Develoment of advanced therapy targeting tumor heterogeneity in refractory cancers

• Project/Area Number: 16H02670
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANAKA Shinji 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30253420)
• Co-Investigator(Kenkyū-buntansha): 森 正樹 大阪大学, 医学系研究科, 教授 (70190999) ; 島田 周 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20609705) ; 秋山 好光 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (80262187) ; 深町 博史 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (70134450)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥47,320,000 (Direct Cost: ¥36,400,000、Indirect Cost: ¥10,920,000); Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2017: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2016: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
• Keywords: 癌 / 幹細胞 / ゲノム編集技術 / クロマチン動的変動 / クロマチン再構築 / ヒストン修飾 / 分子サブタイプ / トランスレーショナルリサーチ / 遺伝子 / ゲノム / 外科 / DNA損傷 / 腫瘍変異負荷 / クロマチンリモデリング / ゲノム編集 / 高頻度変異

Outline of Final Research Achievements

Heterogeneity is one of the essential hallmarks of malignancies. Our stemness-visualization system revealed that epigenetic heterogeneity in chromosomal dynamics and histone modifications can regulate in vitro and in vivo intractability of cancers. Using genome editing technology, we elucidated the biological role and clinical significance of ARID2 chromatin remodeling factor in hepatocellular carcinoma (J Hepatol 2017), DAXX heterochromatin regulator in pancreatic tumor (Endocr Relat Cancer 2018), KDM6A histone modifier in pancreatic cancer (Int J Cancer 2019), and PRMT6 histone arginine methylase in gastric cancer (Carcinogenesis 2019). Identification of molecular subtypes is expected to realize the precise medicine based on the subtype-specific molecules and immune microenvironments (EBioMedicine 2019). Development of multiplex genome editing system can design the actionable strategy and revolutionize advanced therapy targeting tumor heterogeneity in refractory cancers.

Academic Significance and Societal Importance of the Research Achievements

本研究成果の意義は、癌難治性克服におけるクロマチン・ヒストン制御の重要性を明らかにしたことである。高効率のゲノム編集技術の開発により、クロマチン・ヒストン異常のサブタイプ機序を解明しただけでなく、サブタイプ特異的治療も同定しており、予定以上の成果が得られた。さらに臨床検体の解析により新しい分子免疫サブタイプ分類を提唱し、新たな多重ゲノム編集技術の開発にも着手している。免疫正常モデルを用いたサブタイプ・パネルを構築し、どのサブタイプに対して、どのような組み合わせで、どのタイミングが最適であるかを明確にして、免疫複合治療への応用を進めている。

Research Products

• [Int'l Joint Research] Brown University(米国)
• [Int'l Joint Research] Seoul National University/Korea Res Inst Biosci Biotech(韓国)
• [Int'l Joint Research] Brown University(米国)
• [Journal Article] Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence. (2019)
  • Author(s): Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Tanabe M, Wands JR, Tanaka S.
  • Journal Title: EBioMedicine Volume: 40 Pages: 457-470
  • DOI: 10.1016/j.ebiom.2018.12.058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Asymmetric dimethylation at histone H3 arginine 2 by PRMT6 in gastric cancer progression. (2019)
  • Author(s): Okuno K, Akiyama Y, Shimada S, Nakagawa M, Tanioka T, Inokuchi M, Yamaoka S, Kojima K, Tanaka S.
  • Journal Title: Carcinogenesis Volume: 40 Issue: 1 Pages: 15-26
  • DOI: 10.1093/carcin/bgy147
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A subset of diffuse-type gastric cancer is susceptible to mTOR inhibitors and checkpoint inhibitors (2019)
  • Author(s): Fukamachi H、Kim SK、Koh J、Lee HS、Sasaki Y、Yamashita K、Nishikawaji T、Shimada S、Akiyama Y、Byeon SJ、Bae DH、Okuno K、Nakagawa M、Tanioka T、Inokuchi M、Kawachi H、Tsuchiya K、Kojima K、Tokino Takashi、Eishi Y、Kim YS、Kim WH、Yuasa Y、Tanaka S
  • Journal Title: Journal of Experimental & Clinical Cancer Research Volume: 38 Issue: 1 Pages: 127-127
  • DOI: 10.1186/s13046-019-1121-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of KDM6A characterizes a poor prognostic subtype of human pancreatic cancer and potentiates HDAC inhibitor lethality (2019)
  • Author(s): Watanabe S, Shimada S, Akiyama Y, Ishikawa Y, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Yamaoka S, Tanabe M, Tanaka S.
  • Journal Title: International Journal of Cancer Volume: - Issue: 1 Pages: 192-205
  • DOI: 10.1002/ijc.32072
  • Peer Reviewed
• [Journal Article] Orotate phosphoribosyltransferase as a predictor of benefit from S-1 adjuvant chemotherapy for cholangiocarcinoma patients (2019)
  • Author(s): Akahoshi K, Ban D, Kuboki R, Oba A, Ono H, Mitsunori Y, Kudo A, Tanaka S, Tanabe M.
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 6 Pages: 1108-1115
  • DOI: 10.1111/jgh.14477
  • Peer Reviewed
• [Journal Article] A new era for understanding genetic evolution of multistep carcinogenesis (2019)
  • Author(s): Shimada S, Tanaka S.
  • Journal Title: Journal of Gastroenterology Volume: - Issue: 7 Pages: 667-668
  • DOI: 10.1007/s00535-019-01576-8
  • Peer Reviewed
• [Journal Article] A simple and practical index predicting the prognoses of the patients with well-differentiated pancreatic neuroendocrine neoplasms. (2019)
  • Author(s): Liu B, Kudo A, Kinowaki Y, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Tanaka S, Akashi T, Tanabe M.
  • Journal Title: J Gastroenterol. Volume: - Issue: 9 Pages: 819-828
  • DOI: 10.1007/s00535-019-01570-0
  • Peer Reviewed
• [Journal Article] The clinical implications of peripancreatic fluid collection after distal pancreatectomy (2019)
  • Author(s): Yoshino J, Ban D, Ogura T, Ogawa K, Ono H, Mitsunori Y, Kudo A, Tanaka S, Tanabe M
  • Journal Title: World Journal of Surgery Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Precision medicine based on surgical oncology in the era of genome-scale analysis and genome editing technology. (2018)
  • Author(s): Tanaka S.
  • Journal Title: Annals of Gastroenterological Surgery Volume: - Issue: 2 Pages: 106-115
  • DOI: 10.1002/ags3.12059
  • Peer Reviewed / Open Access
• [Journal Article] DEPDC5 deficiency contributes to resistance to leucine starvation via p62 accumulation in hepatocellular carcinoma (2018)
  • Author(s): Mizuno Y, Shimada S, Akiyama Y, Watanabe S, Aida T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Yamaoka S, Tanabe M, Tanaka S
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 106-106
  • DOI: 10.1038/s41598-017-18323-9
  • Peer Reviewed / Open Access
• [Journal Article] Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models. (2018)
  • Author(s): Shimada S, Akiyama Y, Mogushi K, Ishigami-Yuasa M, Kagechika H, Nagasaki H, Fukamachi H, Yuasa Y, Tanaka S.
  • Journal Title: British Journal of Cancer Volume: - Issue: 7 Pages: 972-984
  • DOI: 10.1038/s41416-018-0008-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors (2018)
  • Author(s): Chiyonobu Norimichi、Shimada Shu、Akiyama Yoshimitsu、Mogushi Kaoru、Itoh Michiko、Akahoshi Keiichi、Matsumura Satoshi、Ogawa Kosuke、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Kudo Atsushi、Arii Shigeki、Suganami Takayoshi、Yamaoka Shoji、Ogawa Yoshihiro、Tanabe Minoru、Tanaka Shinji
  • Journal Title: Am. J. Pathol. Volume: 188 Issue: 5 Pages: 1213-1224
  • DOI: 10.1016/j.ajpath.2018.01.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs. (2018)
  • Author(s): Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Endocr Relat Cancer Volume: 25(6) Issue: 6 Pages: 619-631
  • DOI: 10.1530/erc-17-0328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sunitinib shrinks NET-G3 pancreatic neuroendocrine neoplasms (2018)
  • Author(s): Mizuno Yuki、Kudo Atsushi、Akashi Takumi、Akahoshi Keiichi、Ogura Toshiro、Ogawa Kosuke、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Tanaka Shinji、Tateishi Ukihide、Tanabe Minoru
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: - Issue: 6 Pages: 1155-1163
  • DOI: 10.1007/s00432-018-2636-2
  • Peer Reviewed
• [Journal Article] Rapid growth speed of cysts can predict malignant intraductal mucinous papillary neoplasms. (2018)
  • Author(s): Akahoshi K, Ono H, Akasu M, Ban D, Kudo A, Konta A, Tanaka S, Tanabe M.
  • Journal Title: J Surg Res Volume: 231 Pages: 195-200
  • DOI: 10.1016/j.jss.2018.05.056
  • Peer Reviewed
• [Journal Article] Splenic artery as a simple landmark indicating difficulty during laparoscopic distal pancreatectomy (2018)
  • Author(s): Ishikawa Yoshiya、Ban Daisuke、Watanabe Shuichi、Akahoshi Keiichi、Ono Hiroaki、Mitsunori Yusuke、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Asian Journal of Endoscopic Surgery Volume: - Issue: 1 Pages: 81-87
  • DOI: 10.1111/ases.12485
  • Peer Reviewed
• [Journal Article] Polyamine flux suppresses histone lysine demethylases and enhances ID1 expression in cancer stem cells (2018)
  • Author(s): Tamari K, KonnoM , Asai A, Koseki J, Hayashi K, Kawamoto K, Murai N, Matsufuji S, Isohashi F, Satoh T, Gotoh N, Tanaka S, Doki Y, Mori M, Ogawa K, Ishii H.
  • Journal Title: Cell Death Discovery Volume: 4 Issue: 104 Pages: 104-104
  • DOI: 10.1038/s41420-018-0117-7
  • Peer Reviewed / Open Access
• [Journal Article] Downregulated Pancreatic Beta Cell Genes Indicate Poor Prognosis in Patients With Pancreatic Neuroendocrine Neoplasms. (2018)
  • Author(s): Kudo A, Akahoshi K, Ito S, Akashi T, Shimada S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Tateishi U, Tanaka S, Tanabe M.
  • Journal Title: Ann Surg. Volume: - Issue: 4 Pages: 732-739
  • DOI: 10.1097/sla.0000000000002911
  • Peer Reviewed
• [Journal Article] ARID2 modulates DNA damage response in human hepatocellular carcinoma cells. (2017)
  • Author(s): Oba A, Shimada S, Akiyama Y, Nishikawaji T, Mogushi K, Ito H, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Asahara H, Kaida A, Miura M, Tanabe M, Tanaka S.
  • Journal Title: Journal of Hepatology Volume: in press Issue: 5 Pages: 942-951
  • DOI: 10.1016/j.jhep.2016.12.026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acquired resistance with epigenetic alterations under long-term anti-angiogenic therapy for hepatocellular carcinoma. (2017)
  • Author(s): Ohata Y, Akiyama Y, Shimada S, Mogushi K, Nakao K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Molecular Cancer Therapeutics Volume: in press Issue: 6 Pages: 1155-1165
  • DOI: 10.1158/1535-7163.mct-16-0728
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A simple morphological classification to estimate the malignant potential of pancreatic neuroendocrine tumors (2017)
  • Author(s): Oba Atsushi、Kudo Atsushi、Akahoshi Keiichi、Kishino Mitsuhiro、Akashi Takumi、Katsuta Eriko、Iwao Yasuhito、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Tanaka Shinji、Eishi Yoshinobu、Tateishi Ukihide、Tanabe Minoru
  • Journal Title: Journal of Gastroenterology Volume: 52 Issue: 10 Pages: 1140-1146
  • DOI: 10.1007/s00535-017-1349-7
  • Peer Reviewed
• [Journal Article] Refractory Long-Term Cholangitis After Pancreaticoduodenectomy: A Retrospective Study (2017)
  • Author(s): Ueda Hiroki、Ban Daisuke、Kudo Atsushi、Ochiai Takanori、Tanaka Shinji、Tanabe Minoru
  • Journal Title: World Journal of Surgery Volume: 41 Issue: 7 Pages: 1882-1889
  • DOI: 10.1007/s00268-017-3912-z
  • Peer Reviewed
• [Journal Article] Emergency cholecystectomy for patients on antiplatelet therapy. (2017)
  • Author(s): Akahoshi K, Ochiai T, Takaoka A, Kitamura T, Ban D, Kudo A, Tanaka S, Tanabe M.
  • Journal Title: American Surgeon Volume: 83(5) Pages: 486-490
  • Peer Reviewed
• [Journal Article] Surgical pitfalls of jejunal vein anatomy in pancreaticoduodenectomy (2017)
  • Author(s): Ishikawa Yoshiya、Ban Daisuke、Matsumura Satoshi、Mitsunori Yusuke、Ochiai Takanori、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Journal of Hepato-Biliary-Pancreatic Sciences Volume: 24 Issue: 7 Pages: 394-400
  • DOI: 10.1002/jhbp.451
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis and targeted therapy of pancreatic cancer. (2016)
  • Author(s): Tanaka S.
  • Journal Title: Annals of Surgical Oncology Volume: 23 Issue: S2 Pages: 197-205
  • DOI: 10.1245/s10434-015-4463-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis. (2016)
  • Author(s): Ito H, Tanaka S, Akiyama Y, Shimada S, Adikrisna R, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Yamaoka S, Tanabe M.
  • Journal Title: Plos One Volume: - Issue: 1 Pages: e0146564-e0146564
  • DOI: 10.1371/journal.pone.0146564
  • Peer Reviewed / Open Access
• [Journal Article] Proteasome activity is required for the initiation of precancerous pancreatic lesions. (2016)
  • Author(s): Furuyama T, Tanaka S, Shimada S, Akiyama Y, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Fukamachi H, Arii S, Kawaguchi Y, Tanabe M.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27044-27044
  • DOI: 10.1038/srep27044
  • NAID: 120006775931
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Autophagy controls centrosome number by degrading Cep63. (2016)
  • Author(s): Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 13508-13508
  • DOI: 10.1038/ncomms13508
  • NAID: 120007129257
  • Peer Reviewed / Open Access
• [Journal Article] Cancer stem-like properties in colorectal cancer cells with low proteasome activity. (2016)
  • Author(s): Munakata K, Uemura M, Tanaka S, Kawai K, Kitahara T, Miyo M, Kano Y, Nishikawa S, Fukusumi T, Takahashi Y, Hata T, Nishimura J, Takemasa I, Mizushima T, Ikenaga M, Kato T, Murata K, Carethers JM, Yamamoto H, Doki Y, Mori M.
  • Journal Title: Clinical Cancer Research Volume: 22 Issue: 21 Pages: 5277-5286
  • DOI: 10.1158/1078-0432.ccr-15-1945
  • Peer Reviewed
• [Journal Article] CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells. (2016)
  • Author(s): Katsuta, E., Tanaka, S., Mogushi, K., Shimada, S., Akiyama, Y., Aihara, A., Matsumura, S., Mitsunori, Y., Ban, D., Ochiai, T., Kudo, A., Fukamachi, H., Tanaka, H., Nakayama, K., Arii, S., Tanabe, M.
  • Journal Title: Int. J. Oncol. Volume: 48 Issue: 2 Pages: 657-669
  • DOI: 10.3892/ijo.2015.3299
  • Peer Reviewed / Open Access
• [Journal Article] CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells. (2016)
  • Author(s): Katsuta E, Tanaka S, Mogushi K, Shimada S, Akiyama Y, Aihara A, Matsumura S, Mitsunori Y, Ban D, Ochiai T, Kudo A, Fukamachi H, Tanaka H, Nakayama K, Arii S, Tanabe M.
  • Journal Title: International Journal of Oncology Volume: 48 Issue: 9 Pages: 657-69
  • DOI: 10.1007/s00535-015-1159-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reduced expression of SET7/9, a histone mono-methyltransferase, is associated with gastric cancer progression. (2016)
  • Author(s): Akiyama Y, Koda Y, Byeon S, Shimada S, Nishikawaji T, Sakamoto A, Chen Y, Kojima K, Kawano T, Eishi Y, Deng D, Kim WH, Zhu WG, Yuasa Y, Tanaka S.
  • Journal Title: Oncotarget Volume: 7(4) Issue: 4 Pages: 3966-3983
  • DOI: 10.18632/oncotarget.6681
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Overexpression of histone methyltransferase SETDB2 acts an oncogene in gastric cancer. (2016)
  • Author(s): Nishikawaji T, Akiyama Y, Shimada S, Kojima K, Kawano T, Eishi Y, Yuasa Y, Tanaka S.
  • Journal Title: Oncotarget Volume: 7 Issue: 41 Pages: 67251-67265
  • DOI: 10.18632/oncotarget.11625
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features. (2016)
  • Author(s): Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Sayuri Nitta S, Watanabe T, Otani S, Taniguchi M, Goto F, Nagata H, Kaneko S, Tasaka-Fujita M, Nishimura-Sakurai Y, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Takano S, Fukasawa M, Sakamoto M, Maekawa S, Enomoto N, Watanabe M.
  • Journal Title: Journal of Gastroenterology Volume: 51 Issue: 5 Pages: 473-486
  • DOI: 10.1007/s00535-015-1126-4
  • Peer Reviewed
• [Journal Article] Genome-wide DNA methylation analysis in hepatocellular carcinoma. (2016)
  • Author(s): Yamada N, Yasui K, Dohi O, Gen Y, Tomie A, Kitaichi T, Iwai N, Mitsuyoshi H, Sumida Y, Moriguchi M, Yamaguchi K, Nishikawa T, Umemura A, Naito Y, Tanaka S, Arii S, Itoh Y.
  • Journal Title: Oncol Rep. Volume: 35 Issue: 4 Pages: 2228-2236
  • DOI: 10.3892/or.2016.4619
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preoperative direct bilirubin to prothrombin time ratio index to prevent liver failure after minor hepatectomy. (2016)
  • Author(s): Furuyama T, Kudo A, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Tanaka S, Tanabe M.
  • Journal Title: Journal of Hepatobiliary Pancreatic Sciences Volume: 23 Issue: 12 Pages: 763-770
  • DOI: 10.1002/jhbp.400
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Precision medicine for HCC and pancreatic cancer (Symposium) (2018)
  • Author(s): Shinji Tanaka
  • Organizer: The 7th International Forum of The Japanese Society of Gastroenterology Jointly with the 12th International Symposium on ALPD and Cirrhosis
  • Int'l Joint Research / Invited
• [Presentation] Precision immunotherapy for hypermutator and immunogenic subtypes of hepatocellular carcinoma (Workshop) (2018)
  • Author(s): Shinji Tanaka, Atsushi Oba, Shu Shimada, Yoshimitsu Akiyama, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Minoru Tanabe
  • Organizer: 73rd General Meeting of the Japanese Society of Gastroenterological Surgery
  • Int'l Joint Research
• [Presentation] Molecular target therapy for liver cancer under precision medicine (Symposium) (2018)
  • Author(s): Shinji Tanaka
  • Organizer: 77th Annual Meeting of Japanese Cancer Association
  • Int'l Joint Research / Invited
• [Presentation] 肝臓外科からみた代謝関連肝癌の分子機序と治療戦略（シンポジウム） (2018)
  • Author(s): 田中真二
  • Organizer: 第39回日本肥満学会
  • Invited
• [Presentation] 肝癌の予後不良サブタイプの同定とゲノム編集による治療戦略（ワークショップ） (2018)
  • Author(s): 田中真二、水野裕貴、田邉稔
  • Organizer: 第16回日本消化器外科学会大会
• [Presentation] 代謝関連肝癌の特異的バイオマーカーおよび治療標的の同定（ワークショップ） (2018)
  • Author(s): 田中真二、小川佳宏、田邉稔
  • Organizer: 第22回日本肝臓学会大会
• [Presentation] シンポジウム「肝胆膵がんの分子サブタイプと治療抵抗性解析によるprecision medicineの展開」 (2017)
  • Author(s): 田中真二、島田周、秋山好光、松村聡、光法雄介、藍原有弘、落合高徳、伴大輔、工藤篤、有井滋樹、田邉稔
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] ワークショップ「プレシジョン・メディシンによる肝細胞癌の予後予測と治療展開」 (2017)
  • Author(s): 田中真二、大庭篤志、小川康介、小野宏晃、光法雄介、伴大輔、工藤篤、有井滋樹、田邉稔
  • Organizer: 第73回日本消化器外科学会総会
  • Invited
• [Presentation] ワークショップ「生体内における治療抵抗性獲得メカニズム解明と高度進行肝癌への臨床応用」 (2017)
  • Author(s): 田中真二、大畠慶映、田邉稔
  • Organizer: 第15回日本消化器外科学会大会
• [Presentation] ワークショップ「 肝がん難治性サブタイプのゲノム編集解析とプレシジョン・メディシンによる治療戦略」 (2017)
  • Author(s): 田中真二、大庭篤志、島田周、秋山好光、小川康介、小野宏晃、光法雄介、伴大輔、工藤篤、有井滋樹、田邉稔
  • Organizer: 第56回日本癌治療学会学術集会
• [Presentation] シンポジウム：臨床検体のゲノム解析に基づいた遺伝子改変およびゲノム編集技術の臨床応用 (2016)
  • Author(s): 田中真二、島田周、古山貴基、大庭篤志、茂櫛薫、秋山好光、水野裕貴、小川康介、深町博史、伊藤浩光、光法雄介、松村聡、藍原有弘、伴大輔、落合高徳、工藤篤、川口義弥、田邉稔
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: リーガロイヤルホテル大阪（大阪府、大阪市）
• [Presentation] シンポジウム：肝癌の幹細胞性解析とゲノム編集技術を用いた治療応用 (2016)
  • Author(s): 田中真二、藍原有弘、田邉稔
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都、新宿区）
• [Presentation] シンポジウム：肝がん個別化分類に基づいた生体内バイオマーカーの同定による新規分子標的治療の開発と臨床展開 (2016)
  • Author(s): 田中真二、佐藤公太、田邉稔
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張（千葉県、幕張市）
• [Presentation] シンポジウム指定演者：基礎研究から臨床応用への展望 (2016)
  • Author(s): 田中真二
  • Organizer: 第14回日本肝がん分子標的治療研究会
  • Place of Presentation: 梅田スカイビルタワー(大阪府、大阪市)
  • Invited
• [Presentation] パネルディスカッション基調講演：がん分子サブタイプと臨床情報に基づく個別化治療戦略 (2016)
  • Author(s): 田中真二
  • Organizer: 第52回日本肝癌研究会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都、港区）
  • Invited
• [Presentation] シンポジウム：肝胆膵がん個別化分類に基づいた癌幹細胞の治療抵抗性機序の解明と治療展開 (2016)
  • Author(s): 田中真二、伊藤浩光、古山貴基、藍原有弘、松村聡、光法雄介、伴大輔、落合高徳、工藤篤、田邊稔
  • Organizer: 第72回日本消化器外科学会総会
  • Place of Presentation: あわぎんホール（徳島県、徳島市）
• [Presentation] 癌幹細胞のエピジェネティック変化と転移性および治療抵抗性獲得機序 (2016)
  • Author(s): 田中真二、島田周、秋山好光
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県、横浜市）
• [Presentation] ワークショップ：肝癌分子標的薬の生体内感受性バイオマーカー探索と臨床展開 (2016)
  • Author(s): 田中真二、大畠慶映、田邉稔
  • Organizer: 第14回日本消化器外科学会大会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県、神戸市）
• [Book] Molecular analysis for therapeutic targets of pancreatic cancer. IN: Molecular diagnosis and targeting for thoracic and gastrointestinal malignancy (2018)
  • Author(s): Tanaka S. (eds. Shimada Y, Yanaga K)
  • Publisher: Springer
• [Book] Molecular diagnosis and targeting for thoracic and gastrointestinal malignancy (2018)
  • Author(s): Tanaka S.
  • Publisher: Springer
  • ISBN: 9789811064685
• [Book] Human Stem Cell Toxicity (ed. Sherley JL) (2016)
  • Author(s): Tanaka S.
  • Total Pages: 299
  • Publisher: Royal Society of Chemistry (London)
• [Remarks] 胃がんにおいてヒストン修飾の異常により悪性度を増すメカニズムを解明
• [Remarks] 予後不良膵癌サブタイプにおけるヒストン修飾遺伝子の不活化の意義を解明
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20181218_1.pdf
• [Remarks] 肝細胞癌の分子生物学的・免疫学的サブタイプ分類を確立
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20190111_1.pdf
• [Remarks] New liver cancer subtypes revealed immunologically
  • URL: https://www.eurekalert.org/pub_releases/2019-02/tmad-ctd020119.php
• [Remarks]
  • URL: http://www.tmd.ac.jp/grad/monc/
• [Remarks] 肝がん変異遺伝子ARID2による発がんメカニズムを解明
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20170227.pdf
• [Remarks] がんが生体内で治療抵抗性を獲得するメカニズムを解明
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20170301.pdf
• [Remarks] 肝がんがロイシン欠乏耐性を獲得するメカニズムを解明
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20180108_1.pdf
• [Remarks] メタボ関連肝がんに特異的なバイオマーカーを発見
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20180216_1.pdf
• [Remarks] 化合物スクリーニングによりスキルス胃がん特異的に作用する薬剤を発見
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20180313_2.pdf