Research Achievements｜Chiba University Hospital Center for Advanced Medicine

Awards

December, 2015	Our adipocyte-based gene therapy group received the Chiba University President's Award at the Chiba Area Open Forum 2015.
December, 2012	Dr. Masataka Yokoyama received the Young Investigator Award (YIA) from the Japanese Vascular Biology and Medicine Organization.
November, 2011	Dr. Masataka Yokoyama received the Young Investigator Award (YIA) from The Society of Cardiovascular Endocrinology and Metabolism.
November, 2011	Dr. Kaoru Tateno received the Young Investigator Imura Award.
November, 2011	Dr. Ippei Shimizu received the Manpei Suzuki Diabetes Foundation fellowship for study abroad.
October, 2011	Dr. Tohru Minamino received the annual Medical Research Incentive Award from the Japan Medical Association.
April, 2011	Dr. Shinichiro Motohashi received the 3rd Annual Chiba Medical Association Award and the 16th Inohana Alumni Association Award.

Publications

Immunotherapy

Aoki T, Hino M, Koh K, Kyushiki M, Kishimoto H, Arakawa Y, Hanada R, Kawashima H, Kurihara J, Shimojo N, and Motohashi S. Low Frequency of Programmed Death Ligand 1 Expression in Pediatric Cancers. Pediatr. Blood Cancer 2016; 63(8):1461-4.
Hosokawa H, Tanaka T, Endo Y, Kato M, Shinoda K, Suzuki A, Motohashi S, Matsumoto M, Nakayama K I, and Nakayama T. Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells. Nat. Commun. 2016; 7:11289.
Mise N, Takami M, Suzuki A, Kamata T, Harada K, Hishiki T, Saito T, Terui K, Mitsunaga T, Nakata M, Ikeuchi T, Nakayama T, Yoshida H, and Motohashi S. Antibody-dependent cellular cytotoxicity toward neuroblastoma enhanced by activated invariant NKT cells. Cancer Sci. 2016; 107(3):233-241.
Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, and Okamoto Y. Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer. Cancer Sci. 2016; 107(3):207-216.
Hosokawa H, Kato M, Tohyama H, Tamaki Y, Endo Y, Kimura M Y., Tumes D J, Motohashi S, Matsumoto M, Nakayama K I, Tanaka T, and Nakayama T. Methylation of Gata3 at Arg261 regulates transactivation of the Il5 gene in T helper 2 cells. J. Biol. Chem. 2015; 290(21): 13095-13103.
Frigault M J, Lee J, Basil M, Carpenito C, Motohashi S, Scholler J, Kawalekar O U, Guedan S, McGettigan S, Posey A Jr, Ang S, Cooper L J, Platt J M, Johnson F B, Paulos C M, Zhao Y, Kalos M, Milone M C, and June C H. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells. Cancer Immunol. Res. 2015; 3(4): 356-367.
Endo Y, Hirahara K, Iinuma T, Shinoda K, Tumes D J, Asou H K, Matsugae N, Obata-Ninomiya K, Yamamoto H, Motohashi S, Oboki K, Nakae S, Saito H, Okamoto Y, and Nakayama T. The Interleukin-33-p38 Kinase Axis Confers Memory T Helper 2 Cell Pathogenicity in the Airway. Immunity 2015; 42(2): 294-308.
Sun Y, Furihata T, Ishii S, Nagai M, Harada M, Shimozato O, Kamijo T, Motohashi S, Yoshino I, Kamiichi A, Kobayashi K, and Chiba K. Unique expression features of cancer-type organic anion transporting polypeptide 1B3 mRNA expression in human colon and lung cancers: potential biomarker implications. Clin. Transl. Med. 2014; 3: 37.
Watanabe Y, Onodera A, Kanai U, Ichikawa T, Obata-Ninomiya K, Wada T, Kiuchi M, Iwamura C, Tumes D J, Shinoda K, Yagi R, Motohashi S, Hirahara K, and Nakayama T. Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. Proc. Natl. Acad. Sci. USA 2014; 111(35): 12829-12834.
Hamasaki S, Okamoto Y, Yonekura S, Okuma Y, Sakurai T, Iinuma T, Yamamoto H, Sakurai D, Horiguchi S, Yokota M.: Characteristics of the Chiba Environmental Challenge Chamber. Allergol Int.2014；63（1）41-50
Fujii S, Shimizu K, Okamoto Y, Kunii N, Nakayama T, Motohashi S, and Taniguchi M. NKT cells as an ideal anti-tumor immunotherapeutic. Front. Immunol. 2013;4:409
Hosokawa H, Tanaka T, Kato M, Shinoda K, Tohyama H, Hanazawa A, Tamaki Y, Hirahara K, Yagi R, Sakikawa I, Morita A, Nagira M, Poyurovsky, V. M, Suzuki Y, Motohashi S, and Nakayama T. Gata3/Ruvbl2 complex regulates T helper 2 cell proliferation via repression of Cdkn2c expression. Proc. Natl. Acad. Sci. USA. 2013;110(46):18626-18631.
Tumes D.J, Onodera A, Suzuki A, Shinoda K, Endo Y, Iwamura C, Hosokawa H, Koseki H, Tokoyoda K, Suzuki Y, Motohashi S, and Nakayama T. The polycomb protein Ezh2 regulates differentiation and plasticity of CD4+ T helper type-1 and type-2 cells. Immunity. 2013;39(5):819-832.
Okamoto Y, Ohta N, Okano M, Kamijo A, Gotoh M, Suzuki M, Takeno S, Terada T, Hanazawa T, Horiguchi S, Honda K, Matsune S, Yamada T, Yuta A, Nakayama T, Fujieda S. Guiding principles of subcutaneous immunotherapy for allergic rhinitis in Japan. Auris Nasus Larynx.2013；41:1-5.
Yonekura S, Okamoto Y, Yamamoto H, Sakurai T, Iinuma T, Sakurai D, Hanazawa T：Randomized double-blind study of prophylactic treatment with an antihistamine for seasonal allergic rhinitis. Int Arch Allergy Immunol 2013;162:71-8
Higaki T, Okano M, Kariya S, Fujiwara T, Haruna T, Hirai H, Murai A, Gotoh M, Okubo K, Yonekura S, Okamoto Y, Nishizaki K.:Determining minimal clinically important differences in Japanese cedar/cypress pollinosis patients.Allergol Int. 2013;62:487-93
Kinoshita T, Nohata N, Hanazawa T, Kikkawa N, Yamamoto N, Yoshino H, Itesako T, Enokida H, Nakagawa M, Okamoto Y, Seki N. Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by targeting laminin-integrin signalling in head and neck squamous cell carcinoma. Br J Cancer. 2013 ;109:2636-45
Nohata N, Hanazawa T, Kinoshita T, Inamine A, Kikkawa N, Itesako T, Yoshino H, Enokida H, Nakagawa M, Okamoto Y, Seki N. Tumour-suppressive microRNA-874 contributes to cell proliferation through targeting of histone deacetylase 1 in head and neck squamous cell carcinoma. Br J Cancer. 2013 ;108:1648-58.
Kunii N, Zhao Y, Jiang S, Liu X, Scholler J, Balagopalan L, Samelson LE, Milone MC, and June CH. Enhanced function of redirected human T cells expressing linker for activation of T cells that is resistant to ubiquitylation. Hum Gene Ther. 2013 24(1):27-37
Nagato K, Motohashi S, Ishibashi F, Okita K, Yamasaki K, Moriya Y, Hoshino H, Yoshida S, Hanaoka H, Fuji S, Taniguchi M, Yoshino I, and Nakayama T. Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-Galactosylceramide-pulsed antigen presenting cells. J Clin.Immunol. 2012; 32: 1071-1081.
Iwamura C, Shinoda K, Endo Y, Watanabe Y, Tumes D.J, Motohashi S, Kawahara K, Kinjo Y, Nakayama T. Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. Proc Natl Acad Sci U S A. 2012; 109(42): 16992-16997
Kuwahara M, Yamashita M, Shinoda K, Tofukuji S, Onodera A, Shinnakasu R, Motohashi S, Hosokawa H, Tumes D, Iwamura C, Lefebvre V, and Nakayama T. The transcription factor Sox4 is a downstream target of TGF-β signaling and suppresses GATA3-induced TH2 cell differentiation. Nat. Immunol. 2012; 13(8): 778-786
Nagai M, Furihata T, Matsumoto S, Ishii S, Motohashi S, Yoshino I, Ugajin M, Miyajima A, Matsumoto S, and Chiba K. Identification of a new organic anion transporting polypeptide 1B3 mRNA isoform primarily expressed in human cancerous tissues and cells. Biochem Biophys Res Commun. 2012; 418(4): 818-823
Yamashita J, Iwamura C, Mitsumori K, Hosokawa H, Sasaki T, Takahashi M, Tanaka H, Kaneko K, Hanazawa A, Watanabe Y, Shinoda K, Tumes D, Motohashi S, Nakayama T. Murine Schnurri-2 controls Natural Killer cell function and lymphoma development. Leuk. Lymphoma. 2012; 53(3): 479-486
Kitajima M, Ito T, Tumes DJ, Endo Y, Onodera A, Hashimoto K, Motohashi S, Yamashita M, Nishimura T, Ziegler SF, Nakayama T. Memory type 2 helper T cells induce long-lasting antitumor immunity by activating natural killer cells. Cancer Res. 2011; 71(14): 4790-4798.
Motohashi S, Okamoto Y, and Nakayama T. Clinical trials of invariant Natural Killer T cell-based immunotherapy for cancer. In the book "Natural killer T cells. : setting the balance in the regulation of tumor immunity". Edited by Berzofsky and Terabe. 2011; 185-198.
Kurosaki M, Horiguchi S, Yamasaki K, Uchida Y, Motohashi S, Nakayama T, Sugimoto A, and Okamoto Y. Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer. Cancer Immunol. Immunother. 2011; 60(2): 207-215.
Motohashi S, Okamoto Y, Yoshino I, and Nakayama T. Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer. Clin Immunol. 2011; 140(2):167-176.
Yamasaki K, Horiguchi S, Kurosaki M, Kunii N, Nagato K, Hanaoka H, Shimizu N, Ueno N, Yamamoto S, Taniguchi M, Motohashi S, Nakayama T, and Okamoto Y. Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy. Clin. Immunol. 2011; 138(3): 255-265.
Okita K, Motohashi S, Shinnakasu R, Nagato K, Yamasaki K, Sato Y, Kitamura H, Hijikata A, Yamashita M, Shimizu K, Fujii S, Ohara O, Taniguchi M, Sakaida I, and Nakayama T. A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy. Cancer Sci. 2010; 101 (11): 2333-2340.
Ishii Y, Motohashi S, Shimizu K, Nakayama T, Taniguchi M, and Fujii S. Application of NKT cells in immunotherapy. Curr Immunol Rev. 2010; 6: 109-115.
Fujii S, Motohashi S, Shimizu K, Nakayama T, Yoshiga Y, and Taniguchi M. Adjuvant activity mediated by iNKT cells. Semin Immunol. 2010; 22 (2): 97-102.
Suzuki M, Wada H, Yoshino M, Tian L, Shigematsu H, Suzuki H, Alaa M, Tamura H, Fujiwara T, Nagato K, Motohashi S, Moriya Y, Hoshino H, Yoshida S, Shibuya K, Hiroshima K, Nakatani Y, and Yoshino I. Molecular Characterization of Chronic Obstructive Pulmonary Disease-Related Non-Small Cell Lung Cancer Through Aberrant Methylation and Alterations of EGFR Signaling. Ann Surg Oncol. 2010; 17 (3): 878-888.
Alaa M, Suzuki M, Yoshino M, Tian L, Suzuki H, Nagato K, Fujiwara T, Wada H, Moriya Y, Hoshino H, Motohashi S, Yoshida S, Shibuya K, Hiroshima K, Nakatani Y. Abdrabou A, Elkholy M, Mahfouz T, and Yoshino I. Prostaglandin E2 receptor 2 overexpression in squamous cell carcinoma of the lung correlates with p16INK4A methylation and an unfavorable prognosis. Int J Oncol. 2009; 34 (3): 805-812.
Kitajima M, Iwamura C, Miki H T, Shinoda K, Endo Y, Watanabe Y, Shinnakasu R, Hosokawa H, Hashimoto K, Motohashi S, Koseki H, Ohara O, Yamashita M, and Nakayama T. Enhanced Th2 cell differentiation and allergen-induced airway inflammation in Zfp35-deficient mice. J Immunol. 2009; 183 (8): 5388-5396.
Kunii N, Horiguchi S, Motohashi S, Yamamoto H, Ueno N, Yamamoto S, Sakurai D, Taniguchi M, Nakayama T, and Okamoto Y. Combination therapy of in vitro-expanded natural killer T cells and α-galactosylceramide-pulsed antigen-presenting cells in patients with recurrent head and neck carcinoma. Cancer Sci. 2009; 100 (6): 1092-1098.
Miki H T, Hasegawa A, Iwamura C, Shinoda K, Tofukuji S, Watanabe Y, Hosokawa H, Motohashi S, Hashimoto K, Shirai M, Yamashita M, and Nakayama T. CD69 controls the pathogenesis of allergic airway inflammation. J Immunol. 2009; 183 (12): 8203-8215.
Motohashi S, Nagato K, Kunii N, Yamamoto H, Yamasaki K, Okita K, Hanaoka H, Shimizu N, Suzuki M, Yoshino I, Taniguchi M, Fujisawa T, and Nakayama T. A phase I-II study of α-Galactosylceramide(KRN7000)-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrent non-small cell lung cancer. J Immunol. 2009; 182 (4): 2492-2501.
Motohashi S, and Nakayama T. Invariant natural killer T cell-based immunotherapy for cancer. Immunotherapy. 2009; 1 (1): 73-82.
Motohashi S, and Nakayama T. Natural killer T cell-mediated immunotherapy for malignant diseases. Frontiers in Bioscience. 2009; 1(1): 108-116.
Ito T, Hasegawa A, Hosokawa H, Yamashita M, Motohashi S, Naka T, Okamoto Y, Fujita Y, Ishii Y, Taniguchi M, Yano I, and Nakayama T. Human Th1 differentiation induced by lipoarabinomannan / lipomannon from Mycobacterium bovis BCG Tokyo-172. International Immunology. 2008; 20 (7): 849-860.
Shinnakasu R, Yamashita M, Kuwahara M, Hosokawa H, Hasegawa A, Motohashi S, and Nakayama T. Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation. J Biol Chem. 2008; 283(42): 28216-28225.
Suzuki M, Mohamed S, Nakajima T, Kubo R, Tian L, Fujiwara T, Suzuki H, Nagato K, Chiyo M, Motohashi S, Yasufuku K, Iyoda A, Yoshida S, Sekine Y, Shibuya K, Hiroshima K, Nakatani Y, Yoshino I, and Fujisawa T. Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis. Int J Oncol. 2008; 33 (1): 113-119.
Yamashita M, Kuwahara M, Suzuki A, Hirahara K, Shinnakasu R, Hosokawa H, Hasegawa A, Motohashi S, Iwama A, and Nakayama T. Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene. J Exp Med. 2008; 205 (5): 1109-1120.

Therapeutic Neovascularization

Nakagomi A, Okada S, Shoji T, Kobayashi Y. Crucial Effect of Calibration Methods on the Association Between Central Pulsatile Indices and Coronary Atherosclerosis. Am J Hypertens. in press
Saito Y, Okada S, Funabashi N, Kobayashi Y. ANCA-negative eosinophilic granulomatosis with polyangitis (EGPA) manifesting as a large intracardiac thrombus and glomerulonephritis with angionecrosis. BMJ Case Rep. in press
Nakagomi A, Okada S, Shoji T, Kobayashi Y. Aortic pulsatility assessed by an oscillometric method is associated with coronary atherosclerosis in elderly people. Blood Press. 2016 May 4:1-8.
Shimizu I, Yoshida Y, Katsuno T, Minamino T. Adipose tissue inflammation in diabetes and heart failure Microbes and Infection. 2013; 15(1): 11-17
Okada S, Yokoyama M, Toko H, Tateno K, Moriya J, Shimizu I, Nojima A, Ito T, Yoshida Y, Kobayashi Y, Katagiri H, Minamino T and Komuro I. Brain-Deriverd Neurotrophic Factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-mediated pathway. Arterioscler Thromb Vasc Biol. 2012; 32(8): 1902-1909
Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, Shimizu I, Zhu W, Toko H, Katada A, Akazawa H, Oka T, Lee JK, Minamino T, Nagai T, Walsh K, Kikuchi A, Matsumoto M, Botto M, Shiojima I, Komuro I. Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes. Cell. 2012; 149(6): 1298-1313
Shimizu I, Yoshida Y, Katsuno T, Tateno K, Okada S, Moriya J, Yokoyama M, Nojima A, Ito T, Zechner R, Komuro I, Kobayashi Y, Minamino T. p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab. 2012; 15: 51-64.
Nakano D, Lei B, Kitada K, Hitomi H, Kobori H, Mori H, Deguchi K, Masaki T, Minamino T, Nishiyama A. Aldosterone Does Not Contribute to Renal p21 Expression During the Development of Angiotensin II-Induced Hypertension in Mice. Am J Hypertens. 2012; 25 (3) 354-358
Odaka K, Aoki I, Moriya J, Tateno K, Tadokoro H, Kershaw J, Minamino T, Irie T, Fukumura T, Komuro I, and Saga T. In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging. PLoS One. 2011; 6: e25487.
Xiaojing Wu, Yunzeng Zou, Qi Zhou, Lan Huang, Hui Gong, Aijun Sun, Kaoru Tateno, Ken-ichi Katsube, Freddy Radtke, Junbo Ge, Tohru Minamino, Issei Komuro. Role of Jagged1 in Arterial Lesions After Vascular Injury. Arterioscler Thromb Vasc Biol. 2011.
Naito AT, Okada S, Minamino T, Iwanaga K, Liu M, Sumida T, Nomura S, Sahara N, Mizoroki T, Takashima A, Akazawa H, Nagai T, Shiojima I, Komuro I. Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury. Circ Res. 2010; 106 :1692-1702.
Minamino T. Role of cellular senescence in lifestyle-related disease. Circ J. 2010; 74: 2527-2533.
Moriya J, Minamino T, Tateno K, Okada S, Uemura A, Shimizu I, Yokoyama M, Nojima A, Okada M, Koga H, Komuro I. Inhibition of semaphorin as a novel strategy for therapeutic angiogenesis. Circ Res. 2010; 106: 391-398.
Toko H, Takahashi H, Kayama Y, Oka T, Minamino T, Okada S, Morimoto S, Zhan DY, Terasaki F, Anderson ME, Inoue M, Yao A, Nagai R, Kitaura Y, Sasaguri T, Komuro I. Ca2+/calmodulin-dependent kinase IIdelta causes heart failure by accumulation of p53 in dilated cardiomyopathy. Circulation. 2010; 122: 891-899.
Toko H, Takahashi H, Kayama Y, Okada S, Minamino T, Terasaki F, Kitaura Y, and Komuro I. ATF6 is important under both pathological and physiological states in the heart. J Mol Cell Cardiol. 2010; 49:113-20.
Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, Tateno K, Moriya J, Yokoyama M, Nojima A, Koh GY, Akazawa H, Shiojima I, Kahn CR, Abel ED and Komuro I. Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload. J Clin Invest. 2010; 120: 1506-1514.
Kayama Y, Minamino T, Toko H, Sakamoto M, Shimizu I, Takahashi H, Okada S, Tateno K, Moriya J, Yokoyama M, Nojima A, Yoshimura M, Egashira K, Aburatani H and Komuro I. Cardiac 12/15-lipoxygenase-induced inflammation is involved in heart failure. J Exp Med. 2009; 206: 1565-1574.
Minamino T, Orimo M, Shimizu I, Kunieda T, Yokoyama M, Ito T, Nojima A, Nabetani A, Oike Y, Matsubara H, Ishikawa F, Komuro I. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009; 15: 1082-1087.
Minamino, T. Gap junctions mediate the spread of ischemia-reperfusion injury. Circ J. 2009; 73, 1591-1592.
Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, Saito Y and Komuro I. Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circ Cardiovasc Intervent. 2009; 2: 245-254.
Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, Komuro I. Protective role of SIRT1 in diabetic vascular dysfunction. Arterioscler Thromb Vasc Biol. 2009; 29: 889-894.
Kunieda T, Minamino T, Miura K, Katsuno T, Tateno K, Miyauchi H, Kaneko S, Bradfield CA, FitzGerald GA, Komuro I. Reduced nitric oxide causes age-associated impairment of circadian rhythmicity. Circ Res. 2008; 102: 607-614.
Minamino T and Komuro I. Vascular aging: insights from studies on cellular senescence, stem cell aging, and progeroid syndromes. Nat Clin Pract Cardiovasc Med. 2008; 5: 637-648.
Minamino T and Komuro I. Role of telomeres in vascular senescence. Front Biosci. 2008; 13: 2971-2979.
Nishi J, Minamino T, Miyauchi H, Nojima A, Tateno K, Okada S, Orimo M, Moriya J, Fong GH, Sunagawa K, Shibuya M, Komuro I. Vascular Endothelial Growth Factor Receptor-1 Regulates Postnatal Angiogenesis Through Inhibition of the Excessive Activation of Akt. Circ Res. 2008; 103: 261-268.
Toko H, Minamino T, Komuro I. Role of heat shock transcriptional factor 1 and heat shock proteins in cardiac hypertrophy. Trends Cardiovasc Med. 2008; 18: 88-93.
Tateno K, Minamino T, Moriya J, Katada A, Yokoyama M, Miura K, Komuro I. Cell Therapy for Cardiovascular Diseases. Ann Vasc Dis. 2008; 1: 66-79.
Zhu W, Shiojima I, Ito Y, Li Z, Ikeda H, Yoshida M, Naito AT, Nishi J, Ueno H, Umezawa A, Minamino T, Nagai T, Kikuchi A, Asashima M and Komuro I. IGFBP-4 is an inhibitor of canonical Wnt signaling required for cardiogenesis. Nature. 2008; 454: 345-349.

Adipocyte-based gene therapy

Tanino A, Okura T, Nagao T, Kukida M, Enomoto D, Miyoshi K, Higaki J, Kuroda M, Bujo H. (2016) A case of acquired lecithin:cholesterol acyltransferase deficiency with sarcoidosis that remitted spontaneously. CEN Case Rep. 5, 1-5.
Kosaka K, Kubota Y, Adachi N, Akita S, Sasahara Y, Kira T, Kuroda M, Mitsukawa N, Bujo H, and Satoh K. (2016) Human adipocytes from the subcutaneous superficial layer have greater adipogenic potential and lower PPAR-γ DNA methylation levels than deep layer adipocytes. Am. J. Physiol. Cell Physiol. 311, C322-329.
Adachi N, Kubota Y, Kosaka K, Akita S, Sasahara Y, Kira T, Kuroda M, Mitsukawa N, Bujo H, Satoh K. (2015) Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction. Biochem Biophys Res Commun. 463, 1176-1183.
Fujisaki K, Fujimoto H, Sangai T, Nagashima T, Sakakibara M, Shiina N, Kuroda M, Aoyagi Y, Miyazaki M. (2015) Cancer-mediated adipose reversion promotes cancer cell migration via IL-6 and MCP-1. Breast Cancer Res Treat. 150: 255-263
Kuroda M, Holleboom AG, Stroes E, Asada S, Aoyagi Y, Kamata K, Yamashita S, Ishibashi S, Saito Y, Bujo H. Lipoprotein subfractions highly associated with renal damage in familial LCAT deficiency Arterioscler Thromb Vasc Biol. 2014; 34(8), 1756-1762.
Naito S, Kamata M, Furuya M, Hayashi M, Kuroda M, Bujo H, Kamata K. Amelioration of circulating lipoprotein profile and proteinuria in a patient with LCAT deficiency due to a novel mutation (Cys74Tyr) in the lid region of LCAT under a fat-restricted diet and ARB treatment. Atherosclerosis. 2013; 228, 193-197.
Ogita M, Miyauchi K, Dohi T, Tsuboi S, Miyazaki T, Yokoyama T, Yokoyama K, Shimada K, Kurata T, Jiang M, Bujo H, Daida H. Increased circulating soluble LR11 in patients with acute coronary syndrome. Clin Chim Acta. 2013; 415: 191-194.
Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Saito Y, Satoh K, and Bujo H. Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. Exp Mol Med. 2012; 44: 330-339.
Takahashi M, Bujo H, Shiba T, Jiang M, Maeno T, Shirai K. Enhanced circulating soluble LR11 in patients with diabetic retinopathy. Am J Ophthalmol. 2012; 154: 187-192.
Sakai S, Nakaseko C, Takeuchi M, Ohwada C, Shimizu N, Tsukamoto S, Kawaguchi T, Jiang M, Sato Y, Ebinuma H, Yokote K, Iwama A, Fukamachi I, Schneider WJ, Saito Y, and Bujo H. Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. Clin Chim Acta. 2012; 413: 1542-1548.
Harada-Shiba M, Arai H, Okamura T, Yokote K, Oikawa S, Nohara A, Okada T, Ohta T, Bujo H, Watanabe M, Wakatsuki A, Yamashita S. Multicenter study to determine the diagnosis criteria of heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb. 2012; 19: 1019-1026.
Harada-Shiba M, Arai H, Oikawa S, Ohta T, Okada T, Okamura T, Nohara A, Bujo H, Yokote K, Wakatsuki A, Ishibashi S, Yamashita S. Guidelines for the management of familial hypercholesterolemia. J Atheroscler Thromb. 2012; 19: 1043-1060.
Fukaya Y, Kuroda M, Aoyagi Y, Asada S, Kubota Y, Okamoto Y, Nakayama T, Saito Y, Satoh K, Bujo H. Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. Exp Mol Med. 2012; 44(5): 330-339
Aoyagi Y, Kuroda M, Asada S, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, Bujo H. Fibrin glue is a candidate scaffold for long-term therapeutic protein expression in spontaneously differentiated adipocytes in vitro. Exp Cell Res. 2012; 318(1): 8-15.
Katayama A, Wada J, Usui-Kataoka H, Yamasaki H, Teshigawara S, Terami T, Inoue K, Kanzaki M, Murakami K, Nakatsuka A, Sugiyama H, Koide N, Bujo H, Makino H. Two novel mutations of lecithin:cholesterol acyltransferase (LCAT) gene and the influence of APOE genotypes on clinical manifestations. NDT Plus. 2011;4:299-302
Kuroda M, Bujo H, Aso M, and Saito Y. Adipocytes as a vehicle for ex vivo gene therapy: Novel replacement therapy for diabetes and other metabolic diseases. J Diabetes Invest. 2011; 2: 333-340.
Aoyagi Y, Kuroda M, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, and Saito Y. Fibrin glue increases the cell survival and the transduced gene product secretion of the ceiling culture-derived adipocytes transplanted in mice. Exp Mol Med. 2011; 43: 161-7.
Asada S, Kuroda M, Aoyagi Y, Fukaya Y, Tanaka S, Konno S, Tanio M, Aso M, Okamoto Y, Nakayama T, Saito Y, and Bujo H. Ceiling culture-derived proliferative adipocytes retain high adipogenic potential suitable for use as a vehicle for gene transduction therapy. Am J Physiol Cell Physiol. 2011; 301: C181-C185.
Asada S, Kuroda M, Aoyagi Y, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, and Saito Y. Disturbed apolipoprotein A-I-containing lipoproteins in fish-eye disease are improved by the lecithin:cholesterol acyltransferase produced by gene-transduced adipocytes in vitro. Mol Genet Metab. 2011; 102: 229-31.
Kuroda M, Aoyagi Y, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Machida K, Matsumoto F, Satoh K, Aso M, Saito Y. Ceiling culture-derived proliferative adipocytes are a possible delivery vehicle for enzyme replacement therapy in lecithin:cholesterol acyltransferase deficiency. The Open Gene Ther J. 2011; 4: 1-10.
Nakata Z, Nagae M, Yasui N, Bujo H, Nogi T, and Takagi J. Crystallization and preliminary crystallographic analysis of human LR11 Vps10p domain. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011; 67(Pt 1): 129-32.
Ikeuchi T, Hirayama S, Miida T, Fukamachi I, Tokutake T, Ebinuma H, Takubo K, Kaneko H, Kasuga K, Kakita A, Takahashi H, Bujo H, Saito Y, Nishizawa M. Increased Levels of Soluble LR11 in Cerebrospinal Fluid of Alzheimer Disease. Demen Geriat Cognit Disord. 2010; 30 :28-32.
Takahashi M, Bujo H, Jiang M, Noike H, Saito Y, Shirai K. Enhanced circulating soluble LR11 in patients with coronary organic stenosis. Atherosclerosis. 2010; 210: 581-4.
Unoki-Kubota H, Yamagishi SI, Takeuchi M, Bujo H, Saito Y. Pyridoxamine, an Inhibitor of Advanced Glycation End Product (AGE) Formation Ameliorates Insulin Resistance in Obese, Type 2 Diabetic Mice. Protein Pept Lett. 2010; 17: 1177-81.
Unoki-Kubota H, Yamagishi S, Takeuchi M, Bujo H, Saito Y. Pyridoxamine, an inhibitor of advanced glycation end product (AGE) formation ameliorates insulin resistance in obese, type 2 diabetic mice. Protein Pept Lett. 2010; 17: 1177-81.
Matsuo M, Ebinuma H, Fukamachi I, Jiang M, Bujo H, Saito Y. Development of an Immunoassay for the Quantification of Soluble LR11, a Circulating Marker of Atherosclerosis. Clin Chem. 2009; 55: 1801-8.
Neff Y, Bujo H, Miyashita Y, Uchida D, Ban T, Tashiro T, Yamazaki K, Ishikawa K, Tokuyama T, Jiang M, Kawamura T, Saito, Y. The potential role of patient awareness regarding one's own medical data in the management of lifestyle-related. Chiba Medical Journal. 2009; 85: 125-34.
Tashiro J, Miyazaki O, Nakamura Y, Miyazaki A, Fukamachi I, Bujo H, and Saito Y. Plasma Preβ1-HDL level is elevated in unstable angina pectoris. Atherosclerosis. 2009; 204: 595-600.
Jiang M, Bujo H, Ohwaki K, Unoki H, Yamazaki H, Kanaki T, Shibasaki M, Azuma K, Harigaya K, Schnerider W J, Saito Y. AngII - stimulated migration of vascular SMC is dependent on LR11. J Clin Invest. 2008; 118: 2733-46.
Kawamura T, Murakami K, Bujo H, Unoki H, Jiang M, Nakayama T, Saito Y. Matrix metalloproteinase-3 enhances the free fatty acids-induced VEGF expression in adipocytes through toll-like receptor 2. Exp Biol Med. 2008; 283: 1213-21.
Kuramochi D, Unoki H, Bujo H, Kubota Y, Jiang M, Rikihisa N, Udagawa A, Yoshimoto S, Ichinose M, Saito Y. Matrix metalloproteinase 2 improves the transplanted adipocyte survival in mice. Eur J Clin Invest. 2008; 38: 752-9.
Yamashita S, Bujo H, Arai H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa, Y. Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Thromb. 2008; 15: 292-303.

Clinical Research Center

Kobayashi K, Yokoh H, Sato Y, Takemoto M, Uchida D, Kanatsuka A, Kuribayashi N, Terano T, Hashimoto N, Sakurai K, Hanaoka H, Ishikawa K, Onishi S, Yokote K. SUCCESS Study Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with α-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial. Diabetes Obes Metab. 16(8):761-5. 2014 Aug.
Katayama K, Misawa S, Sato Y, Sobue G, Yabe I, Watanabe O, Nishizawa M, Kusunoki A, Kikuchi S, Nakashima I, Ikeda S, Kohara N, Kanda T, Kira J, Hanaoka H, Kuwabara S.Japanese POEMS syndrome with Thalidomide(J-POST) Trial: study protocol for a phase Ⅱ/Ⅲ multicentre, randomised, double-blind, placebo-controlled trial. BMJ Open. 5 (1):e007330. 2015 Jan 8.
Yokoh H, Kobayashi K, Sato Y, Takemoto M, Uchida D, Kanatsuka A, uribayashi N, Terano T, Hashimoto N, Sakurai K, Hanaoka H, Ishikawa K, Onishi S, Yokote K. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with lpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial. J Diabetes Investig. 6(2):182-91. 2015 Mar.
Yoshinaga N, Niitsu T, Hanaoka H, Sato Y, Ohshima F, Matsuki S, Kobori O, Nakazato M, Nakagawa A, Iyo M, Shimizu E. Strategy for treating selective serotonin reuptake inhibitor-resistant social anxiety disorder in the clinical setting: a randomised controlled trial protocol of cognitive behavioural therapy in combination with conventional treatment. BMJ Open. 2013, 3:e002242
Kotooka N, Asaka M, Sato Y, Kinugasa Y, Nochioka K, Mizuno A, Nagatomo D, Mine D, Yamada Y, Eguchi K, Hanaoka H, Inomata T, Fukumoto Y, Yamamoto K, Tsutsui H, Masuyama T, Kitakaze M, Inoue T, Shimokawa H, Momomura S, Seimo Y, Node K, et al.. Home telemonitoring study for Japanese patients with heart failure (HOMES-HF):protocol for a multicenter randomized controlled trial. BMJ Open. 2013, 3:e002972.
Katsuno M, Banno H. Japan SBMA Interventional Trial for TAP-144-SR (JASMITT) study group. Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010; 875-84.
Hanaoka H, Oishi Y, Sakamoto A. Selective Reduction and Recovery of Invariant Vα24JαQ TCR T Cells in Correlation with Disease Activity in Patients with Chronic Graft-versus-Diseases. Chiba Medical Journal. 2009; 85: 113-124.
Motohashi S, Nagato K, Kunii N, Yamamoto H, Yamasaki K, Okita K, Hanaoka H, Shimizu N, Suzuki M, Yoshino I, Taniguchi M, Fujisawa T, Nakayama T. A phase I-II study of alpha-galactosylceramide-pulsed IL-2/GM-CSF-cultured peripheral blood mononuclear cells in patients with advanced and recurrent non-small cell lung cancer. J Immunol. 2009; 15: 182(4): 2492-501.
Yokote K, Saito Y. Influence of statins on glucose tolerance in patients with type 2 diabetes mellitus: subanalysis of the collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study). J Atheroscler Thromb. 2009; 297-8.