Establishment of highly safe gene therapy without usage of double stranded DNA

• Project/Area Number: 17H06269
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: General internal medicine and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Chayama Kazuaki 広島大学, 医系科学研究科(医), 教授 (00211376)
• Co-Investigator(Kenkyū-buntansha): 三木 大樹 広島大学, 医系科学研究科(医), 講師 (10584592) ; 茶山 弘美 広島大学, 医系科学研究科(医), 准教授 (70572329) ; 林 亮平 広島大学, 病院(医), 病院助教 (80772053)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000); Fiscal Year 2019: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000); Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: genome editing / exosome / dsDNA / cancer therapy / lentivirus / cas9 / ゲノム編集

Outline of Final Research Achievements

Gene therapy can be used for many diseases such as hereditary diseases, cancer and viral infections. Many recessive diseases, which account for a large number of inherited diseases, restore the cell function by normalizing one site of the gene. Although gene therapyis a desirable therapy, it has been regarded as difficult to implement because there is no easy method for gene repair. Genes can be normalized by using the recently developed CRISPR / cas9 system, which is expected to make a breakthrough in gene therapy. However, the conventional methods have a risk of causing unnecessary gene modification. In this study, we attempted to perform a safe gene therapy. To perform this we established a method to express cas9 protein in normal hepatocytes.

Academic Significance and Societal Importance of the Research Achievements

本研究は遺伝子治療を安全性に行うという肝炎からの改良を模索したものである。dsDNAを生体に導入することなく、しかもCas9の長期的な非特異切断も防いでいる点で従来の遺伝子治療とは異なっており、Cas9を用いた遺伝子治療の応用を遺伝病のみならず癌やウイルス感染症、代謝性疾患などなど多方面に大きく広げるものとなる。遺伝子治療のもう一つの重要な要因にdeliveryがある。本研究ではそれらのいずれかを応用することを視野に入れつつ、自己の細胞から産生されるexcreted vesicle(EV)をdeliveryに用いることを考案した。

Research Products

• [Journal Article] Three Children Treated with Direct-acting Antivirals for Chronic Hepatitis C Virus Genotype 1b Infection (2020)
  • Author(s): Ohya K, Kawaoka T, Imamura M, Morio K, Nakahara T, Murakami E, Yamauchi M, Hiramatsu A, Tsuge M, Aikata H, Chayama K.
  • Journal Title: Internal Medicine Volume: 59 Issue: 7 Pages: 941-944
  • DOI: 10.2169/internalmedicine.3824-19
  • NAID: 130007825289
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Regression of Idiopathic Thrombocytopenic Purpura in a Patient With Eradication of Hepatitis C Virus by Direct-Acting Antivirals. (2020)
  • Author(s): Johira Y, Hatooka H, Mori N, Fukuhara T, Takaki S, Shimomura Y, Imamura M, Hayes CN, Tsuji K, Chayama K.
  • Journal Title: Hepatology. Volume: 71 Issue: 1 Pages: 389-391
  • DOI: 10.1002/hep.30900
  • Peer Reviewed / Open Access
• [Journal Article] Successful retreatment with 12 weeks of glecaprevir and pibrentasvir for a genotype 2a HCV-infected hemodialysis patient who failed to respond to 8 weeks of prior glecaprevir and pibrentasvir therapy. (2020)
  • Author(s): Ohya K, Imamura M, Osawa M, Teraoka Y, Morio K, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Hiramatsu A, Tsuge M, Aikata H, Hayes CN, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: 13 Issue: 2 Pages: 267-270
  • DOI: 10.1007/s12328-019-01039-w
  • Peer Reviewed / Open Access
• [Journal Article] Management of refractory ascites attenuates muscle mass reduction and improves survival in patients with decompensated cirrhosis. (2020)
  • Author(s): Namba M, Hiramatsu A, Aikata H, Kodama K, Uchikawa S, Ohya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Tsuge M, Imamura M, Chayama K.
  • Journal Title: J Gastroenterol. Volume: 55 Issue: 2 Pages: 217-226
  • DOI: 10.1007/s00535-019-01623-4
  • Peer Reviewed / Open Access
• [Journal Article] Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV-infected Japanese Subjects in Phase 3 CERTAIN-1 and CERTAIN-2 Trials. (2020)
  • Author(s): Suleiman AA, Lin CW, Liu W, Eckert D, Mensing S, Burroughs M, Kato K, Chayama K, Kumada H, Oberoi RK.
  • Journal Title: J Clin Pharmacol. Volume: 60 Issue: 3 Pages: 331-339
  • DOI: 10.1002/jcph.1524
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan. (2020)
  • Author(s): Kawaguchi I, Chayama K, Gonzalez YS, Virabhak S, Mitchell D, Yuen C, Kumada H.
  • Journal Title: Adv Ther. Volume: 37 Issue: 1 Pages: 457-476
  • DOI: 10.1007/s12325-019-01166-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases. (2020)
  • Author(s): Daijo K, Nakahara T, Inagaki Y, Nanba M, Nishida Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Ono A, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Imamura M, Aikata H, Ochi H, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: - Issue: 8 Pages: 1412-1419
  • DOI: 10.1111/jgh.14968
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative PET-CT is useful for predicting recurrent extrahepatic metastasis of hepatocellular carcinoma after resection. (2020)
  • Author(s): Morio K, Kawaoka T, Aikata H, Namba M, Uchikawa S, Kodama K, Ohya K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Nakamura Y, Akagi M, Awai K, Kobayashi T, Ohdan H, Chayama K.
  • Journal Title: Eur J Radiol. Volume: 124 Pages: 108828-108828
  • DOI: 10.1016/j.ejrad.2020.108828
  • NAID: 120007097014
  • Peer Reviewed / Open Access
• [Journal Article] A case of advanced HCC treated with lenvatinib after hepatic arterial infusion chemotherapy combined with radiation therapy treatment for portal vein tumor thrombosis in the main trunk. (2020)
  • Author(s): Kosaka Y, Kawaoka T, Aikata H, Suehiro Y, Yamaoka K, Ando Y, Namba M, Takeuchi Y, Fujii Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Baba Y, Awai K, Kimura T, Nagata Y, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: - Issue: 5 Pages: 839-843
  • DOI: 10.1007/s12328-020-01093-9
  • Peer Reviewed / Open Access
• [Journal Article] Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability. (2020)
  • Author(s): Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Kodama K, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Clin J Gastroenterol. Volume: - Issue: 5 Pages: 867-872
  • DOI: 10.1007/s12328-020-01099-3
  • NAID: 120007167205
  • Peer Reviewed / Open Access
• [Journal Article] Publisher Correction: Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP. (2020)
  • Author(s): Makokha GN, Abe-Chayama H, Chowdhury S, Hayes CN, Tsuge M, Yoshima T, Ishida Y, Zhang Y, Uchida T, Tateno C, Akiyama R, Chayama K.
  • Journal Title: Sci Rep. Volume: 10 Issue: 1 Pages: 2233-2233
  • DOI: 10.1038/s41598-020-58888-6
  • Peer Reviewed / Open Access
• [Journal Article] JNJ-4178 (adafosbuvir, odalasvir, and simeprevir) in Japanese patients with chronic hepatitis C virus genotype 1 or 2 infection with or without compensated cirrhosis: The Phase IIa OMEGA-3 study. (2020)
  • Author(s): Takehara T, Chayama K, Kurosaki M, Yatsuhashi H, Tanaka Y, Hiramatsu N, Sakamoto N, Asahina Y, Nozaki A, Nakano T, Hagiwara Y, Shimizu H, Yoshida H, Huang Y, Biermer M, Vijgen L, Hayashi N.
  • Journal Title: J Gastroenterol Volume: － Issue: 6 Pages: 640-652
  • DOI: 10.1007/s00535-020-01672-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab. (2020)
  • Author(s): Kawaoka T, Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Hepatol Res. Volume: - Issue: 7 Pages: 885-888
  • DOI: 10.1111/hepr.13496
  • Peer Reviewed / Open Access
• [Journal Article] Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease (2020)
  • Author(s): Okamoto, K. Koda, M. Okamoto, T. Onoyama, T. Miyoshi, K. Kishina, M. Matono, T. Kato, J. Tokunaga, S. Sugihara, T. Hiramatsu, A. Hyogo, H. Tobita, H. Sato, S. Kawanaka, M. Hara, Y. Hino, K. Chayama, K. Murawaki, Y. Isomoto, H.
  • Journal Title: PLoS One Volume: 15 Issue: 2 Pages: e0219412-e0219412
  • DOI: 10.1371/journal.pone.0219412
  • Peer Reviewed / Open Access
• [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations. (2020)
  • Author(s): Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
  • Journal Title: EBioMedicine Volume: 53 Pages: 102659-102659
  • DOI: 10.1016/j.ebiom.2020.102659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection. (2020)
  • Author(s): Cheng X, Uchida T, Xia Y, Umarova R, Liu CJ, Chen PJ, Gaggar A, Suri V, Mucke MM, Vermehren J, Zeuzem S, Teraoka Y, Osawa M, Aikata H, Tsuji K, Mori N, Hige S, Karino Y, Imamura M, Chayama K, Liang TJ.
  • Journal Title: J Clin Invest. Volume: - Issue: 6 Pages: 3205-3220
  • DOI: 10.1172/jci135616
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma. (2020)
  • Author(s): Juhling F, Hamdane N, Crouchet E, Li S, El Saghire H, Mukherji A, Fujiwara N, Oudot MA, Thumann C, Saviano A, Roca Suarez AA, Goto K, Masia R, Sojoodi M, Arora G, Aikata H, Ono A, Tabrizian P, Schwartz M, Polyak SJ, Davidson I, Schmidl C, Chayama K, et al.
  • Journal Title: Gut. Volume: - Issue: 1 Pages: 157-169
  • DOI: 10.1136/gutjnl-2019-318918
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy. (2019)
  • Author(s): Nagaoki Y, Imamura M, Nishida Y, Daijo K, Teraoka Y, Honda F, Nakamura Y, Morio K, Fujino H, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Miki D, Hiyama Y, Ochi H, Chayama K, Aikata H.
  • Journal Title: J Med Virol. Volume: 91 Issue: 4 Pages: 650-658
  • DOI: 10.1002/jmv.25352
  • Peer Reviewed / Open Access
• [Journal Article] A nationwide survey on non-B, non-C hepatocellular carcinoma in Japan: 2011-2015 update. (2019)
  • Author(s): Tateishi R, Uchino K, Fujiwara N, Takehara T, Okanoue T, Seike M, Yoshiji H, Yatsuhashi H, Shimizu M, Torimura T, Moriyama M, Sakaida I, Okada H, Chiba T, Chuma M, Nakao K, Isomoto H, Sasaki Y, Kaneko S, Masaki T, Chayama K, Koike K.
  • Journal Title: J Gastroenterol. Volume: 54 Issue: 4 Pages: 367-376
  • DOI: 10.1007/s00535-018-1532-5
  • Peer Reviewed / Open Access
• [Journal Article] HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease. (2019)
  • Author(s): Fujii H, Yoneda M, et al.
  • Journal Title: J Gastroenterol Hepatol. Volume: in press Issue: 8 Pages: 1-6
  • DOI: 10.1111/jgh.14595
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis (2019)
  • Author(s): Kodama Kazuhisa、Kawaguchi Takumi、Hyogo Hideyuki、Nakajima Tomoaki、Ono Masafumi、Sumida Yoshio、Kamada Yoshihiro、Fujii Hideki、Seko Yuya、Takehara Tetsuo、Itoh Yoshito、Nakajima Atsushi、Masaki Naohiko、Torimura Takuji、Saibara Toshiji、Karino Yoshiyasu、Chayama Kazuaki、Tokushige Katsutoshi
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: in press Issue: 9 Pages: 1626-1632
  • DOI: 10.1111/jgh.14608
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous transvenous shunt occlusion for portosystemic encephalopathy due to lenvatinib administration to a patient with hepatocellular carcinoma and portosystemic shunt. (2019)
  • Author(s): Namba M, Kawaoka T, Aikata H, Kodama K, Uchikawa S, Ohya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Baba Y, Awai K, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: 12 Issue: 4 Pages: 341-346
  • DOI: 10.1007/s12328-019-00938-2
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice (2019)
  • Author(s): Tsushima K, Tsuge M, Hiraga N, Uchida T, Murakami E, Makokha GN, Kurihara M, Nomura Motonobu, Hiyama Y, Fujino H, Ono A, Nakahara T, Yamauchi M, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Aikata H, Hayes CN, Chayama K
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 7 Pages: 650-659
  • DOI: 10.1007/s00535-019-01558-w
  • Peer Reviewed / Open Access
• [Journal Article] Reply: Hepatectomy versus stereotactic body radiotherapy for primary early hepatocellular carcinoma: A propensity -matched analysis in a single institution. (2019)
  • Author(s): Nakano R, Ohira M, Kobayashi T, Ide K, Tahara H, Kuroda S, Shimizu S, Kimura T, Nagata Y, Aikata H, Chayama K, Ohdan H.
  • Journal Title: Surgery. Volume: 165 Issue: 5 Pages: 1054-1057
  • DOI: 10.1016/j.surg.2018.10.022
  • Peer Reviewed / Open Access
• [Journal Article] HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response. (2019)
  • Author(s): Hamdane N, Juhling F, Crouchet E, El Saghire H, Thumann C, Oudot MA, Bandiera S, Saviano A, Ponsolles C, Roca Suarez AA, Li S, Fujiwara N, Ono A, Davidson I, Bardeesy N, Schmidl C, Bock C, Schuster C, Lupberger J, Habersetzer F, Doffoel M, Piardi T, Sommacale D, Imamura M, Chayama K. et al.
  • Journal Title: Gastroenterology. Volume: 156 Issue: 8 Pages: 2313-2329.e7
  • DOI: 10.1053/j.gastro.2019.02.038
  • Peer Reviewed / Open Access
• [Journal Article] Real-world virological efficacy and safety of daclatasvir/asunaprevir/beclabuvir in patients with chronic hepatitis C virus genotype 1 infection in Japan. (2019)
  • Author(s): Takaguchi K, Toyoda H, Tsutsui A, Suzuki Y, Nakamuta M, Imamura M, Senoh T, Nagano T, Tada T, Tachi Y, Hiraoka A, Michitaka K, Shibata H, Joko K, Okubo H, Tsuji K, Takaki S, Watanabe T, Ogawa C, Chayama K, Kumada T, Kudo M, Kumada H.
  • Journal Title: J Gastroenterol. Volume: 54 Issue: 8 Pages: 742-751
  • DOI: 10.1007/s00535-019-01568-8
  • Peer Reviewed / Open Access
• [Journal Article] Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection. (2019)
  • Author(s): Naganuma A, Chayama K, Notsumata K, Gane E, Foster GR, Wyles D, Kwo P, Crown E, Bhagat A, Mensa FJ, Otani T, Larsen L, Burroughs M, Kumada H.
  • Journal Title: J Gastroenterol. Volume: 54 Issue: 8 Pages: 752-761
  • DOI: 10.1007/s00535-019-01569-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development. (2019)
  • Author(s): Lupberger J, Croonenborghs T, Roca Suarez AA, Van Renne N, Juhling F, Oudot MA, Virzi A, Bandiera S, Jamey C, Meszaros G, Brumaru D, Mukherji A, Durand SC, Heydmann L, Verrier ER, El Saghire H, Hamdane N, Bartenschlager R, Fereshetian S, Ramberger E, Sinha R, Nabian M, Chayama K. et al.
  • Journal Title: Gastroenterology. Volume: 157 Issue: 2 Pages: 537-551.e9
  • DOI: 10.1053/j.gastro.2019.04.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes (2019)
  • Author(s): Xue Ruidong、Chen Lu、Zhang Chong、Fujita Masashi et al.
  • Journal Title: Cancer Cell Volume: 35 Issue: 6 Pages: 932-947
  • DOI: 10.1016/j.ccell.2019.04.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis. (2019)
  • Author(s): Yen CJ, Yang ST, Chen RY, Huang W, Chayama K, Lee MH, Yang SJ, Lai HS, Yen HY, Hsiao YW, Wang JM, Lin YJ, Hung LY.
  • Journal Title: J Biomed Sci. Volume: 26 Issue: 1 Pages: 44-44
  • DOI: 10.1186/s12929-019-0534-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP (2019)
  • Author(s): Makokha Grace Naswa、Abe-Chayama Hiromi、Chowdhury Sajeda、Hayes C. Nelson、Tsuge Masataka、Yoshima Tadahiko、Ishida Yuji、Zhang Yizhou、Uchida Takuro、Tateno Chise、Akiyama Rie、Chayama Kazuaki
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 8462-8462
  • DOI: 10.1038/s41598-019-44934-5
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of glecaprevir and pibrentasvir treatment for genotype 1b hepatitis C virus drug resistance-associated variants in humanized mice. (2019)
  • Author(s): Osawa M, Uchida T, Imamura M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Abe-Chayama H, Hayes CN, Makokha GN, Aikata H, Ishida Y, Tateno C, Miyayama Y, Hijikata M, Chayama K.
  • Journal Title: J Gen Virol. Volume: 100 Issue: 7 Pages: 1123-1131
  • DOI: 10.1099/jgv.0.001268
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib. (2019)
  • Author(s): Kodama K, Kawaoka T, Namba M, Uchikawa S, Ohya K, Morio K, Nakahara T, Murakami E, Yamauchi M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Oncology. Volume: 97 Issue: 2 Pages: 75-81
  • DOI: 10.1159/000499715
  • Peer Reviewed / Open Access
• [Journal Article] Management of HCV patients in cases of direct-acting antiviral failure. (2019)
  • Author(s): Hayes CN, Imamura M, Chayama K.
  • Journal Title: Expert Rev Gastroenterol Hepatol. Volume: 13 Issue: 9 Pages: 839-848
  • DOI: 10.1080/17474124.2019.1651642
  • Peer Reviewed / Open Access
• [Journal Article] Early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated by lenvatinib therapy. (2019)
  • Author(s): Ohya K, Kawaoka T, Namba M, Uchikawa S, Kodama K, Morio K, Nakahara T, Murakami E, Hiramatsu A, Tsuge M, Yamauchi M, Imamura M, Chayama K, Aikata H.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 12101-12101
  • DOI: 10.1038/s41598-019-48045-z
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of a self-management program in patients with chronic viral hepatitis in China. (2019)
  • Author(s): Cui Y, Moriyama M, Chayama K, Liu Y, Ya C, Muzembo BA, Rahman MM.
  • Journal Title: BMC Nurs. Volume: 18 Issue: 1 Pages: 44-44
  • DOI: 10.1186/s12912-019-0366-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy. (2019)
  • Author(s): Saito Y, Imamura M, Uchida T, Osawa M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Serikawa M, Aikata H, Abe-Chayama H, Hayes CN, Chayama K.
  • Journal Title: J Med Virol. Volume: 92 Issue: 2 Pages: 210-218
  • DOI: 10.1002/jmv.25602
  • Peer Reviewed
• [Journal Article] eVIDENCE: a practical variant filtering for low-frequency variants detection in cell-free DNA (2019)
  • Author(s): Mizuno Kei、Akamatsu Shusuke、Sumiyoshi Takayuki、Wong Jing Hao、Fujita Masashi et al.
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 15017-15017
  • DOI: 10.1038/s41598-019-51459-4
  • NAID: 120006734882
  • Peer Reviewed / Open Access
• [Journal Article] Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis. (2019)
  • Author(s): Fujino H, Tanaka M, Imamura M, Morio K, Ono A, Nakahara T, Murakami E, Kawaoka T, Takahashi S, Miki D, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Chayama K.
  • Journal Title: BMC Gastroenterol. Volume: 19 Issue: 1 Pages: 169-169
  • DOI: 10.1186/s12876-019-1092-z
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Lipids in Hepatocellular Carcinoma. (2019)
  • Author(s): Hayes CN, Zhang P, Chayama K.
  • Journal Title: Hepatocellular Carcinoma. Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolated cardiac metastases of hepatocellular carcinoma after resection: a case report. (2019)
  • Author(s): Tamura Y, Kawaoka T, Aikata H, Namba M, Fujii Y, Morio K, Murakami E, Yamauchi M, Hiramatsu A, Nakahara T, Imamura M, Maruhashi T, Kobayashi T, Ohdan H, Kimura T, Nagata Y, Arihiro K, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: - Issue: 3 Pages: 421-427
  • DOI: 10.1007/s12328-019-01075-6
  • Peer Reviewed / Open Access
• [Journal Article] Comparative study on the replication of HCV1b genome between wild-type and cell culture-adaptive mutant in regard to sensitivities against anti-HCV drugs. (2019)
  • Author(s): Miyayama Y, Lee H, Song H, Abe-Chayama H, Miki D, Imamura M, Chayama K, Hijikata M.
  • Journal Title: Microbiol Immunol. Volume: - Issue: 4 Pages: 296-303
  • DOI: 10.1111/1348-0421.12768
  • Peer Reviewed / Open Access
• [Journal Article] Sinusoidal obstruction syndrome post-treatment with trastuzumab emtansine (T-DM1) in advanced breast cancer. (2019)
  • Author(s): Fujii Y, Doi M, Tsukiyama N, Hattori Y, Ohya K, Shiroma N, Morio K, Morioka T, Aikata H, Shinozaki K, Chayama K.
  • Journal Title: Int Cancer Conf J. Volume: 9 Issue: 1 Pages: 18-23
  • DOI: 10.1007/s13691-019-00392-4
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers. (2018)
  • Author(s): Furuta M, Tanaka H, Shiraishi Y, Unida T, Imamura M, Fujimoto A, Fujita M, Sasaki-Oku A, Maejima K, Nakano K, Kawakami Y, Arihiro K, Aikata H, Ueno M, Hayami S, Ariizumi SI, Yamamoto M, Gotoh K, Ohdan H, Yamaue H, Miyano S, Chayama K, Nakagawa H.
  • Journal Title: Oncotarget. Volume: 9 Issue: 38 Pages: 25075-25088
  • DOI: 10.18632/oncotarget.25308
  • Peer Reviewed / Open Access
• [Journal Article] Genomic Characterization of Biliary Tract Cancers Identifies Driver Genes and Predisposing Mutations (2018)
  • Author(s): Wardell CP, Fujita M, Yamada T, Simbolo M, Fassan M, Karlic R, Polak P, Kim J, Hatanaka Y, Maejima K, Lawlor RT, Nakanishi Y, Mitsuhashi T et al
  • Journal Title: J Hepatol Volume: - Issue: 5 Pages: 959-969
  • DOI: 10.1016/j.jhep.2018.01.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] miR-135a-5p-mediated downregulation of protein tyrosine phosphatase receptor delta is a candidate driver of HCV-associated hepatocarcinogenesis. (2018)
  • Author(s): Van Renne N, Roca Suarez AA, Duong FHT, Gondeau C, Calabrese D, Fontaine N, Ababsa A, Bandiera S, Croonenborghs T, Pochet N, De Blasi V, Pessaux P, Piardi T, Sommacale D, Ono A, Chayama K, Fujita M, Nakagawa H, Hoshida Y, Zeisel MB, Heim MH, Baumert TF, Lupberger J.
  • Journal Title: Gut. Volume: 67 Issue: 5 Pages: 953-962
  • DOI: 10.1136/gutjnl-2016-312270
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serial profiling of circulating tumor DNA for optimization of anti-VEGF chemotherapy in metastatic colorectal cancer patients. (2018)
  • Author(s): Yamauchi M, Urabe Y, Ono A, Miki D, Ochi H, Chayama K.
  • Journal Title: Int J Cancer. Volume: 142 Issue: 7 Pages: 1418-1426
  • DOI: 10.1002/ijc.31154
  • Peer Reviewed / Open Access
• [Journal Article] Silencing of Discoidin Domain Receptor-1 (DDR1) Concurrently Inhibits Multiple Steps of Metastasis Cascade in Gastric Cancer (2017)
  • Author(s): Yuge R, Kitadai Y, Takigawa H, Naito T, Oue N, Yasui W, Tanaka S, Chayama K
  • Journal Title: Transl Oncol Volume: 11 Issue: 3 Pages: 575-584
  • DOI: 10.1016/j.tranon.2018.02.003
  • Peer Reviewed / Open Access
• [Journal Article] Mesenchymal Stem Cells Induce Epithelial to Mesenchymal Transition in Colon Cancer Cells through Direct Cell-to-Cell Contact. (2017)
  • Author(s): Takigawa H, Kitadai Y, Shinagawa K, Yuge R, Higashi Y, Tanaka S, Yasui W, Chayama K.
  • Journal Title: Neoplasia. Volume: 19 Issue: 5 Pages: 429-438
  • DOI: 10.1016/j.neo.2017.02.010
  • Peer Reviewed / Open Access
• [Presentation] HCV治療の今後の展望-ウイルス性肝炎撲滅を目指した最新治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第45回日本急性肝不全研究会
• [Presentation] HCV治療の今後の展望-ウイルス性肝炎撲滅を目指した最新治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第20回日本肝がん分子標的治療研究会
• [Presentation] 最新のC型肝炎、肝硬変の治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第33回日本臨床内科医学会
• [Presentation] ウイルス性肝炎研究の進歩と今後の課題 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第23回日本肝臓学会大会
• [Presentation] 肝硬変診療の課題 (2019)
  • Author(s): 茶山一彰
  • Organizer: 日本消化器関連学会機構（JDDW）2019
• [Presentation] Malignant potential of early-stage serrated adenocarcinoma based on genetic analysis (2018)
  • Author(s): Urabe Y, Tanaka S, Hirano D, Nakamura K, Ninomiya Y, Yuge R, Hayashi R, Oka S, Kitadai Y, Shimamoto F, Arihiro K, Chayama K
  • Organizer: 26th United European Gastroenterology Week (UEGW) 2018
  • Int'l Joint Research
• [Book] 肝原発平滑筋肉腫の一例 (2019)
  • Author(s): 山岡賢治, 児玉健一郎, 河岡友和, 難波麻衣子, 内川慎介, 大屋一輝, 盛生 慶, 中原隆志, 村上英介, 山内理海, 平松 憲, 今村道雄, 相方 浩, 織田麻琴, 有廣光司, 小林 剛, 大段秀樹, 茶山一彰
  • Publisher: 肝臓
• [Remarks] 広島大学大学院 医系科学研究科 消化器・代謝内科学
  • URL: http://shounai.hiroshima-u.ac.jp/
• [Remarks] 広島大学 自立型研究拠点 肝臓・消化器研究拠点
  • URL: http://shounai.hiroshima-u.ac.jp/liverproject/
• [Remarks] 広島大学大学院医系科学研究科 消化器・代謝内科（広島大学病院 旧第一内科）
  • URL: http://shounai.hiroshima-u.ac.jp/
• [Remarks] 広島大学大学院医歯薬保健学研究科 消化器・代謝内科（広島大学病院 旧第一内科）
  • URL: http://shounai.hiroshima-u.ac.jp/
• [Patent(Industrial Property Rights)] Ｂ型肝炎治療用核酸分子 (2019)
  • Inventor(s): 茶山一彰/吉間忠彦/水谷隆之
  • Industrial Property Rights Holder: 茶山一彰/吉間忠彦/水谷隆之
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2019-514692
  • Filing Date: 2019
  • Acquisition Date: 2019