Development of novel therapeutic strategy against highly malignant tumors

• Project/Area Number: 15K08394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KITAGAWA Masanobu 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10177834)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Kouhei 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50451927) ; ABE Shinya 兵庫医科大学, 医学部, 助教 (70596725) ; HASEGAWA Maki 武田薬品 (00431958)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アポトーシス誘導 / MCM2 / 悪性腫瘍の治療 / DNA損傷 / アポトーシス

Outline of Final Research Achievements

Some of malignant tumors are known to show highly　malignant　potential　and　worse　prognosis.　We　have　clarified　the function of MCM2　(minichromosome　maintenance 2) protein as the enhancer of the DNA-damage-induced apoptosis. In the present study, we introduced gp70 protein to tumor cells by the protein transduction experiment system and created the treatment experiments of highly malignant tumors in vitro and in vivo by using the interaction of MCM2 and gp70 to enhance apoptosis. The results showed the prominent enhancement of apoptosis to tumor cells by the treatment with gp70 and DNA-damage stimuli by doxorubicin. Not only leukemia cells but also soid tumors such as breast cancer and ovarian cancer revealed the successful reduction of tumor volume by the novel strategy of MCM2-targeted therapy.

Research Products

• [Journal Article] BCL2 expression in DLBCL: reappraisal of immunohistochemistry with new criteria for therapeutic biomarker evaluation. (2017)
  • Author(s): Tsuyama N, Sakata S, Baba S, Mishima Y, Nishimura N, Ueda K, Yokoyama M, Terui Y, Hatake K, Kitagawa M, Ishizuka N, Tomita N, Takeuchi K.
  • Journal Title: Blood Volume: 130 Pages: 489-500
  • Peer Reviewed
• [Journal Article] Clinical and pathological significance of myeloid differentiation factor 88 expression in human hepatocellular carcinoma tissues (2017)
  • Author(s): Kinowaki K, Soejima Y, Kumagai A, Kondo F, Sano K, Fujii T, Kitagawa M, Fukusato T.
  • Journal Title: Pathology International Volume: 67 Issue: 5 Pages: 256
  • DOI: 10.1111/pin.12529
  • Peer Reviewed
• [Journal Article] Role of microRNA 29b in myelodysplastic syndromes during transformation to overt leukemia. (2016)
  • Author(s): Kirimura S, Kurata M, Nakagawa Y, Onishi I, Abe-Suzuki S, Abe S, Yamamoto K, Kitagawa M.
  • Journal Title: Pathology Volume: 43 Issue: 3 Pages: 233-241
  • DOI: 10.1016/j.pathol.2016.02.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas. (2016)
  • Author(s): Kihara A, Wakana K, Kubota T, Kitagawa M.
  • Journal Title: Histopathology Volume: 69 Issue: 3 Pages: 374-382
  • DOI: 10.1111/his.12971
  • Peer Reviewed
• [Journal Article] Antimyeloma activity of bromodomain inhibitors on the human myeloma cell line U266 by downregulation of MYCL. (2016)
  • Author(s): Suzuki K, Yamamoto K, Arakawa Y, Yamada H, Aiba K, Kitagawa M.
  • Journal Title: Anticancer Drugs. Volume: 27(8) Issue: 8 Pages: 756-65
  • DOI: 10.1097/cad.0000000000000389
  • Peer Reviewed
• [Journal Article] Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors. (2015)
  • Author(s): .Abe S, Yamamoto K, Kurata M, Abe-Suzuki S, Horii R, Akiyama F, Kitagawa M.
  • Journal Title: Oncotarget Volume: 27 Issue: 33 Pages: 34892-34909
  • DOI: 10.18632/oncotarget.5408
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An autopsy case of dementia with Levy bodies with vocal cord abductor paralysis. (2015)
  • Author(s): Toru S, Uchihara T, Hara M, Mae S, Toru M, Hirokawa K, Endo T, Sugawara E, Kitagawa M, Kobayashi T.
  • Journal Title: Eur Neurol Volume: 74 Issue: 3-4 Pages: 186-187
  • DOI: 10.1159/000441448
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 骨髄異形成症候群における造血幹細胞ニッチの関与 (2016)
  • Author(s): 北川昌伸、山本浩平、阿部志保、大西威一郎、桐村進、阿部晋也
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-05-12
• [Presentation] MDS-RAEBとAMO-MRCの病理組織学的鑑別ポイントとその意義 (2015)
  • Author(s): 北川昌伸、山本浩平、阿部志保、大西威一郎、桐村進、阿部晋也
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋市・愛知県・熱田西町）
  • Year and Date: 2015-04-30
  • Invited
• [Presentation] DNA損傷誘発アポトーシス増強による新規腫瘍治療モデル (2015)
  • Author(s): 阿部晋也、山本浩平、阿部志保、北川昌伸
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（名古屋市・愛知県・熱田西町）
  • Year and Date: 2015-04-30