Development of Alkylating PI polyamides targeting oncogenic driver gene mutations

• Project/Area Number: 26290060
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Nagase Hiroki 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究所長 (90322073)
• Co-Investigator(Kenkyū-buntansha): 渡部 隆義 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究員 (60526060) ; 越川 信子 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究員 (90260249)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: がん / ドライバー遺伝子 / 遺伝子変異 / DNA副溝結合化合物 / ピロールイミダゾールポリアミド / アルキル化剤 / 抗癌治療薬 / がんドライバー遺伝子変異 / 変異遺伝子標的治療 / DNA配列認識化合物 / マイナーグルーブバインダー / KRAS / 免疫チェックポイント阻害 / 遺伝子 / 抗生物質 / 薬学 / ゲノム / 抗がん剤 / 分子標的治療

Outline of Final Research Achievements

Critical driver oncogenic proteins, such as RAS and MYC, are difficult therapeutic targets due to the smooth 3D surface. A new approach that directly target driver genes is needed.
Pyrrole-Imidazole polyamide (PIP) specifically recognizes DNA minor groove in a sequence dependent manner. We synthesized a series of PIP-drug conjugates targeting cancer driver genes. PIP conjugates targeting the cancer genome often showed reasonable anti-cancer effect and target gene modification as expected. It is also confirmed the anti-cancer efficacy in mouse models of human cancer with little or no adverse event. Intriguingly, pharmacokinetic studies suggested PIP conjugates showed the enhanced permeability and retention (EPR) like effect, which may take additional advantage of restricted local effects of PI-polyamide conjugates only in tumor and tumor environments for cancer therapeutics.
Thus, PI-polyamide conjugates targeting the mutated cancer genome is a promising strategy for cancer therapeutics.

Research Products

• [Int'l Joint Research] UCSF(米国)
• [Journal Article] Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells. (2017)
  • Author(s): Hoshi R, Watanabe Y, Ishizuka Y, Hirano T, Nagasaki-Maeoka E, Yoshizawa S, Uekusa S, Kawashima H, Ohashi K, Sugito K, Fukuda N, Nagase H, Soma M, Ozaki T, Koshinaga T and Fujiwara K.
  • Journal Title: ONCOLOGY REPORTS Volume: 37 Issue: 4 Pages: 2459-2464
  • DOI: 10.3892/or.2017.5477
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth (2016)
  • Author(s): Obinata D, Takayama K, Fujiwara K, Suzuki T, Tsutsumi S, Fukuda N, Nagase H, Fujimura T, Urano T, Homma Y, Aburatani H, Takahashi S and Inoue S.
  • Journal Title: Oncogene Volume: ３５ Issue: 49 Pages: 6350-6358
  • DOI: 10.1038/onc.2016.171
  • Peer Reviewed
• [Journal Article] Double beta-alanine substitutions incorporated in 12-ring pyrrole-Imidazole Polyamides for lengthened DNA minor groove recognition. (2016)
  • Author(s): Watanabe T, Shinohara K, Shinozaki Y, Uekusa S, Wang X, Koshikawa N, Hiraoka K, Inoue T, Lin J, Bando T, Sugiyama H and Nagase H.
  • Journal Title: Advanced Techniques in Biology & Medicine. Volume: 4 Issue: 02 Pages: 175-175
  • DOI: 10.4172/2379-1764.1000175
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Unfavorable neuroblastoma prognostic factor NLRR2 inhibits cell differentiation by transcriptional induction through JNK pathway (2016)
  • Author(s): Sheikh A, Takatori A, Hossain MS, Hasan MK, Tagawa M, Nagase H, Nakagawara A
  • Journal Title: Cancer Science Volume: 107 Issue: 9 Pages: 1223-32
  • DOI: 10.1111/cas.13003
  • Peer Reviewed
• [Journal Article] Identification of Binding Targets of a Pyrrole-Imidazole Polyamide KR12 in the LS180 Colorectal Cancer Genome. (2016)
  • Author(s): Lin J, Hiraoka K, Watanabe T, Kuo T, Shinozaki Y, Takatori A, Koshikawa N, Chandran A, Otsuki J, Sugiyama H, Horton P and Nagase H.
  • Journal Title: PlosOne Volume: 11 Issue: 10 Pages: e0165581-e0165581
  • DOI: 10.1371/journal.pone.0165581
  • NAID: 120005997725
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of DNA methylation at the MLH1 promoter region using pyrrole-imidazole polyamide. (2016)
  • Author(s): Shinohara K, Yoda N, Takane K, Watanabe T, Fukuyo M, Fujiwara K, Kita K, Nagase H, Nemoto T, Kaneda A.
  • Journal Title: ACS Omega Volume: 1 Issue: 6 Pages: 1164-1172
  • DOI: 10.1021/acsomega.6b00229
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic alterations in Japanese extrahepatic biliary tract cancer. (2016)
  • Author(s): Noguchi R, Yamaguchi K, Ikenoue T, Terakado Y, Ohta Y, Yamashita N, Kainuma O, Yokoi S, Maru Y, Nagase H, Furukawa Y.
  • Journal Title: Oncology Letters Volume: -
  • Peer Reviewed
• [Journal Article] Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth. (2016)
  • Author(s): Inoue S, Obinata D, Takayama K, Urano T, Suzuki T, Takahashi S, Fujimura T, Homma Y, Fujiwara K, Fukuda N, Nagase H, Aburatani H, and Tsutsumi S.
  • Journal Title: Oncogene Volume: -
  • Peer Reviewed
• [Journal Article] Double β-alanine substitutions incorporated in 12-ring pyrrole-Imidazole Polyamides for lengthened DNA minor groove recognition. (2016)
  • Author(s): Watanabe T, Shinohara K, Shinozaki Y, Uekusa S, Wang X, Koshikawa N, Hiraoka K, Inoue T, Lin J, Bando T, Sugiyama H and Nagase H.
  • Journal Title: Advanced Techniques in Biology & Medicine. Volume: -
  • Peer Reviewed
• [Journal Article] Pyrrole-Imidazole (PI) polyamide-mediated silencing of KCNQ1OT1 expression induces cell death in Wilms tumor cells. (2015)
  • Author(s): Yoshizawa S, Fujiwara K, Sugito K, Uekusa S, Kawashima H, Hoshi R, Watanabe Y, Hirano T, Furuya T, Masuko T, Ueno T, Fukuda N, Soma M, Ozaki T, Koshinaga T, Nagase H.
  • Journal Title: International Journal of Oncology Volume: 47(1) Issue: 1 Pages: 115-121
  • DOI: 10.3892/ijo.2015.3018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model. (2015)
  • Author(s): Igarashi J, Fukuda N, Inoue T, Nakai S, Saito K, Fujiwara K, Matsuda H, Ueno T, Matsumoto Y, Watanabe T, Nagase H, Bando T Sugiyama H Itoh T Soma M.
  • Journal Title: PlosOne. Volume: 10(5) Issue: 5 Pages: e0125295-e0125295
  • DOI: 10.1371/journal.pone.0125295
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Silencing of RUNX2 enhances gemcitabine sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the stimulation of TAp63-mediated cell death. (2015)
  • Author(s): Sugimoto H, Nakamura M, Yoda H, Hiraoka K, Shinohara K, Sang M, Fujiwara K, Shimozato O, Nagase H, Ozaki T.
  • Journal Title: Cell Death Discovery Volume: 6 Issue: 10 Pages: e1914-e1914
  • DOI: 10.1038/cddis.2015.242
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The oncogenic role of GASC1 in chemically induced mouse skin cancer. (2015)
  • Author(s): Ozaki Y, Fujiwara K, Ikeda M, Ozaki T, Terui T, Soma M, Inazawa J, Nagase H.
  • Journal Title: Mammalian Genome Volume: 26 Pages: 591-597
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Selective Targeting of the KRAS Codon 12 Mutation Sequence by Pyrrole–Imidazole Polyamide seco-CBI Conjugates. (2015)
  • Author(s): Taylor RD, Chandran A, Kashiwazaki G, Hashiya K, Bando T, Nagase H and Sugiyama H.
  • Journal Title: Chemistry. Volume: 21 Issue: 42 Pages: 14996-5003
  • DOI: 10.1002/chem.201501870
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Runt-related transcription factor 2 (RUNX2) attenuates the transcriptional activity as well as DNA damage-mediated induction of pro-apoptotic TAp73 to regulate chemo-sensitivity (2015)
  • Author(s): Ozaki T, Sugimoto H, Nakamura M, Hiraoka K, Yoda H, Sang M, Fujiwara K, Nagase H.
  • Journal Title: FEBS Journal Volume: 82 Issue: 1 Pages: 114-28
  • DOI: 10.1111/febs.13108
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of a novel E-box binding PI polyamide inhibiting MYC-driven cell-proliferation. (2015)
  • Author(s): Mishra R, Watanabe T, Kimura M, Koshikawa N, Ikeda M, Uekusa S, Kawashima H, Wang X, Igarashi J, Choudhury D, Grandori C, Kemp C, Ohira M, Verma N, Kobayashi Y, Takeuchi J, Koshinaga T, Nemoto N, Fukuda N, Soma M, Kusafuka T, Fujiwara K, Nagase H.
  • Journal Title: Cancer Science Volume: 106(4) Issue: 4 Pages: 421-429
  • DOI: 10.1111/cas.12610
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate. (2014)
  • Author(s): Hiraoka K, Inoue T, Taylor RD, Watanabe T, Koshikawa N, Yoda H, Shinohara K, Takatori A, Sugimoto H, Maru Y, Denda T, Fujiwara K, Balmain A, Ozaki T, Bando T, Sugiyama H, Nagase H.
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 6706-6706
  • DOI: 10.1038/ncomms7706
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nr4a3, a possibile oncogenic factor for neuroblastoma associated with CpGi methylation within the third exon. (2014)
  • Author(s): Uekusa S, Kawashima H, Sugito K, Yoshizawa S, Shinojima Y, Igarashi J, Ghosh S, Wang X, Fjiwara K, Ikeda T, Koshinaga T, Soma M and Nagase H.
  • Journal Title: International Journal of Oncology Volume: 44 Issue: 5 Pages: 1669-1677
  • DOI: 10.3892/ijo.2014.2340
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets E-box. (2014)
  • Author(s): 134. Taniguchi M, Nakai Y, Ozaki T, Koshikawa N, Kojima T, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma T, Nagase H.
  • Journal Title: FEBS Open Bio Volume: 4 Issue: 1 Pages: 328-334
  • DOI: 10.1016/j.fob.2014.03.004
  • Peer Reviewed / Open Access
• [Journal Article] A novel gene regulator, pyrrole-imidazole polyamide targeting ABCA1 gene increases cholesterol efflux from macrophages and plasma HDL concentration (2014)
  • Author(s): Tsunemi A, Ueno T, Fukuda N, Watanabe T, Tahira K, Haketa A, Hatanaka Y, Tanaka S, Matsumoto T, Matsumoto Y, Nagase H, Soma M
  • Journal Title: Journal of Molecular Medicine Volume: 92 Issue: 5 Pages: 509-521
  • DOI: 10.1007/s00109-013-1118-x
  • Peer Reviewed
• [Journal Article] Identification of Frequent Differentially Methylated Region in Sporadic Bladder Cancers. (2014)
  • Author(s): Hasegawa R, Fujiwara K, Obinata D, Kawashima H, Shinojima Y, Igarashi J, Wang X, Ghosh S, Nagase H, Takahashi S.
  • Journal Title: Urol Int. Volume: Sep 6. [Epub ahead of print
  • Peer Reviewed
• [Journal Article] Inhibition of Human Osteosarcoma Cell Migration and Invasion by a Gene Silencer, Pyrrole–Imidazole Polyamide, Targeted at the Human MMP9 NF-κB Binding Site (2014)
  • Author(s): Kojima T, Wang X, Fujiwara K, Osakaa S, Yoshida Y, Osaka E, Taniguchi M, Ueno T, Fukuda N, Soma M, Tokuhashi Y and Nagase H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 37 Issue: 9 Pages: 1460-1465
  • DOI: 10.1248/bpb.b14-00147
  • NAID: 130004684785
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth (2014)
  • Author(s): Obinata D, Ito Akiko, Fujiwara K, Takayama K, Ashikari D, Murata Y, Yamaguchi K, Urano T, Fujimura T, Fukuda N, Soma M, Watanabe T, Nagase H, Inoue S, Takahashi S
  • Journal Title: Cancer Sci Volume: 105 Issue: 10 Pages: 1272-1278
  • DOI: 10.1111/cas.12493
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation. (2014)
  • Author(s): Akter J, Takatori A, Islam MS, Nakazawa A, Ozaki T, Nagase H, Nakagawara A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 453(1) Issue: 1 Pages: 86-93
  • DOI: 10.1016/j.bbrc.2014.09.065
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide screening of aberrant DNA methylation which associated with gene expression in mouse skin cancers (2013)
  • Author(s): Fujiwara K, Ghosh S, Liang P, Morien E, Soma M, Nagase H
  • Journal Title: Molecular Carcinogenesis Volume: e-pub Issue: 3 Pages: 1-11
  • DOI: 10.1002/mc.22085
  • Peer Reviewed
• [Presentation] ・Pyrrole-imidazole polyamide conjugates targeting the cancer genome (2017)
  • Author(s): 永瀬浩喜
  • Organizer: 平成28年度 日本大学学部連携研究推進シンポジウム新規バイオ医療ピロール・イミダゾール（ＰＩ）ポリアミドの創薬開発 国際シンポジウム
  • Place of Presentation: 東京都千代田区
  • Int'l Joint Research / Invited
• [Presentation] ・MYCN遺伝子を標的としたPIポリアミドDNAアルキル化剤の抗腫瘍活性と安全性 (2016)
  • Author(s): 高取敦志、養田裕行、井上貴博、渡部隆義、越川信子、若菜茂晴、永瀬浩喜
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 東京都品川
  • Year and Date: 2016-12-15
• [Presentation] Chem-seq:identifying genomic binding sites of a pyrrole-imidazole polyamide by nxt-generation sequencing (2016)
  • Author(s): Lin Jason,Hiraoka Kiriko,Watanabe takayoshi,kuo Tony, Shinozaki Yoshinao,Takatori Atsushi,Koshikawa Nobuko,Otsuki Joe,Sugiyama Hiroshi,Horton Paul,Nagase Hiroki
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
• [Presentation] ・Comprehensive genetic analysis for the anticancer activity of a novel alkylating targeting KRAS mutation (2016)
  • Author(s): 平岡桐子、Lin Jason、阿久澤夏樹、井上貴博、養田裕行、Krishnamurty Sakthise、渡部隆義、高取敦志、越川信子、尾崎俊文、永瀬浩喜
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-06
• [Presentation] Pyrrole-Imidazole polyamide conjugates targeting the cancer genome (2016)
  • Author(s): Hiroki Nagase, Atsushi Takatori Takayoshi Watanabe, Nobuko Koshikawa, Kiriko Hiraoka, Takahiro Inoue, Hiroyuki Yoda, Jason Lin, Yoshinao Shinozaki, Krishnamurthy Sakthisri, Nina Matsuo, Asuka Hattori
  • Organizer: 第８９回 日本生化学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] Novel Alkylating Agent Targeting KRAS mutation AMEDプロジェクト研究成果の発表 (2016)
  • Author(s): 永瀬浩喜
  • Organizer: バイオインターナショナルコンベンション
  • Place of Presentation: アメリカ・サンフランシスコ
  • Year and Date: 2016-06-06
  • Int'l Joint Research
• [Presentation] ・ピロールイミダゾールポリアミドによる大腸がんドライバー遺伝子標的治療薬の開発 (2016)
  • Author(s): 永瀬浩喜、越川信子
  • Organizer: 第20回日本がん分子標的治療学会学術集会
  • Place of Presentation: 大分県別府市
  • Year and Date: 2016-05-31
• [Presentation] ・Mutated cancer cell-specific cell death activity of alkylating Pyrrole-Imidazole polyamide conjugates targeting a variety of oncogenic driver gene mutations (2016)
  • Author(s): Hiroki Nagase, Kiriko Hiraoka, Takahiro Inoue, Hiroyuki Yoda, Krishnamurthy Sakthisri, Jason Lin, Takayoshi Watanabe, Nobuko Koshikawa, Atsushi Takatori
  • Organizer: American Association for Cancer Research Annual Meeting
  • Place of Presentation: ニューオリンズ 米国
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] PIポリアミド薬物複合体のMYCN遺伝子増幅難治性神経芽腫に対する革新的治療戦略への応用 (2015)
  • Author(s): 養田裕行、高取敦志、井上貴博、渡部隆義、越川信子、尾崎俊文、永瀬浩喜
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Anticancer activities of DNA-alkylating Pyrrole-Imidazole pylyamide conjugate targeting mutant KRAS (2015)
  • Author(s): 平岡桐子、井上貴博、養田裕行、Sakthisri Krishnamurthy、Jason Lin、渡部隆義、坂東俊和、杉山弘、尾崎敏文、永瀬浩喜
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] 神経芽腫に対するPIポリアミドDNAアルキル化剤複合体を用いた治療戦略 (2015)
  • Author(s): 養田裕行,高取敦志,井上貴博,渡部隆義,越川信子,尾崎俊文,永瀬浩喜
  • Organizer: 日本小児血液・がん学会
  • Place of Presentation: 甲府
  • Year and Date: 2015-11-27
• [Presentation] Chemical genomics approaches to modify biological processes and pathological state (2015)
  • Author(s): Hiroki Nagase
  • Organizer: IMPC国際シンポジウム
  • Place of Presentation: 横浜港湾記念会館
  • Year and Date: 2015-11-12
  • Int'l Joint Research / Invited
• [Presentation] Inhibition of KRAS mutant colon cancer using a novel DNA-alkylating Pyrrole-Imidazole polyamide conjugate targeting KRAS Codon12 Mutant DNA (2015)
  • Author(s): Hiroki Nagase, Kiriko Hiraoka, Takahiro Inoue, Takayoshi Watanabe, Ken-Ichi Shinohara, Nobuko Koshikawa, Ozaki Toshinori.
  • Organizer: 3rd International Conference of Federation of Asian Clinical Oncology(FACO)
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2015-10-29
  • Int'l Joint Research / Invited
• [Presentation] KRAS遺伝子G12DおよびG12V 変異DNA配列を標的にした大腸がん治療薬の開発 (2015)
  • Author(s): 永瀬浩喜. 平岡桐子、井上貴博、養田裕行、Krishnamurty Sakthisri、高取敦志、篠原憲一 、渡部隆義、越川信子、尾崎俊文、
  • Organizer: 第74回 日本癌学会 腫瘍別シンポジウム 1 大腸がんにおける標的分子と治療開発
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] 化学物質によるゲノムへの介入 ―疾患（がん）治療への試み ― (2015)
  • Author(s): 永瀬浩喜
  • Organizer: 第29回 モロシヌス研究会
  • Place of Presentation: 神戸・有馬温泉
  • Year and Date: 2015-07-03
• [Presentation] 変異型 KRAS 遺伝子を標的とした塩基配列特異的アルキル化剤の大腸癌細胞における抗腫瘍効果. (2015)
  • Author(s): 平岡桐子、井上貴博、養田裕行、Krishnamurty Sakthisri、高取敦志、篠原憲一 、渡部隆義、越川信子、尾崎俊文、永瀬浩喜
  • Organizer: 第24回癌病態治療研究会 ワークショップ
  • Place of Presentation: 日光
  • Year and Date: 2015-06-25
• [Presentation] KRASコドン12変異を標的としたDNAアルキル化 (2015)
  • Author(s): 永瀬浩喜
  • Organizer: 日本がん分子標的治療学会第19回学術集会 ワークショップ
  • Place of Presentation: 松山
  • Year and Date: 2015-06-10
• [Presentation] Tumor accumulation of a novel alkylating pyrrole-imidazole polyamide (KR12) targeting KRAS codon 12 mutations in murine xenograft models of human colon cancer (2015)
  • Author(s): Takahiro Inoue, Kiriko Hiraoka, Yusei Suzuki, Hiroyuki Yoda, Takayoshi Watanabe, Atsushi Takatori, Nobuko Koshikawa, Toshinori Ozaki, Hiroki Nagase.
  • Organizer: AACR American Association for Cancer Research ANUAL MEETING 2015 ミニシンポジウム Exploiting the MAPK pathway in cancer
  • Place of Presentation: フィラデルフィア 米国
  • Year and Date: 2015-04-18
  • Int'l Joint Research / Invited
• [Presentation] A novel alkylating pyrrole-imidazole polyamide, KR12, specifically recognizes mutant KRAS genes and potently induces cell death (2015)
  • Author(s): Kiriko Hiraoka, Takahiro Inoue, Hiroyuki Yoda, Atsushi Takatori, Takayoshi Watanabe, Nobuko Koshikawa, Toshinori Ozaki, Hiroki Nagase.
  • Organizer: AACR American Association for Cancer Research ANUAL MEETING 2015 ミニシンポジウム Exploiting the MAPK pathway in cancer
  • Place of Presentation: フィラデルフィア 米国
  • Year and Date: 2015-04-18
  • Int'l Joint Research / Invited
• [Presentation] ドライバー遺伝子変異を標的としたアルキル化剤による治療法の開発 (2015)
  • Author(s): 永瀬浩喜
  • Organizer: 第37回近畿小児血液・がん研究会
  • Place of Presentation: 京都
  • Year and Date: 2015-02-14
  • Invited
• [Presentation] Allele-specific knock-down of KRAS mutations in cancers by using a novel alkylating Pyrrole-Imidazole Polyamide (KR12) (2014)
  • Author(s): ・Atsushi Takatori, AKiriko Hiraoka, Takahiro Inoue, Takayoshi Watanabe, Ken-Ichi Shinohara, Nobuko Koshikawa, Ozaki Toshinori. and Hiroki Nagase
  • Organizer: The 28th International Mammalian Genome Conference.
  • Place of Presentation: Bar Harbor, USA
  • Year and Date: 2014-10-26 – 2014-10-29
• [Presentation] 変異型KRASを標的とした塩基配列特異的アルキル化剤によるヒト大腸癌細胞移植マウスの抗腫瘍効果 (2014)
  • Author(s): ・井上貴博、平岡桐子、養田裕行、丸喜明、杉本博一、篠原憲一、渡部隆義、高取敦志、越川信子、板東俊和、杉山弘、尾崎俊文、永瀬 浩喜
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] A novel anti-cancer agent of DNA-alkylating Pyrrole-Imidazole polyamide conjugate targeting KRAS Codon 12 Mutant DNA (2014)
  • Author(s): ・Hiroki nagase, Kiriko Hiraoka, Takahiro Inoue, Nobuko Koshikawa, Takayoshi Watanabe
  • Organizer: 52st JSCO 2014 International Session Anti cancer agen
  • Place of Presentation: 横浜
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] がんドライバーミューテーション特異的アルキル化剤の開発 (2014)
  • Author(s): ・永瀬浩喜、平岡桐子、井上貴博、越川信子、渡部隆義
  • Organizer: 第２8回 モロシヌス研究会
  • Place of Presentation: 修善寺
  • Year and Date: 2014-06-27 – 2014-06-28
• [Presentation] KRASコドン12変異を標的とした分子標的アルキル化剤 (2014)
  • Author(s): 永瀬浩喜、平岡桐子、井上貴博、越川信子、渡部隆義
  • Organizer: 第18回日本癌分子標的治療学会
  • Place of Presentation: 仙台
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] Precision Medicineを目指したオンコジェニックドライバーを標的とした治療 (2014)
  • Author(s): ・永瀬浩喜、平岡桐子、井上隆博、渡部隆義、越川信子、尾崎俊文
  • Organizer: 第23回癌病態治療研究会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-06-12 – 2014-06-13
  • Invited
• [Presentation] これからのがん予防とがん治療 ― 個人個人に合わせたがんの予防と治療の考え方 ― (2014)
  • Author(s): 永瀬浩喜
  • Organizer: 千葉県市民公開講座
  • Place of Presentation: 千葉 キボール
  • Year and Date: 2014-06-08
  • Invited
• [Book] がんのエピジェネティクス研究の進歩 (2016)
  • Author(s): 永瀬浩喜
  • Total Pages: 6
  • Publisher: 臨床免疫・アレルギー科
• [Book] 「がんのエピジェネティクス研究の進歩」臨床免疫・アレルギー科 (2016)
  • Author(s): 永瀬浩喜
  • Total Pages: 6
  • Publisher: 化学評論社
• [Remarks] 千葉県がんセンター研究所
  • URL: http://www.pref.chiba.lg.jp/gan/kenkyujo/
• [Remarks] Chiba Cancer Center Research Institute
  • URL: https://www.facebook.com/CCCRI.chiba.gan.kenkyujo
• [Remarks] 千葉県がんセンター研究所がん遺伝創薬研究室
  • URL: http://www.pref.chiba.lg.jp/gan/kenkyujo/soshiki/iden/index.html
• [Remarks] 千葉県がんセンター研究所の研究がNature Communications誌に掲載されました。
  • URL: http://www.pref.chiba.lg.jp/gan/oshirase/cccri_nature_communications.html
• [Remarks] プレスリリース資料（平成27年4月27日）（PDF：755KB）
  • URL: http://www.pref.chiba.lg.jp/gan/kenkyujo/documents/150501-naturecommunications.pdf
• [Patent(Industrial Property Rights)] 新規アルキル化剤 (2016)
  • Inventor(s): 永瀬浩喜、服部あすか、高取敦志、渡部隆義
  • Industrial Property Rights Holder: 千葉県
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-184892
  • Filing Date: 2016-09-21
• [Patent(Industrial Property Rights)] ピロールイミダゾール含有ポリアミドを用いた標的二本鎖核酸分子の濃縮方法およびキット ： (2015)
  • Inventor(s): 永瀬 浩喜、塚本 圭、北野 史朗
  • Industrial Property Rights Holder: 永瀬 浩喜、塚本 圭、北野 史朗
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-10-08
• [Patent(Industrial Property Rights)] ドライバーオンコジーンの遺伝子変異を標的にアルキル化する新規アルキル化剤 (2014)
  • Inventor(s): 永瀬浩喜、杉山 弘、板東俊和
  • Industrial Property Rights Holder: 千葉県および京都大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-10-14
  • Overseas