Molecular basis for the inhibition of hypoxia-induced apoptosis by thymidine phosphorylase

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790139
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kagoshima University
• Principal Investigator: IKEDA Ryuji Kagoshima University, 医学部・歯学部附属病院, 薬剤師 (50398278)
• Project Period (FY): 2008 – 2009
• Keywords: Thymidine Phosphorylase / 2-Deoxy-D-ribose / Hypoxia-inducible factor -1

Research Abstract

An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. TP and 2-deoxy-D-ribode, a degradation product of thymidine generated by TP enzymatic activity, inhibited the upregulation of hypoxia-inducible factor (HIF) 1α induced by hypoxia. We investigated the molecular basis for the suppressive effect of TP and 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced interaction of HIF-1α and pVHL under hypoxic condition. 2-Deoxy-D-ribose did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA. 2-Deoxy-D-ribose also enhanced interaction of HIF-1α and PHD2 under hypoxic condition. Further study is needed to elucidate the mechanism about the augmented interaction of HIF-1α with pVHL and PHD2.

Research Products

• [Journal Article] SUVmax of FDG-PET correlates with the effects of neoadjuvant chemoradiotherapy for oral squamous cell carcinoma (2010)
  • Author(s): Miyawaki, A., Ikeda, R., Hijioka, H., Ishida, T., Ushiyama, M., Nozoe, E., Nakamura, N.
  • Journal Title: Oncol. Rep. 23 Pages: 1205-1212
• [Journal Article] The role of thymidine phosphorylase in the induction of early growth response protein-1 and thrombospondin-1 by 5-fluorouracil in human cancer carcinoma cells (2010)
  • Author(s): Matsushita, S., Ikeda, R., Nishizawa Y., Che X.F., Furukawa T., Miyadera K., Tabata S., Ushiyama M., Tajitsu Y., Yamamoto M., Takeda Y., Minami K., Mataki H., Kanzaki, T., Yamada K., Kanekura T., Akiyama S.
  • Journal Title: Int. J. Oncol. 36 Pages: 1193-1200
• [Journal Article] Major vault protein forms complexes with hypoxia-inducible factor (HIF)-1α and reduces HIF-1α level in ACHN human renal adenocarcinoma cells (2010)
  • Author(s): Iwashita K., Ikeda R., Takeda Y., Sumizawa T., Furukawa T., Yamaguchi T., Akiyama S., Yamada K.
  • Journal Title: Cancer Sci. 101 Pages: 920-926
• [Journal Article] Adverse effects of superselective intra-arterial infusion chemotherapy in patients with oral cancer (2009)
  • Author(s): Ushiyama, M., Ikeda, R., Yamaguchi, H., Miyawaki, A., Nitta, T., Yamaguchi, T., Matsumoto, K., Shimodouzono, Y., Furukawa, T., Akiyama, S., Nakamura N., Yamada, K.
  • Journal Title: Journal of Applied Therapeutic Research 7 Pages: 58-64
• [Journal Article] Stability of hospital preparations of Azunol Water Gargles for pain relief in oral cancer patients with oral mucositis (2009)
  • Author(s): Ushiyama, M., Ikeda, R., Nitta, T., Tazitsu, Y., Miyawaki, A., Nishizawa, Y., Yamaguchi, T., Yamaguchi, H., Akatsuka, C., Shimodouzono, Y., Ushinohama, K., Sugawara, H., Sugihara, K., Nakamura, N., Takeda, Y., Yamada, K.
  • Journal Title: Cancer Therapy 7 Pages: 277-281
• [Journal Article] Enhanced platelet responsiveness due to chilling and its relation to CD40 ligand level and platelet-leukocyte aggregate formation (2009)
  • Author(s): Ayukawa, O., Nakamura, K., Kariyazono, H., Ikeda, R., Arima, J., Shinkawa, T., Iwase, H., Sakata, R., Yamada, K.
  • Journal Title: Blood Coagul. Fibrinolysis 20 Pages: 176-184
• [Journal Article] Contactin-associated protein (Caspr) 2 interacts with carboxypeptidase E in the CNS (2009)
  • Author(s): Oiso, S., Takeda, Y., Futagawa, T., Miura, T., Kuchiiwa, S., Nishida, K., Ikeda, R., Kariyazono, H., Watanabe, K., Yamada, K.
  • Journal Title: J. Neurochem. 109 Pages: 158-167
• [Journal Article] Copper transport systems are involved in multidrug resistance and drug transport (2009)
  • Author(s): Furukawa, T., Komatsu, M., Ikeda, R., Tsujikawa, K., Akiyama, S.
  • Journal Title: Curr. Med. Chem. 15 Pages: 3268-3278
• [Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells (2008)
  • Author(s): Zhao, H.Y., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T., Che, X.F., Iwashita, K., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., Akiyama, S.
  • Journal Title: Cancer Lett. Pages: 156-163
• [Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-fluorouracil (2008)
  • Author(s): Zhao, H.Y., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T., Che, X.F., Zhang, S., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., Akiyama, S.
  • Journal Title: Cancer Res. 68 Pages: 7035-7041
• [Journal Article] Hyperosmotic stress up-regulates the expression of major vault protein in SW620 human colon cancer cells (2008)
  • Author(s): Ikeda, R., Iwashita, K., Sumizawa, T., Beppu, S., Tabata, S., Tajitsu, Y., Shimamoto, Y., Yoshida, K., Furukawa, T., Che, X.F., Yamaguchi, T., Ushiyama, M., Miyawaki, A., Takeda, Y., Yamamoto, M., Zhao, H.Y., Shibayama, Y., Yamada, K., Akiyama, S.
  • Journal Title: Exp. Cell Res. 314 Pages: 3017-3026
• [Presentation] チミジンホスホリラーゼ発現腫瘍での5-fluorouracil (5-FU)によるearly gr owth response factor-1 (EGR-1)発現誘導 (2009)
  • Author(s): 西澤由紀彦、池田龍二、田實裕介、俣木博徳、武田泰生、古川龍彦、牛山美奈、山口辰哉、車暁芳、山本雅達、松下茂人、秋山伸一、山田勝士
  • Organizer: 第2 6回日本薬学会九州支部大会
  • Place of Presentation: 九州大学大学院薬学研究院(福岡市)
  • Year and Date: 2009-12-12
• [Presentation] 高浸透圧によって誘導されるmajor vault protein (MVP)の発現亢進機構の解明 (2009)
  • Author(s): 田實裕介、池田龍二、岩下健一、田畑祥、西澤由紀彦、山口辰哉、牛山美奈、山本雅達、車暁芳、古川龍彦、武田泰生、秋山伸一、山田勝士
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: リジェール松山(松山市)
  • Year and Date: 2009-11-27
• [Presentation] RNA-タンパク質複合体vaultはヒト腎癌由来細胞株ACHN細胞においてhypoxia-induci ble factor-1α(HIF-1α)と結合し、そのユビキチン依存的な分解を促進する (2009)
  • Author(s): 岩下健一、池田龍二、武田泰生、住澤知之、古川龍彦、山口辰哉、秋山伸一、山田勝士
  • Organizer: 第62回日本薬理学会西南部会
  • Place of Presentation: リジェール松山(松山市)
  • Year and Date: 2009-11-27
• [Presentation] Gemcitabine耐性細胞でのCNT1、RRM1の発現変化 (2009)
  • Author(s): 古川龍彦、池田龍二、小松正治、秋山伸一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-03
• [Presentation] チミジンホスホリラーゼによるNF-KBの活性化機構 (2009)
  • Author(s): 田畑祥、山本雅達、池田龍二、古川龍彦、車暁芳、新里能成、南謙太朗、向田直史、武田泰生、山田勝士、秋山伸一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-03
• [Presentation] 咽頭がん細胞KCP-4のシスプラチン耐性機序の解明 (2009)
  • Author(s): 大磯茂、池田龍二、中村和男、武田泰生、秋山伸一、山田勝士
  • Organizer: 日本薬学会第129回年会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2009-03-28
• [Presentation] 口腔癌治療における抗がん剤感受性試験の取り組み (2009)
  • Author(s): 牛山美奈、池田龍二、宮脇昭彦、田實裕介、西澤由紀彦、山口辰哉、中村典史、武田泰生、山田勝士
  • Organizer: 日本薬学会第129回年会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2009-03-28
• [Presentation] 銅輸送体ATP7A・核酸輸送体CNTの関する抗癌剤耐性 (2009)
  • Author(s): 古川龍彦、池田龍二、小松正治、秋山伸一
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-03-16
• [Presentation] 骨芽細胞分化におけるPLZFの機能的関与 (2008)
  • Author(s): 池田龍二、吉田建一、武田泰生、井ノ上逸朗、山田勝士
  • Organizer: 第2回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 京都大学薬学部記念講堂(京都市)
  • Year and Date: 2008-12-20
• [Presentation] チミジンホスホリラーゼ発現腫瘍細胞におけるNF-κBを介したIL-8の発現亢進機構 (2008)
  • Author(s): 田畑祥、山本雅達、池田龍二、古川龍彦、車暁芳、趙紅業、王嘉、向田直史、武田泰生、山田勝士、秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] ヒト大腸癌における5-FUによる血管新生阻害因子TSP-1の誘導 (2008)
  • Author(s): 趙紅業、大山明雄、山本雅達、池田龍二、原口みさ子、田畑祥、古川龍彦、車暁芳、岡俊範、福島正和、小野眞弓、桑野信彦、秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 膵癌細胞株MIAPaCa-2由来Gemcitabine耐性細胞の耐性機構の解析 (2008)
  • Author(s): 古川龍彦、小松正治、池田龍二、秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] survivinペプチド(89-104アミノ酸)によるATL細胞のアポトーシス誘導 (2008)
  • Author(s): 車暁芳、鄭春雷、古川龍彦、山本雅達、王嘉、池田龍二、有馬直道、秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] 低酸素によるヒト線維芽細胞でのPGISの高発現 (2008)
  • Author(s): 王嘉、車暁芳、大山明雄、山本雅達、古川龍彦、池田龍二、鄭春雷、蓮井和久、岡俊範、秋山伸一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-29
• [Presentation] P53R2標的siRNAは悪性黒色腫の腫瘍増殖を抑制して抗癌剤感受性を高める (2008)
  • Author(s): 松下茂人、池田龍二、奥村浩、秋山伸一、金蔵拓郎
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2008-10-28
• [Presentation] 高浸透圧によるMajor Vault Protein (MVP)の発現亢進機構
  • Author(s): 田實裕介、池田龍二、岩下建一、武田泰生、田畑祥、西澤由紀彦、牛山美奈、山口辰哉、山本雅達、車暁芳、古川龍彦、秋山伸一、山田勝士
  • Organizer: 20090317
  • Place of Presentation: パシフィコ横浜(横浜市)
• [Book] Focus on Zinc Finger Protein Research(Roles of PLZF and FAZF in osteoblast differentiation) (2009)
  • Author(s): Ikeda, R., Yoshida, K., Inoue, I.
  • Total Pages: 293-301