Influence of bone related cells on leukemic cells

• Project/Area Number: 21591201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Saga University
• Principal Investigator: KIMURA Shinya 佐賀大学, 医学部, 教授 (80359794)
• Co-Investigator(Kenkyū-buntansha): FUKUSHIMA Noriyasu 佐賀大学, 医学部, 講師 (20346894) ; HISATOMI Takashi 佐賀大学, 医学部, 助教 (10398125)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白血病 / 骨 / ニッチ / 骨芽細胞 / 破骨細胞 / 慢性骨髄性白血病 / ナノチャンバー / ABLチロシンキナーゼ

Research Abstract

We have established co-culture system with osteoblasts, osteoclasts, bones and leukemic cells to investigate the influence of bone related cells on leukemic cells. With this system, we found that osteoblasts stimulated the proliferation of leukemic cells, and leukemic cells which were introduced to quiescent phase by TGF-・that was released from bone via osteoclasts acquired the resistance to ABL tyrosine kinase inhibitors.

Research Products

• [Journal Article] Co-existence of MET FISH positive with EGFR mutations causes poor prognosis in lung adenocarcinoma patients (2012)
  • Author(s): Tanaka A, Sueoka-Aragane N, Nakamura T, Takeda Y, Mitsuoka M, Yamasaki F, Hayashi S, Sueoka E, Kimura S.
  • Journal Title: Lung Cancer Volume: 75 Pages: 89-94
• [Journal Article] Antitumor effect of sunitinib against skeletal metastatic renal cell carcinoma through inhibition of osteoclast function (2012)
  • Author(s): Maita S, Yuasa T, Tsuchiya N, Mitobe Y, Horikawa S, Hatake K, Fukui I, Kimura S, Maekawa T, Habuchi T.
  • Journal Title: Int J Cancer Volume: 130 Pages: 677-684
• [Journal Article] NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIa and DNA-dependent protein kinase (2011)
  • Author(s): Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kunimasa A, Okamoto K, Kimura S, Sueoka E.
  • Journal Title: Blood Volume: 117 Pages: 3575-3584
• [Journal Article] Clinical presentation and outcome in patients of over 75 years old with malignant lymphoma (2011)
  • Author(s): Fukushima N, Itamura H, Urata C, Tanaka M, Hisatomi T, Kunota Y, Sueoka E, Kimura S.
  • Journal Title: Int J Clin Med Volume: 2 Pages: 246-253
• [Journal Article] Rapid automated detection of ABL kinase domain mutations in imatinib-resistant patients (2011)
  • Author(s): Tanaka R, Kimura S, Ashihara E, Yoshimura M, Takahashi N, Wakita H, Itoh K, Nishiwaki K, Suzuki K, Nagao R, Yao H, Hayashi Y, Satake S, Hirai H, Sawada K, Ottmann OG, Melo JV, Maekawa T.
  • Journal Title: Cancer Lett Volume: 312 Pages: 228-234
• [Journal Article] Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia adaptation by AV65, a novel Wnt/β-catenin signaling inhibitor (2011)
  • Author(s): Nagao R, Ashihara E, Kimura S, Strovel JW, Yao H, Takeuchi M, Tanaka R, Hayashi Y, Hirai H, Padia J, Strand K, Maekawa T.
  • Journal Title: Cancer Lett Volume: 312 Pages: 91-100
  • NAID: 120003437105
• [Journal Article] Lenalidomide in combination with dexamethasone induced rhabdomyolysis in a multiple myeloma patient treated with pravastatin (2011)
  • Author(s): Urata C, Yoshimura M, Itamura H, Hisatomi T, Kubota Y, Fukushima N, Sueoka E, Kimura S.
  • Journal Title: Int J Hematol Volume: 94 Pages: 216-217
  • NAID: 10029537258
• [Journal Article] A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA (2011)
  • Author(s): Nakamura T, Sueoka-Aragane N, Iwanaga K, Sato A, Komiya K, Abe T, Ureshino N, Hayashi S, Hosomi T, Hirai M, Sueoka E, Kimura S.
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 1639-1648
• [Journal Article] Fully Integrated, Automated and Rapid Detection System for KRAS Mutations (2011)
  • Author(s): Ureshino N, Sueoka-Aragane N, Nakamura T, Sato A, Komiya K, Iwanaga K, Mitsuoka M, Takeda Y, Hayashi S, Sueoka E, Kimura S.
  • Journal Title: Oncol Rep Volume: 26 Pages: 609-613
• [Journal Article] Identification of a small molecule inhibitor of DNA topoisomerase II by proteomic profiling (2011)
  • Author(s): Kawatani M, Takayama H, Muroi M, Kimura S, Maekawa T. Osada H.
  • Journal Title: Chem Biol Volume: 18 Pages: 743-751
• [Journal Article] Single-step, label-free quantification of antibody in human serum for clinical applications based on localized surface plasmon resonance (2011)
  • Author(s): Yamamichi J, Ojima T, Yurugi K, Iida M, Imamura T, Ashihara E, Kimura S, Maekawa T.
  • Journal Title: Nanomedicine Volume: 7 Pages: 889-895
• [Journal Article] Combined effects of novel heat shock protein 90 inhibitor NVP-AUY922 and nilotinib in a random mutagenesis screen (2011)
  • Author(s): Tauchi T, Okabe S, Kimura S, Maekawa T, Ohyashiki K.
  • Journal Title: Oncogene Volume: 30 Pages: 2789-2797
• [Journal Article] Rakicidin A effectively induces apoptosis in hypoxia adapted Bcr-Abl positive leukemic cells (2011)
  • Author(s): Takeuchi M, Ashihara E, Yamazaki Y, Kimura S, Nakagawa Y, Tanaka R, Yao H, Nagao R, Hayashi Y, Hirai H, Maekawa T.
  • Journal Title: Cencer Sci Volume: 102 Pages: 591-596
  • NAID: 10029291246
• [Journal Article] Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma (2011)
  • Author(s): Jin L, Tabe Y, Kimura S, Zhou Y, Kuroda J, Asou H, Inaba T, Konopleva M, Andreeff M, Miida T.
  • Journal Title: Brit J Cance Volume: 104 Pages: 91-100
• [Journal Article] Galectin-9 ameliorates acute GVH disease through the induction of T-cell apoptosis (2011)
  • Author(s): Sakai K, Kawata E, Ashihara E, Nakagawa Y, Yamauchi A, Yao H, Nagao R, Tanaka R, Yokota A, Takeuchi M, Hirai H, Kimura S, Hirashima M, Yoshimura N, Maekawa T.
  • Journal Title: Eur J Immunol Volume: 41 Pages: 67-75
• [Journal Article] A Fully Integrated and Automated Detection System for Single Nucleotide Polymorphisms of UGT1A1 and CYP2C19 (2011)
  • Author(s): Ureshino N, Aragane N, Nakamura T, Ide M, Mochinaga S, Fukushima N, Hayashi S, Sueoka E, Kimura S.
  • Journal Title: Oncol Res Volume: 19 Pages: 111-114
• [Journal Article] Targeting ATF-3 by Galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia (2011)
  • Author(s): Kuroda J, Kobayashi T, Nagoshi H, Yamamoto M, Sasaki N, Taki T, Kimura S, Yamauchi A, Hirashima M, Taniwaki M.
  • Journal Title: Mol Cancer Res Volume: 8 Pages: 994-1001
• [Journal Article] Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia adaptation by AV65, a novel Wnt/ss-catenin signaling inhibitor (2011)
  • Author(s): Nagao R
  • Journal Title: Cancer Letter Volume: 312 Pages: 91-100
  • Peer Reviewed
• [Journal Article] A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA (2011)
  • Author(s): Nakamura T
  • Journal Title: Journal of Thoracic Oncology Volume: 6 Pages: 1639-1648
  • Peer Reviewed
• [Journal Article] Noninvasive tracking of donor cell homing by near-infrared fluorescence imaging shortly after bone marrow transplantation (2010)
  • Author(s): Ushiki T, Kizaki-Kondoh S, Ashihara E, TanakaS, Nasuko M, Hirai H, Kimura S, Aizawa Y, Maekawa T, Hiraoka M.
  • Journal Title: PLoS One Volume: 5
  • NAID: 120002511315
• [Journal Article] Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type is associated with chronic inflammatory process (2010)
  • Author(s): Tanaka M, Fukushima N, Yamasaki F, Ohshima K, Sueoka E, Kimura S.
  • Journal Title: Open J Hemato Volume: 1 Pages: 1-5
• [Journal Article] Combined effects of bisphosphonate and radiation on osteosarcoma cells (2010)
  • Author(s): Ryu K, Murata H, Koto K, Horie N, Matsui T, Nishigaki Y, Sakabe T, Takeshita H, Itoi M, Kimura S, Ashihara E, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Anticancer Res Volume: 30 Pages: 2713-2720
• [Journal Article] Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents (2010)
  • Author(s): Koto K, Murata H, Kimura S, Horie N, Matsui T, Nishigaki Y, Ryu K, Sakabe T, Ashihara E, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Oncol Rep Volume: 24 Pages: 233-239
• [Journal Article] Activity of the multi-targeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL positive leukemic cells (2010)
  • Author(s): Tanaka R, Squires MS, Kimura S, Yokota A, Nagao R, Yamauchi T, Takeuchi M, Yao H, Reule M, Smyth T, Lyon JF, Thompson NT, Ashihara E, Ottmann OG, Maekawa T.
  • Journal Title: Blood Volume: 116 Pages: 2089-2095
• [Journal Article] Uncommon case of chronic myeloid leukemia with multiple myeloma (2010)
  • Author(s): Ide M, Kuwahara N, Matsuishi E, Kimura S, Gondo H.
  • Journal Title: Int J Hemmatol Volume: 91 Pages: 699-704
  • NAID: 10026402271
• [Journal Article] A combination of a DNA-chimera 1 siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro (2010)
  • Author(s): Kawata E, Ahihara E, Nakagawa Y, Kiuchi T, Ogura M, Yao H, Sakai K, Tanaka R, Nagao R, Yokota A, Takeuchi M, Kimura S, Hirai H, Maekawa T.
  • Journal Title: Cancer Lett Volume: 294 Pages: 245-253
• [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in hypoxic environment (2010)
  • Author(s): Takeuchi M, Kimura S, Kuroda J, Ashihara E, Kawatani M, Osada H, Umezawa K, Yasui E, Imoto M, Tsuruo T, Yokota A, Tanaka R, Nagao R, Nakahara T, Fujiyama Y, Maekawa T.
  • Journal Title: Cell Death Diff Volume: 17 Pages: 1211-1220
• [Journal Article] Gangrenous cheilitis associated with all-trans retinoic acid therapy for acute promyelocyt c leukemia (2010)
  • Author(s): Tanaka M, Fukushima N, Urata C, Yokoo M, Ide M, Hisatomi T, Tomimasu R, Sueoka E, Kimura S.
  • Journal Title: Int J Hematol Volume: 91 Pages: 132-135
• [Journal Article] Blockade of the ERK or PI3K-Akt signaling pathway enhances the cytotoxicity of histone deacetylase inhibitors in tumor cells resistant to gefitinib or imatinib (2010)
  • Author(s): Ozaki K, Kosugi M, Baba N, Fujio K, Sakamoto T, Kimura S, Tanimura S, Kohno M.
  • Journal Title: Biochem Biophys Res COMMUll Volume: 391 Pages: 1610-1615
  • NAID: 120006983583
• [Journal Article] Phase I study of INNO-406, a dual Abl/ Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias post-imatinib resistance or intolerance (2010)
  • Author(s): Kantarjian H, le Coutre P, Cortes J, Pinilla-lbarz J, Nagler A, Hochhaus A, Kimura S, Ottmann 0.
  • Journal Title: Cancer Volume: 16 Pages: 2665-2672
• [Journal Article] Osteoclasts are involved in the maintenance of dormant leukemic cells (2010)
  • Author(s): Yokota A, Kimura S, Tanaka R, Takeuchi M, Yao H, Sakai K, Nagao R, Kuroda J, Kamitsuji Y, Kawata E, Ashihara E, Maekawa T.
  • Journal Title: Leuk Res Volume: 34 Pages: 793-799
• [Journal Article] Isolation of mesenchymal stem cells from bone marrow in the closed system using a new device made by non-woven fabrics (2010)
  • Author(s): Ito K, Aoyama T, Fukiage K, Otsuka S, Furu M, Jin Y, Nasu A, Ueda M, Kasai Y, Ashihara E, Kimura S, Maekawa T, Kobayashi A, Yoshida S, Otsuka T, Nakamura T, Toguchida J.
  • Journal Title: Tissue Eng Part C Methods Volume: 16 Pages: 81-91
• [Journal Article] Loxoprofen Sodium, a Non-Selective NSAID, Reduces Atherosclerosis in Mice by Reducing Inflammation (2010)
  • Author(s): Hamaguchi M, Seno T, Yamamoto A, Kohno M, Kadoya M, Ishino H, Ashihara E, Kimura S, Tsubakimoto Y, Takata H, Yoshikawa T, Maekawa T, Kawahito Y.
  • Journal Title: JClin Biochem Nutr Volume: 47 Pages: 138-147
  • NAID: 130004879204
• [Journal Article] Glyoxalase-I is a novel target against Bcr-Abl^+ leukemic cells acquiring stem-like characteristics in hypoxic environment (2010)
  • Author(s): Takeuchi M
  • Journal Title: Cell Death and Differentiation Volume: 17 Pages: 1211-1220
  • Peer Reviewed
• [Journal Article] Combined effects of bisphosphonate and radiation on osteosarcoma cells (2010)
  • Author(s): Ryu K
  • Journal Title: Anticancer Research Volume: 30 Pages: 2713-2720
  • Peer Reviewed
• [Journal Article] Osteoclasts are involved in the maintenance of dormant leukemic cells (2010)
  • Author(s): Yokota A
  • Journal Title: Leukemia Research (末定(in press))
  • Peer Reviewed
• [Journal Article] β-catenin siRNA successfully suppressed progression of multiple myeloma in a mouse model (2009)
  • Author(s): Ashihara E, Kawata E, Nakagawa Y, Shimazaski C, Kuroda J, Tanaka R, Yokota A, Murotani Y, Takeuchi M, Kamitsuji Y, Inaba T, Taniwaki T, Kimura S, Maekawa T.
  • Journal Title: Clin Cancer Res Volume: 15 Pages: 2731-2738
• [Journal Article] Wada. Monitoring with a non-invasive bioluminescent in vivo imaging system of successful treatment of disseminated pleural tumors by intra-pleural docetaxel administration (2009)
  • Author(s): Matsumoto S, Tanaka F, Sato K, Kimura S, Maekawa T, Hasegawa S
  • Journal Title: Lung Cancer Volume: 66 Pages: 75-79
• [Journal Article] Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model (2009)
  • Author(s): Koto K, Horie N, Kimura S, Murata H, Sakabe T, Matsui T, Watanabe M, Adachi S, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Cancer Lett Volume: 274 Pages: 271-278
• [Journal Article] Intravesical administration of・・T cells successfully prevents the growth of bladder cancer in the murine model (2009)
  • Author(s): Yuasa T, Sato K, Ashihara E, Takeuchi M, Maita S, Tsuchiya N, Habuchi T, Maekawa T, Kimura S.
  • Journal Title: Cancer Immunol Immun Volume: 58 Pages: 493-502
• [Journal Article] β-catenin siRNA successfully suppressed progression of multiple myeloma in a mouse model. (2009)
  • Author(s): Ashihara E
  • Journal Title: Clinical Cancer Research 15 Pages: 2731-2738
  • Peer Reviewed
• [Journal Article] Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model. (2009)
  • Author(s): Koto K
  • Journal Title: Cancer Letters 274 Pages: 493-502
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 木村晋也
  • Journal Title: 造血器腫瘍アトラス(日本医事新報社) Pages: 476-480
• [Presentation] Wnt/ b-catenin signaling inhibitors in combination with TKI (2011)
  • Author(s): Kimura S.
  • Organizer: 13th Intrenational Conference on Chronic Myeloid Leukemia : Biology and Therapy
  • Place of Presentation: Estoril, Portugal
  • Year and Date: 2011-09-23
• [Presentation] 新規HSP90阻害剤の発見と創薬展開 (2011)
  • Author(s): 木村晋也
  • Organizer: 化学療法基盤支援第2回シンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 2011-02-22
• [Presentation] ABL tyrosine kinase inhibitors (2010)
  • Author(s): Kimura S.
  • Organizer: The15th JFCR-International Symposium on Cancer Chemotherapy
  • Place of Presentation: 東京都
  • Year and Date: 2010-12-02
• [Presentation] ABL tyrosine kinase inhibitors (2010)
  • Author(s): Kimura S
  • Organizer: The 15th JFCR-International Symposium on Cancer Chemotherapy
  • Place of Presentation: 東京都
  • Year and Date: 2010-12-02
• [Presentation] ABL阻害剤の新展開 (2009)
  • Author(s): 木村晋也
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2009-10-23
• [Book] 秒進分歩する癌研究の最前線.実験医学増刊 (2011)
  • Author(s): 木村晋也
  • Total Pages: 8
  • Publisher: 羊土社
• [Book] がん骨転移治療 (2011)
  • Author(s): 福島伯泰、木村晋也
  • Total Pages: 7
  • Publisher: 先端医学社
• [Book] がん骨転移治療(分担執筆) (2011)
  • Author(s): 福島伯泰、木村晋也
  • Total Pages: 7
  • Publisher: 先端医学社
• [Book] 秒進分歩する癌研究の最前線.実験医学増刊(分担執筆) (2011)
  • Author(s): 木村晋也
  • Total Pages: 8
  • Publisher: 羊土社
• [Book] 造血腫瘍アトラス (2009)
  • Author(s): 木村晋也
  • Total Pages: 5
  • Publisher: 日本医事新報社
• [Remarks]
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/index.html
• [Remarks]
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/index.html
• [Remarks]
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/index.html
• [Remarks]
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/index.html