Clinical impact of viable circulating tumor cells (v-CTC) detection and PD-L1 expression on v-CTC in the patients with resectable pancreatic cancer
Project/Area Number |
16K10618
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Osaka University (2017-2018) Department of Clinical Research, National Hospital Organization Kure Medical Center (2016) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
三善 英知 大阪大学, 医学系研究科, 教授 (20322183)
江口 英利 大阪大学, 医学系研究科, 准教授 (90542118)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 膵癌 / 微小循環癌細胞 / 腹腔内遊離癌細胞 / テロメスキャン / バイオマーカー / 糖鎖 / 糖鎖医薬 / 創薬 / オリゴデンドリマー |
Outline of Final Research Achievements |
We tested novel methods for viable CTCs (v-CTC) isolation in pancreatic cancer (PC) as “liquid biopsy”. We analyzed the PD-L1(L1) expression in both PC tumors and v-CTCs. To detect v-CTCs, we employed a telomerase-specific replication-selective adenovirous expressing GFP.To assess L1 expression in PC tissues (IHC) and v-CTCs, L1 IHC kit and anti-human L1 mAb were employed. S group: 24 pts were enrolled. No v-CTCs were detected in 6 pts at both before and after resection, and 5 of 6 pts survived without recurrence. N group: 15 PC pts were enrolled. No v-CTCs were detected in 5 pts, and 5 pts survived without recurrence. Marked increase in CTC counts was observed after NACRT in 5 of 6 CTC-positive pts before NACRT, and 3 of 5 pts developed liver metastasis and died. PD-L1 expression:89% of detectable v-CTCs were positive for L1-expression. In conclusion, viable CTC detection appears as a promising prognostic marker. Immunotherapy with anti-PD-1/PD-L1 Abs may target v-CTCs.
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Academic Significance and Societal Importance of the Research Achievements |
v-CTC検出の有無から見た切除可能膵癌に対する治療方針として、術前v-CTC陰性例ではNACRTまたはNACを先行し根治切除を行い術後補助療法を追加する。 一方、術前v-CTC検出陽性例では、術前化学療法を行い、その後根治切除を実施する治療選択が予後改善につながる可能性が示唆された。 膵癌患者の末梢血中で検出されたv-CTC上にはPD-L1発現を高率(約90%)に確認でき、切除膵癌の原発腫瘍巣でのPD-L1発現率 (<1% [negative]:9例, 10%:6例, 20%:4例, 40%:2例)と大きな差を認めた。膵癌根治をめざす治療戦略として免疫チエックポイント阻害剤の有効性が期待できる。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Prolonged Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer.2018
Author(s)
Eguchi H, Yamada D, Iwagami Y, Gotoh K, Kawamoto K, Wada H, Asaoka T, Noda T, Takeda Y, Tanemura M, Sakai D, Satoh T, Kudo T, Isohashi F, Mori M, Doki Y.
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Journal Title
Dig Surg.
Volume: 35
Issue: 1
Pages: 70-76
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The role of histone deacetylase 1 in distant metastasis of pancreatic ductal cancer.2018
Author(s)
Shinke G, Yamada D, Eguchi H, Iwagami Y, Asaoka T, Noda T, Wada H, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Cancer Sci.
Volume: 109
Issue: 8
Pages: 2520-2531
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructive colorectal cancer.2018
Author(s)
Yamashita S, Tanemura M, Sawada G, Moon JH, Shimizu Y, Yamaguchi T, Kuwai T, Urata Y, Kuraoka K, Hatanaka N, Yamashita Y, Taniyama K.
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Journal Title
Oncology Letters.
Volume: 15
Pages: 400-406
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer2018
Author(s)
Okumura Y, Noda T, Eguchi H, Sakamoto T, Iwagami Y, Yamada D, Asaoka T, Wada H, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M
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Journal Title
Ann Surg Oncol
Volume: 25
Issue: 12
Pages: 3728-3737
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Primary Intrahepatic Squamous Cell Carcinoma with Histological Collision of Adenocarcinoma and Squamous Cell Carcinoma: A Case Report.2018
Author(s)
Tamaoka K, Tanemura M, Furukawa K, Mikamori M, Saito T, Ohtsuka M, Suzuki Y, Tei M, Kishi K, Yasuoka H, Tsujimoto M, Akamatsu H.
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Journal Title
Am J Case Rep.
Volume: 19
Pages: 1184-1191
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Impact of Preoperative Sarcopenia on the Postoperative Outcomes After Pancreas Transplantation2018
Author(s)
Fukuda Y, Asaoka T, Eguchi H, Sasaki K, Iwagami Y, Yamada D, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Ito T, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
World J Surg.
Volume: 42
Issue: 10
Pages: 3364-3371
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Vitamin D Supplementation is a Promising Therapy for Pancreatic Ductal Adenocarcinoma in Conjunction with Current Chemoradiation2018
Author(s)
Mukai Y, Yamada D, Eguchi H, Iwagami Y, Asaoka T, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Ann Surg Oncol.
Volume: 25
Issue: 7
Pages: 1868-1879
DOI
Related Report
Peer Reviewed
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[Journal Article] A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes.2017
Author(s)
Furukawa K, Tanemura M, Miyoshi E, Eguchi H, Nagano H, Matsunami K, Nagaoka S, Yamada D, Asaoka T, Noda T, Wada H, Kawamoto K, Goto K, Taniyama K, Mori M, Doki Y.
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Journal Title
PLOS ONE
Volume: 12
Issue: 10
Pages: e0184901-e0184901
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Patients Treated with Preoperative Chemoradiation for Pancreatic Ductal Adenocarcinoma have Impaired Bone Density, a Predictor of Distant Metastasis.2017
Author(s)
Yamada D, Eguchi H, Iwagami Y, Mukai Y, Hashimoto Y, Asaoka T, Noda T, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Ann Surg Oncol.
Volume: 24
Issue: 12
Pages: 3715-3724
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of carbonic anhydrase IX is associated with poor prognosis through regulation of the epithelial-mesenchymal transition in hepatocellular carcinoma.2017
Author(s)
Hyuga S, Wada H, Eguchi H, Otsuru T, Iwgami Y, Yamada D, Noda T, Asaoka T, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M.
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Journal Title
Int J Oncol
Volume: 51(4)
Issue: 4
Pages: 1179-1190
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CT Density in the Pancreas is a Promising Imaging Predictor for Pancreatic Ductal Adenocarcinoma.2017
Author(s)
Fukuda Y, Yamada D, Eguchi H, Hata T, Iwagami Y, Noda T, Asaoka T, Kawamoto K, Gotoh K, Kobayashi S, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Ann Surg Oncol.
Volume: 24
Issue: 9
Pages: 2762-2769
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The basal nutritional state of PDAC patients is the dominant factor for completing adjuvant chemotherapy.2017
Author(s)
Yamada D, Eguchi H, Asaoka T, Tomihara H, Noda T, Wada H, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Surg Today.
Volume: 47
Issue: 11
Pages: 1361-1371
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MicroRNA-155 Controls Exosome Synthesis and Promotes Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.2017
Author(s)
Mikamori M, Yamada D, Eguchi H, Hasegawa S, Kishimoto T, Tomimaru Y, Asaoka T, Noda T, Wada H, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 42339-42339
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The feasibility and safety of single-incision totally extraperitoneal inguinal hernia repair after previous lower abdominal surgery: 350 procedures at a single center.2017
Author(s)
Wakasugi M, Suzuki Y, Tei M, Anno K, Mikami T, Tsukada R, Koh M, Furukawa K, Masuzawa T, Kishi K, Tanemura M, Akamatsu H.
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Journal Title
Surg Today.
Volume: 47
Issue: 3
Pages: 307-312
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma.2017
Author(s)
Tomihara H, Eguchi H, Yamada D, Gotoh K, Kawamoto K, Wada H, Asaoka T, Noda T, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Surg Today.
Volume: 47
Issue: 2
Pages: 218-226
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MiR-181b-5p, ETS1 and c-Met pathway exacerbates the prognosis of pancreatic ductal adenocarcinoma after radiation therapy.2017
Author(s)
Tomihara H, Yamada D, Eguchi H, Iwagami Y, Noda T, Asaoka T, Wada H, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Mori M, Doki Y.
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Journal Title
Cancer Sci.
Volume: 108
Issue: 3
Pages: 398-407
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Two cases of resectable pancreatic cancer diagnosed by open surgical biopsy after endoscopic ultrasound fine-needle aspiration failed to yield diagnosis: case reports.2017
Author(s)
Toshiyama R, Noda T, Eguchi H, Iwagami Y, Yamada D, Asaoka T, Wada H, Kawamoto K, Gotoh K, Takeda Y, Tanemura M, Morii E, Umeshita K, Mori M, Doki Y.
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Journal Title
Surg Case Rep
Volume: 3(1)
Issue: 1
Pages: 39-39
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Single-incision totally extraperitoneal inguinal hernia repair as a teaching procedure: one center's experience of more than 300 procedures.2016
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.
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Journal Title
Surg Today.
Volume: 46
Issue: 9
Pages: 1039-1044
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[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.
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Journal Title
Surg Today.
Volume: 46
Issue: 11
Pages: 1318-1324
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[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.
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Journal Title
Surg. Case. Rep.
Volume: 2
Issue: 1
Pages: 29-29
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Single-incision totally extraperitoneal inguinal hernia repair is safe and feasible in elderly patients: A single-center experience of 365 procedures.2016
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.
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Journal Title
Asian J Endosc Surg.
Volume: 9
Issue: 4
Pages: 281-284
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Clinical Experience with Pancreas Graft Rescue from Severe Thrombus after Simultaneous Pancreas-Kidney Transplantation by Early Detection with Doppler Ultrasound: A Case Report.2016
Author(s)
Takeda M, Yamada D, Eguchi H, Asaoka T, Noda T, Wada H, Goto K, Kawamoto K, Takeda Y, Tanemura M, Ito T, Mori M, Doki Y.
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Journal Title
Am J Case Rep.
Volume: 17
Pages: 899-904
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A Case of Surgical Resection for Liver Metastasis of Gastric Cancer Treated with Neoadjuvant Chemotherapy.2016
Author(s)
Mori S, Tanemura M, Kishi K, Tei M, Masuzawa T, Suzuki Y, Otsuka M, Furukawa K, Sakano Y, Mori K, Akamatsu H.
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Journal Title
Gan To Kagaku Ryoho.
Volume: 43
Pages: 1776-1778
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A Case of Angiomyolipoma Occurring in the Mesentery of the Transverse Colon and Treated Using Laparoscopic Excision2016
Author(s)
Inoue M, Tanemura M, Hatanaka N, Miyamoto T, Seo S, Yamaguchi M, Misumi T, Shimizu W, Irei T, Onoe T, Suzuki T, Sudo T, Shimizu Y, Hinoi T, Tashiro H.
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Journal Title
Gan To Kagaku Ryoho.
Volume: 43
Pages: 2271-2273
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] A practical strategy to pancreatic cancer immunotherapy using resected human lysate vaccines remodeled to express α-gal epitopes2018
Author(s)
Masahiro Tanemura, Kenta Furukawa, Eiji Miyoshi, Hidetoshi Eguchi, Hiroaki Nagano, Katsuyoshi Matsunami, Satoshi Nagaoka, Kentaro Kishi, Hiroki Akamatsu, Masaki Mori, Yuichiro Doki
Organizer
American Association for Cancer Research Annual Meeting 2018
Related Report
Int'l Joint Research
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