p53 and autophagy in colorectal cancer : function mechanism and Therapeutic applications

• Project/Area Number: 23591966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: MIYAMOTO Yuji 熊本大学, 医学部附属病院, 助教 (80551259)
• Co-Investigator(Kenkyū-buntansha): BABA Hideo 熊本大学, 大学院生命科学研究部, 教授 (20240905) ; HAYASHI Naoko 熊本大学, 医学部附属病院, 非常勤診療医師 (20452899) ; BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 大腸癌 / オートファジー / p53 / colorectal cancer / colorectal cancer / autophagy / 抗癌剤感受性 / 肝転移

Research Abstract

Autophagy is a celluar response to adverse environment and stress. Recent evidence suggests that tumor cells induce autophagy during treatment of anticancer drugs. However, the effect of these events on cancer is not known. The aime was to evaluate the effect of p53 status and autophagy activity on the chemosensitivity of colorectal cancer.
1.Autophagy was induced in response to DNA damage in p53 wild-type and p53 knockdown(p53-KD) colorectal cancer cells. The accumulation of LC-II was more intense in p53-KD cell than that in p53-cont cell. Furtheremore, we confirmed that apoptosis was induced in response to DNA damage in p53-cont and p53-KD cells after treating with siATG5. Apoptosis in p53-KD cell was less than that in p53-cont cell.
2.Immunohistochemical staining of resected liver tumor revealed that hte expression of some autophagic related protein(Protein A) was markedly decreased. Patients in high Protein A expression group was associated with lymphphatic invation.

Research Products

• [Journal Article] Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer (2014)
  • Author(s): Miyamoto Y, Watanabe M, Sakamoto Y, Shigaki H, Murata A, Sugihara H, Etoh K, Ishimoto T, Iwatsuki M, Baba Y, Iwagami S, Yoshida N, Baba H.
  • Journal Title: Surg Today Volume: (Epub ahead of print)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24623012
  • Peer Reviewed
• [Journal Article] Fascia lata onlay patch for repairing infected incisional hernias (2014)
  • Author(s): Miyamoto Y, Watanabe M, Ishimoto T, Baba Y, Iwagami S, Sakamoto Y, Yoshida N, Masuguchi S, Ihn H, Baba H.
  • Journal Title: Surg Today Volume: (Epub ahead of print) Issue: 1 Pages: 121-124
  • DOI: 10.1007/s00595-014-0936-y
  • Peer Reviewed
• [Journal Article] Chemotherapy and targeted therapy for patients with initially unresectable colorectal liver metastases, focusing on conversion hepatectomy and long-term survival (2014)
  • Author(s): Beppu T, Miyamoto Y(equal contributor), Sakamoto Y, Imai K, Nitta H, Hayashi H, Chikamoto A, Watanabe M, Ishiko T, Baba H.
  • Journal Title: Ann Surg Oncol Volume: 21 Suppl 3 Issue: S3 Pages: 405-13
  • DOI: 10.1245/s10434-014-3577-x
  • Peer Reviewed
• [Journal Article] Simultaneous laparoscopic resection of primary tumor and liver metastases for colorectal cancer: Surgical technique and short-term outcome. (2014)
  • Author(s): Miyamoto Y et al.
  • Journal Title: Hepatogastroenterology Volume: in press
  • Peer Reviewed
• [Journal Article] Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer. (2014)
  • Author(s): Miyamoto Y et al.
  • Journal Title: Surg Today Volume: in press
  • Peer Reviewed
• [Journal Article] Use of a fascia lata onlay patch for repairing infected incisional hernias. (2014)
  • Author(s): Miyamoto Y et al.
  • Journal Title: Surg Today Volume: in press
  • Peer Reviewed
• [Journal Article] Effects of obesity on the outcome of laparoscopic surgery for colorectal cancer. (2014)
  • Author(s): Miyamoto Y et al.
  • Journal Title: Surg Today Volume: in press
  • Peer Reviewed
• [Journal Article] Chemotherapy and Targeted Therapy for Patients with Initially Unresectable Colorectal Liver Metastases, Focusing on Conversion Hepatectomy and Long-Term Survival. (2014)
  • Author(s): Beppu T, Miyamoto Y (equal contributor) et al.
  • Journal Title: Ann Surg Oncol Volume: in press
• [Journal Article] Hepatic resection combined with radiofrequency ablation for initially unresectable colorectal liver metastases after effective chemotherapy is a safe procedure with a low incidence of local recurrence (2013)
  • Author(s): Mima K, Beppu T, Chikamoto A, Miyamoto Y, Nakagawa S, Kuroki H, Okabe H, Hayashi H, Sakamoto Y, Watanabe M, Kikuchi K, Baba H.
  • Journal Title: Int J Clin Oncol Volume: 18(5) Issue: 5 Pages: 847-55
  • DOI: 10.1007/s10147-012-0471-z
  • Peer Reviewed
• [Journal Article] Hepatic resection combined with radiofrequency ablation for initially unresectable colorectal liver metastases after effective chemotherapy is a safe procedure with a low incidence of local recurrence. (2013)
  • Author(s): Mima K, Miyamoto Y, et al.
  • Journal Title: Int J Clin Oncol. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. (2012)
  • Author(s): Saito S, Miyamoto Y, et al.
  • Journal Title: Oncol Rep. Volume: 29 Issue: 4 Pages: 1570-8
  • DOI: 10.3892/or.2013.2273
  • Peer Reviewed
• [Journal Article] 【抗がん剤または分子標的薬治療の効果判定と変更のタイミング-私はこうしている-(その1)】大腸癌における抗がん剤治療の効果判定と変更のタイミング (2012)
  • Author(s): 宮本裕士、坂本快郎、尾崎宣之、石本崇胤、岩槻政晃、馬場祥史、岩上志朗、吉田直矢、渡邊雅之、馬場秀夫
  • Journal Title: 癌と化学療法39 Volume: 39(9) Pages: 1326-1329
  • URL: http://mol.medicalonline.jp/library/journal/download?GoodsID=ab8gtkrc/2012/003909/005&name=1326-1329j&UserID=133.95.84.91
  • Peer Reviewed
• [Journal Article] Usefulness of transcription-reverse transcription concerted reaction method for detecting circulating tumor cells in patients with colorectal cancer. (2012)
  • Author(s): 佐藤伸隆
  • Journal Title: Annals of Surgical Oncology Volume: 19 Issue: 6 Pages: 2060-5
  • DOI: 10.1245/s10434-011-1889-7
  • Peer Reviewed
• [Journal Article] 大腸癌のリンパ節中微量癌細胞検出の意義2～MASA法～ (2012)
  • Author(s): 岩槻政晃、林尚子、渡邊雅之、石本崇胤、馬場祥史、宮本裕士、馬場秀夫
  • Journal Title: 大腸癌FRONTIER Volume: 5 Pages: 41-44
  • URL: http://med.m-review.co.jp/magazine/detail1/J46_5_1_41-44.html
• [Journal Article] 大腸癌における抗がん剤治療の効果判定と変更のタイミング (2012)
  • Author(s): 宮本裕士
  • Journal Title: 癌と化学療法 Volume: 39 Pages: 1326-1329
  • Peer Reviewed
• [Journal Article] Usefulness of Transcription-Reverse Transcription Concerted Reaction Method for Detecting Circulating Tumor Cells in Patients With Colorectal Cancer.Ann Surg Oncol. (2012)
  • Author(s): Sato N, Hayashi N, Imamura Y, Tanaka Y, Kinoshita K, Kurashige J, Saito S, Karashima R, Hirashima K, Nagai Y, Miyamoto Y, Iwatsuki M, Baba Y, Watanabe M, Baba H,
  • Journal Title: Ann Surg Oncol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] 大腸癌のリンパ節中微量癌細胞検出の意義2 ～MASA法～ (2012)
  • Author(s): 岩槻政晃 、林 尚子、渡邊雅之、石本崇胤、馬場祥史、宮本裕士、馬場秀夫
  • Journal Title: 大腸癌Frontier Volume: 5 Pages: 41-44
• [Journal Article] Possible existence of lysosome-like organella within mitochondria and its role in mitochondrial quality control (2011)
  • Author(s): Miyamoto Y, Kitamura N, Nakamura Y, Futamura M, Miyamoto T, Yoshida M, Ono M, Ichinose S, Arakawa H.
  • Journal Title: PLoS One Volume: 6(1) Issue: 1 Pages: e16054-e16054
  • DOI: 10.1371/journal.pone.0016054
  • Peer Reviewed
• [Journal Article] Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria (2011)
  • Author(s): Kitamura N, Nakamura Y, Miyamoto Y, Miyamoto T, Kabu K, Yoshida M, Futamura M, Ichinose S, Arakawa H.
  • Journal Title: PLoS One Volume: 6(1) Issue: 1 Pages: e16060-e16060
  • DOI: 10.1371/journal.pone.0016060
  • Peer Reviewed
• [Journal Article] 大腸癌における分子標的治療Convention therapyを念頭においた切除不能大腸癌肝転移に対する分子標的治療 (2011)
  • Author(s): 美馬浩介、別府透、林尚子、増田稔郎、宮本裕士、近本亮、石河隆敏、渡邊雅之、高森啓史、馬場秀夫
  • Journal Title: 外科 Volume: 73 Pages: 257-261
• [Journal Article] 大腸癌発癌におけるSPINK1の発現と意義 (2011)
  • Author(s): 井田智、宮本裕士、坂本快郎、渡邊雅之、馬場秀夫
  • Journal Title: 消化器内科 Volume: 53 Pages: 627-631
• [Journal Article] Possible Existence of Lysosome-Like Organella within Mitochondria and Its Role in Mitochondrial Quality Control (2011)
  • Author(s): Miyamoto Y, Kitamura N, Nakamura Y, Futamura M, Miyamoto T, Yoshida M, Ono M, Ichinose S, Arakawa H
  • Journal Title: Plos One Volume: 6
  • Peer Reviewed
• [Journal Article] a p53-Inducible Protein, Controls Mitochondrial Quality by Repairing or Eliminating Unhealthy Mitochondria. (2011)
  • Author(s): Kitamura N, Nakamura Y, Miyamoto Y, Miyamoto T, Kabu K, Yoshida M, Futamura M, Ichinose S, Arakawa H.
  • Journal Title: Plos one Volume: 6
  • Peer Reviewed
• [Journal Article] 大腸癌における分子標的治療 Convention therapyを念頭においた切除不能大腸癌肝転移に対する分子標的治療 (2011)
  • Author(s): 美馬浩介、別府 透、林 尚子、増田稔郎、宮本裕士、近本 亮、石河隆敏、渡邊雅之、高森啓史、馬場秀夫
  • Journal Title: 外科 Volume: 73 Pages: 257-261
• [Journal Article] Simultaneous laparoscopic resection of primary tumor and liver metastases for colorectal cancer : Surgical technique and short-term outcome
  • Author(s): Miyamoto Y, Beppu T, Sakamoto Y, Imai K, Hayashi H, Nitta H, Ishiko T, Watanabe M, Baba H.
  • Journal Title: Hepatogastroenterology Volume: (accept)
  • Peer Reviewed
• [Presentation] 当院におけるbevacizumabを使用した切除不能大腸癌症例の検討 (2012)
  • Author(s): 宮本裕士、坂本快郎、井田智、長井洋平、石本崇胤、岩槻政晃、馬場祥史、岩上志朗、渡邊雅之、馬場秀夫
  • Organizer: 第45回制癌剤適応研究会
  • Place of Presentation: 東京都・国際ファッションセンター(両国)
  • Year and Date: 2012-03-02
• [Presentation] Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer. (2012)
  • Author(s): Miyamoto Y, Sakamoto Y, Ida S, Watanabe M, Baba H.
  • Organizer: ASCO 2012 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2012-01-21
• [Presentation] Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer. (2012)
  • Author(s): Miyamoto Y, Sakamoto Y, Ida S, watanabe M, Baba H
  • Organizer: ASCO 2012 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco,USA
• [Presentation] 当院におけるbevacizumabを使用した切除不能大腸癌症例の検討 (2012)
  • Author(s): 宮本裕士、坂本快郎 井田 智 長井洋平 石本崇胤 岩槻政晃 馬場祥史 岩上志朗 渡邊雅之 馬場秀夫 "
  • Organizer: 第45回制癌剤適応研究会
  • Place of Presentation: 東京 国際ファッションセンター（両国）
• [Presentation] 大腸癌肝転移切除後の術後補助療法としてのFOLFOX療法の検討 (2011)
  • Author(s): 宮本裕士、坂本快郎、井田智、齋藤誠哉、土居浩一、渡邊雅之、馬場秀夫
  • Organizer: 第66回日本大腸肛門病学会学術集会
  • Place of Presentation: 東京都・ホテルニューオータニ
  • Year and Date: 2011-11-26
• [Presentation] Effects of obesity in laparoscopic surgery for colorectal cancer (2011)
  • Author(s): Miyamoto Y, Baba H, Yamaguchi S.
  • Organizer: INTERNATIONAL SURGICAL WEEK 2011
  • Place of Presentation: 神奈川県・パシフィコ横浜
  • Year and Date: 2011-08-29
• [Presentation] 高齢者大腸癌症例の検討 (2011)
  • Author(s): 宮本裕士, 林尚子、斎藤誠哉、平島浩太郎、辛島龍一、長井洋平、岩槻政晃、馬場祥史、渡邊雅之、馬場秀夫
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-07-13
• [Presentation] Laparoscopic palliative resection of primary tumor for stage iv colorectal cancer. (2011)
  • Author(s): Miyamoto Y, Ishii S, Tashiro J, Satoh T, Baba H, Yamaguchi S.
  • Organizer: EAES
  • Place of Presentation: Turin, Italy
  • Year and Date: 2011-06-18
• [Presentation] 同時性肝転移を有する大腸癌患者に対する腹腔鏡補助下大腸・肝同時切除術の検討/ Simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases (2011)
  • Author(s): 宮本裕士、林尚子、今村裕、長井洋平、岩上志朗、増田稔郎、近本亮、石河隆俊、渡邊雅之、別府透、馬場秀夫
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 誌上
  • Year and Date: 2011-05-27
• [Presentation] "同時性肝転移を有する大腸癌患者に対する腹腔鏡補助下大腸・肝同時切除術の検討 / Simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases " (2011)
  • Author(s): 宮本裕士, 林 尚子, 今村 裕, 長井 洋平, 岩上 志朗, 増田 稔郎, 近本 亮, 石河 隆俊, 渡邊 雅之, 別府 透, 馬場 秀夫
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 誌上開催
• [Presentation] 高齢者大腸癌症例の検討 (2011)
  • Author(s): 宮本裕士, 林 尚子、斎藤誠哉、平島浩太郎、辛島龍一、長井洋平、岩槻政晃、馬場祥史、渡邊雅之、馬場秀夫
  • Organizer: 第66回日本消化器外科学会総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Laparoscopic palliative resection of primary tumor for stage iv colorectal cancer (2011)
  • Author(s): Miyamoto Y, Ishii S, Tashiro J, SatohT, Baba H, Yamaguchi S
  • Organizer: EAES
  • Place of Presentation: Turin, Italy
• [Presentation] Effects of obesity in laparoscopic surgery for colorectal cancer (2011)
  • Author(s): Miyamoto Y, Baba H, Yamaguchi S
  • Organizer: "INTERNATIONAL SURGICAL WEEK 2011
  • Place of Presentation: Pacifico Yokohama
• [Presentation] 大腸癌肝転移切除後の術後補助療法としてのFOLFOX療法の検討 (2011)
  • Author(s): 宮本裕士、坂本快郎、井田 智、齋藤誠哉、土居浩一、渡邊雅之、馬場秀夫
  • Organizer: 第66回日本大腸肛門病学会学術集会
  • Place of Presentation: 東京 ホテルニューオータニ