Mechanism of distant metastasis after radiotherapy for rectal cancer.

• Project/Area Number: 23591935
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: HIGASHIJIMA Jun 徳島大学, 大学病院, 特任助教 (30467815)
• Co-Investigator(Kenkyū-buntansha): YASUTOMO Koji 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (30333511) ; NISHIOKA Masanori 徳島大学, 病院, 助教 (50398020) ; IKEMOTO Tetsuya 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助教 (20398019) ; TAKASU Chie 徳島大学, 大学院ヘルスバイオサイエンス研究部, 特任助教 (70582823) ; NISHI Masaaki 徳島大学, 病院, 医員 (70464344)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 直腸癌 / 術前放射線治療 / 調節性T細胞 / Foxp3 / Notchシグナル / Delta / Jagged / CD47 / THBS-1 / 調節性T細胞 Treg

Research Abstract

(Aim)To clarify the mechanisim of distant metastasis after radiotherapy for rectal cancer.(Methods)We used Balb/c nude mice. We cut anterior wall of rectum, and implanted HT-29 cells into posterior wall. Seven days after, we compared the several immune factors between radiation therapy group and non-therapy group using RT-PCR and flow cytometric analysis.(Result)In radiotherapy group, Foxp3, Notch1, Jagged1 mRNA ratio in tumor were not significantly increased compared with non-therapy group. Foxp3 ratio in spleen tended to be higher in radiotherapy group, compared with control and non-therapy group.(Conculusion)In radiotherapy for rectal cancer, immune tolerance by Foxp3 up-regulation in blood may increase distant metastasis. Foxp3 may be a important factor to regulate distant metastasis in rectal cancer patients with radiotherapy or chemoradiotherapy.

Research Products

• [Journal Article] Benefits of simultaneous laparoscopic resection of primary colorectal cancer and liver metastases. (2014)
  • Author(s): Takasu C, Shimada M, Sato H, Miyatani T, Imura S, Morine Y, Ikemoto T, Kanamoto M, Kurita N, Eto S, Utsunomiya T.
  • Journal Title: Asian J Endosc Surg. Volume: 7 Issue: 1 Pages: 31-37
  • DOI: 10.1111/ases.12066
  • Peer Reviewed
• [Journal Article] Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer (2013)
  • Author(s): Takasu C, Shimada M, Kurita N, Iwata T, Sato H, Nishioka M, Morimoto S, Yoshikawa K, Miyatani T, Kashihara H,Utsunomiya T, Uehara H.
  • Journal Title: Int J Clin Oncol Volume: 18(5) Issue: 5 Pages: 869-876
  • DOI: 10.1007/s10147-012-0470-0
  • Peer Reviewed
• [Journal Article] Impact of C-reactive protein on prognosis of patients with coorectal carcinoma (2013)
  • Author(s): Takasu C, Shimada M, Kurita N, Iwata T, Nishioka M, Morimoto S, Yoshikawa K, Miyatani T, Kashihara H, Utsunomiya T.
  • Journal Title: Hepatogastroenterology Volume: 60(123) Pages: 507-511
  • Peer Reviewed
• [Journal Article] Impact of C-reactive protein on prognosis of patients with coorectal carcinoma. (2013)
  • Author(s): Takasu C, Shimada M, Kurita N, Iwata T, Nishioka M, Morimoto S, Yoshikawa K, Miyatani T, Kashihara H, Utsunomiya T.
  • Journal Title: Hepatogastroenterology Volume: 60 Pages: 507-511
  • 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) Pages: 2142-2146
  • Peer Reviewed
• [Journal Article] Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer (2012)
  • Author(s): Iwata T, Shimada M, Kurita N, Nishioka M, Morimoto S, Yoshikawa K, Higashijima J, Nakao T, Komatsu M.
  • Journal Title: Hepatogastroenterology Volume: 59(116) Pages: 990-993
  • 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) Pages: 2142-2146
  • Peer Reviewed
• [Journal Article] Short-term results of laparoscopic surger after preoperative chemoradiation for clinically staged T3 and T4 rectal cancer (2012)
  • Author(s): Hotchi M, Shimada M, Kurita N, Iwata T, Sato H, Morimoto S, Yoshikawa K, Higashijima J, Miyatani T, Mikami C, Kashihara H.
  • Journal Title: Asian J Endosc Surg Volume: 5(4) Issue: 4 Pages: 157-163
  • DOI: 10.1111/j.1758-5910.2012.00148.x
  • Peer Reviewed
• [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) Issue: 2 Pages: 199-205
  • DOI: 10.1016/j.canlet.2011.12.010
  • Peer Reviewed
• [Journal Article] Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer. (2012)
  • Author(s): Iwata T
  • Journal Title: Hepatogastroenterology Volume: 59(116) Pages: 990-993
  • Peer Reviewed
• [Journal Article] Impact of Education with Authorized Technical Experts on Colorectal Laparoscopic Skills. (2012)
  • Author(s): Iwata T
  • Journal Title: Hepatogastroenterology Volume: 59(117) Pages: 1412-1414
  • 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: CancerGenomics&Proteomics Volume: 8(2) Pages: 87-92
  • 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: 10.3892/or.2011.1312
  • 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.
  • Journal Title: Oncology Reports Volume: 26 Pages: 343-348
  • Peer Reviewed
• [Journal Article] Clinicopathological Analysis of Distal Margin for Rectal Cancer after Preoperative Chemoradiation Therapy (2011)
  • Author(s): Nishioka M.
  • Journal Title: Hepatogastroenterology Volume: 59
  • Peer Reviewed
• [Journal Article] Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer. (2011)
  • Author(s): Nishioka M.
  • Journal Title: Cancer Genomics Proteomics Volume: 8 Pages: 87-92
  • Peer Reviewed
• [Presentation] 進行下部直腸癌に対する術前化学放射線療法の長期成績について (2013)
  • Author(s): 佐藤宏彦, 島田光生, 栗田信浩, 吉川幸造, 東島潤
  • Organizer: 第68回日本大腸肛門病学会学術集会
  • Place of Presentation: 東京都(京王プラザホテル)
• [Presentation] 局所進行下部直腸癌に対する術前化学放射線療法併用内肛門括約筋切除術(ISR)の成績 (2013)
  • Author(s): 東島潤, 佐藤宏彦, 栗田信浩, 岩田貴, 吉川幸造, 近清素也, 西正暁, 柏原秀也, 松本規子, 島田光生
  • Organizer: JDDW 2013
  • Place of Presentation: 東京都(グランドプリンスホテル新高輪)
• [Presentation] 癌幹細胞制御におけるソニックヘッジホッグシグナルの意義 (2013)
  • Author(s): 栗田信浩, 島田光生, 岩田貴, 佐藤宏彦, 吉川幸造, 東島潤, 近清素也, 西正暁, 柏原秀也, 松本規子, 江藤祥平
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川県(パシフィコ横浜)
• [Presentation] Predictive Factors in Chemoradiotherapy for Rectal Cancer (2013)
  • Author(s): Higashijima J, Shimada M, Kurita N、Iwata T, Sato H, Yoshikawa K, Chikakiyo M, Nishi M, Kashihara H, Matsumoto N
  • Organizer: International Association of Surgeons, Gastroenterologists and Oncologists 2013(IASGO)
  • Place of Presentation: ルーマニア(The Palace of the Parliament)
• [Presentation] Predictive Factors in Chemoradiotherapy for Rectal Cancer. (2013)
  • Author(s): Higashijima J, Shimada M, Kurita N、Iwata T, Sato H, Yoshikawa K, Chikakiyo M, Nishi M, Kashihara H, Matsumoto N.
  • Organizer: International Association of Surgeons, Gastroenterologists and Oncologists 2013(IASGO)
  • Place of Presentation: The palace of the Parliament(ルーマニア)
• [Presentation] 局所進行下部直腸癌に対する術前化学放射線療法併用肛門温存術(ISR)の成績 (2013)
  • Author(s): 佐藤宏彦, 島田光生, 栗田信浩, 岩田貴, 吉川幸造, 宮谷知彦, 柏原秀也, 髙須千絵, 松本規子
  • Organizer: 第113回 日本外科学会定期学術集会
  • Place of Presentation: マリンメッセ福岡(福岡県)
• [Presentation] 局所進行下部直腸癌に対する術前化学放射線療法の短期・長期成績について (2013)
  • Author(s): 佐藤宏彦, 島田光生, 栗田信浩, 岩田貴, 吉川幸造, 宮谷知彦, 柏原秀也, 髙須千絵, 松本規子
  • Organizer: 第68回 日本消化器外科学会総会
  • Place of Presentation: シーガイヤコンベンションセンター(宮崎県)
• [Presentation] 早期下部直腸癌に対する術前化学放射線局所切除術の短期・長期成績について (2013)
  • Author(s): 佐藤宏彦, 島田光生, 栗田信浩
  • Organizer: JDDW 2013 第21回 日本消化器関連学会週間
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール(東京都)
• [Presentation] 腹腔鏡下直腸切除術におけるICG蛍光法を用いた腸管血流評価と確実な手術手技 (2013)
  • Author(s): 東島潤, 島田光生, 栗田信浩, 岩田貴, 佐藤宏彦, 吉川幸造, 近清素也, 西正暁, 柏原秀也, 松本規子, 江藤祥平
  • Organizer: 第75回 日本臨床外科学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
• [Presentation] Predictive factors in chemoradiotherapy for rectal cancer (2012)
  • Author(s): 宮谷知彦, 島田光生, 宇都宮徹, 栗田信浩, 岩田貴, 佐藤宏彦, 吉川幸造, 東島潤, 髙須千絵, 柏原秀也, 松本規子
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道(ロイトン札幌)
• [Presentation] 大腸癌におけるmicroRNA223発現の意義についての研究(第二報) (2012)
  • Author(s): 東島潤, 島田光生, 西岡将規, 栗田信浩, 岩田貴, 佐藤宏彦, 森本慎也, 吉川幸造, 宮谷知彦, 後藤正和, 小松正人, 髙須千絵, 柏原秀也
  • Organizer: 第112回日本外科学会学術集会
  • Place of Presentation: 千葉県(幕張メッセ)
• [Presentation] CD133はmicroRNAの制御により直腸癌の化学放射線療法耐性に関与する (2012)
  • Author(s): 宮谷知彦, 島田光生, 佐藤宏彦, 栗田信浩, 岩田貴, 西岡将規, 森本慎也, 吉川幸造, 東島潤, 柏原秀也, 髙須千絵
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 栃木県(京王プラザ)
• [Presentation] Randomized clinical trial of preoperative chemoradiotherapy by S-1 versus UFT to rectal cancer for personalized therap (2012)
  • Author(s): Miyatani T, Utsunomiya T, Kurita N, Iwata T, Sato H, Nishioka M, Morimoto S, Yoshikawa K, Higashijima J, Kashihara H, Takasu C, Shiamda M.
  • Organizer: ASCO-GI
  • Place of Presentation: アメリカ(The Moscone West Building)
• [Presentation] 大腸癌におけるmicroRNA223発現の意義についての研究(第二報) (2012)
  • Author(s): 東島 潤 他
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 直腸癌に対するDPD阻害フッ化ピリミジンを用いた術前化学放射線療法のrandomized clinical trial～個別化治療を目指して～ (2012)
  • Author(s): 宮谷 知彦 他
  • Organizer: 第112回 日本外科学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Duodenal-jejunal bypassによる耐糖能異常改善効果に関する研究 (2012)
  • Author(s): 東島 潤 他
  • Organizer: 第67回 日本消化器外科学会総会
  • Place of Presentation: 富山国際会議場（富山）
• [Presentation] Predictive factors in chemoradiotherapy for rectal cancer. (2012)
  • Author(s): 宮谷 知彦 他
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] miRNA-223による直腸癌の化学放射線療法効果予測は可能か? (2011)
  • Author(s): 髙須千絵, 島田光生, 栗田信浩, 岩田貴, 佐藤宏彦, 西岡将規, 森本慎也, 吉川幸造, 宮谷知彦, 東島潤, 柏原秀也
  • Organizer: 第22回日本消化器癌発生学会総会
  • Place of Presentation: 佐賀県(ホテルニューオータニ佐賀)
• [Presentation] Investigation of expression of RAD51 in biopsied apecimen as a predictive factor of chemo-radiation therapy for advancer rectal cancer (2011)
  • Author(s): Iwata T, Shimada M, Kurita N, Nishioka M, Morimoto S, Yoshikawa K, Higashijima J, Mikami C, Kashihara H.
  • Organizer: 102d American Association for Cancer Research(AACR2011)
  • Place of Presentation: アメリカ(Orange Country Convention Center)
• [Presentation] 直腸癌の化学放射線療法耐性におけるmi-croRNA223と癌修復遺伝子RAD51の関係に関する研究 (2011)
  • Author(s): 東島潤, 島田光生, 三上千絵, 西岡将規, 岩田貴, 栗田信浩, 森本慎也, 吉川幸造, 宮谷知彦, 柏原秀也, 宇都宮徹, 三宅秀則
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 震災のため紙面開催
• [Presentation] 直腸癌の化学放射線療法耐性における癌幹細胞およびmiRNAの検討 (2011)
  • Author(s): 江藤祥平, 島田光生, 栗田信浩, 岩田貴, 西岡将規, 森本慎也, 吉川幸造, 東島潤, 宮谷知彦, 柏原秀也, 三上千絵, 三宅秀則
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 震災のため紙面開催
• [Presentation] 腹腔鏡下直腸切除術における新たな工夫 術前化学放射線療法を併用した腹腔鏡下直腸切除術の工夫と肛門機能 (2011)
  • Author(s): 西岡将規
  • Organizer: 第66回 日本消化器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）
• [Presentation] Randomized clinical trial of preoperative chemoradiotherapy by S-1 vs UFT to rectal cancer for personalized therapy.
  • Author(s): Miyatani T et al
  • Organizer: The13th KOREA-JAPAN-CHINA COLORECTAL CANCER
  • Place of Presentation: seoul Catholic University Hospital(ソウル)
• [Presentation] 直腸癌の化学放射線療法耐性におけるmicroRNA223と癌修復遺伝子RAD51の関係に 関する研究
  • Author(s): 東島潤
  • Organizer: 第111回 日本外科学会定期学術集会
  • Place of Presentation: 震災のため紙面での発表