Research of innovative development of antagomirs regulating inflammation-associated carcinogenesis in hepatic microenvironment

• Project/Area Number: 22390149
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Fukui
• Principal Investigator: NAKAMOTO Yasunari 福井大学, 医学部, 教授 (40293352)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA Taro 金沢大学, 大学病院, 助教 (90377432)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2010: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 癌 / 遺伝子 / 核酸 / 動物 / 内科

Research Abstract

The current study was designed to develop antagomirs, anti-microRNA oligonucleotides, regulating inflammation-associated carcinogenesis in hepatic microenvironment. Eight of microRNAs identified in a unique mouse model of chronic hepatitis B were evaluated for the expression profiles in the serial samples of liver tissues, the transformation of cell lines, the effects on expression of host genes, the relation to gene expression profiles during hepatocarcinogenesis. Collectively, these microRNAswere suggested to be targets in the development of antagomirs for hepatocellular carcinoma.

Research Products

• [Journal Article] Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration (2013)
  • Author(s): Matsunaga A, Ikawa M, Fujii A, Nakamoto Y, Kuriyama M, Yoneda M
  • Journal Title: Eur. Neurol Volume: 69 Pages: 14-20
  • Peer Reviewed
• [Journal Article] Treatment strategies for hepatocellular carcinoma in Japan (2013)
  • Author(s): Yamashita T, Kaneko S
  • Journal Title: Hepatol. Res Volume: 43 Pages: 44-50
  • Peer Reviewed
• [Journal Article] Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma. (2013)
  • Author(s): Yamashita T, Nakamoto Y, et al.
  • Journal Title: Hepatology Volume: 57 Pages: 1484-1497
  • DOI: 10.1002/hep.26168
  • Peer Reviewed
• [Journal Article] Clinical relevance and sequence analysis of the Helicobacter pylori dupAregion from two areas in Japan with different gastric cancer risks (2012)
  • Author(s): Matsuda H, Ito Y, Suto H, Yamakawa A, Satomi S, Ohtani M Yamazaki Y, Kusaka Y, Shimabukuro Y, Kikuchi K, Keida Y, Azuma T, Nakamoto Y
  • Journal Title: Immuno-Gatroenterology Volume: 1:2 Pages: 127-135
  • URL: http://www.stmconnect.com/ig
  • Peer Reviewed
• [Journal Article] Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma (2012)
  • Author(s): Marukawa Y, Nakamoto Y, Kakinoki K, Tsuchiyama T, Iida N, Kagaya T, Sakai Y, Naito M, Mukaida N, Kaneko S
  • Journal Title: Cancer Gene Ther. Volume: 19 Pages: 312-319
  • NAID: 120003989046
  • Peer Reviewed
• [Journal Article] Nucleostemin in Injury-Induced Liver Regeneration (2012)
  • Author(s): Shugo H, Ooshio T, Naito M, Naka K, Hoshii T, Tadokoro Y, Muraguchi T, Tamase A, Uema N, Yamashita T, Nakamoto Y, Suda T, Kaneko S, Hirao A
  • Journal Title: Stem Cells Dev Volume: 21 Pages: 3044-3054
  • Peer Reviewed
• [Journal Article] Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update (2012)
  • Author(s): Kaneko S, Furuse J, Kudo M, Ikeda K, Honda M, Nakamoto Y, Onchi M, Shiota G, Yokosuka O, Sakaida I, Takehara T, Ueno Y, Hiroishi K, Nishiguchi S, Moriwaki H, Yamamoto K, Sata M, Obi S, Miyayama S, Imai Y
  • Journal Title: Hepatol. Res Volume: 42 Pages: 523-542
  • NAID: 10031144267
  • Peer Reviewed
• [Journal Article] Evaluation of systemic redox states in patients carrying the MELAS A3243G mutation in mitochondrial DNA (2012)
  • Author(s): Ikawa M, Arakawa K, Hamano T, Nagata M, Nakamoto Y, Kuriyama M, Koga Y, Yoneda M
  • Journal Title: Eur. Neurol Volume: 67 Pages: 232-237
  • Peer Reviewed
• [Journal Article] Acyclic retinoid targets platelet-derived growth factor signaling in the prevention of hepatic fibrosis and hepatocellular carcinoma development (2012)
  • Author(s): Okada H, Honda M, Campbell JS, Sakai Y, Yamashita T, Takebuchi Y, Hada K, Shirasaki T, Takabatake R, Nakamura M, Sunagozaka H, Tanaka T, Fausto N, Kaneko S
  • Journal Title: CANCER RES Volume: 72 Pages: 4459-4471
  • Peer Reviewed
• [Journal Article] Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma (2012)
  • Author(s): Oishi N, Kumar MR, Roessler S, Ji J, Forgues M, Budhu A, Zhao X, Andersen JB, Ye QH, Jia HL, Qin LX, Yamashita T, Goo Woo H, Jun Kim Y, Kaneko S, Tang ZY, Thorgeirsson SS, Wei Wang X
  • Journal Title: HEPATOLOGY Volume: 56 Pages: 1792-1803
  • Peer Reviewed
• [Journal Article] Clinical relevance and sequence analysis of the Helicobacter pylori dupA region from two areas in Japan with different gastric cancer risks. (2012)
  • Author(s): Matsuda H, Nakamoto Y, et al.
  • Journal Title: Immuno-Gatroenterology Volume: 1 Pages: 127-135
  • Peer Reviewed
• [Journal Article] Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma (2012)
  • Author(s): Marukawa Y
  • Journal Title: Cancer Gene Ther Volume: 19(5) Pages: 312-319
  • DOI: 10.1038/cgt.2012.3
  • NAID: 120003989046
  • Peer Reviewed
• [Journal Article] Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization (2011)
  • Author(s): Nakamoto Y, Mizukoshi E, Kitahara M, Arihara F, Sakai Y, Kakinoki K, Fujita Y, Marukawa Y, Arai K, Yamashita T , Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Journal Title: Clin. Exp. Immunol Volume: 163 Pages: 165-177
  • NAID: 120003141443
  • Peer Reviewed
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, Kagaya T, Yamashita T, Honda M, Kaneko S
  • Journal Title: HEPATOLOGY Volume: 53 Pages: 1206-1216
  • Peer Reviewed
• [Journal Article] Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma (2011)
  • Author(s): Takata Y, Nakamoto Y, Nakada A, Terashima T, Arihara F, Kitahara M, Kakinoki K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S
  • Journal Title: Cancer Lett Volume: 307 Pages: 165-173
  • NAID: 120003141809
  • Peer Reviewed
• [Journal Article] Hokuriku Liver Study Group: Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C (2011)
  • Author(s): Honda M, Takehana K, Sakai A, Tagata Y, Shirasaki T, Nishitani S, Muramatsu T, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Yamashita T, Nakamura M, Shimakami T, Yi M, Lemon SM, Suzuki T, Wakita T, Kaneko S
  • Journal Title: GASTROENTEROLOGY Volume: 141 Pages: 128-140
  • Peer Reviewed
• [Journal Article] Randomized, phase II study comparing interferon combined with hepatic arterial infusion of fluorouracil plus cisplatin and fluorouracil alone in patients with advanced hepatocellular carcinoma. (2011)
  • Author(s): Yamashita T, Arai K, Sunagozaka H, Ueda T, Terashima T, Yamashita T, Mizukoshi E, Sakai A, Nakamoto Y, Honda M, Kaneko S
  • Journal Title: Oncology Volume: 81 Pages: 281-290
  • NAID: 120003674297
  • Peer Reviewed
• [Journal Article] Frequency of CD45RO(+) subset in CD4(+)CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma (2011)
  • Author(s): Takata Y, Nakamoto Y, et al
  • Journal Title: Cancer Lett. Volume: 307 Pages: 165-173
  • NAID: 120003141809
  • Peer Reviewed
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma. (2011)
  • Author(s): Honda M, (他9名, 9番目)
  • Journal Title: HEPATOLOGY Volume: 53(4) Pages: 1206-1216
  • DOI: 10.1002/hep.24149
  • Peer Reviewed
• [Journal Article] Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization. (2011)
  • Author(s): Nakamoto Y, Mizukoshi E, Kitahara M, Arihara F, Sakai Y, Kakinoki K, Fujita Y, Marukawa Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O, and Kaneko S
  • Journal Title: Clin. Exp. Immunol. Volume: 163(2) Pages: 165-177
  • DOI: 10.1111/j.1365-2249.2010.04246.x
  • NAID: 120003141443
  • Peer Reviewed
• [Journal Article] Prevention of intrahepatic metastasis of liver cancer by suicide gene therapy and chemokine ligand 2/monocyt e chemoattractant protein-1 delivery in mice (2010)
  • Author(s): Kakinoki K, Nakamoto Y, Kagaya T, Tsuchiyama T, Sakai Y, Nakahama T, Mukaida N, Kaneko S
  • Journal Title: J.Gene Med Volume: 12 Pages: 1002-1013
  • Peer Reviewed
• [Journal Article] Antitumor effect after radio-frequency ablation of murine hepatoma is augmented by an active variant of cc chemokine ligand 3/macrophage inflammatory protein -1alpha (2010)
  • Author(s): Iida N, Nakamoto Y, Baba T, Nakagawa H, Mizukoshi E, Naito M, Mukaida N and Kaneko S
  • Journal Title: CANCER RES Volume: 70 Pages: 6556-6565
  • Peer Reviewed
• [Journal Article] Differential gene expression profiling in blood from patients with digestive system cancers (2010)
  • Author(s): Honda M, Sakai Y, Yamashita T, Yamashita T, Sakai A, Mizukoshi E, Nakamoto Y, Tatsumi I, Miyazaki Y, Tanno H, Kaneko S; Hokuriku Liver Study Group
  • Journal Title: Biochem Biophys Res Commun. Volume: 400 Pages: 7-15
  • Peer Reviewed
• [Journal Article] Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation (2010)
  • Author(s): Yamashita T, Honda M, Nio K, Nakamoto Y, Yamashita T, Takamura H, Tani T, Zen Y, Kaneko S
  • Journal Title: CANCER RES Volume: 70 Pages: 4687-4697
  • NAID: 120002220837
  • Peer Reviewed
• [Journal Article] Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C (2010)
  • Author(s): Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Yamashita T, Nakamura M, Shirasaki T, Horimoto K, Tanaka Y, Tokunaga K, Mizokami M, Kaneko S; Hokuriku Liver Study Group
  • Journal Title: GASTROENTEROLOGY Volume: 139 Pages: 499-509
  • NAID: 120002463530
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-specific T -cell responses by transcatheter arterial embolization with dendritic cell infusion for hepatocellular carcinoma (2010)
  • Author(s): Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Mukaida N, Matsushima K, Matsui O,Kaneko S
  • Journal Title: Int. J. Cancer Volume: 126 Pages: 2164-2174
  • Peer Reviewed
• [Journal Article] Accelerated hepatocellular carcinoma development in mice expressing the Pim-3 transgene selectively in the liver (2010)
  • Author(s): Wu Y, Wang YY, Nakamoto Y, Li YY, Baba T, Kaneko S, Fujii C, Mukaida N
  • Journal Title: Oncogene Volume: 29 Pages: 2228-2237
  • NAID: 120002165222
  • Peer Reviewed
• [Journal Article] A liver-derived secretory protein, selenoprotein P, causes insulin resistance (2010)
  • Author(s): Misu H, Takamura T, Takayama H, Hayashi H, Matsuzawa-Nagata N, Kurita S, Ishikura K, Ando H, Takeshita Y, Ota T, Sakurai M, Yamashita T, Mizukoshi E, Yamashita T, Honda M, Miyamoto K, Kubota T, Kubota N, Kadowaki T, Kim HJ, Lee IK, Minokoshi Y, Saito Y, Takahashi K, Yamada Y, Takakura N, Kaneko S
  • Journal Title: CELL METAB Volume: 12 Pages: 483-495
  • NAID: 120002661942
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-specific T-cell responses by transcatheter arterial embol ization with dendritic cell infusion for hepatoc ellular carcinoma. (2010)
  • Author(s): Mizukoshi E, Nakamoto Y, Araik, Yamashita T, et al.
  • Journal Title: Int.J.Cancer Volume: 126 Pages: 2164-2174
  • Peer Reviewed
• [Journal Article] Antitumor effect after radio-frequency ablation of murine hepat oma is augmented by an active variant of cc chemokine ligand 3/ macrophage inflammatory protein-lalpha. (2010)
  • Author(s): IidaN, Nakamoto Y, et al.
  • Journal Title: Cancer Res. Volume: 70 Pages: 6556-6565
  • Peer Reviewed
• [Journal Article] Prevention of intrahepatic metastasis of hepatocellular carcinoma by combination of suicide gene therapy and monocyte chemoatt ractant proteinl delivery in mice. (2010)
  • Author(s): Kakinoki K, Nakamoto Y, et al.
  • Journal Title: J.Gene Med. Volume: 12 Pages: 1002-1013
  • Peer Reviewed
• [Presentation] MicroRNA Dynamics in Precancerous Lesions in a Mouse Model of Chronic Hepatitis B (2012)
  • Author(s): Nakamoto Y, Yamashita T, Kaneko S
  • Organizer: 第63回 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: Boston, Massachusetts, U.S.A
  • Year and Date: 2012-11-13
• [Presentation] High Incidence of HBV Reactivation after R-CHOP and CHOP Regimens among Patients Treated with Six Immunosuppressive Chemotherapies (2012)
  • Author(s): Naito T, Nemoto T, Matsuda H, Ohtani M, Suto H Nakamoto Y
  • Organizer: 第63回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: Boston, Massachusetts, U.S.A
  • Year and Date: 2012-11-11
• [Presentation] Differential Dynamics of the NF-kappaB subunits RELA and RELB in a Mouse Model of Chronic Hepatitis B (2011)
  • Author(s): Nakamoto Y, Yamashita T, Kaneko S
  • Organizer: 第62回 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: San Francisco, California, U.S.A
  • Year and Date: 2011-11-08
• [Presentation] Increase of CD14+HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma and its impact forprognosis of patients (2011)
  • Author(s): Arihara F, Mizukoshi E, Kitahara M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • Organizer: 第62回 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: San Francisco, California, U.S.A
  • Year and Date: 2011-11-08
• [Presentation] Differential Dynamics of the NF-kappaB subunits RELA and RELB in a Mouse Model of Chronic Hepatitis B (2011)
  • Author(s): Nakamoto Y, Yamashita T, Kaneko S
  • Organizer: 第62回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: San Francisco, California (USA)
  • Year and Date: 2011-11-08
• [Presentation] #1725; NFkB activation precedes dynamics of oxidative stress-related procarcinogenic signalings in a mouse model of chronic hepatitis B. (2010)
  • Author(s): Nakamoto Y, Yamashita T, Kaneko S
  • Organizer: 第61回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: Boston, Massachusetts, U.S.A
  • Year and Date: 2010-11-01
• [Presentation] #1268 ; NFkB activation precedes dynamics of oxidative stress-related procarcinogenic signalings in a mouse model of chronic he patitis B. (2010)
  • Author(s): Nakamoto Y, Yamashita T, et al.
  • Organizer: 第61回American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: Boston,Massachusetts(USA)
  • Year and Date: 2010-11-01
• [Presentation] Dendritic Cell Transfer during Locoregional Treatments Induces Prolonged Recurrence-Free Survival in Patients with Hepatocellular Carcinoma (2010)
  • Author(s): Nakamoto Y, Mizukoshi E, Kitahara M, Arihara F, Sakai Y, Kakinoki K, Fujita Y, Marukawa Y, Arai K, Yamashita T , Mukaida N, Matsushima K, Matsui O, Kaneko S
  • Organizer: International Symposium on Tumor Biology in Kanazawa "Cancer and Host Response
  • Place of Presentation: Kanazawa, Japan
  • Year and Date: 2010-08-29
• [Presentation] MicroRNA Dynamics in Precancerous Lesions in a Mouse Model of Chronic Hepatitis B.
  • Author(s): Nakamoto Y, Yamashita T, Kaneko S
  • Organizer: 第63回 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
  • Place of Presentation: Boston, Massachusetts, U.S.A.