Mechanism of radio-sensitizing effect caused by angiogenesis inhibitor

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591726
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: NISHIOKA Masanori 徳島大学, 病院, 助教 (50398020)
• Co-Investigator(Kenkyū-buntansha): KURITA Nobuhiro 徳島大学, 病院, 特任教授 (30335814) ; IWATA Takashi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (00380022) ; YOSHIKAWA Kozo 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (80448331)
• Project Period (FY): 2009 – 2011
• Keywords: 癌 / 放射線 / 血管新生 / 放射線増感剤 / 低酸素 / HIF-1 / Oridonin / TPI(Thymidine phosphorylase inhibitor)

Research Abstract

Combination of TPI and RT synergistically inhibited the cell viability in a time-and dose-dependent manner. The combination of TPI and RT reduced the tumor growth compared with RT alone. The mRNA levels of VEGF, TGF-b and Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. The combination markedly increased the TUNEL positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. Oridonin suppressed growth of HCT-15 and HT-29 cells through induction of apoptosis and autophagy. However, combined with RT and Oridonin augmented growth suppression through induction of apoptosis. In orthotpoic model, combination of RT and Oridonin showed significant reductions in tumor volume.

Research Products

• [Journal Article] Platelet-derived endothelial cell growth factor/ thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer. (2012)
  • Author(s): Miyatani T, Kurita N, Utsunomiya T, Iwata T, Nishioka M, Yoshikawa K, Higashijima J, Kashihara H, Takasu C, Fukushima M, Shimada M.
  • Journal Title: Cancer Lett Volume: 318(2) Pages: 199-205
  • DOI: doi:10.1016/j.canlet.2011.12.010.Epub2011Dec13
  • Peer Reviewed
• [Journal Article] Clinicopathological Analysis of Distal Margin for Rectal Cancer after Preoperative Chemoradiation Therapy (2012)
  • Author(s): Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, Higashijima J, Miyatani T.
  • Journal Title: Hepatogastroenterology Volume: 59(119)
  • DOI: doi:10.5754/hge11840
  • Peer Reviewed
• [Journal Article] Kampo medicine" Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats (2012)
  • Author(s): Chikakiyo M, Shimada M, Nakao T, Higashijima J, Yoshikawa K, Nishioka M, Iwata T, Kurita N.
  • Journal Title: Surg Today Volume: 42(1) Pages: 60-7
  • Peer Reviewed
• [Journal Article] The effects of the Kampo medicine(Japanese herbal medicine)" Daikenchuto" on the surgical inflammatory response following laparoscopic colorectal resection (2011)
  • Author(s): Yoshikawa K, Shimada M, Nishioka M, Kurita N, Iwata T, Morimoto S, Miyatani T, Komatsu M, Kashihara H, Mikami C.
  • Journal Title: Surg Today
  • Peer Reviewed
• [Journal Article] Preoperative Radiotherapy Combined with S-1 for Advanced Lower Rectal Cancer : Phase I Trial (2011)
  • Author(s): Morimoto S, Shimada M, Kurita N, Sato H, Iwata T, Nishioka M, Yoshikawa K, Miyatani T, Kashihara H, Takasu C, Ikushima H.
  • Journal Title: Hepatogastroenterology Volume: 59(117)
  • DOI: doi:10.5754/hge11699
  • Peer Reviewed
• [Journal Article] Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer (2011)
  • Author(s): Higashijima J, Kurita N, Miyatani T, Yoshikawa K, Morimoto S, Nishioka M, Iwata T, Shimada M.
  • Journal Title: Oncol Rep Volume: 26(2) Pages: 343-8
  • DOI: doi:10.3892/or.2011.1312
  • Peer Reviewed
• [Journal Article] The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen (2011)
  • Author(s): Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, Higashijima J, Miyatani T, Kono T.
  • Journal Title: Int J Clin Oncol Volume: 16(4) Pages: 322-7
  • Peer Reviewed
• [Journal Article] Malignant potential of Barrett' s esophagus : special reference to HDAC-1 and MTA-1 expression (2011)
  • Author(s): Miyatani T, Kurita N, Mikami C, Kashihara H, Higashijima J, Yoshikawa K, Nishioka M, Sato H, Iwata T, Shimada M.
  • Journal Title: Hepatogastroenterology Volume: 58(106) Pages: 472-6
  • Peer Reviewed
• [Journal Article] Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer (2011)
  • Author(s): Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, Higashijima J, Miyatani T.
  • Journal Title: Cancer Genomics Proteomics Volume: 8(2) Pages: 87-92
  • Peer Reviewed
• [Journal Article] Serum evaluation of soluble interferon-alpha/ beta receptor and high-sensitivity C-reactive protein for diagnosis of the patients with gastrointestinal and hepatobiliary-pancreatic cancer (2010)
  • Author(s): Miyake K, Imura S, Nishioka M, Batmunkh E, Sugimoto K, Ohmoto Y, Shimada M.
  • Journal Title: Cytokine Volume: 49(3) Pages: 251-5
  • Peer Reviewed
• [Journal Article] Sonic hedgehog relates to colorectal carcinogenesis (2009)
  • Author(s): Yoshikawa K, Shimada M, Miyamoto H, Higashijima J, Miyatani T, Nishioka M, Kurita N, Iwata T, Uehara H.
  • Journal Title: J Gastroenterol Volume: 44(11) Pages: 1113-7
  • Peer Reviewed
• [Journal Article] Downregulation of matrix metalloprotease-9 and urokinase plasminogen activator by TX-1877 results in decreased tumor growth and metastasis on xenograft model of rectal cancer (2009)
  • Author(s): Miyake K, Shimada M, Nishioka M, Sugimoto K, Batmunkh E, Uto Y, Nagasawa H, Hori H.
  • Journal Title: Cancer Chemother Pharmacol Volume: 64(5) Pages: 885-92
  • Peer Reviewed
• [Presentation] Utsunomiya T. Rediosensitizing effects of oridonin for human colon cancer.(オリドニンの放射線増感作用に関する検討.) (2010)
  • Author(s): Mikami C, Shimada M, Kurita N, Iwata T, Nishioka M, Morimoto S, Yoshikawa K, Miyatani T, Komatsu M, Kashihara H,
  • Organizer: 第69回日本癌学術総会
  • Place of Presentation: 大阪国際会議場大阪市
  • Year and Date: 2010-09-23
• [Presentation] オリドニンの放射線増感作用に関する検討 (2010)
  • Author(s): 小松正人, 島田光生, 西岡将規, 栗田信浩, 岩田貴, 森本慎也, 吉川幸造, 東島潤, 宮谷知彦, 中尾寿宏, 柏原秀也, 宇都宮徹
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場名古屋市
  • Year and Date: 2010-04-08
• [Presentation] 直腸癌に対するThymidine phospholyrase inhibitorの放射線増感作用に関する基礎的研究 (2009)
  • Author(s): 宮谷知彦、島田光生、小松正人、中尾寿宏、近清素也、東島潤、吉川幸造、西岡将規、岩田貴、栗田信浩、福島正和
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: マリンメッセ福岡大会議場福岡市
  • Year and Date: 2009-04-03