Deployment to personalized medicine targeting pancreatic cancer stem cells and tumor microenvironment
Project/Area Number |
18K08646
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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 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Yamaguchi University |
Principal Investigator |
Nagano Hiroaki 山口大学, 大学院医学系研究科, 教授 (10294050)
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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)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 癌幹細胞 / 膵癌 / 癌周辺微小環境 / 形質転換 / 腫瘍微小環境 / 個別化医療 |
Outline of Final Research Achievements |
We have developed a method for inducing pancreatic cancer stem cell-like cells (P-CSLC) and reported that calreticulin (CRT) is a novel marker for cancer stem cells. In this study, we applied this result and identified a new therapeutic target potential for pancreatic cancer stem cells through a comprehensive approach of proteomics and mRNA analysis using a next-generation sequencer. In particular, we identified several types of molecules highly expressed in CRT-positive P-CSLC by a comprehensive approach and activated metabolic pathways in the same cells, and showed their potential as therapeutic targets. Furthermore, we were able to analyze the surface antigens associated with P-CSLC and cancer associated fibroblasts (CAFs).
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Academic Significance and Societal Importance of the Research Achievements |
本研究により解明された膵癌の治療抵抗性に関する知見は、癌幹細胞とも強く関連していると推察されるだけでなく、CAFや免疫逃避機構と癌幹細胞の関与についての可能性までをも追求してきた。 このことによる、膵癌の治療成績向上におけるこれらの機序解明の学術的意義は高い。
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Report
(4 results)
Research Products
(71 results)
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[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., Cho W., 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., Hatori T., Yang CY., Yamaue H., Hirono S., Satoi S., Fujii T., Hirano S., Lou W., Hashimoto Y., Shimizu Y etal.
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Journal Title
Sci. Rep.
Volume: 10
Issue: 1
Pages: 20140-20140
DOI
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Peer Reviewed / Open Access
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[Journal Article] Serum LOX-1 is a novel prognostic biomarker of colorectal cancer.2020
Author(s)
Nakashima-Nakasuga C, Hazama S, Suzuki N, Nakagami Y, Xu M, Yoshida S, Tomochika S, Fujiwara N, Matsukuma S, Matsui H, Tokumitsu Y, Kanekiyo S, Shindo Y, Maeda N, Tsunedomi R, Iida M, Takeda S, Yoshino S, Ueno T, Hamamoto Y, Ogihara H, Hoshii Y, Nagano H.
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Journal Title
Int J Clin Oncol.
Volume: -
Issue: 7
Pages: 1308-1317
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Peer Reviewed
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[Journal Article] Novel Liquid Biopsy Test Based on a Sensitive Methylated SEPT9 Assay for Diagnosing Hepatocellular Carcinoma. Hepatol Commun2020
Author(s)
Kotoh Y, Suehiro Y, Saeki I, Hoshida T, Maeda M, Iwamoto T, Matsumoto T, Hidaka I, Ishikawa T, Takami T, Higaki S, Fujii I, Suzuki C, Shindo Y, Tokumitsu Y, Nagano H, Sakaida I, Yamasaki T
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Journal Title
Hepatol Commun
Volume: 4(3)
Issue: 3
Pages: 461-470
DOI
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Peer Reviewed / Open Access
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[Journal Article] Efficacy of primary liver organoid culture from different stages of non-alcoholic steatohepatitis (NASH) mouse model2020
Author(s)
Elbadawy Mohamed, Yamanaka Megumi, Goto Yuta,Hayashi Kimika,Tsunedomi Ryouichi,Hazama Shoichi,Nagano Hiroaki,Yoshida Toshinori,Shibutani Makoto,Ichikawa Ryo,Nakahara Junta,Omatsu Tsutomu,Mizutani Tetsuya,Katayama Yukie,Shinohara Yuta,Abugomaa Amira,Kaneda Masahiro,Yamawaki Hideyuki,Usui Tatsuya,Sasaki Kazuaki
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Journal Title
Biomaterials
Volume: 237
Pages: 119823-119823
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] A prospective, multi-center Phase I study of postoperative enoxaparin treatment in patients undergoing curative hepatobiliary-pancreatic surgery for malignancies2020
Author(s)
Eguchi H, Kawamoto K, Tsujie M, Yukawa M, Kubota M, Asaoka T, Takeda Y, Noda T, Shimizu J, Nagano H, Doki Y, Mori M
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Journal Title
Dig Surg
Volume: 37(1)
Issue: 1
Pages: 81-86
DOI
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Peer Reviewed
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[Journal Article] “Logic-based medicine” is more feasible than “evidence-based medicine” in the local treatment for hepatocellular carcinoma2020
Author(s)
Sakon M, Kobayashi S, Wada H, Eguchi H, Marubashi S, Takahashi H, Akita H, Gotoh K, Yamada D, Asukai K, Hasegawa S, Ohue M, Yano M, Nagano H
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Journal Title
Oncology
Volume: 98(5)
Issue: 5
Pages: 259-266
DOI
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Peer Reviewed
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[Journal Article] Fecal DNA Testing of TWIST1 Methylation Identifies Patients With Advanced Colorectal Adenoma Missed by Fecal Immunochemical Test for Hemoglobin2020
Author(s)
Suehiro Y, Hashimoto S, Goto A, Yamaoka Y, Yamamoto N, Suzuki N, Higaki S, Fujii I, Suzuki C, Matsumoto T, Hoshida T, Koga M, Tsutsumi T, Lim LA, Matsubara Y, Takami T, Yoshida S, Hazama S, Yotsuyanagi H, Nagano H, Sakaida I, Yamasaki T.
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Journal Title
Clinical and Translational Gastroenterology
Volume: 11
Issue: 6
Pages: e00176-e00176
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Peer Reviewed / Open Access
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[Journal Article] Surgical Outcomes of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus2020
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
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Journal Title
Annals of Surgery
Volume: 271
Issue: 5
Pages: 913-921
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Peer Reviewed
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[Journal Article] TCR sequencing analysis of cancer tissues and tumor draining lymph nodes in colorectal cancer patients2019
Author(s)
Matsuda T, Miyauchi E, Hsu YW, Nagayama S, Kiyotani K, Zewde M, Park JH, Kato T, Harada M, Matsui S, Ueno M, Fukuda K, Suzuki N, Hazama S, Nagano H, Takeuchi H, Vigneswaran WT, Kitagawa Y, Nakamura Y
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Journal Title
Oncoimmunology
Volume: 8(6)
Issue: 6
Pages: e1588085-e1588085
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Peer Reviewed
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[Journal Article] A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy.2019
Author(s)
Katsuda M, Miyazawa M, Ojima T, Katanuma A, Hakamada K, Sudo K, Asahara S, Endo I, Ueno M, Hara K, Yamada S, Fujii T, Satoi S, Ioka T, Ohira M, Akahori T, Kitano M, Nagano H, Furukawa M, Adachi T, Yamaue H.
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Journal Title
Trials
Volume: 20
Issue: 1
Pages: 242-242
DOI
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Peer Reviewed / Open Access
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[Journal Article] A Prospective, Randomized Phase II Study of Adjuvant Gemcitabine Versus S-1 After Major Hepatectomy for Biliary Tract Cancer (KHBO 1208): Kansai Hepato-Biliary Oncology Group2019
Author(s)
Kobayashi S, Nagano H, Tomokuni A, Gotoh K, Sakai D, Hatano E, Seo S, Terajima H, Uchida Y, Ajiki T, Satake H, Kamei K, Tohyama T, Hirose T, Ikai I, Morita S, Ioka T; Kansai Hepato-Biliary Oncology (KHBO) Group
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Journal Title
Ann Surg
Volume: 270(2)
Issue: 2
Pages: 230-237
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Peer Reviewed
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[Journal Article] Identification of a Promiscuous Epitope Peptide Derived From HSP70.2019
Author(s)
Matsui H, Hazama S, Tamada K, Udaka K, Irie A, Nishimura Y, Miyakawa T, Doi S, Nakajima M, Kanekiyo S, Tokumitsu Y, Shindo Y, Tomochika S, Yoshida S, Iida M, Suzuki N, Takeda S, Yamamoto S, Yoshino S, Ueno T, Nagano H
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Journal Title
J Immunother
Volume: 42
Issue: 7
Pages: 244-250
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Peer Reviewed / Open Access
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[Journal Article] Utility of scoring systems combining the product of tumor number and size with liver function for predicting the prognosis of patients with hepatocellular carcinoma after hepatectomy2019
Author(s)
Tokumitsu Y, Shindo Y, Matsui H, Matsukuma S, Nakajima M, Suzuki N, Takeda S, Wada H, Kobayashi S, Eguchi H, Ueno T, Nagano H
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Journal Title
Oncol Lett
Volume: 18(4)
Pages: 3903-3913
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intratumoural-infiltrating CD4+ and FOXP3+ T Cells as strong positive predictive markers for the prognosis of resectable colorectal cancer2019
Author(s)
Kuwahara T, Hazama S, Suzuki N, Yoshida S, Tomochika S, Nakagami Y, Matsui H, Shindo Y, Kanekiyo S, Tokumitsu Y, Iida M, Tsunedomi R, Takeda S, Yoshino S, Okayama N, Suehiro Y, Yamasaki T, Fijita T, Kawakami Y, Ueno T, Nagano H
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Journal Title
Br J Cancer
Volume: 121(11)
Issue: 8
Pages: 983-984
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Peer Reviewed
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[Journal Article] Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes2019
Author(s)
Oga T, Yamashita Y, Soda M, Kojima S, Ueno T, Kawazu M, Suzuki N, Nagano H, Hazama S, Izumiya M, Koike K, Mano H
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Journal Title
Cancer Sci
Volume: 110(9)
Issue: 9
Pages: 2973-2981
DOI
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Peer Reviewed
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[Journal Article] Multicenter phase II study of biweekly XELIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study)2019
Author(s)
Suzuki N, Hazama S, Nagasaka T, Tanioka H, Iwamoto Y, Negoro Y, Yamauchi M, Kobayashi M, Okuda H, Fujishima N, Nishimura T, Yamanaka N, Toyota K, Mori Y, Nakagami Y, Shimokawa M, Nagano H, Okajima M
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Journal Title
Int J Clin Oncol
Volume: 24(10)
Issue: 10
Pages: 1223-1230
DOI
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[Journal Article] A Prospective, Open-Label, Multicenter Phase 2 Trial of Neoadjuvant Therapy Using Full-Dose Gemcitabine and S-1 Concurrent with Radiation for Resectable Pancreatic Ductal Adenocarcinoma2019
Author(s)
Eguchi H, Takeda Y, Takahashi H, Nakahira S, Kashiwazaki M, Shimizu J, Sakai D, Isohashi F, Nagano H, Mori M, Doki Y
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Journal Title
Ann Surg Oncol
Volume: 26(13)
Issue: 13
Pages: 4498-4505
DOI
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Peer Reviewed
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[Journal Article] Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2017 (4th JSH-HCC Guidelines) a 2019 update2019
Author(s)
Kokudo N, Takemura N, Hasegawa K, Takayama T, Kubo S, Shimada M, Nagano H, Hatano E, Izumi N, Kaneko S, Kudo M, Iijima H, Genda T, Tateishi R, Torimura T, Igaki H, Kobayashi S, Sakurai H, Murakami T, Watadani T, Matsuyama Y
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Journal Title
Hepatol Res
Volume: 49(10)
Issue: 10
Pages: 1109-1113
DOI
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[Journal Article] Objective Response by mRECIST Is an Independent Prognostic Factor for Overall Survival in Hepatocellular Carcinoma Treated with Sorafenib in the SILIUS Trial2019
Author(s)
Kudo M, Ueshima K, Chiba Y, Ogasawara S, Obi S, Izumi N, Aikata H, Nagano H, Hatano E, Sasaki Y, Hino K, Kumada T, Yamamoto K, Imai Y, Iwadou S, Ogawa C, Okusaka T, Kanai F, Arai Y
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Journal Title
Liver Cancer
Volume: 8(6)
Issue: 6
Pages: 505-519
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[Journal Article] Establishment of a Screening Method for Epstein-Barr Virus-Associated Gastric Carcinoma by Droplet Digital PCR.2019
Author(s)
Shuto T, Nishikawa J, Shimokuri K, Yanagi A, Takagi T, Takagi F, Miura O, Iida M, Nagano H, Takemoto Y, Harada E, Suehiro Y, Yamasaki T, Okamoto T, Sakaida I.
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Journal Title
Microorganisms
Volume: 7(12)
Issue: 12
Pages: 628-628
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[Journal Article] Association between polymorphisms in EGFR and tumor response during cetuximab and oxaliplatin-based combination therapy in metastatic colorectal cancer: Analysis of data from two clinical trials2019
Author(s)
Maeda H, Hazama S, Iwamoto S, Oba K, Tsunedomi R, Okayama N, Suehiro Y, Yamasaki T, Nakagami Y, Suzuki N, Nagano H, Sakamoto J, Mishima H, Nagata N
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Journal Title
Oncol Lett
Volume: 18(5)
Pages: 4555-4562
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[Journal Article] Expression levels of UL16 binding protein 1 and natural killer group 2 member D affect overall survival in patients with gastric cancer following gastrectomy2018
Author(s)
Kamei R, Yoshimura K, Yoshino S, Inoue M, Asao T, Fuse M, Wada S, Kuramasu A, Furuya-Kondo T, Oga A, Iizuka N, Suzuki N, Maeda N, Watanabe Y, Matsukuma S, Iida M, Takeda S, Ueno T, Yamamoto N, Fukagawa T, Katai H, Sasaki H, Hazama S, Oka M, Nagano H.
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Journal Title
Oncology Letters
Volume: 15
Pages: 747-754
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[Journal Article] IgG response to MHC class I epitope peptides is a quantitative predictive biomarker in the early course of treatment of colorectal cancer using therapeutic peptides2018
Author(s)
Kanekiyo S, Hazama S, Takenouchi H, Nakajima M, Shindo Y, Matsui H, Tokumitsu Y, Tomochika S, Tsunedomi R, Tokuhisa Y, Iida M, Sakamoto K, Suzuki N, Takeda S, Yamamoto S, Yoshino S, Okuno K, Udaka K, Kawakami Y, Matsueda S, Ito K, Nagano H.
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Journal Title
Oncology Reports
Volume: 39
Pages: 2385-2392
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[Presentation] Induction of antigen specific CD8+T cell infiltration by a novel neoadjuvant vaccine containing HSP70 and GPC3 peptides plus soluble LAG-3 and Poly-IC: LC : Interim results of a Phase I study2019
Author(s)
Tokumitsu Y, Hazama S, Doi S, Tamada K, Udaka K,Akinaga S, Koki Y, Uematsu T, Nakagami Y, Matsui H,Shindo Y, Kanekiyo S, Tomochika S, Iida M, Yoshida S,Suzuki N, Takeda S, Yoshino S, Ueno T, Nagano H
Organizer
2019 ASCO Annual Meeting
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[Presentation] Cancer stem-like phenotypes including immune surveillance and its responsible genes in induced liver cancer stem-like cells. Poster2019
Author(s)
Tsunedomi R, Yoshimura K, Kimura Y, Nishiyama M,Matsukuma S, Tokumitsu Y, Tomochika S, Iida M, Suzuki N, Takeda S, Yoshino S, Hazama S, Nagano H
Organizer
ESMO Asia Congress
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[Presentation] Analysis of T cells of HCC patients: From a phase I study of novel neoadjuvant vaccine PBMCs and TILs2019
Author(s)
Nakagami Y, Hazama S, Doi S, Tamada K, Udaka K,Akinaga S, Adachi K, Ming Xu, Tokumitsu Y, Matsui H,Shindo Y, Tsunedomi R, Kanekiyo S, Tomochika S, Iida M,Yoshida S, Suzuki N, Takeda S, Yoshino S, Nagano H
Organizer
7th International Conference of Federation of Asian Clinical Oncology(FACO)
Related Report
Int'l Joint Research
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