New construction of in vivo reprogramming technology by modified microRNA

• Project/Area Number: 15K15496
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: ISHII Hideshi 大阪大学, 医学系研究科, 特任教授(常勤) (10280736)
• Co-Investigator(Kenkyū-buntansha): 今野 雅允 大阪大学, 医学系研究科, 寄附講座助教 (80618207) ; 西田 尚弘 大阪大学, 医学系研究科, 助教 (50588118) ; 川本 弘一 大阪大学, 医学系研究科, 特任助教(常勤) (30432470) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669)
• Co-Investigator(Renkei-kenkyūsha): Mori Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999) ; Obika Satoshi 大阪大学, 大学院薬学系研究科, 教授 (80243252) ; Nishiyama Nobuhiro 東京工業大学, 化学生命科学研究所, 教授 (10372385)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / 核酸 / ゲノム

Outline of Final Research Achievements

In order to optimize endogenous microRNAs expressed in embryonic phase as pharmaceuticals, crosslinked modification as covalent bonds and others and drug delivery system (DDS) have been constructed (patented). Applicable range embodies direct reprogramming of somatic cells including cancer cell culture in vitro and animal model in vivo. The innovative cell modification based on the epigenetic control by nucleotide medicine will be valuable for the construction of a new therapeutic strategy and innovative disease control, as well as acceleration to drug optimization and corporative relocation, towards the future clinical application.

Research Products

• [Journal Article] Clinical significance of histone demethylase NO66 in invasive colorectal cancer. (2017)
  • Author(s): Nishizawa, Y., Nishida, N., Konno, M., Kawamoto, K., Asai, A., Koseki, J., Takahashi, H., Haraguchi, N., Nishimura, J., Hata, T., Matsuda, C., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Ann. Surg. Oncol. Volume: 24 Issue: 3 Pages: 841-849
  • DOI: 10.1245/s10434-016-5395-9
  • Peer Reviewed / Open Access
• [Journal Article] The importance of mitochondrial folate enzymes in human colorectal cancer. (2017)
  • Author(s): Miyo, M., Konno, M., Colvin, S. H., Nishida, N., Koseki, J., Kawamoto, K., Tsunekuni, K., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Oncol. Rep. Volume: 37 Issue: 1 Pages: 417-425
  • DOI: 10.3892/or.2016.5264
  • Peer Reviewed / Open Access
• [Journal Article] Fetal hepatocyte derived culture medium elicits adipocyte differentiation to bile duct cell lineages in mouse. (2016)
  • Author(s): Ogawa, H., Konno, M., Kawamoto, K., Nishida, N., Koseki, J., Mizushima, T., Satoh, T., Eguchi, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Biomedical. Reports. Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] c-Met affects gemcitabine resistance over carcinogenesis in a mouse model of pancreatic cancer. (2016)
  • Author(s): Noguchi, K., Konno, M., Eguchi, H., Kawamoto, K., Mukai, R., Nishida, N., Koseki, J., Wada, H., Akita, H., Satoh, T., Marubashi, S., Nagano, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Oncol. Lett. Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA miR-374, a potential radiosensitizer for carbon ion beam radiotherapy. (2016)
  • Author(s): Baek, SJ., Sato, K., Nishida, N., Koseki, J., Azuma, R., Kawamoto, K., Konno, M., Hayashi, K., Satoh, T., Doki, Y., Mori, M., Ishii, H., Ogawa, K.
  • Journal Title: Oncol. Rep. Volume: 36 Issue: 5 Pages: 2946-2950
  • DOI: 10.3892/or.2016.5122
  • Peer Reviewed / Open Access
• [Journal Article] Oncometabolite D-2-hydroxyglurate directly induces epithelial-mesenchymal transition and is associated with distant metastasis in colorectal cancer. (2016)
  • Author(s): Colvin, S. H., Nishida, N., Konno, M., Haraguchi, N., Takahashi, H., Nishimura, J., Hata, T., Kawamoto, K. Asai, A., Tsunekuni, K., Koseki, J., Mizushima, T., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Sci. Rep Volume: 6 Issue: 1 Pages: 36289-36289
  • DOI: 10.1038/srep36289
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. (2016)
  • Author(s): G. Sawada (他43名, 山本21番目)
  • Journal Title: Gastroenterology Volume: 150 Issue: 5 Pages: 1171-1182
  • DOI: 10.1053/j.gastro.2016.01.035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic adaptation to nutritional stress in human colorectal cancer. (2016)
  • Author(s): Miyo, M., Konno, M., Nishida, N. Sueda, T., Noguchi, K., Matsui, H., Colvin, H., Kawamoto, K., Koseki, J., Haraguchi, N., Nishimura, J., Hata, T., Gotoh, N., Mastuda, F., Saatoh, T., Mizushima, T., Shimizu, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 38415-38415
  • DOI: 10.1038/srep38415
  • Peer Reviewed / Open Access
• [Journal Article] Intestinal epithelial culture under an air-liquid interface: a tool for studying human and mouse esophagi. (2015)
  • Author(s): Yokobori T, Suzuki S, Miyazaki T, Sohda M, Sakai M, Tanaka N, Ozawa D, Hara K, Honjo H, Altan B, Fukuchi M, Ishii H, Iwatsuki M, Sugimachi K, Sudo T, Iwaya T, Nishida N, Mimori K, Kuwano H, Mori M.
  • Journal Title: Dis Esophagus. Volume: [Epub ahead of print] Issue: 7 Pages: 843-847
  • DOI: 10.1111/dote.12346
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pyruvate kinase M2, but not M1, allele maintains immature metabolic states of murine embryonic stem cells (2015)
  • Author(s): Konno, M., Ishii, H., Koseki, J., Tanuma, N., Nishida, N., Kawamoto, K., Nishimura, T., Nakata, A., Matsui, H., Noguchi, K., Ozaki, M., Noguchi, Y., Shima, H., Gotoh N., Nagano, H., Doki, Y. and Mori, M.
  • Journal Title: Regenerative Therapy Volume: 1 Pages: 63-71
  • DOI: 10.1016/j.reth.2015.01.001
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs induce epigenetic reprogramming and suppress malignant phenotypes of human colon cancer cells. (2015)
  • Author(s): Ogawa, H., Wu, X., Kawamoto, K., Nishida, N., Konno, M., Koseki, J., Matsui, H., Noguchi, K., Gotoh, N., Yamamoto, T., Miyata, K., Nishiyama, N., Nagano, H., Yamamoto, H., Obika, S., Kataoka, K., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: PLoS One. Volume: 10
  • Peer Reviewed / Open Access
• [Journal Article] Embryonic microRNA-369 controls metabolic splicing factors and urges cellular reprograming. (2015)
  • Author(s): Masamitsu Konno, Jun Koseki, Koichi Kawamoto, Naohiro Nishida, Hidetoshi Matsui, Dyah Laksmi Dewi, Miyuki Ozaki, Yuko Noguchi, Koshi Mimori, Noriko Gotoh, Nobuhiro Tanuma, Hiroshi Shima, Yuichiro Doki, Masaki Mori , Hideshi Ishii
  • Journal Title: PLOS ONE Volume: 10(7) Issue: 7 Pages: 1-16
  • DOI: 10.1371/journal.pone.0132789
  • Peer Reviewed / Open Access
• [Journal Article] Susceptibility of pancreatic cancer stem cells to reprogramming. (2015)
  • Author(s): Noguchi, K., Eguchi, H., Konno, M., Kawamoto, K., Nishida, N., Koseki, J., Wada, H., Marubashi, S., Nagano, H., Doki, Y., Mori, M., Ishii, H.
  • Journal Title: Cancer Sci. Volume: 106 Issue: 9 Pages: 1182-1187
  • DOI: 10.1111/cas.12734
  • Peer Reviewed / Open Access
• [Journal Article] Cyclin G2: A novel independent prognostic marker in pancreatic cancer. (2015)
  • Author(s): Hasegawa, S., Nagano, H., Konno, M., Eguchi, H., Tomokuni, A., Tomimaru, Y., Wada, H., Hama, N., Kawamoto, K., Kobayashi, S., Marubashi, S., Nishida, N., Koseki, J., Gotoh, N., Ohno, S., Yabuta, N., Nojima, H., Mori, M., Doki, Y., Ishii, H.
  • Journal Title: Oncol. Lett. Volume: 10 Pages: 2986-2990
  • Peer Reviewed / Open Access
• [Presentation] 多能性幹細胞の種差に関わる内在性因子 (2017)
  • Author(s): 石井秀始、今野雅允
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター(宮城）
  • Year and Date: 2017-03-07
• [Presentation] Overcoming therapy-resistant cancer stem cells (2016)
  • Author(s): 石井秀始
  • Organizer: 15th World Congress on CANCER THERAPY, BIOMARKER ＆CLINCAL RESEARCH
  • Place of Presentation: DoubleTree by Hilton Hotel Philadelphia Airport（アメリカ）
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] NEW STRATEGY FOR OVERCOMING MULTIFACETED THERAPY-RESISTANT CANCER STEM CELLS (2016)
  • Author(s): 石井秀始
  • Organizer: 第47回高松宮妃癌研究基金国際シンポジウム
  • Place of Presentation: パレスホテル東京(東京）
  • Year and Date: 2016-11-08
• [Presentation] 大腸癌の飢餓ストレスに適応した代謝変化 (2016)
  • Author(s): 今野雅允、三代雅明、西田尚弘、川本弘一、小関準、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-10-06
• [Presentation] Innovative Medicine for Metabolic Reprogramming of Intractable Cancer Stem Cells (2015)
  • Author(s): 石井秀始
  • Organizer: 第46回高松宮妃癌研究基金国際シンポジウム
  • Place of Presentation: パレスホテル東京(東京）
  • Year and Date: 2015-11-17
• [Presentation] 難治性消化器癌幹細胞の可視化とシステム的理解 (2015)
  • Author(s): 石井秀始、土岐祐一郎、森正樹
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知）
  • Year and Date: 2015-10-08
• [Presentation] 癌医療における機能性核酸の応用 (2015)
  • Author(s): 石井秀始
  • Organizer: 第7回日本RNAi研究会 (第2回日本細胞外小胞学会)
  • Place of Presentation: グランドプリンスホテル広島(広島）
  • Year and Date: 2015-08-26
• [Patent(Industrial Property Rights)] がんを検出、又はがんの進行期を判定する方法 (2016)
  • Inventor(s): 石井秀始、西田尚弘、森正樹、土岐祐一郎 他7名
  • Industrial Property Rights Holder: 石井秀始、西田尚弘、森正樹、土岐祐一郎 他7名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-162203
  • Filing Date: 2016-08-22
• [Patent(Industrial Property Rights)] タンパク質の部分立体構造を予測する方法 (2016)
  • Inventor(s): 石井秀始、小関準、西田尚弘、今野雅允、川本弘一 他2名
  • Industrial Property Rights Holder: 石井秀始、小関準、西田尚弘、今野雅允、川本弘一 他2名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-058220
  • Filing Date: 2016-03-23
• [Patent(Industrial Property Rights)] 炭素線感受性バイオマーカー、炭素線感受性の評価方法およびキット、ならびに炭素線増感剤 (2016)
  • Inventor(s): 小川和彦、石井秀始、西田尚弘、今野雅允、小関準、川本弘一 他4名
  • Industrial Property Rights Holder: 小川和彦、石井秀始、西田尚弘、今野雅允、小関準、川本弘一 他4名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-069684
  • Filing Date: 2016-03-31