難治性の肝・胆道疾患に関する調査研究　厚生労働省難治性疾患政策研究事業

研究の成果

肝循環の基礎・臨床病理研究

最終更新日：2022年5月30日
  1. Hsu SJ, Zhang C, Jeong J, et al. Enhanced meningeal lymphatic drainage ameliorates neuroinflammation and hepatic encephalopathy in cirrhotic rats. Gastroenterology 2021, 160(4):1315-1329. https://pubmed.ncbi.nlm.nih.gov/33227282/
  2. Su T, Yang Y, Lai S, et al. Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis. Cellular and Molecular Gastroenterology and Hepatology 2021, 11(4):1139-1161. https://pubmed.ncbi.nlm.nih.gov/33340713/
  3. Yang Y, Sangwung P, Jung Y, et al. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcoholic liver disease. Journal of Hepatology. 2021. Mar 3: S0168-8278(21)00162-8. https://pubmed.ncbi.nlm.nih.gov/33675874/
  4. McConnell MJ, Kawaguchi N, Kondo R, et al. Liver injury in COVID-19 from IL-6 trans-signaling-induced endotheliopathy. Journal of Hepatology. 2021. 75(2):377-386.   https://pubmed.ncbi.nlm.nih.gov/33991637/
  5. Kondo R, Kawaguchi N, McConnell MJ, et al. Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: a series of 43 cases. Hepatology Research. 2021. 51(9):1000-1006. https://pubmed.ncbi.nlm.nih.gov/34260803/
  6. Atsushi Nanashima, Naoya Imamura, Masahide Hiyoshi1, Takeomi Hamada, Koichi Yano, Takashi Wada, Hiroshi Kawakami, Tesshin Ban, Yoshimasa Kubota, Yuichiro Sato, Kenichi Harada. Planned limited resection of the extrahepatic bile duct in a case of intraductal papillary neoplasm of the bile duct based on preoperative examinations. Clinical Journal of Gastroenterology. 2020 13(2) 233-239. https://pubmed.ncbi.nlm.nih.gov/31598905/
  7. Minako Yamamura, Yasunori Sato, Kenta Takahashi, Motoko Sasaki, Kenichi Harada. The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma. ONCOLOGY REPORTS   2020; 43: 306-317. https://pubmed.ncbi.nlm.nih.gov/31746435/
  8. Yoshio Sakai, Shinya Fukunishi, Masayuki Takamura, Oto Inoue, Shinichiro Takashima,Soichiro Usui, Akihiro Seki, Alessandro Nasti, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Akira Asai, Yusuke Tsuchimoto, Taro Yamashita, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Yasuhito Imai, Kenichi Yoshimura,Toshinori Murayama,Takashi Wada, Kenichi Harada, Kazuhide Higuchi, Shuichi Kaneko. Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial.  JMIR RESEARCH PROTOCOLS 2020  vol.9  iss.3  e17904  p1-7.   https://pubmed.ncbi.nlm.nih.gov/32229470/
  9. Mikiko Kobayashi, Yuki Matsumoto, Maki Ohya, Kenichi Harada, Hiroyuki kanno.　Histologic and immunohistochemical evaluation of infiltrating inflammatory cells in Kawasaki disease arteritis lesions. Immunohistochemistry & Molecular Morphology 2020 Apr 21. https://pubmed.ncbi.nlm.nih.gov/32324629/
  10. Risa Nakagawa, Nguyen Canh Hiep, Hirofumi Ouchi, Yasunori Sato, Kenichi Harada. Expression of fatty‑acid‑binding protein 5 in intrahepatic and extrahepatic cholangiocarcinoma: the possibility of different energy metabolisms in anatomical location Medical Molecular Morphology (2020) 53:42-49. https://pubmed.ncbi.nlm.nih.gov/31432248/
  11. Kumi Ozaki, Kenichi Harada, Noboru Terayama, Nobuyuki Kosaka, Hirohiko Kimura, Toshifumi Gabata. FDG‑PET/CT imaging findings of hepatic tumors and tumor‑like lesions based on molecular background. Japanese Journal of Radiology. 2020 38(8):697-718.  https://pubmed.ncbi.nlm.nih.gov/32246350/
  12. Margaux Sala , Delphine Gonzales , Thierry Leste-Lasserre , Nathalie Dugot-Senant, Valérie Paradis ,Sylvaine Di Tommaso ,Jean-William Dupuy ,Vincent Pitard ,Cyril Dourthe ,Amedeo Sciarra ,Christine Sempoux, Linda D. Ferrell, Andrew D. Clouston, Gregory Miller, Mathew M. Yeh, Swan Thung,　Annette S.H. Gouw,Alberto Quaglia, Jing Han, Ji Huan, Cathy Fan, James Crawford, Yasuni Nakanuma,Kenichi Harada, Brigitte le Bail , Claire Castain , Nora Frulio , Hervé Trillaud , Laurent Possenti,Jean-Frédéric Blanc , Laurence Chiche , Christophe Laurent, Charles Balabaud , Paulette Bioulac-Sage ,Anne Aurélie Raymond , and Frédéric Saltel. ASS1 Overexpression: A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice. Hepatology Communications. 2020 Jun;4(6):809-824. https://pubmed.ncbi.nlm.nih.gov/32490318/
  13. Yasuni Nakanuma, Kenichi Harada, Yasunori Sato, et al.　Gastric subtype of intraductal papillary neoplasm of the bile duct: The pathologic spectrum. Journal of Hepato-Biliary-Pancreatic Sciences. 2020 27(7) :402-413.　https://pubmed.ncbi.nlm.nih.gov/32356328/
  14. Takashi Kosone, Hitoshi Takagi, Satoshi Takakusagi, Takashi Hoshino, Yozo Yokoyama,Kazuko Kizawa , Kyoko Marubashi , Akira Watanabe , Kenichiro Araki ,Norifumi Harimoto , Hayato Ikota , Ken Shirabe , Kenichi Harada, Satoru Kakizaki6 and Toshio Uraoka. A Resected Case of Follicular Cholangitis that was Positive on 18F-fluorodeoxyglucose-Positron Emission Tomography. Internal Medicine 2020 59(17):2123-2128. https://pubmed.ncbi.nlm.nih.gov/32448841/
  15. Kazuto Kozaka, Satoshi Kobayashi, Hiroyuki Takamura,Yasunori Sato, Azusa Kitao, Dai Inoue, Norihide Yoneda, Hidehiro Tajima, Seigo Kinuya, Kenichi Harada, Tetsuo Ohta, Wataru Koda,Osamu Matsui, and Toshifumi Gabata. Differences in 18F-FDG Uptake and Expression of Glucose Transporter Between 2 Distinct Subtypes of Mass-Forming Intrahepatic Cholangiocarcinomas. Clinical Nuclear Medicine 2020 45(6): e267-e273. https://pubmed.ncbi.nlm.nih.gov/32366791/
  16. Nozomi Amano, Sho Sato, Ayato Murata, Hironori Tsuzura, Ko Tomishima, Shunsuke Sato, Kohei Matsumoto, Yuji Shimada,  Katsuyori Iijima, Kenichi Harada, Takuya Genda.  A case of primary biliary cholangitis overlapping with type 2 autoimmune hepatitis. Clinical Journal of Gastroenterology 2020 13(1) 79-82. https://pubmed.ncbi.nlm.nih.gov/31286423/
  17. Ryosuke Gabata, Kenichi Harada, Yuki Mizutani, Hirohumi Ouchi, Kaori Yoshimura, Yasunori Sato, Azusa Kitao, Kiminori Kimura, hiroyuki kouji, Oymoharu Miyashita, Hidehiro Tajima, and Tetsuo Outa. Anti-tumor Activity of the Small Molecule Inhibitor PRI-724 Against β-catenin-activated Hepatocellular Carcinoma. Anticancer Research 2020 40: 5211-5219. https://pubmed.ncbi.nlm.nih.gov/32878809/
  18. Yasunori Sato, Shogo Tanaka, Masahiko Kinoshita, Shigekazu Taakemura, Hiroji Shinkawa, Takashi kokudo, Kiyoshi Hasegawa, Hiromu Tanaka, Hidero Yoshimoto, Akita Mori, Minako Yamamura, Motoko Sasaki, Kenichi Harada, Shoji Kubo. Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma: Supportive evidence for the efficacy of immune checkpoint inhibitor therapy.　J Hepatobiliary Pancreat Sci 2020 27(11):860-869　https://pubmed.ncbi.nlm.nih.gov/32506715/
  19. Takuya Seike, Eishiro Mizukoshi, Kazutoshi Yamada, Hikari Okada,Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Taro Yamashita,Yoshio Sakai, Masao Honda, Kenichi Harada,Shuichi Kaneko.　Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients. J Gastroenterol (2020) 55:701–711. https://pubmed.ncbi.nlm.nih.gov/32124081/
  20. Saiho Sugimoto, Takeshi Terashima, Tatsuya Yamashita, Noriho Iida, Masaaki Kitahara, Yuji Hodo, Tetsuro Shimakami, Hajime Takatori, Kuniaki Arai, Kazunori Kawaguchi, Kazuya Kitamura, Taro Yamashita,Yoshio Sakai,Yukihiro Shirota, Katsuaki Sato, Eishiro Mizukoshi, Masao Honda, Kenichi Harada, Shuichi Kaneko. Tumor lysis syndrome in a patient with metastatic melanoma treated with nivolumab. Clinical Journal of Gastroenterology (2020) 13:935–939.   https://pubmed.ncbi.nlm.nih.gov/32594423/
  21. Takuya Seike, Takuya Komura, Yoshiaki Shimizu, Hitoshi Omura, Tatsuo Kumai, Takashi Kagaya, Hajime Ohta, Atsuhiro Kawashima, Kenichi Harada, Shuichi Kaneko and Masashi Unoura. The Serum Mac-2-binding Protein Glycosylation Isomer Dynamics in Acute Liver Injury. Intern Med 59: 1581-1588, 2020.　https://pubmed.ncbi.nlm.nih.gov/32269188/
  22. Akemi Tsutsui, Kenichi Harada, Koichi Tsuneyama,Hiep Nguyen Canh,Midori Ando, Satoko Nakamura, Koichi Mizobuchi, Nobuyuki Baba, Tomonori Senoh, Takuya Nagano,Hiroshi Shibata,Tomoko Aoki and Koichi Takaguchi.  Histopathological analysis of autoimmune hepatitis with “acute” presentation: Differentiation from drug-induced liver injury. Hepatology Research 2020; 50: 1047–1061. https://pubmed.ncbi.nlm.nih.gov/32515851/
  23. Hiroyuki Takamura, Ryousuke Gabata,Yoshinao Obatake, Shinichi Nakanuma, Hironori Hayashi, Kazuto Kozaka, Motoko Sasaki,  Mitsuyoshi Okazaki, Takahisa Yamaguchi, Hiroyuki Shimbashi, Shiro Terai, Koichi Okamoto, Isamu Makino, Jun Kinoshita, Keishi Nakamura, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Sachio Fushida, Azusa Kitao, Masaaki Kitahara, Kuniaki Arai, Taro Yamashita, Tatsuya Yamashita, Hiroko Ikeda, Yasunori Satoh, Kenichi Harada, Syuichi Kaneko, Toshihumi Gabata, Tateo Kosaka, and Tetsuo Ohta.  Clinical features and diagnostic imaging of cholangiolocellular carcinoma compared with other primary liver cancers: a surgical perspective. Technology in Cancer Research & Treatment  2020; 19: 1-17.   https://pubmed.ncbi.nlm.nih.gov/33073719/
  24. Yumie Takeshita , Takehiro Kanamori , Takeo Tanaka , Yuka Kaikoi,. Yuki Kita , Noboru Takata , Noriho Iida, Kuniaki Arai, Tatsuya Yamashita, Kenichi Harada, Toshifumi Gabata, Hiroyuki Nakamura, Shuichi Kaneko, Toshinari Takamura. Study Protocol for Pleiotropic Effects and Safety of Sodium–Glucose Cotransporter 2 Inhibitor Versus Sulfonylurea in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease. Diabetes Ther. (2020) 11:549-560.   https://pubmed.ncbi.nlm.nih.gov/31956961/
  25. Satoshi Takakusagi, Yozo Yokoyama, Kazuko Kizawa, Kyoko Marubashi, Takashi Kosone, Ken Sato, Satoru Kakizaki, Kenichi Harada, Hitoshi Takagi and Toshio Uraoka. Successfully Treated Case of Cholangiolocellular Carcinoma with a Poor Hepatic Functional Reserve Reporting with Various Imaging Findings. Internal Medicine 2021 60(6): 873-881. https://pubmed.ncbi.nlm.nih.gov/33055484/
  26. Kazuhito Kawata, Satoru Joshita, Shinji Shimoda, Yuki Yamashita, Maho Yamashita, Kensuke Kitsugi, Shingo Takatori, Kazuyoshi Ohta, Jun Ito, Shin Shimoyama, Hidenao Noritake, Takafumi Suda and Kenichi Harada. The ursodeoxycholic acid response score predicts pathological features in primary biliary cholangitis. Hepatology Research. 2021 51(1):80-89. https://pubmed.ncbi.nlm.nih.gov/33055484/
  27. Hiroshi Yaegashi, Yuki Kato, Takahiro Nohara, Kouji Izumi, Yoshifumi Kadono, Hiroshi Yaegashi, Yuki Kato, Takahiro Nohara, Kouji Izumi, Yoshifumi Kadono, Tohru Miyagi, Takao Nakashima, Kaori Yoshimura, Yasunori Sato, Kenichi Harada, Atsushi Mizokami. Histiocytic sarcoma following combination chemotherapy for primary mediastinal germ cell tumor: a diagnostic dilemma. International Cancer Conference Journal.  2021 Jan 9;10(2):144-148. https://pubmed.ncbi.nlm.nih.gov/33786289/
  28. Nazmul Hasan, Naoto Nagata, Jun-ichi Morishige, Md Tarikul Islam, Zheng Jing, Ken-ichi Harada, Michihiro Mieda, Masanori Ono, Hiroshi Fujiwara, Takiko Daikoku, Tomoko Fujiwara, Yoshiko Maida, Tsuguhito Ota, Shigeki Shimba, Shuichi Kaneko, Akio Fujimura, Hitoshi Ando. Brown adipocyte-specific knockout of Bmal1 causes mild but significant impairment of thermogenesis in mice. Molecular Metabolism. 49 (2021) 101202.  https://pubmed.ncbi.nlm.nih.gov/33676029/
  29. Takeshi Okanoue, Toshihide Shima, Yasuhide Mitsumoto, Atsushi Umemura, Kanji Yamaguchi, Yoshito Itoh, Masato Yoneda, Atsushi Nakajima, Eishiro Mizukoshi, Shuichi Kaneko, Kenichi Harada. Artificial intelligence/neural network system for the screening of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology Research. 2021 May;51(5):554-569. https://pubmed.ncbi.nlm.nih.gov/33594747/
  30. Tadashi Toyohara, Takahiro Nakazawa, Kais Zakharia, Shuya Shimizu, Katsuyuki Miyabe , Kenichi Harada, Kenji Notohara, Tomohiro Yamada, Katsumi Hayashi, Itaru Naitoh, Kazuki Hayashi and Hiromi Kataoka.　A Case of IgG4-related Sclerosing Cholangitis Complicated with Cholangiocarcinoma and Detected by Forkhead Box P3 Immunohistochemical Staining. Intern Med. 60: 859-866, 2021. https://pubmed.ncbi.nlm.nih.gov/33087673/
  31. Ryuji Komine, Motohiro Kojima, Genichiro Ishi, Masashi Kudo, Motokazu Sugimoto,Shin Kobayashi, Shinichiro Takahashi, Masaru Konishi, Tatsushi Kobayashi,Tetsuo Akimoto, Ayumi Murakami, Motoko Sasaki, Mariko Tanaka, Akiko Matsuzaki, Nobuyuki Ohike, Katsunori Uchida, Tomoko Sugiyama, Kenichi Hirabayashi, Takuma Tajiri, Kazuyuki Ishida, Keita Kai, Yuko Omori, Kenji Notohara, Hiroshi Yamaguchi,Yoko Matsuda, Yoshiki Naito, Yuki Fukumura, Yoshihiro Hamada, Yumi Mihara,Yohei Masugi, Naoto Gotohda, Kenichi Harada, Noriyoshi Fukushima, Toru Furukawa. Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin. Cancer Medicine. 2021 Jun;10(11):3499-3510. https://pubmed.ncbi.nlm.nih.gov/34008914/
  32. Kosuke Ishida , Akihiro Seki , Kazunori Kawaguchi , Alessandro Nasti ,Masatoshi Yamato , Hiiro Inui , Takuya Komura , Taro Yamashita , Kuniaki Arai ,Tatsuya Yamashita , Eishiro Mizukoshi , Masao Honda , Takashi Wada , Kenichi Harada ,Shuichi Kaneko ,Yoshio Sakai.　Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice. Stem Cell Research 54 (2021) 102425. https://pubmed.ncbi.nlm.nih.gov/34119957/
  33. Guiqiang Wang, Atsushi Tanaka, Hong Zhao, Jidong Jia, Xiong Ma, Kenichi Harada, Fu‑Sheng Wang, Lai Wei, Qixia Wang, Ying Sun, Yuan Hong, Huiying Rao, Cumali Efe, George Lau, Diana Payawal, Rino Gani, Keith Lindor, Wasim Jafri, Masao Omata, Shiv Kumar Sarin.  The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis. Hepatology International. 15, 223–257 (2021).  https://pubmed.ncbi.nlm.nih.gov/33942203/
  34. Takeshi Okanoue, Michiie Sakamoto, Kenichi Harada, Masaya Inagaki,Naoko Totsuka, Gaia Hashimoto, Hiromitsu Kumada. Efficacy and safety of apararenone (MT‐3995) in patients with nonalcoholic steatohepatitis: A randomized controlled study. Hepatology Research. 2021;1–14. https://pubmed.ncbi.nlm.nih.gov/34260795/
  35. Satomi Kasashima, Atsuhiro Kawashima, Nozomu Kurose, Satoru Ozaki, Hiroko Ikeda, Ken‑Ichi Harada. Regional disturbance of the distribution of T regulatory cells and T helper cells associated with irregular‑shaped germinal centers in immunoglobulin G4‑related sialadenitis. Virchows Archiv. 2021 Dec;479(6):1221-1232.  https://pubmed.ncbi.nlm.nih.gov/34415430/
  36. Kenta Takahashi, Yasunori Sato, Minako Yamamura, Satoko Nakada, Yuko Tamano, Motoko Sasaki, Kenichi Harada. Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease. Pathology International. 2021;71:521–529. https://pubmed.ncbi.nlm.nih.gov/34166554/
  37. Jindan Sheng, Susumu Kohno, Nobuhiro Okada, Nobuyuki Okahashi, Kana Teranishi, Fumio Matsuda, Hiroshi Shimizu, Paing Linn, Naoko Nagatani, Minako Yamamura,Kenichi Harada, Shin-ichi　Horike, Hiroshi Inoue, Seiji Yano, Sharad Kumar, Shunsuke Kitajima, Itsuki Ajioka, and Chiaki Takahashi. Treatment of Retinoblastoma 1–Intact Hepatocellular Carcinoma With Cyclin-Dependent Kinase 4/6 Inhibitor　Combination Therapy. Hepatology. 2021 74(4):1971-1993.  https://pubmed.ncbi.nlm.nih.gov/33931882/
  38. Takeshi Okanoue, Toshihide Shima, Yasuhide Mitsumoto, Atsushi Umemura, Kanji Yamaguchi, Yoshito Itoh, Masato Yoneda, Atsushi Nakajima, Eishiro Mizukoshi, Shuichi Kaneko, Kenichi Harada.  Novel artificial intelligent/neural network system for staging of nonalcoholic steatohepatitis. Hepatology Research. 2021 51(10) 1044-1057. https://pubmed.ncbi.nlm.nih.gov/34124830/
  39. Hiep Nguyen Canh, Kenta Takahashi, Minako Yamamura, Zihan Li, Yasunori Sato, Kaori Yoshimura, Kazuto Kozaka, Minoru Tanaka, Yasuni Nakanuma, & Kenichi Harada.  Diversity in cell differentiation, histology, phenotype and vasculature of mass-forming intrahepatic cholangiocarcinomas. Histopathology. 2021, 79, 731–750. https://pubmed.ncbi.nlm.nih.gov/34018212/
  40. Minako Yamamura, Yasunori Sato, Kenta Takahashi, Hiep Nguyen Canh, Zihan Li, Tatsuya Kimoto, Shuichi Terasaki, Kenichi Harada. Hilar cholangiocarcinoma with extensive immunoglobulin G4 reaction. Int J Clin Exp Pathol. 2021;14(9):987-992. https://pubmed.ncbi.nlm.nih.gov/34646417/
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