Development of innovative nucleic acid medicine for gastroenterological cancer

• Project/Area Number: 16K15615
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: KONNO Masamitsu 大阪大学, 医学系研究科, 寄附講座講師 (80618207)
• Co-Investigator(Kenkyū-buntansha): 石井 秀始 大阪大学, 医学系研究科, 特任教授(常勤) (10280736) ; 川本 弘一 大阪大学, 医学部附属病院, その他 (30432470) ; 西田 尚弘 大阪大学, 医学系研究科, 助教 (50588118) ; 小関 準 大阪大学, 医学系研究科, 特任助教(常勤) (20616669)
• Co-Investigator(Renkei-kenkyūsha): 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) ; MORI Masaki 大阪大学, 大学院医学系研究科, 教授 (70190999)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌 / 核酸 / 創薬

Outline of Final Research Achievements

We designed 20 kinds of guide chain and a passenger chain based on natural sequence of miR302 or miR200c. 400 kinds of artificial nucleic acid medicine were elaborated. The arrangement expected that a RNase in the body could be endured based on the former experience was designed. A screening was performed and even about 3 kinds of the artificial building type miR302, 200c was narrowed down respectively. These nucleic acids were injected to natural pancreatic cancer and a colon cancer carcinogenic model mouse. The volume of the cancer was measured and a presence of adverse event was monitored. Finally we identified the most efficient artificial building type nucleic acid medicine.

Research Products

• [Journal Article] Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells (2018)
  • Author(s): Konno Masamitsu、Matsui Hidetoshi、Koseki Jun、Asai Ayumu、Kano Yoshihiro、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 899-899
  • DOI: 10.1038/s41598-018-19284-3
  • Peer Reviewed / Open Access
• [Journal Article] Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis (2018)
  • Author(s): Koseki Jun、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Kawamoto Koichi、Nishida Naohiro、Sakai Daisuke、Kudo Toshihiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 303-303
  • DOI: 10.1038/s41598-017-18456-x
  • Peer Reviewed / Open Access
• [Journal Article] The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review) (2017)
  • Author(s): Konno Masamitsu、Asai Ayumu、Kawamoto Koichi、Nishida Naohiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Int. J. Oncol. Volume: 50 Issue: 4 Pages: 1057-1063
  • DOI: 10.3892/ijo.2017.3885
  • Peer Reviewed / Open Access
• [Journal Article] Micro-RNA-130a-3p Regulates Gemcitabine?Resistance via PPARG in Cholangiocarcinoma (2017)
  • Author(s): Asukai Kei、Kawamoto Koichi、Eguchi Hidetoshi、Konno Masamitsu、Asai Ayumu、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Noda Takehiro、Wada Hiroshi、Gotoh Kunihito、Nishida Naohiro、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Ann. Surg. Oncol. Volume: 24 Issue: 8 Pages: 2344-2352
  • DOI: 10.1245/s10434-017-5871-x
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA profiles involved in trifluridine resistance (2017)
  • Author(s): Tsunekuni Kenta、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kobunai Takashi、Takechi Teiji、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncotarget. Volume: 8 Issue: 32 Pages: 53017-53027
  • DOI: 10.18632/oncotarget.18078
  • Peer Reviewed / Open Access
• [Journal Article] Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism (2017)
  • Author(s): Yamada Naoki、Honda Yuto、Takemoto Hiroyasu、Nomoto Takahiro、Matsui Makoto、Tomoda Keishiro、Konno Masamitsu、Ishii Hideshi、Mori Masaki、Nishiyama Nobuhiro
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 6077-6077
  • DOI: 10.1038/s41598-017-06438-y
  • Peer Reviewed / Open Access
• [Journal Article] The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells (2017)
  • Author(s): Taketo Kosuke、Konno Masamitsu、Asai Ayumu、Koseki Jun、Toratani Masayasu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi、Ogawa Kazuhiko
  • Journal Title: Int. J. Oncol. Volume: 52 Pages: 621-629
  • DOI: 10.3892/ijo.2017.4219
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA LINC00152 in colorectal cancer (2017)
  • Author(s): Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Int. J. Oncol. Volume: 52 Pages: 453-460
  • DOI: 10.3892/ijo.2017.4218
  • Peer Reviewed / Open Access
• [Journal Article] Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer (2017)
  • Author(s): Nishizawa Yujiro、Konno Masamitsu、Asai Ayumu、Koseki Jun、Kawamoto Koichi、Miyoshi Norikatsu、Takahashi Hidekazu、Nishida Naohiro、Haraguchi Naotsugu、Sakai Daisuke、Kudo Toshihiro、Hata Taishi、Matsuda Chu、Mizushima Tsunekazu、Satoh Taroh、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncotarget. Volume: 9 Issue: 7 Pages: 7476-7486
  • DOI: 10.18632/oncotarget.23554
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma (2017)
  • Author(s): Ohashi Tomofumi、Eguchi Hidetoshi、Kawamoto Koichi、Konno Masamitsu、Asai Ayumu、Colvin Hugh、Ueda Yuji、Takaoka Hirofumi、Iwagami Yoshifumi、Yamada Daisaku、Asaoka Tadafumi、Noda Takehiro、Wada Hiroshi、Gotoh Kunihito、Kobayashi Shogo、Koseki Jun、Satoh Taroh、Ogawa Kazuhiko、Doki Yuichiro、Mori Masaki、Ishii Hideshi
  • Journal Title: Oncol. Rep. Volume: 39 Pages: 1276-1282
  • DOI: 10.3892/or.2017.6172
  • 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] 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] 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] 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
• [Presentation] New Trans-omics Analysis revealed Novel Functions of the Cancer Specific Metabolic Pathway in Cancer Stem Cells (2017)
  • Author(s): Konno, M., Nishida, N., Koseki, J., Matsui, H., Asai, A., Kawamoto, K., Satoh, T., Doki, Y., Mori, M., Ishii, H.
  • Organizer: 2017 Cellular and Molecular Bioengineering Annual Conference
  • Place of Presentation: Hapuna Beach Prince Hotel (アメリカ）
  • Year and Date: 2017-01-03
  • Int'l Joint Research
• [Presentation] 消化器がん幹細胞の代謝制御 (2017)
  • Author(s): 今野雅允、三代雅明、浜部敦史、佐藤太郎、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第5回がんと代謝研究会 in 札幌
• [Presentation] 転移性癌幹細胞に特異的な代謝機構の究明 (2017)
  • Author(s): 今野雅允、三代雅明、浜部敦史、佐藤太郎、土岐祐一郎、森正樹、石井秀始
  • Organizer: 第26回日本がん転移学会学術集会・総会
• [Presentation] 消化器癌の悪性度に関わるメカノバイオロジー (2017)
  • Author(s): 今野雅允、松下克則、柳澤公紀、佐藤太郎、出口真次、土 岐祐一郎、森正樹、石井秀始
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 新規数理解析手法を用いた癌幹細胞の治療抵抗性に関わる因子の同定 (2016)
  • Author(s): 今野 雅允、松井 秀俊、小関 準、浅井 歩、西田 尚弘、川本 弘一、佐藤 太郎、森 正樹、 土岐 祐一郎、石井 秀始
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川）
  • Year and Date: 2016-11-30
• [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] TCAサイクル非依存的大腸癌細胞の代謝制御機構の解明 (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4回がんと代謝研究会
  • Place of Presentation: かごしま県民交流センター(鹿児島）
  • Year and Date: 2016-07-07