Therapeutic development for pancreatic cancer via cancer specific glucose metabolism

• Project/Area Number: 16K10604
• 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: HASHIMOTO Daisuke 熊本大学, 医学部附属病院, 助教 (80508507)
• Co-Investigator(Kenkyū-buntansha): 澤山 浩 熊本大学, 医学部附属病院, 非常勤診療医師 (40594875) ; 今井 克憲 熊本大学, 大学院生命科学研究部(医), 助教 (60555746) ; 東 孝暁 熊本大学, 医学部附属病院, 非常勤診療医師 (70594878)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵臓外科学 / 癌糖代謝 / Glut1

Outline of Final Research Achievements

The diagnosis of malignant diseases has been determined using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glucose transporter type 1 (Glut-1) is a key protein associated with the accumulation of FDG in cancer cells.
In this study the expression of Glut-1 and the corrected maximum standardized uptake value (cSUVmax) of FDG-PET were examined in 138 surgically resected pancreatic cancers. Glut-1 was positive in 69 patients. The median relapse-free and overall survival times were significantly shorter in the Glut-1-positive group (11 vs. 22 months, respectively) than in the Glut-1-negative group (23 vs. 42 months, respectively). The cSUVmax was significantly associated with long-term survival. The relapse free and overall survival rates were significantly poorer in the high-cSUVmax group than in the low-cSUVmax group. Glut-1 expression was associated with cSUVmax accumulation. In the multivariate analysis, high cSUVmax was identified as an independent prognostic factor.

Academic Significance and Societal Importance of the Research Achievements

膵癌は多くの症例で発見時既に切除不能である。また切除可能であっても、術後ほとんどの症例で再発をきたす難治性癌である。現在手術や抗がん剤による化学療法が治療の中心であるが、膵癌の更なる予後向上のために新しい治療法の開発は必要不可欠である。
今回我々は癌細胞にグルコースを能動的に取り込むGlucose transporter 1: Glut1がある一定の膵癌患者の癌細胞の表面に多く発現していることを示した。Glut1の発現が多い症例はPET検査におけるFDGの集積も多く、また予後が悪いことが分かった。これは、Glut1をターゲットとした新しい分子標的治療の可能性を示すものである。

Research Products

• [Journal Article] Neuroendocrine Tumor of the Hilar Bile Duct (2019)
  • Author(s): 4.Umezaki N, Hashimoto D, Yamashita Y, Nakagawa S, Nakao Y, Itoyama R, Yusa T, Yamao T, Okabe H, Imai K, Hayashi H, Chikamoto A, Baba H.
  • Journal Title: Anticancer Research Volume: 39 Issue: 2 Pages: 903-907
  • DOI: 10.21873/anticanres.13192
  • Peer Reviewed
• [Journal Article] Pancreatic cancer arising from the remnant pancreas after pancreatectomy: a multicenter retrospective study by the Kyushu Study Group of Clinical Cancer (2018)
  • Author(s): Hashimoto Daisuke、Arima Kota、Nakagawa Shigeki、Negoro Yuji、Hirata Toshihiko、Hirota Masahiko、Inomata Masafumi、Fukuzawa Kengo、Ohga Takefumi、Saeki Hiroshi、Oki Eiji、Yamashita Yo-ichi、Chikamoto Akira、Baba Hideo、Maehara Yoshihiko
  • Journal Title: Journal of Gastroenterology Volume: 54 Issue: 5 Pages: 437-448
  • DOI: 10.1007/s00535-018-01535-9
  • Peer Reviewed
• [Journal Article] Anticoagulant Therapy for Disseminated Intravascular Coagulation After Gastrointestinal Surgery (2018)
  • Author(s): 2.Hashimoto D, Okawa T, Maruyama R, Matsumura F, Shibata Y, Kohrogi H.
  • Journal Title: Anticancer Research Volume: 39 Issue: 1 Pages: 25-31
  • DOI: 10.21873/anticanres.13076
  • Peer Reviewed
• [Journal Article] Multiple primary cancers in patients with pancreatic cancer. (2018)
  • Author(s): Yamamura K, Hashimoto D, Kitano Y, Kuroda D, Eto T, Arima K, Kaida T, Miyata T, Nakagawa S, Imai K, Yamashita Y, Chikamoto A, Matsumura F, Baba H.
  • Journal Title: Am Surg Volume: 84(12)
  • Peer Reviewed
• [Journal Article] Number of acinar cells at the pancreatic stump predicts pancreatic fistula after pancreaticoduodenectomy. (2018)
  • Author(s): Umezaki N, Hashimoto D, Nakagawa S, Kitano Y, Yamamura K, Chikamoto A, Matsumura F, Baba H
  • Journal Title: Surg Today Volume: 48(8) Issue: 8 Pages: 790-795
  • DOI: 10.1007/s00595-018-1656-5
  • Peer Reviewed
• [Journal Article] Pancreatic cancer arising from the remnant pancreas: is it a local recurrence or new primary lesion? (2017)
  • Author(s): Hashimoto D, Chikamoto A, Masuda T, Nakagawa S, Imai K, Yamashita Y, Reber HA, Baba H.
  • Journal Title: Pancreas Volume: 46(9) Issue: 9 Pages: 1083-1090
  • DOI: 10.1097/mpa.0000000000000897
  • Peer Reviewed
• [Journal Article] Cystic gastric metastasis from pancreatic cancer. (2017)
  • Author(s): Umezaki N, Hashimoto D, Nakagawa S, Yamao T, Tsukamoto M, Kitano Y, Arima K, Yamamura K, Miyata T, Okabe H, Chikamoto A, Matsumura F, Baba H.
  • Journal Title: Surg Case Rep Volume: in press
  • Peer Reviewed
• [Journal Article] Preoperative high SUVmax, associated with glucose transporter 1, predicts poor prognosis in pancreatic cancer. (2017)
  • Author(s): Chikamoto A, Inoue R, Komohara Y, Sakamaki K, Hashimoto D, Shiraishi S, Takamori H, Yamashita Y, Yoshida N, Yamanaka T, Yamashita Y, Baba H
  • Journal Title: Ann Surg Oncol Volume: in press Issue: 7 Pages: 2040-2046
  • DOI: 10.1245/s10434-017-5799-1
  • Peer Reviewed
• [Journal Article] Efficacy and safety of postoperative anticoagulation prophylaxis with enoxaparin in patients undergoing pancreatic surgery: a prospective trial and literature review. (2017)
  • Author(s): Hashimoto D, Nakagawa S, Umezaki N, Yamao T, MD, Kitano Y, Yamamura K, Kaida T, Arima K, Imai K, Yamashita Y, Chikamoto A, Baba H
  • Journal Title: Pancreatol Volume: 29 Issue: 3 Pages: 464-470
  • DOI: 10.1016/j.pan.2017.03.010
  • Peer Reviewed
• [Journal Article] Shape and enhancement characteristics of pancreatic neuroendocrine tumor on preoperative contrast-enhanced computed tomography may be prognostic indicators. (2017)
  • Author(s): Okabe H, Hashimoto D, Chikamoto A, Morikatsu Y, Taki K, Arima K, Imai K,Tamura Y, Ikeda O, Ishiko T, Uchiyama H, Ikegami T, Harimoto N, Itoh S, Yamashita Y, Yoshizumi T, Beppu T, Yamashita Y, Baba H, Maehara Y.
  • Journal Title: Ann Surg Oncol Volume: 24(5) Issue: 5 Pages: 1399-1405
  • DOI: 10.1245/s10434-016-5630-4
  • Peer Reviewed / Open Access
• [Journal Article] A comparative study on the complications of conventional and end-to-side inserting pancreatojejunostomy after pancreaticoduodenectomy. (2017)
  • Author(s): Hashimoto D, Chikamoto A, Harimoto N, Ikegami T, Uchiyama H, Yoshizumi T, Baba H, Maehara Y.
  • Journal Title: Surg Today Volume: 47(2) Issue: 2 Pages: 238-244
  • DOI: 10.1007/s00595-016-1364-y
  • Peer Reviewed
• [Journal Article] Residual total pancreatectomy: short- and long-term outcome Pancreatol. (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: Pancreatol Volume: in press Issue: 4 Pages: 646-51
  • DOI: 10.1016/j.pan.2016.04.034
  • Peer Reviewed
• [Journal Article] Heterogeneity of KRAS Mutations in Pancreatic Ductal Adenocarcinoma (2016)
  • Author(s): Hashimoto D, Arima K, Yokoyama N, Chikamoto A, Taki K, Inoue R, Kaida T, Higashi T, Nitta H, Ohmuraya M, Hirota M, Beppu T, Baba H
  • Journal Title: Pancreas Volume: 45 Issue: 8 Pages: 1111-1114
  • DOI: 10.1097/mpa.0000000000000624
  • Peer Reviewed / Open Access
• [Presentation] 膵頭十二指腸切除術における安全性確保と教育の両立 (2018)
  • Author(s): 橋本大輔、中尾陽佑、梅﨑直紀、北野雄希、有馬浩太、中川茂樹、岡部弘尚、今井克憲、山下洋市、近本 亮、馬場秀夫
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 残膵全摘術の安全性と長期成績 (2018)
  • Author(s): 橋本大輔、梅﨑直紀、山村謙介、有馬浩太、中川茂樹、近本 亮、松村富二夫、馬場秀夫
  • Organizer: 第49回日本膵臓学会大会
• [Presentation] Treatment strategy for severe complication after pancreatectomy: toward to zero mortality. (2018)
  • Author(s): Daisuke Hashimoto, Rumi Itoyama, Yosuke Nakao, Naoki Umezaki, Kota Arima, Kensuke Yamamura, Shigeki Nakagawa, Akira Chikamoto, Fujio Matsumura, Hideo Baba
  • Organizer: 第30回日本肝胆膵外科学会・学術集会
• [Presentation] 膵癌，胆道癌の腹膜播種に対する審査腹腔鏡の意義と治療戦略 (2018)
  • Author(s): 橋本大輔、伊東山瑠美、中尾陽佑、梅﨑直紀、北野雄希、有馬浩太、中川茂樹、近本 亮、松村富二夫、馬場秀夫
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] Pancreatic cancer arising from the remnant pancreas after pancreatectomy: A multicenter retrospective study (2018)
  • Author(s): Daisuke Hashimoto, Kota Arima, Shigeki Nakagawa, Yuji Negoro, Toshihiko Hirata, Masahiko Hirota, Masafumi Inomata, Kengo Fukuzawa, Takefumi Ohga, Hiroshi Saeki, Eiji Oki, Yo-ichi Yamashita, Akira Chikamoto, Hideo Baba, Yoshihiko Maehara
  • Organizer: 第29回日本消化器癌発生学会総会
• [Presentation] 三種類の膵消化管吻合法とその短期および長期成績 (2017)
  • Author(s): 橋本大輔、梅崎直紀、山尾宣暢、塚本雅代、山村謙介、有馬浩太、甲斐田剛圭、中川茂樹、今井克憲、山下洋市、近本 亮、馬場秀夫
  • Organizer: 第117回 日本外科学会定期学術集会
• [Presentation] Residual total pancreatectomy: technique and outcome. (2017)
  • Author(s): Daisuke Hashimoto, Shigeki Nakagawa, Naoki Umezaki, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunori Imai, Yo-ichi Yamashita, Akira Chikamoto, Hideo Baba
  • Organizer: The Joint Congress of the 6th Biennial Congress of the Asian-Pacific Hepato-Pancreato-Biliary Association & the 29th Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery.
• [Presentation] Efficacy and safety of postoperative anticoagulation therapy with enoxaparin in patients undergoing pancreatic surgery: a prospective clinical trial. Poster presentation. (2017)
  • Author(s): Daisuke Hashimoto, Shigeki Nakagawa, Naoki Umesaki, Takanobu Yamao, Yuki Kitano, Kensuke Yamamura, Kota Arima, Takayoshi Kaida, Katsunori Imai, Yo-ichi Yamashita, Akira Chikamoto, Hideo Baba
  • Organizer: The 49th European Pancreatic Club.
• [Presentation] 膵神経内分泌腫瘍に対する手術術式の選択とリンパ節郭清の意義 (2017)
  • Author(s): 橋本大輔、梅﨑直紀、山尾宣暢、山村謙介、有馬浩太、甲斐田剛圭、中川茂樹、美馬浩介、今井克憲、山下洋市、近本 亮、馬場秀夫
  • Organizer: 第48回日本膵臓学会大会
• [Presentation] 手術関連死亡ゼロの膵頭十二指腸切除術 (2017)
  • Author(s): 橋本大輔、中川茂樹、梅崎直紀、山下洋市、北野雄希、山村謙介、甲斐田剛圭、有馬浩太、近本 亮、馬場秀夫
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 膵頭十二指腸切除術後の手術関連死亡ゼロを目指して (2016)
  • Author(s): 橋本大輔、近本 亮、有馬浩太、甲斐田剛圭、髙城克暢、東孝暁、今井克憲、山下洋市、別府 透、馬場秀夫
  • Organizer: 第28回日本肝胆膵外科学会・学術集会
  • Place of Presentation: 大阪国際会議場（大阪府）
• [Presentation] Conventional versus end-to-side inserting pancreaticojejunostomy after pancreaticoduodenectomy. (2016)
  • Author(s): Hashimoto D、Yamamura K, Kitano Y, Arima K, Kaida T, Taki K, Imai K, Yamashita YI, Chikamoto A, Baba H
  • Organizer: 第47回 日本膵臓学会大会
  • Place of Presentation: 仙台国際センター（宮城県）
• [Presentation] 食道癌における癌代謝 (Nrf2, Glut1) の特徴と臨床病理学的因子との相関 (2016)
  • Author(s): 北野雄希、馬場祥史、澤山 浩、山村謙介、中村健一、木下浩一、岩槻政晃、坂本快郎、吉田直矢、馬場秀夫
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 城山観光ホテル（鹿児島県）
  • Int'l Joint Research
• [Presentation] Borderline resectable膵癌に対して術前療法が奏功する症例のmolecular subtype等の遺伝子学的背景を明らかにする前向き観察研究 (2016)
  • Author(s): 橋本大輔、中川茂樹、梅崎直紀、山尾宣暢、塚本雅代、山村謙介、有馬浩太、甲斐田剛圭、今井克憲、山下洋市、近本 亮、馬場秀夫
  • Organizer: 第11回膵癌術前治療研究会
  • Place of Presentation: 星陵オーディトリアム（宮城県）
• [Presentation] 残膵全摘術の安全性と長期成績 (2016)
  • Author(s): 橋本大輔、梅崎直紀、山尾宣暢、塚本雅代、山村謙介、有馬浩太、甲斐田剛圭、中川茂樹、今井克憲、山下洋市、近本 亮、馬場秀夫
  • Organizer: 第78回 日本臨床外科学会総会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都）