New treatment strategy via autophagy for pancreatic adenocarcinoma.

• Project/Area Number: 26861089
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: HASHIMOTO Daisuke 熊本大学, 医学部附属病院, 助教 (80508507)
• Research Collaborator: SAKATA Kazuya 熊本大学, 医学部附属病院, 非常勤診療医師
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: オートファジー / 膵癌 / ゲムシタビン / フルオロウラシル / ５－ＦＵ

Outline of Final Research Achievements

Autophagy is a regulated process of degradation and recycling of cellular constituents. The role of autophagy in pancreatic cancer is still not clear. The aim of this study was to investigate the role of autophagy in pancreatic cancer, and to provide insights into new strategies for treatment.
During study period, about 50 patients with pancreatic cancer underwent pancreatic resection. Autophagy was significantly induced in pancreatic ductal adenocarcinoma compared to healthy pancreatic tissue in these patients. The association of autophagy status with long-term survival has been analyzed.
In pancreatic cancer cell lines, autophagy contributes to pancreatic cancer cell growth, and has a cytoprotective effect against anti-cancer drug. These data were published in Euro J Cancer.

Research Products

• [Journal Article] Residual total pancreatectomy: short- and long-term outcome Pancreatol: short- and long-term outcome. (2016)
  • Author(s): Hashimoto D, Chikamoto A, Sakata K, Taki K, Inoue R, Arima K, Hayashi H, Ohmuraya M, Hirota M, Baba H
  • Journal Title: Pancreatology Volume: in press Pages: 646-51
  • DOI: 10.1016/j.pan.2016.04.034
  • Peer Reviewed
• [Journal Article] Unused sterile instruments for closure prevents wound SSI after pancreatic surgery. (2016)
  • Author(s): Hashimoto D, Chikamoto A, Arima K, Taki T, Inoue R, Imai K, Yamashita Y, Baba H.
  • Journal Title: J Surg Res Volume: in press
  • DOI: 10.1016/j.jss.2016.02.044
  • Peer Reviewed
• [Journal Article] Heterogeneity of KRAS mutations in pancreatic ductal adenocarcinoma. (2016)
  • Author(s): Hashimoto D, Arima K, Yokoyama N, Chikamoto A, Taki T, Inoue R, Kaida T, Higashi T, Nitta H, Ohmuraya M, Hirota M, Beppu T, Baba H.
  • Journal Title: Pancreas Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] KRAS, BRAF, and PIK3CA mutations, and patient prognosis in 126 pancreatic cancers: pyrosequencing technology and literature review. (2016)
  • Author(s): Zhou L, Baba Y, Kitano Y, Miyake K, Zhang X, Yamamura K, Kosumi K, Kaida T, Arima K, Taki K, Higashi T, Imai K, Hashimoto D, Yamashita Y, Chikamoto A, Beppu T, Tan X, Baba H.
  • Journal Title: Med Oncol Volume: 33(4) Pages: 32-32
  • DOI: 10.1007/s12032-016-0745-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting pancreatic ductal adenocarcinoma in patients with pancreatic diseases. (2016)
  • Author(s): Arima K, Okabe H, Hashimoto D, Chikamoto A, Tsuji A, Yamamura K, Kitano Y, Inoue R, Kaida T, Higashi T, Taki K, Imai K, Beppu T, Baba H.
  • Journal Title: Int J Clin Oncol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] miR-9-3p promotes cell proliferation by targeting TAZ (WWTR1) in hepatocellular carcinoma cells. (2015)
  • Author(s): Higashi, T., Hayashi, H., Ishimoto, T., Takeyama, H., Kaida, T., Arima, K., Taki, K., Sakamoto, K., Kuroki, H., Okabe, H., Nitta, H., Hashimoto, D., Chikamoto, A., Beppu, T., Baba, H.
  • Journal Title: Br J Cancer Volume: 14;113(2) Pages: 252-8
  • DOI: 10.1038/bjc.2015.170
  • Peer Reviewed
• [Journal Article] mpact of Postoperative Weight Loss on Survival After Resection for Pancreatic Cancer (2015)
  • Author(s): Hashimoto D, Chikamoto A, Ohmuraya M, Abe S, Nakagawa S, Beppu T, Takamori H, Hirota M, Baba H.
  • Journal Title: JPEN J Parenter Enteral Nutr Volume: Epub ahead of print Pages: 598-603
  • DOI: 10.1177/0148607114520992
  • Peer Reviewed
• [Journal Article] Recombinant soluble thrombomodulin for postoperative disseminated intravascular coagulation. (2015)
  • Author(s): Hashimoto D, Chikamoto A, Miyanari N, Ohara C, Kuramoto M, Horino K, Ohshima H, Baba H.
  • Journal Title: J Surg Res Volume: 197(2) Pages: 405-11
  • DOI: 10.1016/j.jss.2015.04.048
  • Peer Reviewed
• [Journal Article] Staging laparoscopy leads to rapid induction of chemotherapy for unresectable pancreato-biliary cancers. (2015)
  • Author(s): Hashimoto, D., Chikamoto, A., Sakata, K., Nakagawa, S., Hayashi, H., Ohmuraya, M., Hirota, M., Yoshida, N., Beppu, T. and Baba, H.
  • Journal Title: Asian J Endoscopic Surg Volume: 8 Pages: 59-62
  • DOI: 10.1111/ases.12138
  • Peer Reviewed / Open Access
• [Journal Article] Accessory right hepatic artery branched from gastroduodenal artery. (2015)
  • Author(s): Yamashita K, Hashimoto D, Itoyama R, Okabe H, Chikamoto A, Beppu T, Baba H.
  • Journal Title: Surg Case Rep Volume: 1 Pages: 90-90
  • DOI: 10.1186/s40792-015-0092-7
  • Peer Reviewed / Open Access
• [Journal Article] Successful surgical internal drainage of postoperative pancreatic pseudocyst through pancreaticojejunostomy with distal pancreatectomy: a case report. (2015)
  • Author(s): Sakata K, Hashimoto D, Taki K, Nakahara O, Ohmuraya M, Chikamoto A, Beppu T, Baba H
  • Journal Title: Surg Case Rep. Volume: 1 Pages: 54-54
  • DOI: 10.1186/s40792-015-0057-x
  • Peer Reviewed / Open Access
• [Journal Article] Hepatobiliary and Pancreatic: Skin metastases from cholangiocarcinoma mimicking herpes zoster. (2015)
  • Author(s): Okabe H, Hashimoto D, Chikamoto A, Hayashi H, Nitta H, Taki K, Higashi T, Arima K, Ishiko T, Beppu T, Baba H
  • Journal Title: J Gastroenterol Hepatol Volume: 30(9) Pages: 1337-1337
  • DOI: 10.1111/jgh.12964
  • Peer Reviewed
• [Journal Article] Reactive lymphoid hyperplasia of the liver requires differential diagnosis of hepatocellular carcinoma. (2015)
  • Author(s): Higashi T, Hashimoto D, Beppu T, Kaida T, Arima K, Takeyama H, Taki K, Sakamoto K, Sakata K, Hayashi H, Nitta H, Chikamoto A, Honda Y, Inomata Y, Baba H.
  • Journal Title: Surg Case Rep Volume: 1 Pages: 31-31
  • DOI: 10.1186/s40792-015-0034-4
  • Peer Reviewed / Open Access
• [Journal Article] Acute gastric volvulus in a patient with trisomy 21. (2015)
  • Author(s): Arima K, Hashimoto D, Takata N, Doi Y, Yoshinaka I, Harada K, Baba H.
  • Journal Title: Surg Case Rep Volume: 1 Pages: 5-5
  • DOI: 10.1186/s40792-014-0005-1
  • Peer Reviewed / Open Access
• [Journal Article] A case of occult intrahepatic cholangiocarcinoma diagnosed by autopsy. (2015)
  • Author(s): Eri Oda, Daisuke Hashimoto, Yuko Shiomi, Koji Ohnishi, Hiromitsu Hayashi, Akira Chikamoto, Motohiro Takeya, Hideo Baba
  • Journal Title: Surg Case Rep Volume: 1 Pages: 101-101
  • DOI: 10.1186/s40792-015-0106-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreas-preserving partial duodenectomy of the distal regionpart for large duodenal adenoma: Rreport of a case. (2015)
  • Author(s): Shimizu K, Hashimoto D, Abe S, Chikamoto A, Baba H.
  • Journal Title: Surg Today Volume: 45(3) Pages: 390-393
  • DOI: 10.1007/s00595-014-0868-6
  • Peer Reviewed
• [Journal Article] Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs (2014)
  • Author(s): Hashimoto D, Bläuer M, Hirota M, Ikonen NH, Sand J, Laukkarinen J
  • Journal Title: Eur J Cancer Volume: 50(7) Pages: 1382-90
  • DOI: 10.1016/j.ejca.2014.01.011
  • Peer Reviewed
• [Journal Article] Pancreaticodigestive anastomosis and the postoperative management strategies to prevent postoperative pancreatic fistula formation after pancreaticoduodenectomy (2014)
  • Author(s): Hashimoto D, Chikamoto A, Ohmuraya M, Hirota M, Baba H
  • Journal Title: Surg Today. Volume: - Pages: 1207-1213
  • DOI: 10.1007/s00595-013-0662-x
  • Peer Reviewed
• [Journal Article] Pancreatic cancer in the remnant pancreas following primary pancreatic resection (2014)
  • Author(s): Hashimoto D, Chikamoto A, Ohmuraya M, Sakata K, Miyake K, Kuroki H, Watanabe M, Beppu T, Hirota M, Baba H.
  • Journal Title: Surg Today. Volume: - Pages: 1313-1320
  • DOI: 10.1007/s00595-013-0708-0
  • Peer Reviewed
• [Presentation] 高齢者に対して膵頭十二指腸切除術を安全に行うために (2015)
  • Author(s): 橋本大輔、近本 亮、辻 顕、山村謙介、井上梨沙、有馬浩太、髙城克暢、東孝暁、新田英利、別府透、馬場秀夫
  • Organizer: 第77回日本臨床外科学会総会
  • Place of Presentation: 福岡サンパレス
  • Year and Date: 2015-11-28
• [Presentation] Heterogeneity of KRAS mutation in pancreatic ductal adenocarcinoma. (2015)
  • Author(s): Daisuke Hashimoto、Kota Arima,Akira Chikamoto,Katsunobu Taki,Risa Inoue,Takayoshi Kaida,Takaaki Higashi,Hidetoshi Nitta,Hiromitsu Hayashi,Hideo Baba
  • Organizer: The 47th European Pancreatic Club
  • Place of Presentation: Palacio de Congresos de Toledo El Greco
  • Year and Date: 2015-06-25
• [Presentation] 膵液瘻はゼロにできるのか？膵空腸挿入吻合法と膵管空腸吻合法 (2015)
  • Author(s): 橋本大輔、有馬浩太、井上梨沙、髙城克暢、甲斐田剛圭、東孝暁、武山秀晶、新田英利、林洋光、岡部弘尚、近本亮、別府透、馬場秀夫
  • Organizer: 第27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: ホテルグランパシフィック LE DAIBA（東京都）
  • Year and Date: 2015-06-12
• [Presentation] 膵頭十二指腸切除術後の合併症死亡ゼロを目指して (2015)
  • Author(s): 橋本大輔、近本亮、坂田和也、岡部弘尚、髙城克暢、井上梨沙、有馬浩太、新田英利、林洋光、別府透、馬場秀夫
  • Organizer: 第115回 日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-04-16
• [Presentation] オートファジー機能不全がもたらす慢性膵炎の発症機構 (2014)
  • Author(s): 坂田 和也
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2014-04-03 – 2014-04-05