo Takada Corresponding Author Kenzo Takada Department of Tumor Virology, Institute for Genetic Medicine, ... Japan Search for more papers by this author Kenzo Takada Corresponding Author Kenzo Takada Department of Tumor Virology, Institute for Genetic Medicine, ... Asuka Nanbo1, Kaori Inoue1, Kumi Adachi-Takasawa1 and Kenzo Takada 1 1Department of Tumor Virology, Institute for Genetic ...
Tópico(s): Viral-associated cancers and disorders
2002 - Springer Nature | The EMBO Journal
... Japan Search for more papers by this author Kenzo Takada Corresponding Author Kenzo Takada Department of Tumor Virology, Institute for Genetic Medicine, ... Japan Search for more papers by this author Kenzo Takada Corresponding Author Kenzo Takada Department of Tumor Virology, Institute for Genetic Medicine, ... Ken-ichiro Hino6, Toshiya Suzuki7, Satoru Todo2 and Kenzo Takada 1 1Department of Tumor Virology, Institute for Genetic ...
Tópico(s): Cytomegalovirus and herpesvirus research
2000 - Springer Nature | The EMBO Journal
Katsuro Koike, Kunitada Shimotouno, Shuiti Okada, Hiroaki Okamoto, Norio Hayashi, Keiji Ueda, Shuichi Kaneko, Kazuhiko Koike, Osamu Yokosuka, Tsutomu Chiba, Hiroyuki Marusawa, Okio Hino, Toshikazu Utida, Masao Omata, Takeo Juji, Noriyuki Nojiri, Kenzo Takada, Tatsuo Miyamura, Toshiaki Osuga, Yoshiaki Ito,
... CrossSearch for more papers by this authorKenzo Takada, Kenzo Takada Cancer Institute, Hokkaido UniversitySearch for more papers by ... CrossSearch for more papers by this authorKenzo Takada, Kenzo Takada Cancer Institute, Hokkaido UniversitySearch for more papers by ...
Tópico(s): Liver Disease Diagnosis and Treatment
1999 - Oxford University Press | Japanese Journal of Cancer Research
Aya Shinozaki‐Ushiku, Akiko Kunita, Maya Isogai, Takashi Hibiya, Tetsuo Ushiku, Kenzo Takada, Masashi Fukayama,
ABSTRACT Epstein-Barr virus (EBV) is one of the major oncogenic viruses and is found in nearly 10% of gastric carcinomas. EBV is known to encode its own microRNAs (miRNAs); however, their roles have not been fully investigated. The present report is the largest series to comprehensively profile the expression of 44 known EBV miRNAs in tissue samples from patients with EBV-associated gastric carcinoma. Several miRNAs were highly expressed in EBV-associated gastric carcinoma, and in silico analysis ...
Tópico(s): RNA modifications and cancer
2015 - American Society for Microbiology | Journal of Virology
Shih-Hsin Chiu, Meng-Chuan Wu, Chung-Chun Wu, Yu‐Ching Chen, Su‐Fang Lin, John Hsu, Chung‐Shi Yang, Ching-Hwa Tsai, Kenzo Takada, Mei‐Ru Chen, Jen‐Yang Chen,
ABSTRACT Epstein-Barr virus (EBV) lytic replication involves complex processes, including DNA synthesis, DNA cleavage and packaging, and virion egress. These processes require many different lytic gene products, but the mechanisms of their actions remain unclear, especially for DNA cleavage and packaging. According to sequence homology analysis, EBV BALF3, encoded by the third leftward open reading frame of the BamHI-A fragment in the viral genome, is a homologue of herpes simplex virus type 1 UL28. ...
Tópico(s): Herpesvirus Infections and Treatments
2014 - American Society for Microbiology | Journal of Virology
Yu-Yan Lan, Tzu-Hao Yeh, Wei‐Hung Lin, Shih-Yi Wu, Hsiao-Ching Lai, Fang-Hsin Chang, Kenzo Takada, Yao Chang,
Zta is a lytic transactivator of Epstein-Barr virus (EBV) and has been shown to promote migration and invasion of epithelial cells. Although previous studies indicate that Zta induces expression of matrix metalloproteinase (MMP) 9 and MMP1, direct evidence linking the MMPs to Zta-induced cell migration and invasion is still lacking. Here we performed a series of in vitro studies to re-examine the expression profile and biologic functions of Zta-induced MMPs in epithelial cells derived from nasopharyngeal ...
Tópico(s): Peptidase Inhibition and Analysis
2013 - Public Library of Science | PLoS ONE
Guitao Zhang, Chi Man Tsang, Wen Deng, Yim Ling Yip, Vivian Wai Yan Lui, Sze Chuen Cesar Wong, Annie L.M. Cheung, Pok Man Hau, Mu‐Sheng Zeng, Maria Li Lung, Honglin Chen, Kwok Wai Lo, Kenzo Takada, Sai Wah Tsao,
Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection. However, the exact role of EBV in NPC pathogenesis remains elusive. Activation of signal transducer and activator of transcription 3 (STAT3) is common in human cancers including NPC and plays an important role in the pathogenesis and progression of human cancers. Interleukin-6 (IL-6), a major inflammatory cytokine, is a potent activator of STAT3. In this study, we report that EBV-infected immortalized ...
Tópico(s): Cytokine Signaling Pathways and Interactions
2013 - Public Library of Science | PLoS ONE
Asuka Nanbo, Haruna Terada, Kunihiro Kachi, Kenzo Takada, Tadashi Matsuda,
ABSTRACT Epstein-Barr virus (EBV), a human gamma herpesvirus, establishes a life-long latent infection in B lymphocytes and epithelial cells following primary infection. Several lines of evidence indicate that the efficiency of EBV infection in epithelial cells is accelerated up to 10 4 -fold by coculturing with EBV-infected Burkitt's lymphoma (BL) cells compared to infection with cell-free virions, indicating that EBV infection into epithelial cells is mainly mediated via cell-to-cell contact. However, ...
Tópico(s): Lymphoma Diagnosis and Treatment
2012 - American Society for Microbiology | Journal of Virology
Koichi R. Katsumura, Seiji Maruo, Kenzo Takada,
Epstein-Barr virus (EBV) establishes lifelong latency in B-lymphocytes following infection. Although in immune-competent individuals EBV remains in a quiescent state, in immunodeficient individuals, such as those with AIDS or transplant recipients, B-lymphocytes infected with EBV proliferate to give rise to lymphoproliferative diseases. Similarly, in vitro, EBV transforms human B-lymphocytes into indefinitely growing lymphoblastoid cell lines (LCLs) in the absence of cytotoxic T-lymphocytes. Although ...
Tópico(s): Parvovirus B19 Infection Studies
2012 - Wiley | Journal of Medical Virology
Chi Man Tsang, Yim Ling Yip, Kwok Wai Lo, Wen Deng, Ka‐Fai To, Pok Man Hau, Victoria Ming Yi Lau, Kenzo Takada, Vivian Wai Yan Lui, Maria Li Lung, Honglin Chen, Mu‐Sheng Zeng, Jaap M. Middeldorp, Annie Lai-Man Cheung, Sai Wah Tsao,
Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is ...
Tópico(s): Parvovirus B19 Infection Studies
2012 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Maelinda Daker, Saatheeyavaane Bhuvanendran, Munirah Ahmad, Kenzo Takada, Alan Soo Beng Khoo,
Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein‑Barr virus (EBV). EBV‑encoded RNAs (EBERs) are small non‑polyadenylated RNAs that are abundantly expressed in latent EBV‑infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV‑negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer ...
Tópico(s): Cancer-related molecular mechanisms research
2012 - Spandidos Publishing | Molecular Medicine Reports
Minhua Sun, Hiroshi Uozaki, Rumi Hino, Akiko Kunita, Aya Shinozaki‐Ushiku, Tetsuo Ushiku, Takashi Hibiya, Kimiko Takeshita, Maya Isogai, Kenzo Takada, Masashi Fukayama,
Tópico(s): Gender Studies in Language
2012 - Springer Science+Business Media | Virchows Archiv
Chih‐Yeu Fang, Sheng‐Yen Huang, Chung-Chun Wu, Hui‐Yu Hsu, Sheng‐Ping Chou, Ching-Hwa Tsai, Yao Chang, Kenzo Takada, Jen‐Yang Chen,
Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). N-nitroso compounds, phorbols, and butyrates are chemicals found in food and herb samples collected from NPC high-risk areas. These chemicals have been reported to be risk factors contributing to the development of NPC, however, the underlying mechanism is not fully understood. We have demonstrated previously that low dose N-methyl-N’-nitro-N-nitrosoguanidine ( ...
Tópico(s): Polyomavirus and related diseases
2012 - Public Library of Science | PLoS ONE
Yu-Hsin Chang, Chung‐Pei Lee, Mei-Tzu Su, Jiin-Tarng Wang, Jen‐Yang Chen, Su‐Fang Lin, Ching‐Hwa Tsai, Min-Jei Hsieh, Kenzo Takada, Mei‐Ru Chen,
Epstein-Barr virus (EBV) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus. The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1. However, the observation that RB is hyperphosphorylated in the presence of ...
Tópico(s): Polyomavirus and related diseases
2012 - Public Library of Science | PLoS ONE
Ritsuro Suzuki, Motoko Yamaguchi, Koji Izutsu, Go Yamamoto, Kenzo Takada, Yasuaki Harabuchi, Yasushi Isobe, Hiroshi Gomyo, Tadashi Koike, Masataka Okamoto, Rie Hyo, Junji Suzumiya, Shigeo Nakamura, Keisei Kawa, Kazuo Oshimi,
Abstract Epstein-Barr virus (EBV)–DNA was prospectively analyzed in plasma and mononuclear cells (MNCs) from peripheral blood in patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, to evaluate the clinical significance for diagnosis, monitoring the tumor burden, and prognostication. Thirty-three patients were enrolled, and 32 were evaluable. Pretreatment plasma and MNC EBV-DNA was detectable in 14 (range, 50-71 000 copies/mL) and 6 patients (range, 20-780 copies/μg DNA), respectively, ...
Tópico(s): Immune Cell Function and Interaction
2011 - Elsevier BV | Blood
Takeharu Minamitani, Dai Iwakiri, Kenzo Takada,
The current study demonstrates that adenovirus virus-associated RNA (VA) is recognized by retinoic acid-inducible gene I (RIG-I), a cytosolic pattern recognition receptor, and activates RIG-I downstream signaling, leading to the induction of type I interferons (IFNs), similarly to Epstein-Barr virus-encoded small RNA. Further analysis revealed that adenovirus infection leads to biphasic type I IFN induction at 12 to 24 h and 48 to 60 h postinfection. The later induction coincided with VA expression ...
Tópico(s): Animal Virus Infections Studies
2011 - American Society for Microbiology | Journal of Virology
Kei Sato, Naoko Misawa, Chuanyi Nie, Yorifumi Satou, Dai Iwakiri, Masao Matsuoka, Rei Takahashi, Kiyotaka Kuzushima, Mamoru Ito, Kenzo Takada, Yoshio Koyanagi,
Tópico(s): Parvovirus B19 Infection Studies
2011 - Elsevier BV | Blood
Keisuke Matsusaka, Atsushi Kaneda, Genta Nagae, Tetsuo Ushiku, Yasuko Kikuchi, Rumi Hino, Hiroshi Uozaki, Yasuyuki Seto, Kenzo Takada, Hiroyuki Aburatani, Masashi Fukayama,
Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric cancers ...
Tópico(s): Cancer-related gene regulation
2011 - American Association for Cancer Research | Cancer Research
Teru Kanda, Sachiko Shibata, Satoru Saito, Takayuki Murata, Hiroki Isomura, Hironori Yoshiyama, Kenzo Takada, Tatsuya Tsurumi,
A group of repetitive sequences, known as the Family of Repeats (FR), is a critical cis-acting sequence required for EBV latent infection. The FR sequences are heterogeneous among EBV strains, and they are sometimes subject to partial deletion when subcloned in E. coli-based cloning vectors. However, the FR stability in EBV-BAC (bacterial artificial chromosome) system has never been investigated. We found that the full length FR of the Akata strain EBV was not stably maintained in a BAC vector. By ...
Tópico(s): Plant Virus Research Studies
2011 - Public Library of Science | PLoS ONE
Chien-Hsun Lee, Tzu-Hao Yeh, Hsiao-Ching Lai, Shih-Yi Wu, Ih‐Jen Su, Kenzo Takada, Yao Chang,
During lytic infection with Epstein-Barr virus (EBV), several viral lytic proteins function to evade immune recognition or to actively suppress immune cells. An EBV lytic transactivator, Zta, induces an immunosuppressive cytokine interleukin 10 (IL-10) in B cells, but whether it regulates IL-10 in the context of epithelial cells is unclear. In this study, we tested nasopharyngeal carcinoma (NPC) cell lines and found that Zta did not induce IL-10 in these epithelial cells. Interestingly, the conditioned ...
Tópico(s): Chemokine receptors and signaling
2011 - American Society for Microbiology | Journal of Virology
Epstein-Barr virus (EBV)-encoded small RNA (EBER) is the most abundant EBV viral transcript and is used as a target molecule to detect EBV-infected cells in tissues by in situ hybridization. EBER is expected to form double-stranded RNA-like structures. The results of the present study show that EBER contributes to oncogenesis by modulating innate immunity in patients with NPC and Burkett's lymphoma. BARF1 is a homolog of the human proto-oncogene c-fms and is expressed as a latent gene in NPC. Reconstitution ...
Tópico(s): Cancer-related molecular mechanisms research
2011 - Elsevier BV | Seminars in Cancer Biology
Seiji Maruo, Bo Zhao, Eric Johannsen, Elliott Kieff, James Zou, Kenzo Takada,
Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and EBNA3A are each essential for EBV conversion of primary human B lymphocytes into continuously proliferating lymphoblast cell lines (LCLs) and for maintaining LCL growth. We now find that EBNA3C and EBNA3A's essential roles are to repress p16(INK4A) and p14(ARF). In the absence of EBNA3C or EBNA3A, p16(INK4A) and p14(ARF) expression increased and cell growth ceased. EBNA3C inactivation did not alter p16(INK4A) promoter CpG methylation, but reduced ...
Tópico(s): Epigenetics and DNA Methylation
2011 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Stéphanie Fiola, David Gosselin, Kenzo Takada, Jean Gosselin,
Abstract TLR9 plays an important role in innate defense against viruses by the detection of CpG motifs of foreign DNA within intracellular compartments. In this study, we evaluated the ability of EBV to promote monocyte and plasmacytoid dendritic cell (pDC) activation and cytokine release through TLR9 activation. We demonstrated that treatment of primary monocytes with EBV and with purified EBV DNA induced the release of IL-8 through TLR9. Activation of TLR9 by viral DNA requires endosomal maturation ...
Tópico(s): Immune Response and Inflammation
2010 - American Association of Immunologists | The Journal of Immunology
Hsiao-Ching Lai, Jenn-Ren Hsiao, Chaio-Wei Chen, Shih-Yi Wu, Chien-Hsun Lee, Ih‐Jen Su, Kenzo Takada, Yao Chang,
Tumor-infiltrating T lymphocytes are considered to facilitate development of Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), but how EBV in NPC tumor cells directs T cell infiltration remains unclear. Here we compare EBV-infected NPC cells with and without spontaneous expression of viral latent membrane protein 1 (LMP1) and find that culture supernatants of LMP1-positive NPC cells exert enhanced chemoattraction to primary T cells. Knockdown of endogenous LMP1 in the cells suppresses ...
Tópico(s): Histiocytic Disorders and Treatments
2010 - Elsevier BV | Virology
Chi Man Tsang, Guitao Zhang, Eri Seto, Kenzo Takada, Wen Deng, Yim Ling Yip, Cornelia Man, Pok Man Hau, Honglin Chen, Ya Cao, Kwok Wai Lo, Jaap M. Middeldorp, Annie Lai Man Cheung, Sai Wah Tsao,
Abstract Epstein‐Barr virus (EBV) infection has been postulated to be an early event involved in the pathogenesis of nasopharyngeal carcinomas (NPC). The lack of representative premalignant nasopharyngeal epithelial cell system for EBV infection has hampered research investigation into the regulation and involvement of EBV infection in NPC pathogenesis. We have compared the efficiency of EBV infection in nasopharyngeal epithelial cells with different biological properties including immortalized, primary ...
Tópico(s): Cholangiocarcinoma and Gallbladder Cancer Studies
2010 - Wiley | International Journal of Cancer
Sheng‐Yen Huang, Chih‐Yeu Fang, Ching-Hwa Tsai, Yao Chang, Kenzo Takada, Tsuey-Ying Hsu, Jen‐Yang Chen,
Seroepidemiological studies implicate a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). Moreover, N-nitroso compounds are known chemical carcinogens in preserved foodstuffs and cigarettes and have been implicated as risk factors contributing to the development of NPC. Here, NPC cell lines latently infected with EBV, NA and HA, and the corresponding EBV-negative NPC cell lines, NPC-TW01 and HONE-1, were used as the model system in this ...
Tópico(s): Polyomavirus and related diseases
2010 - Elsevier BV | Chemico-Biological Interactions
Bo Zhao, Jessica C. Mar, Seiji Maruo, Sung Wook Lee, Benjamin E. Gewurz, Eric Johannsen, Kristina M. Holton, Renee Rubio, Kenzo Takada, John Quackenbush, Elliott Kieff,
EBV nuclear antigen 3C (EBNA3C) is an essential transcription factor for EBV transformed lymphoblast cell line (LCL) growth. To identify EBNA3C-regulated genes in LCLs, microarrays were used to measure RNA abundances in each of three different LCLs that conditionally express EBNA3C fused to a 4-OH-Tamoxifen–dependent estrogen receptor hormone binding domain (EBNA3CHT). At least three RNAs were assayed for each EBNA3CHT LCL under nonpermissive conditions, permissive conditions, and nonpermissive conditions ...
Tópico(s): Cancer-related molecular mechanisms research
2010 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Epstein–Barr virus (EBV)-encoded small RNAs (EBERs) are noncoding RNAs that are expressed abundantly in latently EBV-infected cells. Previous studies demonstrated that EBERs (EBER1 and EBER2) play significant roles in various EBV-infected cancer cells. EBERs are responsible for malignant phenotypes of Burkitt's lymphoma (BL) cells including resistance to apoptosis. In addition, EBERs induce the expression of interleukin (IL)-10 in BL cells, insulin-like growth factor (IGF)-1 in gastric carcinoma and nasopharyngeal ...
Tópico(s): Immune Cell Function and Interaction
2010 - Elsevier BV | Advances in cancer research
Aya Shinozaki‐Ushiku, Takashi Sakatani, Tetsuo Ushiku, Rumi Hino, Maya Isogai, Shunpei Ishikawa, Hiroshi Uozaki, Kenzo Takada, Masashi Fukayama,
Abstract EBV-associated gastric carcinoma is a distinct gastric carcinoma subtype with characteristic morphologic features similar to those of cells that undergo epithelial-to-mesenchymal transition. The effect of microRNA abnormalities in carcinogenesis was investigated by measuring the expression of the epithelial-to-mesenchymal transition–related microRNAs, miR-200a and miR-200b, in 36 surgically resected gastric carcinomas using quantitative reverse transcription-PCR analysis. MiR-200 family ...
Tópico(s): Circular RNAs in diseases
2010 - American Association for Cancer Research | Cancer Research
Hisashi Iizasa, Bjorn‐Erik Wulff, Nageswara R. Alla, Manolis Maragkakis, Molly Megraw, Artemis G. Hatzigeorgiou, Dai Iwakiri, Kenzo Takada, Andreas Wiedmer, Louise C. Showe, Paul M. Lieberman, Kazuko Nishikura,
Certain primary transcripts of miRNA (pri-microRNAs) undergo RNA editing that converts adenosine to inosine. The Epstein-Barr virus (EBV) genome encodes multiple microRNA genes of its own. Here we report that primary transcripts of ebv-miR-BART6 (pri-miR-BART6) are edited in latently EBV-infected cells. Editing of wild-type pri-miR-BART6 RNAs dramatically reduced loading of miR-BART6-5p RNAs onto the microRNA-induced silencing complex. Editing of a mutation-containing pri-miR-BART6 found in Daudi Burkitt ...
Tópico(s): Parvovirus B19 Infection Studies
2010 - Elsevier BV | Journal of Biological Chemistry