小島 研介(准教授)

Kensuke Kojima, M.D., Ph.D.

小島 研介(准教授)

Kensuke Kojima

 

MD Anderson Cancer Center

白血病科客員准教授併任

専門分野 血液内科学、臨床腫瘍学
専門領域

血液腫瘍学、がん分子標的治療

所属学会・資格

日本内科学会(認定内科医、総合内科専門医、指導医)、

日本血液学会(評議員、認定血液専門医、指導医)、

日本感染症学会(ICD制度協議会認定インフェクションコントロールドクター)、

日本癌学会、日本がん分子標的治療学会、米国血液学会(ASH)、米国癌研究学会(AACR)、

International Journal of Hematology Editorial Board

略歴

1991年 岡山大学医学部卒業

1995年 岡山大学医学部大学院課程修了(医学博士)

2007年 和歌山県立医科大学血液内科(講師)

2009年 MD Anderson Cancer Center白血病科分子血液治療科(准教授)

2013年 佐賀大学医学部血液・呼吸器・腫瘍内科(准教授)、

             MD Anderson Cancer Center白血病科分子血液治療科(客員准教授)

研究課題

造血器腫瘍に対する分子標的治療、

ことにp53シグナル制御と治療に関する研究は、950回以上、

他の研究論文で引用されています。

受賞・助成金

上原記念生命科学財団(2004年)、持田記念医学薬学振興財団(2004年)、

かなえ医薬振興財団(2004年、2007年)、ノバルティス科学振興財団(2007年)、

日本白血病基金(2008年、2011年)、安田記念医学財団(2008年)、

大阪癌研究会(2013年)、佐賀大学医学部学術国際交流基金(2013年、2014年)、

佐賀大学研究者海外派遣(2013年)、National Cancer Institute Leukemia SPORE(2013年)、

佐賀大学医学部医学部研究者育成支援(2014年)、高松宮妃癌研究基金(2014年)

業績

(1)原著(査読をうけて掲載された97本の論文のうち、20本を以下に掲載)

1.        Kojima K, Sakai I, Hasegawa A, Niiya H, Azuma T, Matsuo Y, Fujii N, Tanimoto M, Fujita S.  FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).  Leukemia. 2004;18:998-1005.

2.        Kojima K, Sakai I, Hasegawa A, Niiya H, Azuma T, Matsuo Y, Fujii N, Tanimoto M, Fujita S.  FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).  Leukemia. 2004;18:998-1005.

3.        Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T, Ruvolo V, Tsao T, Zeng Z, Vassilev LT, Andreeff M.  MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy.  Blood. 2005;106:3150-3159.

4.        Kojima K, Konopleva M, McQueen T, O'brien S, Plunkett W, Andreeff M. Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia.  Blood. 2006;108:993-1000.

5.        Kojima K, Konopleva M, Samudio IJ, Schober WD, Bornmann WG, Andreeff M. Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AML.  Cell Cycle. 2006;5:2778-2786.

6.        Kojima K, Konopleva M, Samudio IJ, Ruvolo V, Andreeff M. MEK inhibition enhances nuclear proapoptotic function of p53 in AML cells.  Cancer Res. 2007;67:3210-3219.

7.        Kojima K, Shimanuki M, Shikami M, Samudio IJ, Ruvolo V, Corn P, Hanaoka N, Konopleva M, Andreeff M, Nakakuma H. The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML. Leukemia. 2008;22:1728-1736.

8.        Kojima K, Konopleva M, Tsao T, Nakakuma H, Andreeff M. Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood. 2008;112:2886-2895.

9.        Kojima K, Shimanuki M, Shikami M, Andreeff M, Nakakuma H. Cyclin-dependent kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis in AML. Cancer Sci. 2009;100:1128-1136.

10.       Kojima K, Konopleva M, Tsao T, Andreeff M, Ishida H, Shiotsu Y, Jin L, Tabe Y, Nakakuma H. Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 via Mcl-1/Noxa axis. Leukemia. 2010;24:33-43.

11.       Kojima K, Burks JK, Arts J, Andreeff M. The novel tryptamine derivative JNJ-26854165 induces wild-type p53- and E2F1-mediated apoptosis in acute myeloid and lymphoid leukemias. Mol Cancer Ther. 2010;9:2545-2557.

12.       Kojima K, McQueen T, Chen Y, Jacamo R, Konopleva M, Shinojima N, Shpall E, Huang X, Andreeff M. p53 activation of mesenchymal stromal cells partially abrogates microenvironment-mediated resistance to FLT3 inhibition in AML through HIF-1a-mediated down-regulation of CXCL12. Blood. 2011;118:4431-4439.

13.       Kojima K, Duvvuri S, Ruvolo V, Samaniego F, Younes A, Andreeff M. Decreased sensitivity of 17p-deleted chronic lymphocytic leukemia cells to a small molecule BCL-2 antagonist ABT-737. Cancer. 2012;118:1023-1031.

14.       Sugihara E, Shimizu T, Kojima K, Onishi N, Kai K, Ishizawa J, Nagata K, Hashimoto N, Honda H, Kanno M, Miwa M, Okada S, Andreeff M, Saya H. Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor. Oncogene.2012;31:2849-2861.

15.       Kojima K, Kornblau SM, Ruvolo V, Dilip A, Duvvuri S, Davis RE, Zhang M, Wang Z, Coombes KR, Zhang N, Qiu YH, Burks JK, Kantarjian H, Shacham S, Kauffman M, Andreeff M. Prognostic impact and targeting of CRM1 in acute myeloid leukemia. Blood. 2013;16;121:4166-4174.

16.       Yoshimura M, Ishizawa J, Ruvolo V, Dilip A, Quintas-Cardama A, McDonnell TJ, Neelapu SS, Kwak LW, Shacham S, Kauffman M, Tabe Y, Yokoo M, Kimura S, Andreeff M, Kojima K. Induction of p53-mediated transcription and apoptosis by Exportin-1  (XPO1) inhibition in mantle cell lymphoma. Cancer Sci. 2014;105:795-801.

17.       Tabe Y*, Kojima K*, Yamamoto S, Sekihara K, Matsushita H, Davis RE, Wang Z, Ma W, Ishizawa J, Kazuno S, Kauffman M, Shacham S, Fujimura T, Ueno T, Miida T, Andreeff M (*equal contribution). Ribosomal biogenesis and translational flux inhibition by the selective inhibitor of nuclear export (SINE) XPO1 antagonist KPT-185. PLoS One. 2015;10(9):e0137210.

18.       Ishizawa J, Kojima K, McQueen T, Ruvolo V, Chachad D, Nogueras-Gonzalez GM, Huang X, Pierceall WE, Dettman EJ, Cardone MH, Shacham S, Konopleva M, Andreeff M. Mitochondrial profiling of acute myeloid leukemia in the assessment of response to apoptosis modulating drugs. PLoS One. 2015;10(9):e0138377.

19.       Andreeff M, Kelly KR, Yee KW, Assouline SE, Strair R, Popplewell L, Bowen D, Martinelli G, Drummond MW, Vyas P, Kirschbaum MH, Padmanabhan Iyer S, Ruvolo VR, Nogueras-Gonzalez GM, Huang X, Chen G, Graves B, Blotner S, Bridge P, Jukofsky L, Middleton S, Reckner M, Rueger R, Zhi J, Nichols G, Kojima K. Results of the Phase 1 Trial of RG7112, a Small-molecule MDM2 Antagonist in Leukemia. Clin Cancer Res, in press.

20.     Nishida Y, Maeda A, Chachad D, Ishizawa J, Yi Hua Q, Kornblau SM, Kimura S,Andreeff M, Kojima K. Preclinical activity of the novel BMI-1 inhibitor PTC-209 in acute myeloid leukemia: implications for leukemia therapy. Cancer Sci, in press.

 

 

(2)教科書・テキスト・総説

1.        Kojima K, Vassilev LT. Targeting p53 tumor suppressor for AML therapy. In: Michael A, editor. Targeted Therapy of Acute Myeloid Leukemia. Berlin: Springer, Germany; 2015. p.135-150.

2.        Ishizawa J, Kojima K, Hail N Jr, Tabe Y, Andreeff M. Expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (CRM1) protein. Pharmacol Ther. 2015;153:25-35

3.        Kojima K, Andreeff M. In: Tsimberidou AM, Anderson KC, Kurzrock R, editors. Targeted Therapy in Cancer. Oxford, England: 2015. In press.

 

連絡先
kkojima*cc.saga-u.ac.jp
kkojima*mdanderson.org
(*を@に置き換えてください)

English

Name Kensuke Kojima, M.D., Ph.D.
Present Title and Affiliation

Primary Appointment

Associate Professor

Division of Hematology, Respiratory Medicine and Oncology,

Department of Internal Medicine,

Faculty of Medicine, Saga University

 

Dual Appointment

Visiting Associate Professor

Section of Molecular Hematology and Therapy

Department of Leukemia

The University of Texas M. D. Anderson Cancer Center

Education

Sep. 1995  Ph.D.  Doctor of Medical Science/Hematology, 

Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan

 

 May 1991   M.D. Okayama University Medical School, Japan

Personal Statement

I have been one of the pioneers in bench-to-bedside translation of MDM2 inhibitors,
the entirely novel class of cancer therapeutics. My papers have been frequently
cited, leading to further work by many researchers. I first reported the therapeutic
potential of MDM2 inhibitors in hematologic malignancies in 2005, and identified
expression levels of MDM2 as biomarker for response in acute myeloid leukemia. The
paper has been cited in > 270 research papers, mainly in the field of cancer
therapeutics, suggesting a critical impact on translational research in oncology. My
papers on MDM2 inhibition and p53 have been cited over 950 times in other
publications. We conducted Phase I study of the first-in-class MDM2 inhibitor
RG7112. The study has established the safety, tolerability and proof-of-concept
(Clin Cancer Res, 2015). I have more than 25 years experience both in research and
clinical medicine, with over 100 peer-reviewed publications. I am specialized in
clinical hematology and oncology with experience in clinical stem cell
transplantation (85 allogeneic and 43 autologous stem cell transplantation cases) as
the primary physician. My research and clinical papers have been cited over 1,000
times in other publications.

Publications

Selected peer-reviewed publications (selected from 97 peer-reviewed publications)

 

1.      Kojima K, Kaneda K, Yoshida C, Dansako H, Fujii N, Yano T, Shinagawa K,
Yasukawa M, Fujita S, Tanimoto M.  A novel fusion variant of the MORF and CBP genes
detected in therapy-related myelodysplastic syndrome with t(10;16)(q22;p13).  Br J
Haematol 2003;120:271-273.
2.      Kojima K, Sakai I, Hasegawa A, Niiya H, Azuma T, Matsuo Y, Fujii N, Tanimoto
M, Fujita S.  FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell
line CNLBC1 derived from chronic neutrophilic leukemia in transformation with
t(4;11)(q21;q23).  Leukemia. 2004;18:998-1005.
3.      Kojima K, Konopleva M, Samudio IJ, Shikami M, Cabreira-Hansen M, McQueen T,
Ruvolo V, Tsao T, Zeng Z, Vassilev LT, Andreeff M.  MDM2 antagonists induce
p53-dependent apoptosis in AML: implications for leukemia therapy.  Blood.
2005;106:3150-3159.
4.      Kojima K, Konopleva M, McQueen T, O'brien S, Plunkett W, Andreeff M. Mdm2
inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and
transcription-independent mechanisms and may overcome Atm-mediated resistance to
fludarabine in chronic lymphocytic leukemia.  Blood. 2006;108:993-1000.
5.      Kojima K, Konopleva M, Samudio IJ, Schober WD, Bornmann WG, Andreeff M.
Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce
mitochondrial apoptosis in AML.  Cell Cycle. 2006;5:2778-2786.
6.      Kojima K, Konopleva M, Samudio IJ, Ruvolo V, Andreeff M. MEK inhibition
enhances nuclear proapoptotic function of p53 in AML cells.  Cancer Res.
2007;67:3210-3219.
7.      Kojima K, Shimanuki M, Shikami M, Samudio IJ, Ruvolo V, Corn P, Hanaoka N,
Konopleva M, Andreeff M, Nakakuma H. The dual PI3 kinase/mTOR inhibitor PI-103
prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial
apoptosis in p53 wild-type AML. Leukemia. 2008;22:1728-1736.
8.      Kojima K, Konopleva M, Tsao T, Nakakuma H, Andreeff M. Concomitant
inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent
postmitotic checkpoints and synergistically induces p53-mediated mitochondrial
apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood.
2008;112:2886-2895.
9.      Kojima K, Shimanuki M, Shikami M, Andreeff M, Nakakuma H. Cyclin-dependent
kinase 1 inhibitor RO-3306 enhances p53-mediated Bax activation and mitochondrial
apoptosis in AML. Cancer Sci. 2009;100:1128-1136.
10.     Kojima K, Konopleva M, Tsao T, Andreeff M, Ishida H, Shiotsu Y, Jin L, Tabe
Y, Nakakuma H. Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances
p53-mediated apoptosis in AML cells with activating mutations of FLT3 via Mcl-1/Noxa
axis. Leukemia. 2010;24:33-43.
11.     Kojima K, Burks JK, Arts J, Andreeff M. The novel tryptamine derivative
JNJ-26854165 induces wild-type p53- and E2F1-mediated apoptosis in acute myeloid and
lymphoid leukemias. Mol Cancer Ther. 2010;9:2545-2557.
12.     Kojima K, McQueen T, Chen Y, Jacamo R, Konopleva M, Shinojima N, Shpall E,
Huang X, Andreeff M. p53 activation of mesenchymal stromal cells partially abrogates
microenvironment-mediated resistance to FLT3 inhibition in AML through
HIF-1a-mediated down-regulation of CXCL12. Blood. 2011;118:4431-4439.
13.     Kojima K, Duvvuri S, Ruvolo V, Samaniego F, Younes A, Andreeff M. Decreased
sensitivity of 17p-deleted chronic lymphocytic leukemia cells to a small molecule
BCL-2 antagonist ABT-737. Cancer. 2012;118:1023-1031.
14.     Sugihara E, Shimizu T, Kojima K, Onishi N, Kai K, Ishizawa J, Nagata K,
Hashimoto N, Honda H, Kanno M, Miwa M, Okada S, Andreeff M, Saya H. Ink4a and Arf
are crucial factors in the determination of the cell of origin and the therapeutic
sensitivity of Myc-induced mouse lymphoid tumor. Oncogene.2012;31:2849-2861.
15.     Kojima K, Kornblau SM, Ruvolo V, Dilip A, Duvvuri S, Davis RE, Zhang M, Wang
Z, Coombes KR, Zhang N, Qiu YH, Burks JK, Kantarjian H, Shacham S, Kauffman M,
Andreeff M. Prognostic impact and targeting of CRM1 in acute myeloid leukemia.
Blood. 2013;16;121(20):4166-4174.
16.     Yoshimura M, Ishizawa J, Ruvolo V, Dilip A, Quintas-Cardama A, McDonnell TJ,
Neelapu SS, Kwak LW, Shacham S, Kauffman M, Tabe Y, Yokoo M, Kimura S, Andreeff M,
Kojima K. Induction of p53-mediated transcription and apoptosis by Exportin-1
(XPO1) inhibition in mantle cell lymphoma. Cancer Sci. 2014;105:795-801.
17.     Tabe Y*, Kojima K*, Yamamoto S, Sekihara K, Matsushita H, Davis RE, Wang Z,
Ma W, Ishizawa J, Kazuno S, Kauffman M, Shacham S, Fujimura T, Ueno T, Miida T,
Andreeff M (*equal contribution). Ribosomal biogenesis and translational flux
inhibition by the selective inhibitor of nuclear export (SINE) XPO1 antagonist
KPT-185. PLoS One. 2015;10(9):e0137210.
18.     Ishizawa J, Kojima K, McQueen T, Ruvolo V, Chachad D, Nogueras-Gonzalez GM,
Huang X, Pierceall WE, Dettman EJ, Cardone MH, Shacham S, Konopleva M, Andreeff M.
Mitochondrial profiling of acute myeloid leukemia in the assessment of response to
apoptosis modulating drugs. PLoS One. 2015;10(9):e0138377.
19.     Andreeff M, Kelly KR, Yee KW, Assouline SE, Strair R, Popplewell L, Bowen D,
Martinelli G, Drummond MW, Vyas P, Kirschbaum MH, Padmanabhan Iyer S, Ruvolo VR,
Nogueras-Gonzalez GM, Huang X, Chen G, Graves B, Blotner S, Bridge P, Jukofsky L,
Middleton S, Reckner M, Rueger R, Zhi J, Nichols G, Kojima K. Results of the Phase 1
Trial of RG7112, a Small-molecule MDM2 Antagonist in Leukemia. Clin Cancer Res, in
press.
20.     Nishida Y, Maeda A, Chachad D, Ishizawa J, Yi Hua Q, Kornblau SM, Kimura S,
Andreeff M, Kojima K. Preclinical activity of the novel BMI-1 inhibitor PTC-209 in
acute myeloid leukemia: implications for leukemia therapy. Cancer Sci, in press.

最終更新日:2015年12月8日

(C)佐賀大学医学部附属病院血液・呼吸器・腫瘍内科