Deployment to personalized medicine targeting pancreatic cancer stem cells and tumor microenvironment

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K08646
• Research Institution: Yamaguchi University
• Principal Investigator: 永野 浩昭 山口大学, 大学院医学系研究科, 教授 (10294050)
• Co-Investigator(Kenkyū-buntansha): 恒富 亮一 山口大学, 医学部附属病院, 講師 (10420514) ; 松隈 聰 山口大学, 医学部附属病院, 助教 (10634743) ; 徳光 幸生 山口大学, 医学部, 助教(寄附講座等) (40593299)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 癌幹細胞 / 膵癌 / 癌周辺微小環境

Outline of Annual Research Achievements

膵癌幹細胞様細胞（P-CSLC）を誘導しCalreticulin（CRT）が膵癌幹細胞の新規マーカーとなることを報告した。本研究では、特に、誘導した膵癌CSLC (P-CSLC)より豊富な細胞集と親細胞に発現している分子を、Proteomicsの手法で比較し、プロテオミクス、メタボロミクス、次世代シーケンサーを用いたmRNA解析という網羅的なアプローチを通して、膵癌幹細胞の新たな治療標的としてさらにAnnexinおよびCathepsinの関与について確認した。これらの分子生物学的な機能解析をもとに、癌幹細胞に関与する活性化した代謝経路を同定し、さらに治療標的としての可能性という点から、P-CSLCとcancer associated fibroblasts (CAFs）の相互に関連している表面抗原などについても解析を開始した。今後は、これらの成果を通して、膵癌幹細胞をターゲットとした新規治療法開発の礎を築きたい。

Research Products

• [Journal Article] Efficacy of intraoperative recurrent laryngeal neuromonitoring during surgery for esophageal cancer (2020)
  • Author(s): Takeda Shigeru、Iida Michihisa、Kanekiyo Shinsuke、Nishiyama Mitsuo、Tokumitsu Yukio、Shindo Yoshitaro、Yoshida Shin、Suzuki Nobuaki、Yoshino Shigefumi、Nagano Hiroaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 5 Pages: 83～92
  • DOI: 10.1002/ags3.12394
  • Peer Reviewed
• [Journal Article] Clinical implications of cancer stem cells in digestive cancers: acquisition of stemness and prognostic impact (2020)
  • Author(s): Tsunedomi Ryouichi、Yoshimura Kiyoshi、Suzuki Nobuaki、Hazama Shoichi、Nagano Hiroaki
  • Journal Title: Surgery Today Volume: 50 Pages: 1560～1577
  • DOI: 10.1007/s00595-020-01968-x
  • Peer Reviewed
• [Journal Article] The impact of peritoneal lavage cytology in biliary tract cancer (KHBO1701): Kansai Hepato‐Biliary Oncology Group (2020)
  • Author(s): Matsukuma Satoshi、Nagano Hiroaki、Ohmura Yoshiaki、Takeda Yutaka、Miyamoto Atsushi、Nakashima Shinsuke、Yamada Terumasa、Ajiki Tetsuo、Tsuji Akihito、Yoshimura Kenichi、Eguchi Hidetoshi、Hatano Etsuro、Ioka Tatsuya、Kansai Hepato‐Biliary Oncology (KHBO) Group
  • Journal Title: Cancer Reports Volume: 4 Pages: -
  • DOI: 10.1002/cnr2.1323
  • Peer Reviewed
• [Journal Article] Risk prediction for malignant intraductal papillary mucinous neoplasm of the pancreas: logistic regression versus machine learning (2020)
  • Author(s): Kang JS, Lee C, Song W, Choo W, Lee S, Lee S, Han Y, Bassi C, Salvia R, Marchegiani G, Wolfgang CL, He J, Blair AB, Kluger MD, Su GH, Kim SC, Song KB, Yamamoto M, Higuchi R, Nagano H, Jang JY.
  • Journal Title: Scientific Reports Volume: 10 Pages: 20140
  • DOI: 10.1038/s41598-020-76974-7
  • Peer Reviewed
• [Journal Article] Viral elimination is essential for improving surgical outcomes of hepatitis C virus‐related hepatocellular carcinoma: Multicenter retrospective analysis (2020)
  • Author(s): Nakajima Masao、Kobayashi Shogo、Wada Hiroshi、Tomokuni Akira、Takahashi Hidenori、Noda Takehiro、Matsui Hiroto、Matsukuma Satoshi、Kanekiyo Shinsuke、Shindo Yoshitaro、Tokumitsu Yukio、Nakagami Yuki、Suzuki Nobuaki、Takeda Shigeru、Tanabe Masahiro、Ito Katsuyoshi、Hoshii Yoshinobu、Eguchi Hidetoshi、Nagano Hiroaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 4 Pages: 710～720
  • DOI: 10.1002/ags3.12377
  • Peer Reviewed
• [Journal Article] Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer (2020)
  • Author(s): Mlecnik B, Bifulco C, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Fox BA, Galon J
  • Journal Title: Journal of Clinical Oncology Volume: 38 Pages: 3638～3651
  • DOI: 10.1200/JCO.19.03205
  • Peer Reviewed
• [Journal Article] Randomized clinical trial of pancreaticogastrostomy versus pancreaticojejunostomy regarding incidence of delayed gastric emptying after pancreaticoduodenectomy (2020)
  • Author(s): Eguchi Hidetoshi、Iwagami Yoshifumi、Matsushita Katsunori、Tomimaru Yoshito、Akita Hirofumi、Noda Takehiro、Gotoh Kunihito、Kobayashi Shogo、Nagano Hiroaki、Mori Masaki、Doki Yuichiro
  • Journal Title: Langenbeck's Archives of Surgery Volume: 405 Pages: 921～928
  • DOI: 10.1007/s00423-020-01982-0
  • Peer Reviewed
• [Journal Article] Clinical outcomes of chemotherapy in patients with undifferentiated carcinoma of the pancreas: a retrospective multicenter cohort study (2020)
  • Author(s): Imaoka Hiroshi、Ikeda Masafumi、Maehara Kosuke、Umemoto Kumiko、Ozaka Masato、Kobayashi Satoshi、Terashima Takeshi、Inoue Hiroto、Sakaguchi Chihiro、Tsuji Kunihiro、Shioji Kazuhiko、Okamura Keiya、Kawamoto Yasuyuki、Suzuki Rei、Shirakawa Hirofumi、Nagano Hiroaki、Ueno Makoto、Morizane Chigusa、Furuse Junji
  • Journal Title: BMC Cancer Volume: 20 Pages: 946
  • DOI: 10.1186/s12885-020-07462-4
  • Peer Reviewed
• [Journal Article] No Significant Effect of Daikenchuto (TJ-100) on Peritoneal IL-9 and IFN-γ Levels After Pancreaticoduodenectomy (2020)
  • Author(s): Maeda Hiromichi、Okada Ken-ichi、Fujii Tsutomu、Oba Mari S、Kawai Manabu、Hirono Seiko、Kodera Yasuhiro、Sho Masayuki、Akahori Takahiro、Shimizu Yasuhiro、Ambo Yoshiyasu、Kondo Naru、Murakami Yoshiaki、Ohuchida Jiro、Eguchi Hidetoshi、Nagano Hiroaki、Sakamoto Junichi、Yamaue Hiroki
  • Journal Title: Clinical and Experimental Gastroenterology Volume: Volume 13 Pages: 461～466
  • DOI: 10.2147/CEG.S262082
  • Peer Reviewed
• [Journal Article] A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial (2020)
  • Author(s): Nakajima M, Hazama S, Tamada K, Udaka K, Kouki Y, Uematsu T, Tomochika S, Iida M, Yoshida S, Nakagami Y, Suzuki N, Takeda S, Yamamoto S, Yoshino S, Ueno T, Nagano H
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 69 Pages: 1651～1662
  • DOI: 10.1007/s00262-020-02518-7
  • Peer Reviewed
• [Journal Article] Serum LOX-1 is a novel prognostic biomarker of colorectal cancer (2020)
  • Author(s): Nakashima-Nakasuga C, Hazama S, Tsunedomi R, Iida M, Takeda S, Yoshino S, Ueno T, Hamamoto Y, Ogihara H, Hoshii Y, Nagano H.
  • Journal Title: International Journal of Clinical Oncology Volume: 25 Pages: 1308～1317
  • DOI: 10.1007/s10147-020-01673-2
  • Peer Reviewed
• [Journal Article] The effect of the visceral fat area on the predictive accuracy of C‐reactive protein for infectious complications after laparoscopy‐assisted gastrectomy (2020)
  • Author(s): Iida Michihisa、Takeda Shigeru、Nakagami Yuki、Kanekiyo Shinsuke、Nakashima Chiyo、Nishiyama Mitsuo、Yoshida Shin、Suzuki Nobuaki、Yoshino Shigefumi、Nagano Hiroaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 4 Pages: 386～395
  • DOI: 10.1002/ags3.12329
  • Peer Reviewed
• [Journal Article] COVID-19: clinical issues from the Japan Surgical Society (2020)
  • Author(s): Mori Masaki、Ikeda Norihiko、Taketomi Akinobu、Asahi Yo、Takesue Yoshio、Orimo Tatsuya、Ono Minoru、Kuwayama Takashi、Nakamura Seigo、Yamada Yohei、Kuroda Tatsuo、Yuzawa Kenji、Hibi Taizo、Nagano Hiroaki、Unno Michiaki、Kitagawa Yuko
  • Journal Title: Surgery Today Volume: 50 Pages: 794～808
  • DOI: 10.1007/s00595-020-02047-x
  • Peer Reviewed
• [Journal Article] Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: High rate of early recurrence and its predictors (2020)
  • Author(s): Yamashita Yo‐ichi、Aishima Shinichi、Nakao Yosuke、Yoshizumi Tomoharu、Nagano Hiroaki、Kuroki Tamotsu、Takami Yuko、Ide Takao、Ohta Masayuki、Takatsuki Mitsuhisa、Nanashima Atsushi、Ishii Fuminori、Kitahara Kenji、Iino Satoshi、Beppu Toru、Baba Hideo、Eguchi Susumu
  • Journal Title: Hepatology Research Volume: 50 Pages: 863～870
  • DOI: 10.1111/hepr.13507
  • Peer Reviewed
• [Journal Article] Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function (2020)
  • Author(s): Tomimaru Yoshito、Eguchi Hidetoshi、Iwagami Yoshifumi、Akita Hirofumi、Noda Takehiro、Gotoh Kunihito、Kobayashi Shogo、Nagano Hiroaki、Mori Masaki、Doki Yuichiro
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 85 Pages: 537～545
  • DOI: 10.1007/s00280-019-04005-y
  • Peer Reviewed
• [Journal Article] Novel Liquid Biopsy Test Based on a Sensitive Methylated SEPT9 Assay for Diagnosing Hepatocellular Carcinoma (2020)
  • Author(s): Kotoh Yurika、Suehiro Yutaka、Saeki Issei、Hoshida Tomomi、Maeda Masaki、Iwamoto Takuya、Matsumoto Toshihiko、Hidaka Isao、Ishikawa Tsuyoshi、Takami Taro、Higaki Shingo、Fujii Ikuei、Suzuki Chieko、Shindo Yoshitaro、Tokumitsu Yukio、Nagano Hiroaki、Sakaida Isao、Yamasaki Takahiro
  • Journal Title: Hepatology Communications Volume: 4 Pages: 461～470
  • DOI: 10.1002/hep4.1469
  • Peer Reviewed
• [Journal Article] Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model (2020)
  • Author(s): 2.Elbadawy M, Yamanaka M, Goto Y, Hayashi K, Tsunedomi R, Hazama S, Nagano H, Omatsu T, Mizutani T, Katayama Y, Shinohara Y, Abugomaa A, Kaneda M, Yamawaki H, Usui T, Sasaki K
  • Journal Title: Biomaterials Volume: 237 Pages: 119823～119823
  • DOI: 10.1016/j.biomaterials.2020.119823
  • Peer Reviewed
• [Journal Article] A Prospective, Multi-Center Phase I Study of Postoperative Enoxaparin Treatment in Patients Undergoing Curative Hepatobiliary-Pancreatic Surgery for Malignancies (2020)
  • Author(s): Eguchi Hidetoshi、Kawamoto Koichi、Tsujie Masanori、Yukawa Masao、Kubota Masaru、Asaoka Tadafumi、Takeda Yutaka、Noda Takehiro、Shimizu Junzo、Nagano Hiroaki、Doki Yuichiro、Mori Masaki
  • Journal Title: Digestive Surgery Volume: 37 Pages: 81～86
  • DOI: 10.1159/000497451
  • Peer Reviewed
• [Journal Article] “Logic-Based Medicine” Is More Feasible than “Evidence-Based Medicine” in the Local Treatment for Hepatocellular Carcinoma (2020)
  • Author(s): Sakon Masato、Kobayashi Shogo、Wada Hiroshi、Eguchi Hidetoshi、Marubashi Shigeru、Takahashi Hidenori、Akita Hirofumi、Gotoh Kunihito、Yamada Daisaku、Asukai Kei、Hasegawa Shinichiro、Ohue Masayuki、Yano Masahiko、Nagano Hiroaki
  • Journal Title: Oncology Volume: 98 Pages: 259～266
  • DOI: 10.1159/000505554
  • Peer Reviewed
• [Journal Article] The time has come for Japanese surgeons to work in English (2020)
  • Author(s): Nagano Hiroaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 4 Pages: 5～5
  • DOI: 10.1002/ags3.12313
  • Peer Reviewed
• [Journal Article] Fecal DNA Testing of TWIST1 Methylation Identifies Patients With Advanced Colorectal Adenoma Missed by Fecal Immunochemical Test for Hemoglobin (2020)
  • Author(s): Suehiro Y, Hashimoto S, Goto A, Yamaoka Y, Yamamoto N, Suzuki N, Higaki S, Fujii I, Suzuki C, Yoshida S, Hazama S, Yotsuyanagi H, Nagano H, Sakaida I, Yamasaki T
  • Journal Title: Clinical and Translational Gastroenterology Volume: 11 Pages: e00176～e00176
  • DOI: 10.14309/ctg.0000000000000176
  • Peer Reviewed
• [Journal Article] Surgical Outcomes of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus (2020)
  • Author(s): Kim DS, Kim BW, Hatano E, Nagano H, Yamasaki O, Yu HC, Han DH, Seo HI, Park IY, Yang KS, Yamamoto M, Wang HJ
  • Journal Title: Annals of Surgery Volume: 271 Pages: 913～921
  • DOI: 10.1097/SLA.0000000000003014
  • Peer Reviewed
• [Journal Article] Laparoscopic total biopsy for suspected gallbladder cancer: A case series (2020)
  • Author(s): Tokumitsu Yukio、Shindo Yoshitaro、Matsui Hiroto、Matsukuma Satoshi、Nakajima Masao、Yoshida Shin、Iida Michihisa、Suzuki Nobuaki、Takeda Shigeru、Nagano Hiroaki
  • Journal Title: Health Science Reports Volume: 3(2) Pages: e156
  • DOI: 10.1002/hsr2.156
  • Peer Reviewed
• [Journal Article] Liver resection with thrombectomy improves the survival of patients with hepatocellular carcinoma and tumor thrombi in the inferior vena cava or right atrium (2020)
  • Author(s): Matsukuma S, Eguchi H, Wada H, Noda T, Shindo Y, Tokumitsu Y, Matsui H, Takahashi H, Kobayashi S, Nagano H
  • Journal Title: BJS Open Volume: 4(2) Pages: 241-251
  • Peer Reviewed / Open Access