A fundamental study to develop novel targeted drug delivery systems for multiple myeloma therapy

• Project/Area Number: 26640101
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: The University of Tokyo
• Principal Investigator: Imai Kohzoh 東京大学, 医科学研究所, 特任研究員 (60117603)
• Co-Investigator(Kenkyū-buntansha): YASUI Hiroshi 東京大学, 医科学研究所, 特任准教授 (40448593)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 多発性骨髄腫 / Drug Delivery System / 橋渡し研究 / 骨髄微小環境 / 免疫細胞 / ＤＤＳ / 抗体医薬 / 核酸治療

Outline of Final Research Achievements

In the present study, we developed novel therapeutics using drug delivery systems (DDS) for multiple myeloma (MM) treatment. Since MM cells closely interact with their bone marrow microenvironment, thereby contributing to their pathophysiology, we selected polymeric micelles suitable to MM cells and their microenvironment, as well as ligand molecules to be integrated with the micelles. In addition, we developed a novel DDS to induce anti-MM activities by recruiting immune cells to tumor cells. Thus, a fundamental system to develop novel therapeutics using DDS suitable for MM and its microenvironment was established in this study.

Research Products

• [Journal Article] Report of the Japan diabetes society/Japanese cancer association joint committee on diabetes and cancer, Second report. (2016)
  • Author(s): Goto A, Noto H, Noda M, Ueki K, Kasuga M, Tajima N, Ohashi K, Sakai R, Tsugane S, Hamajima N, Tajima K, Imai K, Nakagama H.
  • Journal Title: Cancer Science Volume: 107(3) Issue: 3 Pages: 369-71
  • DOI: 10.1111/cas.12889
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer, Second Report (2016)
  • Author(s): Goto A, Noto H, Noda M, Ueki K, Kasuga M, Tajima N, Ohashi K, Sakai R, Tsugane S, Hamajima N, Tajima K, Imai K, Nakagama H.
  • Journal Title: Diabeto Int. Volume: 7 Issue: 1 Pages: 12-15
  • DOI: 10.1007/s13340-016-0257-z
  • NAID: 130005142004
  • Peer Reviewed
• [Journal Article] Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. (2016)
  • Author(s): Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H, Kanno S, Yamamoto I, Ishigami K, Igarashi H, Maruyama R, Imai K, Yamamoto H, Shinomura Y.
  • Journal Title: World J Gastroenterol Volume: 22 Issue: 2 Pages: 557-566
  • DOI: 10.3748/wjg.v22.i2.557
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway. (2016)
  • Author(s): Kurihara H, Maruyama R, Ishiguro K, Kanno S, Yamamoto I, Ishigami K, Mitsuhashi K, Igarashi H, Ito M, Tanuma T, Sukawa Y, Okita K, Hasegawa T, Imai K, Yamamoto H, Shinomura Y, Nosho K.
  • Journal Title: Oncotarget Volume: 7 Issue: 11 Pages: 12704-12717
  • DOI: 10.18632/oncotarget.7260
  • Peer Reviewed / Open Access
• [Journal Article] HHV-6 encephalitis may complicate the early phase after allogeneic hematopoietic stem cell transplantation: Detection by qualitative multiplex PCR and subsequent quantitative real-time PCR (2016)
  • Author(s): Inazawa N, Hori T, Yamamoto M, Hatakeyama N, Yoto Y, Nojima M, Yasui H, Suzuki N, Shimizu N, Tsutsumi H.
  • Journal Title: J Med Virol Volume: 88 Issue: 2 Pages: 319-323
  • DOI: 10.1002/jmv.24340
  • Peer Reviewed
• [Journal Article] Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. (2015)
  • Author(s): Ito M, Kanno S, Nosho K, Sukawa Y, Mitsuhashi K, Kurihara H, Igarashi H, Takahashi T, Tachibana M, Takahashi H, Yoshii S, Takenouchi T, Hasegawa T, Okita K, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y.
  • Journal Title: Int J Cancer Volume: 137 Issue: 6 Pages: 1258-1268
  • DOI: 10.1002/ijc.29488
  • Peer Reviewed
• [Journal Article] Establishment of patient-derived cancer xenografts in immunodeficient NOG mice. (2015)
  • Author(s): Chijiwa T, Kawai K, Noguchi A, Sato H, Hayashi A, Cho H, Shiozawa M, Kishida T, Morinaga S, Yokose T, Katayama M, Takenaka N, Suemizu H, Yamada R, Nakamura Y, Ohtsu T, Takano Y, Imai K, Miyagi Y, Nakamura M
  • Journal Title: International Journal of Oncology Volume: 47 Issue: 1 Pages: 61-70
  • DOI: 10.3892/ijo.2015.2997
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors (2015)
  • Author(s): Kamimae S, Yamamoto E, Kai M, Niinuma T, Yamano HO, Nojima M, Yoshikawa K, Kimura T, Takagi R, Harada E, Harada T, Maruyama R, Sasaki Y, Tokino T, Shinomura Y, Sugai T, Imai K, Suzuki H
  • Journal Title: Oncotarget Volume: 6 Issue: 30 Pages: 29975-90
  • DOI: 10.18632/oncotarget.5034
  • NAID: 130005161526
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of microRNA-31-5p with clinical efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer (2015)
  • Author(s): Igarashi H, Kurihara H, Mitsuhashi K, Ito M, Okuda H, Kanno S, Naito T, Yoshii S, Takahashi H, Kusumi T, Hasegawa T, Sukawa Y, Adachi Y, Okita K, Hirata K, Imamura Y, Baba Y, Imai K, Suzuki H, Yamamoto H, Nosho K, Shinomura Y
  • Journal Title: Ann Surg Oncol Volume: 14 Issue: 8 Pages: 4264-4267
  • DOI: 10.1245/s10434-014-4264-7
  • Peer Reviewed / Open Access
• [Journal Article] Low-frequency IL23R coding variant associated with Crohn's disease susceptibility in Japanese subjects identified by personal genomics analysis (2015)
  • Author(s): Onodera K, Arimura Y, Isshiki H, Kawakami K, Nagaishi K, Yamashita K, Yamamoto E, Niinuma T, Naishiro Y, Suzuki H, Imai K, Shinomura Y
  • Journal Title: PLoS ONE Volume: 10 Issue: 9 Pages: e0137801-e0137801
  • DOI: 10.1371/journal.pone.0137801
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of the molecular features of rectal carcinoid tumors to identify new biomarkers that predict biological malignancy (2015)
  • Author(s): Mitsuhashi K, Yamamoto I, Kurihara H, Kanno S, Ito M, Igarashi H, Ishigami K, Sukawa Y, Tachibana M, Takahashi H, Tokino T, Maruyama R, Suzuki H, Imai K, Shinomura Y, Yamamoto H, Nosho K
  • Journal Title: ONCOTARGET Volume: 6 Issue: 26 Pages: 22114-22125
  • DOI: 10.18632/oncotarget.4294
  • Peer Reviewed / Open Access
• [Journal Article] Role of interleukin-32 in the mechanism of chronic inflammation in IgG4-related disease and as a predictive biomarker for drug-free remission. (2015)
  • Author(s): Shimizu Y, Yamamoto M, Yajima H, Suzuki C, Naishiro Y, Takahashi H, Imai K, Shinomura Y.
  • Journal Title: Modern Rheumatology Volume: 26(3) Pages: 391-7
  • Peer Reviewed
• [Journal Article] Screening of drugs to treat 8p11 myeloproliferative syndrome using patient-derived induced pluripotent stem cells with fusion gene CEP110-FGFR1 (2015)
  • Author(s): Yamamoto S, Otsu M, Matsuzaka E, Konishi C, Takagi H, Hanada S, Mochizuki S, Nakauchi H, Imai K, Tsuji K, Ebihara Y.
  • Journal Title: Plos One Volume: -
  • Peer Reviewed
• [Journal Article] Clinicopathological and molecular characteristics of serrated lesions in Japanese elderly patients (2015)
  • Author(s): Nosho K, Igarashi H, Ito M, Mitsuhashi K, Kurihara H, Kanno S, Yoshii S, Mikami M, Takahashi H, Kusumi T, Hosokawa M, Sukawa Y, Adachi Y, Hasegawa T, Okita K, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y
  • Journal Title: Digestion Volume: 91(1) Issue: 1 Pages: 57-63
  • DOI: 10.1159/000368820
  • Peer Reviewed
• [Journal Article] Microsatellite instability:an update (2015)
  • Author(s): Yamamoto H, Imai K.
  • Journal Title: Archives of Toxicology Volume: -
  • Peer Reviewed
• [Journal Article] Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis (2015)
  • Author(s): Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, Tachibana M, Tanuma T, Maguchi H, Shinohara T, Hasegawa T, Imamura M, Kimura Y, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y.
  • Journal Title: Oncotarget Volume: -
  • Peer Reviewed
• [Journal Article] Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model (2015)
  • Author(s): Nakagaki S, Arimura Y, Nagaishi K, Isshiki H, Nasuno M, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y.
  • Journal Title: J Gastroenterol Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Panitumumab for locally advanced head and neck squamouse-cell carcinoma (2015)
  • Author(s): Ishiki H, Iwase S, Shimada N, Chiba T, Imai K.
  • Journal Title: Lancet Oncology Volume: 16(4) Issue: 4 Pages: e156-e156
  • DOI: 10.1016/s1470-2045(15)70101-4
  • Peer Reviewed
• [Journal Article] 抗体医薬 (2015)
  • Author(s): 安井寛, 今井浩三
  • Journal Title: PHARMA TECH JAPAN Volume: 31(2) Pages: 94-101
  • Peer Reviewed
• [Journal Article] 抗体治療 (2015)
  • Author(s): 佐々木茂, 篠村恭久, 今井浩三
  • Journal Title: Drug Delivery System Volume: 30(1) Pages: 16-24
  • NAID: 130005066112
  • Peer Reviewed
• [Journal Article] Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: Results from the SMART database. (2014)
  • Author(s): Yamamoto M, Yajima H, Takahashi H, Yokoyama Y, Ishigami K, Shimizu Y, Tabeya T, Suzuki C, Naishiro Y, Takano KI, Yamashita K, Hashimoto M, Keira Y, Honda S, Abe T, Suzuki Y, Mukai M,Himi T, Hasegawa T, Imai K, Shinomura Y
  • Journal Title: Mod Rheumatol Volume: 27 Issue: 2 Pages: 1-6
  • DOI: 10.3109/14397595.2014.950036
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells cancel azoxymethane-induced tumor initiation (2014)
  • Author(s): Nasuno M, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nakagaki S, Watanabe S, Idogawa M, Yamashita K, Naishiro Y, Adachi Y, Suzuki H, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: Stem Cells Volume: 32 Issue: 4 Pages: 913-925
  • DOI: 10.1002/stem.1594
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions (2014)
  • Author(s): Ito M, Mitsuhashi K, Igarashi H, Nosho K, Yamamoto H
  • Journal Title: Int J Cancer Volume: (Epub ahead of print) Issue: 11 Pages: 2507-2515
  • DOI: 10.1002/ijc.28920
  • Peer Reviewed / Open Access
• [Journal Article] The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma (2014)
  • Author(s): Adachi Y, Ohashi H, Imsumran A, Yamamoto H, Matsunaga Y, Taniguchi H, Nosho K, Suzuki H, Sasaki Y, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Tumour Biol Volume: 35 Issue: 2 Pages: 973-985
  • DOI: 10.1007/s13277-013-1131-2
  • Peer Reviewed
• [Journal Article] Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer. (2014)
  • Author(s): Harada T, Yamamoto E, Yamano HO, Nojima M, Maruyama R, Kumegawa K, Ashida M, Yoshikawa K, Kimura T, Harada E, Takagi R, Tanaka Y, Aoki H, Nishizono M, Nakaoka M, Tuyada A, Niinuma T, Kai M, Shimoda K, Shinomura Y, Sugai T, Imai K, Suzuki H.
  • Journal Title: Cancer Prev Res (Phila) Volume: 7(10) Issue: 10 Pages: 1002-1010
  • DOI: 10.1158/1940-6207.capr-14-0162
  • Peer Reviewed
• [Journal Article] Overview and Future prospect of “Promotion plan for the platform of human resource development for cancer” (2014)
  • Author(s): Imai K.
  • Journal Title: Juntendo Medical Journal Volume: 60(3) Pages: 234-237
  • Peer Reviewed
• [Journal Article] IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions (2014)
  • Author(s): Naito T, Nosho K, Ito M, Igarashi H, Mitsuhashi K, Yoshii S, Aoki H, Nomura M, Sukawa Y, Yamamoto E, Adachi Y, Takahashi H, Hosokawa M, Fujita M, Takenouchi T, Maruyama R, Suzuki H, Baba Y, Imai K, Yamamoto H, Ogino S, Shinomura Y.
  • Journal Title: World J Gastroenteroｌ Volume: 20(29) Issue: 29 Pages: 10050-61
  • DOI: 10.3748/wjg.v20.i29.10050
  • Peer Reviewed
• [Journal Article] DNA synthesis inhibitors for the treatment of gastrointestinal cancer (2014)
  • Author(s): Yasui H, Tsurita G, Imai K
  • Journal Title: Expert Opin Pharmacother Volume: 15 Issue: 16 Pages: 2361-2372
  • DOI: 10.1517/14656566.2014.958074
  • Peer Reviewed
• [Journal Article] The Use of Bone Marrow Stromal Cells (Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells) for Alveolar Bone Tissue Engineering: Basic Science to Clinical Translation (2014)
  • Author(s): Kagami H, Agata H, Inoue M, Asahina I, Tojo A, Yamashita N, Imai K.
  • Journal Title: Tissue Engineering Part B: Reviews Volume: 20(3) Issue: 3 Pages: 229-232
  • DOI: 10.1089/ten.teb.2013.0578
  • Peer Reviewed
• [Journal Article] Association of microRNA-31-5p with clinical efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer (2014)
  • Author(s): Igarashi H, Kurihara H, Mitsuhashi K, Ito M, Okuda H, Kanno S, Naito T, Yoshii S, Takahashi H, Kusumi T, Hasegawa T, Sukawa Y, Adachi Y, Okita K, Hirata K, Imamura Y, Baba Y, Imai K, Suzuki H, Yamamoto H, Nosho K, Shinomura Y.
  • Journal Title: Annals of Surgical Oncology Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] 総説 橋渡し研究の展開と我が国の医療 (2014)
  • Author(s): 今井浩三
  • Journal Title: 東京都病院薬剤師会雑誌 Volume: 63(2) Pages: 5-8
  • Peer Reviewed
• [Journal Article] 人口動態に基づいた日本医療の未来予測－高齢多死社会の到来 (2014)
  • Author(s): 湯地晃一郎，井元清哉，山口類，宮野悟，上昌広，今井浩三
  • Journal Title: 南江堂臨床雑誌「外科」 Volume: 76(5) Pages: 457-463
  • Peer Reviewed
• [Journal Article] 大規模コホートを用いた大腸癌のノンコーディングＲＮＡ発現異常と生活習慣の分子疫学的解析 (2014)
  • Author(s): 能正勝彦，五十嵐央祥，伊藤美樹，三橋 慧，栗原弘義，菅野伸一，内藤崇史，須河安恭敬，松永康孝，足立 靖，野島正寛，今井浩三，丸山玲緒，鈴木 拓，山本博幸，篠村恭久.
  • Journal Title: 日本癌病態治療研究会誌 Volume: 20(1) Pages: 60-63
  • Peer Reviewed
• [Journal Article] がんエピゲノム異常を理解し、応用し、そして制御するために (2014)
  • Author(s): 鈴木拓，今井浩三
  • Journal Title: 実験医学 Volume: 32 Pages: 3024-3029
  • Peer Reviewed
• [Journal Article] High Level of Serum Soluble Interleukin-2 Receptor at Transplantation Predicts Poor Outcome of Allogeneic Stem Cell Transplantation for Adult T Cell Leukemia. (2014)
  • Author(s): Shigematsu A, Kobayashi N, Yasui H, Shindo M, Kakinoki Y, Koda K, Iyama S, Kuroda H, Tsutsumi Y, Imamura M, Teshima T.
  • Journal Title: Biol Blood Marrow Transplant Volume: － Issue: 6 Pages: 801-805
  • DOI: 10.1016/j.bbmt.2014.02.014
  • NAID: 120005455889
  • Peer Reviewed / Open Access
• [Journal Article] Epstein-Barr Virus-infected Cells in IgG4-related Lymphadenopathy With Comparison With Extranodal IgG4-related Disease. (2014)
  • Author(s): Takeuchi M, Sato Y, Yasui H, Ozawa H, Ohno K, Takata K, Gion Y, Orita Y, Tachibana T, Itoh T, Asano N, Nakamura S, Swerdlow SH, Yoshino T.
  • Journal Title: Am J Surg Pathol. Volume: － Issue: 7 Pages: 946-955
  • DOI: 10.1097/pas.0000000000000206
  • Peer Reviewed
• [Presentation] A new approach to the tumor suppression by an anti-erbB-2 trifunctional antibody. Poster Session (2016)
  • Author(s): Kato Y, Hirata H, Tsujisaki M, Matsune T, Adachi Y, Hinoda Y, Sasaki S, Imai K.
  • Organizer: 10th Joint Conference of the American Association for Cancer Research（AACR）and the Japanese Cancer Association（JCA）
  • Place of Presentation: Maui, Hawaii, U.S.A.
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] Serum biomarker screening for BRCTF1-targeted therapy. Poster Session (2016)
  • Author(s): Gunji H, Taniguchi H, Imai K, Kutomi G, Shima H, Miyagi Y, Zembutsu H.
  • Organizer: 10th Joint Conference of the American Association for Cancer Research（AACR）and the Japanese Cancer Association（JCA）
  • Place of Presentation: Maui, Hawaii, U.S.A.
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] 今後の余生を如何にして健康に暮らすか (2015)
  • Author(s): 今井浩三
  • Organizer: 東京いそ会15周年特別講演
  • Place of Presentation: 東京ＩＶＹホール（東京都渋谷区）
  • Year and Date: 2015-12-16
  • Invited
• [Presentation] がんの新規分子診断・治療を目指したトランスレーショナル研究の展開 （口頭） (2015)
  • Author(s): 今井浩三
  • Organizer: 日本癌学会・長與賞受賞記念講演
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-10
  • Invited
• [Presentation] がん治療認定医の到達点と今後 (2015)
  • Author(s): 今井浩三
  • Organizer: 朝日がん大賞受賞講演
  • Place of Presentation: 前橋市市民文化会館（群馬県前橋市）
  • Year and Date: 2015-09-03
  • Invited
• [Presentation] 東大医科研における橋渡し研究とその発展 (2014)
  • Author(s): 今井浩三
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] 我が国におけるトランスレーショナルリサーチの現状とこれからの展望 (2014)
  • Author(s): 今井浩三
  • Organizer: 第51回日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-11 – 2014-04-12
  • Invited
• [Book] 多発性骨髄腫に対する新たな抗体医薬開発の現状 血液内科 特集「新規ターゲットおよび医薬品による血液がん治療の新たな展開」 (2015)
  • Author(s): 安井寛, 石田禎夫
  • Total Pages: 284
  • Publisher: 科学評論社
• [Book] Multiple myeloma: risk factors, diagnosis and treatments.(The role of DNA methylation in the genetics and epigenetics of multiple myeloma.) (2014)
  • Author(s): Yasui H, Ishida T, Imai K.
  • Total Pages: 249
  • Publisher: Nova Science Publishers
• [Book] 核酸を用いるＤＤＳ治療の現状と将来 医薬ジャーナル 特集「Drug delivery system (DDS) の最新展望」 (2014)
  • Author(s): 安井寛
  • Total Pages: 200
  • Publisher: 医薬ジャーナル社
• [Patent(Industrial Property Rights)] 膜型ムチン様タンパク質の認識とその医療応用 (2016)
  • Inventor(s): 辻祥太郎、今井浩三、ほか
  • Industrial Property Rights Holder: 辻祥太郎、今井浩三、ほか
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-025689
  • Filing Date: 2016-02-15
• [Patent(Industrial Property Rights)] 結合体及びその使用 (2015)
  • Inventor(s): 辻祥太郎、今井浩三
  • Industrial Property Rights Holder: 辻祥太郎、今井浩三
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-03-05
• [Patent(Industrial Property Rights)] がん幹細胞分子マーカー (2014)
  • Inventor(s): 谷口博昭、今井浩三、片岡一則、西山伸宏、宮田完二郎、前田芳周
  • Industrial Property Rights Holder: 谷口博昭、今井浩三、片岡一則、西山伸宏、宮田完二郎、前田芳周
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-07-09