The detection of viable human circulating tumor cellsin resectable pancreatic cancer

• Project/Area Number: 25462129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Department of Clinical Research, National Hospital Organization Kure Medical Center
• Principal Investigator: TANEMURA Masahiro 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, その他 (30379250)
• Co-Investigator(Kenkyū-buntansha): MIYOSHI Eiji 大阪大学, 医学系研究科, 教授 (20322183) ; EGUCHI Hidetoshi 大阪大学, 医学系研究科, 准教授 (90542118)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 膵癌 / 循環癌細胞 / 癌幹細胞 / 糖鎖 / 創薬 / テロメスキャン / 循環器細胞

Outline of Final Research Achievements

The detection of increase in the number of circulating tumor cells (CTCs) during a patient’s clinical course may be a harbinger of forthcoming overt metastasis. To detect live CTCs (l-CTCs) in blood samples of patients (pts), we employed a genetically modified telomerase-specific replication-selective adenovirous, expressing GFP (TelomeScanF35). We assessed the l-CTCs burden in pts treated with NACRT. 15 pts aged 44-78 years (4 males, 11 females) were enrolled. 5 of 15 enrolled pts had l-CTCs detected before NACRT. An increase in CTCs was seen in 4 of 5 pts after NACRT, but no detectable l-CTCs were observed in only 1 pt after NACRT. These 4 CTC-positive pts continuously had CTCs detected after surgery. 2 of 4 CTC-positive pts early developed liver metastasis and died, despite R0 resection. We may consider surgery first for the CTC-positive pts before NACRT. The capture of l-CTCs may be useful biomarker for prognosis assessment or stratification.

Research Products

• [Int'l Joint Research] University of Massachusetts(米国)
• [Journal Article] Incidence and risk factors of postoperative delirium in elderly patients who underwent laparoscopic surgery for colorectal cancer. (2016)
  • Author(s): Tei M, Wakasugi M, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Int J Colorectal Dis. Volume: 31(1) Pages: 67-73
  • Peer Reviewed / Open Access
• [Journal Article] Single-incision laparoscopic surgery as a teaching procedure: a single-center experience of more than 2100 procedures. (2016)
  • Author(s): Wakasugi M, Tei M, Omori T, Anno K, Mikami T, Tsukada R, Koh M, Gakuhara A, Furukawa K, Suzuki Y, Masuzawa T, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Surg Today. Volume: なし
  • Peer Reviewed / Open Access
• [Journal Article] Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report. (2016)
  • Author(s): Mukai Y, Wada H, Eguchi H, Yamada D, Asaoka T, Noda T, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Umeshita K, Hori Y, Morii E, Doki Y, Mori M.
  • Journal Title: Surg Case Rep. Volume: 2(1) Pages: 29-29
  • Peer Reviewed / Open Access
• [Journal Article] Clinico-Pathological Significance of Leucine-Rich Alpha-2-Glycoprotein-1 in Sera of Patients with Pancreatic Cancer. (2015)
  • Author(s): Furukawa K, Kawamoto K, Eguchi H, Tanemura M, Tanida T, Akita H, Hama N, Wada H, Kobayashi S, Nonaka Y, Takamatsu S, Shinzaki S, Kumada T, Satomura S, Serada S, Naka T, Mori M,Doki Y, Miyoshi E, Nagano H.
  • Journal Title: Pancreas Volume: 44(1) Pages: 93-98
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreatic cancer immunotherapy using a tumor lysate vaccine, engineered to express α-gal epitopes, targets pancreatic cancer stem cells. (2015)
  • Author(s): Tanida T, Tanemura M, Miyoshi E, Nagano H, Furukawa K, Nonaka Y, Akita H, Hama N, Wada H, Kawamoto K, Kobayashi K, Eguchi H, Mori M, Doki Y.
  • Journal Title: Int J Oncol. Volume: 46(1) Pages: 78-90
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Discovery of α-gal epitope/natural anti-Gal antibody reaction and its clinical relevance to immunotherapy for pancreatic cancer. (2015)
  • Author(s): Tanemura M, Miyoshi E, Nagano H,Taniyama K, Mori M,Doki Y.
  • Journal Title: E-Book Volume: なし
  • Peer Reviewed / Open Access
• [Journal Article] Liver hilar tuberculous lymphadenitis successfully diagnosed by laparoscopic lymph node biopsy. (2015)
  • Author(s): Wakasugi M, Tanemura M, Mikami T, Furukawa K, Tsujimoto M, Akamatsu H
  • Journal Title: Int J Surg Case Rep. Volume: 10 Pages: 191-194
  • Peer Reviewed / Open Access
• [Journal Article] Signet ring cell carcinoma of the ampulla of vater: Report of a case and a review of the literature. (2015)
  • Author(s): Wakasugi M, Tanemura M, Furukawa K, Murata M, Miyazaki M, Oshita M, Yoshida K, Yasuoka H, Akamatsu H.
  • Journal Title: Int J Surg Case Rep. Volume: 12 Pages: 108-111
  • Peer Reviewed / Open Access
• [Journal Article] Cancer immunotherapy for pancreatic cancer utilizing the α-gal epitope/natural anti-Gal antibody reaction (2015)
  • Author(s): Tanemura M, Miyoshi E, Nagano H, Eguchi H, Matsunami K, Yamashita Y, Taniyama K, Hatanaka N, Akamatsu H, Mori M, Doki Y.
  • Journal Title: World Journal of Gastroenterology Volume: 21(40) Pages: 11396-11410
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Single-incision totally extraperitoneal inguinal hernia repair as a teaching procedure: one center's experience of more than 300 procedures. (2015)
  • Author(s): Wakasugi M, Tei M, Anno K, Mikami T, Tsukada R, Koh M, Furukawa K, Suzuki Y, Masuzawa T, Kishi K, Tanemura M, Akamatsu H.
  • Journal Title: Surg Today. Volume: なし
  • Peer Reviewed / Open Access
• [Journal Article] Clinico-Pathological Significance of Leucine-Rich Alpha-2-Glycoprotein-1 in Sera of Patients with Pancreatic Cancer. (2014)
  • Author(s): Furukawa K, Kawamoto K, Eguchi H, Tanemura M, Tanida T, Akita H, Hama N, Wada H, Kobayashi S, Nonaka Y, Takamatsu S, Shinzaki S, Kumada T, Satomura S, Serada S, Naka T, Mori M, Doki Y, Miyoshi E, Nagano H.
  • Journal Title: Pancreas Volume: In press
  • Peer Reviewed
• [Journal Article] Adipose Tissue-Derived Stem Cells Suppress Acute Cellular Rejection via TSG-6 and CD44 interaction in Rat Kidney Transplantation. (2014)
  • Author(s): Kato T, Okumi M, Tanemura M, Yazawa K, Kakuta Y1, Yamanaka K1, Tsutahara K, Doki Y, Mori M, Takahara S, Nonomura N.
  • Journal Title: Transplantation Volume: In press
  • Peer Reviewed
• [Journal Article] Pancreatic Steatosis and Fibrosis as Predisposing Factors of Cancer Development. (2014)
  • Author(s): Tomita Y, Azuma K, Nonaka Y, Kamada Y, Tomoeda M, Kishida M, Tanemura M, Miyoshi E.
  • Journal Title: Pancreas Volume: In press
  • Peer Reviewed
• [Journal Article] Significant Improvement in Islet Yield and Survival with Modified ET-Kyoto Solution (ET-Kyoto/Neutrophil Elastase Inhibitor). (2013)
  • Author(s): Machida T, Tanemura M, Ohmura Y, Tanida T, Wada H, Kobayashi S, Marubashi S, H Eguchi , Ito T, Nagano H, Mori M, Doki Y, Sawa Y.
  • Journal Title: Cell Transplant. Volume: 22（１） Pages: 159-73
  • Peer Reviewed
• [Journal Article] Role of -gal epitope/anti-Gal antibody reaction in immunotherapy and its clinical application in pancreatic cancer. (2013)
  • Author(s): Tanemura M, Miyoshi E, Nagano H, Eguchi H, Taniyama K, Kamiike W, Mori M, Doki Y
  • Journal Title: Cancer Science Volume: 104(3) Pages: 282-90
  • Peer Reviewed
• [Journal Article] Involvement of microRNA-181b in the gemcitabine resistance of (2013)
  • Author(s): Takiuchi D, Eguchi H, Nagano H, Iwagami Y, Tomimaru Y, Wada H, Kawamoto K, Kobayashi S, Marubashi S, Tanemura M, Mori M, Doki Y.
  • Journal Title: Pancreatology Volume: 13(5) Pages: 517-23
  • Peer Reviewed
• [Journal Article] Effect of in vivo administration of reprogramming factors in the mouse liver. (2013)
  • Author(s): Tomokuni A, Eguchi H, Hoshino H, Dewi DL, Nishikawa S, Kano Y, Miyoshi N, Tojo A, Kobayashi S, Gotoh N, Hinohara K, Fusaki N, Saito T, Suemizu H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Doki Y, Mori M, Ishii H, Nagano H.
  • Journal Title: Oncol Lett. Volume: 6(2) Pages: 323-328
  • Peer Reviewed
• [Journal Article] CD90- (Thy-1-) High Selection Enhances Reprogramming Capacity of Murine Adipose-Derived Mesenchymal Stem Cells. (2013)
  • Author(s): Kawamoto K, Konno M, Nagano H, Nishikawa S, Tomimaru Y, Akita H, Hama N, Wada H, Kobayashi S, Eguchi H, Tanemura M, Ito T, Doki Y, Mori M, Ishii H.
  • Journal Title: Disease Markers. Volume: 35(5) Pages: 573-579
  • Peer Reviewed
• [Presentation] 脂肪由来幹細胞(ADSC)を応用した次世代型膵島移植療法の開発 ― 生着改善に向けた膵島移植のブレイクスルー ― (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本臨床外科学会総会
  • Place of Presentation: 福岡、博多
  • Year and Date: 2015-11-26
• [Presentation] Significant cross-reactive responses to pancreatic cancer cells induced by tumor lysate vaccine remodeled to express α-gal epitopes and their implications for a universal cancer vaccine (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本癌学会総会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-10-10
• [Presentation] The detection of viable human circulating tumor cells in resectable pancreatic cancer (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] 糖鎖リモデリングによる多様性癌抗原に対応したユニバーサル膵癌ワクチン療法確立への可能性 (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本肝胆膵外科学会総会
  • Place of Presentation: 東京、台場
  • Year and Date: 2015-06-12
• [Presentation] Viable Circulating Tumor Cells測定(v-CTC値)から見た局所進行膵癌に対する術前化学放射線療(NACRT)の功罪 ―NACRTによりv-CTCs遊出を誘導する― (2015)
  • Author(s): 種村匡弘（筆頭演者）
  • Organizer: 日本外科学会定期学術集会
  • Place of Presentation: 名古屋、名古屋国際会議場
  • Year and Date: 2015-04-16
• [Presentation] 膵癌根治をめざした強度変調放射線治療（IMRT）併用術前化学放射線療法の確立 (2013)
  • Author(s): 種村 匡弘
  • Organizer: 日本臨床外科学会総会
  • Place of Presentation: 東京、新宿
• [Presentation] 癌幹細胞を標的とした糖鎖リモデリング膵癌ワクチン療法の開発 (2013)
  • Author(s): 種村 匡弘
  • Organizer: 日本肝胆膵外科学会総会
  • Place of Presentation: 栃木、宇都宮
• [Presentation] 脂肪由来幹細胞(ADSC)を応用した次世代型膵島移植療法の開発 (2013)
  • Author(s): 種村 匡弘
  • Organizer: 日本移植学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Significant protection against gemcitabine-resistant pancreatic cancer cells with tumor lysate vaccine, expressing -gal epitopes (2013)
  • Author(s): Masahiro Tanemura
  • Organizer: アメリカ癌学会総会（AACR Annual Meeting）
  • Place of Presentation: ワシントン
• [Book] 膵島の再生医療 –膵β細胞の発生と再生をめぐる新展開– 脂肪組織由来幹細胞を応用した次世代型膵島移植の確立 (2015)
  • Author(s): 種村匡弘
  • Publisher: 診断と治療社