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教育

久保田　俊一郎

役職：特任教授

主な研究と活動

久保田　俊一郎

がんは、我が国の死因の第1位であり、新規の治療法の開発が望まれている。がんが治療困難になる主な要因は、がんが転移するためである。また、抗がん剤が効かなくなる（抗がん剤耐性）ことも、がん治療が困難になる要因である。転移の機構および抗がん剤耐性の機序を明らかにすることが主な研究課題である。
キーワード がん　
専門分野 内科学、腫瘍学（がん転移、抗がん剤耐性）、分子生物学
主な研究対象 がん　
主な研究課題 がん転移の機構　抗がん剤耐性の機構
学位 医学博士（東京大学）
免許・資格 医師　産業医　健康スポーツ医　スポーツドクター

ページ内目次

学歴・経歴

  • 東京大学 医学部 卒業
  • 東大病院内科および生化学教室にて臨床と研究に従事
  • 米国国立衛生研究所 (N.I.H.) visiting associate
  • 東京大学 医学部 栄養学講座 助教授
  • 東京大学大学院 生命環境科学系 教授
  • 帝京平成大学 地域医療学部 柔道整復学科 教授（2012年）
  • 帝京平成大学 薬学部 教授（2013年）
  • 帝京科学大学 医学教育センター 特任教授（2018年）

主な著書

  1. ポリアミン「臨床検査」分担　医学書院　1989年
  2. ポリアミン「広範囲　血液、尿化学検査」分担　日本臨床　1990年
  3. 人工マトリックス「糖鎖工学と医薬品開発」分担　薬業時報社　1993年
  4. ポリアミン「検査値のみかた」分担 　中外医学社　1993年
  5. 細胞外基質への接着性の測定 「がんの浸潤、転移マニュアル」分担　金芳堂　1994年
  6. ザイモグラムによるゼラチナーゼ／コラゲナーゼの検出 「がんの浸潤、転移マニュアル」分担　金芳堂　1994年
  7. ポリアミンとオルニチン脱炭酸酵素「広範囲　血液、尿化学検査」 分担　日本臨床　増刊号　1995年
  8. プリン誘導体とその関連酵素「広範囲　血液、尿化学検査」分担　日本臨床　増刊号　1995年
  9. ジゴキシゲニン標識による遺伝子の検出「PCR法の最前線ー基礎技術から応用まで」分担　蛋白質 核酸 酵素　共立出版　1996年
  10. ラミニンファミリー 「細胞接着」分担　羊土社　1996年
  11. 癌転移機構「消化器病」分担　羊土社　1996年
  12. ラミニンの遺伝子レベルでの検出　「がんの浸潤、転移マニュアル（続編）」分担　金芳堂　1997年
  13. ラミニンの蛋白レベルでの検出法　「がんの浸潤、転移マニュアル（続編）」分担　金芳堂　1997年
  14. 分子細胞生物学事典　分担　東京化学同人　1997年
  15. 生化学事典　分担（第3版）東京化学同人　1998年
  16. ポリアミンとオルニチン脱炭酸酵素「広範囲　血液、尿化学検査」分担　日本臨床　1999年
  17. コンパクト栄養学　分担　南江堂　2000年
  18. 脳腱黄色腫症「高脂血症」分担　下巻　日本臨床　2001年
  19. 脳腱黄色腫症研究ー最近の進歩　医学のあゆみ 別冊「高脂血症と動脈硬化」馬渕宏（編）2002年
  20. 人体の構造と機能　分担　東京化学同人　2003年
  21. ポリアミンとオルニチン脱炭酸酵素「血液・尿化学検査、免疫学的検査」分担　日本臨床　2005年　
  22. 「コンパクト栄養学」分担　改訂第2版　南江堂　2006年　
  23. 「総合診療マニュアル」分担　金芳堂　2010年
  24. 「生化学」分担　東京化学同人　2014年
  25. 「解剖生理学」分担　東京化学同人　2016年
  26. 「やさしい臨床医学テキスト」　第4版　分担　薬事日報社　2018年

主な論文

  1. A new method for the preparation of a calcium activated neutral protease highly sensitive to calcium ions. Biochem Biophys Res Commun. 100:1189-1194,1981.
  2. Limited autolysis of calcium-activated neutral protease changes its sensitivity to calcium ions. J.Biochem. 90:275-278, 1981.
  3. Autolysis of calcium-activated neutral protease of chicken skeletal muscle. J.Biochem. 90:1787-1793, 1981.
  4. Comparison of two forms of low calcium-requiring protease. Biomed.Res. 3:699-702, 1982.
  5. A new simple enzymatic assay method for urinary polyamines in humans. Cancer Res. 43:2363-2367, 1983.
  6. Purification of a calcium-activated neutral protease from human placenta. Biochim.Biophys.Acta 802:379-383, 1984.
  7. Urinary polyamines as a tumor marker. Cancer Detection and Prevention 8:189-192, 1985.
  8. Urinary polyamines as a marker of response in cancer treatment. Recent Prog. in Polyamine Res. 8:459-468, 1985.
  9. The value of urinary polyamine assay in stomach cancer: comparison with serum carcinoembryonic antigen. Cancer 56:1630-1635, 1985.
  10. Polyamines. Methods of Enzymatic Analysis 8:566-572, 1985.
  11. Purification and characterization of high calcium-requiring neutral proteases from porcine and bovine brains. Biochemistry 25:8396-8402, 1986.
  12. Effects of DL-alpha-difluoromethyl- ornithine on the growth and metastasis of B16 melanoma in vivo. Int. J. Cancer 39:244-247, 1987.
  13. Epidermal growth factor expression in the congenital polycystic mouse kidney. Kidney Int. 39:57-62, 1991.
  14. Transforming growth factor-β suppresses the invasiveness of human fibrosarcoma cells in vitro by increasing expression of tissue inhibitor of metalloprotease. Biochem.Biophys.Res.Commun. 176:129-136, 1991.
  15. Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoro-methylornithine against human gastric cancer cells in vitro. Cancer 69:2395-2399, 1992.
  16. Signaling site of laminin with mitogenic activity. J.Biol.Chem. 267:4285-4288, 1992.
  17. Induction of a 92 kDa typeIV collagenase/gelatinase by invasive human fibrosarcoma genomic DNA transfection leads to an invasive phenotype. Biochem.Biophys.Res.Commun. 181:1539-1547, 1992.
  18. Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX). J.Lipid Res. 35:1031-1039, 1994.
  19. Ornithine decarboxylase is directly involved in mouse mammary carcinoma cell invasion through reconstituted basement membrane (matrigel). Biochem.Biophys.Res.Commun. 208:1106-1115, 1995.
  20. Tumor Necrosis Factor Alpha- and lymphotoxin stimulate human myeloblastic leukemia cell (ML-1) invasion through a reconstituted basement membrane (matrigel) with concomitant induction of 92kDa gelatinase secretion. Cancer Lett. 98:233-240, 1996.
  21. Genetic analysis of a Japanese cerebrotendinous xanthomatosis family: identification of a novel mutation in the adrenodoxin binding region of the CYP27 gene. Biochim.Biophys.Acta 1317:119-126, 1996.
  22. Molecular cloning and expression of a rabbit sterol 12-hydroxylase. J. Biol. Chem. 271:32269-32275, 1996.
  23. PET analysis of a case of cerebrotendinous xanthomatosis presenting hemiparkinsonism. J.Neurol.Sci. 138: 145-149, 1996.
  24. Anti-α3 integrin antibody induces the activated form of matrix metalloprotease-2 (MMP-2) with concomitant stimulation ofinvasion through matrigel by human rhabdomyosarcoma cells. Int.J.Cancer 70:106-111, 1997.
  25. Ornithine decarboxylase overexpression in mouse 10T1/2 fibroblasts: Cellular transformation and invasion. J.Natl.Cancer Inst. 89:567-571, 1997.
  26. Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis　in three Japanese patients from two unrelated families. J.Lipid Res. 38:870-879, 1997.
  27. Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP27) caused by a "G" to "A" mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX). J.Lipid Res. 39: 509-517, 1998.
  28. Silent nucleotide substitution in the sterol 27 hydroxylase gene (CYP27) leads to alternative pre-mRNA splicing by activating a cryptic 5' splice site at the mutant codon in cerebrotendinous xanthomatosis patients. Biochemistry 37:4420-4428, 1998.
  29. Genetic analysis enables definite and rapid diagnosis of cerebrotendinous xanthomatosis Neurology 51:865-867, 1998.
  30. A novel Arg362Ser mutation in the sterol 27 hydroxylase gene (CYP27); its effects on pre-mRNA splicing, and enzyme activity. Biochemistry 37:15050-15056, 1998.
  31. Ornithine decarboxylase and cancer. Cancer J. 11:294-297, 1998.
  32. Cholestanol induces apoptosis of cerebellar neuronal cells. Biochem.Biophys.Res.Commun. 256:198-203, 1999.
  33. Human rhabdomyosarcoma cells retain insulin-regulated glucose transport activity through glucose transporter 1. Arch.Biochim.Biophys. 373: 72-82, 2000.
  34. Cholestanol induces apoptosis of corneal endothelial and lens epithelial cells. Invest.Ophthalmol.Vis.Sci. 41:991-997, 2000.
  35. Convenient method for analyzing differential expressing gene in the plural cells. Bioimages 8:91-96, 2000.
  36. Overexpression of vacuolar ATPase 16 kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2. Biochem.Biophys.Res.Commun. 278:390-394, 2000.
  37. Formation of hydroxy radicals by environmental estrogen-like chemicals in rat striatum. Neurosci.Lett. 296:41-44, 2000.
  38. Effects of para-nonylphenol on 92kDa gelatinase secretion by human peripheral lymphocytes and U937 cells in vitro. Biochem.Biophys.Res.Commun. 279:270-274, 2000.
  39. p53 independent G1 arrest induced by DL-a-difluoromethylornithine. Biochem.Biophys.Res.Commun. 280: 848-854, 2001.
  40. Genetic analysis of phytosterolemia. J.Inherit.Metab.Dis. 24:43-50, 2001.
  41. Anti-alpha integrin antibody induces secretion and activation of 72 kDa progelatinase by human fibroblasts. Biochem.Mol.Biol.Int. 51: 1-7, 2001.
  42. Histamine increases interstitial adenosine concentration via activation of ecto-5'-nucleotidase in rat hearts in vivo. J. Pharmacol. Exp.Ther. 298: 1-6, 2001.
  43. Calreticulin is directly involved in anti-α3 integrin antibody-mediated secretion and activation of matrix metalloprotease-2. Biochem.Biophys.Res. Commun. 283: 297-302, 2001.
  44. Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene (CYP27). J.Inherit.Metab.Dis. 24: 379-392, 2001.
  45. Protective effect of tamoxifen on 1-methyl-4-phenylpyridine-induced hydroxyl radical generation in the rat striatum. Neurosci.Lett. 308:87-90, 2001.
  46. Allopurinol suppresses paranonylphenol and 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum. Neurosci.Lett. 306 :9-12, 2001.
  47. Matrix metalloproteinase-2 and -9 in bile as a marker of liver metastasis in colorectal cancer. Biochem. Biophys.Res.Commun. 288:212-216, 2001.
  48. Protective effect of histidine on para-nonylphenol enhanced hydroxyl free radical generation induced by 1-methyl-4-phenylpyridinium ion (MPP+) in rat striatum. Biochim.Biophys.Acta 1568:171-175, 2001.
  49. Antisense oligonucleotides targetted to midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells. Cancer Res. 61:8486-8491, 2001
  50. Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression. Blood 99:1478-1481, 2002.
  51. 5'-, 3'-Inverted-thymidine-modified antisense oligodeoxynucleotide targeting midkine: its design and application for cancer therapy. J.Biol.Chem. 277:23800-23806, 2002.
  52. Coexpression of glucose transporter 1 and matrix metalloproteinase-2 in human cancers. J. Natl. Cancer Inst. 94:1080-1091, 2002.
  53. Determining the levels of matrix metalloproteinase-9 in portal and peripheral blood is useful for predicting liver metastasis of colorectal cancer. Jpn. J. Clin. Oncol. 33: 186-191, 2003.
  54. Enhanced susceptibility of LDL to oxidativemodification in a CTX patient: role of chenodeoxycholic acid in xanthoma formation. J Atheroscler Thromb. 11:167-172, 2004.
  55. In utero and lactational exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD) affects tooth development in Rhesus monkeys. Reproductive Toxicology 20: 21-30, 2005.
  56. Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors. World J. Gastroenterology 11: 3065-3069, 2005.
  57. Exercise-related novel gene is involved in myoblast differentiation. Biomed. Res. 26:79-85, 2005.
  58. PACAP Receptor (PAC1-R) Expression in Rat and Rhesus Monkey Thymus.Annals of the New York Academy of Sciences 1070: 581-585, 2006.
  59. Short time exposure to hypoxia promotes H9c2 cell growth.Biochim.Biophys.Acta 1760: 1293-1297, 2006.
  60. Ornithine decarboxylase overexpression enhances phosphorylation of ERK and p38 and matrix metalloproteinase-2 expression. Cell Biol. Int. 31:141-147,2007.
  61. Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo p-dioxin on the liver of Rhesus monkeys. Chemosphere 67:399-404, 2007.
  62. A single-injection ornithine decarboxylase-directed antisense therapy using atelocollagen to suppress human cancer growth. Cancer 109:993-1002, 2007.
  63. Pro-MMP-9 is associated with poor prognosis in gastric cancer. Scandinavian J. Gastroenterology 42:1070-1072, 2007.
  64. Polyamine depletion induces G1 and S phase arrest in human retinoblastoma Y79 cells. Cancer Cell Int. 8:2-9, 2008.
  65. Mouse AKR1E1 is orthologue of pig liver NADPH dependent 1,5-anhydro-D-fructose reductase. Bioscience, Biotechnology, and Biochemistry 72: 872-876, 2008.
  66. Developmentally regulated expression of matrix metalloproteinases during fetal rat colon morphogenesis. 
Development, Growth and Differentiation 50 (1): 41–48, 2008.
  67. Protective effect of captopril and enaraprilat, angiotensin-converting enzyme inhibitors, on para-nonylphenol-induced •OH generation and dopamine efflux in rat striatum. Toxicology 250: 96-99, 2008.
  68. In utero and lactational exposure to 2,3,7,8-tetrachloro- dibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys. Toxicology 253:147-52, 2008.
  69. Application of radical chain reactions to drug release controlling of liposomal carriers under high magnetic fields. J. Applied Physiology 105, 07B323 (2009); DOI:10.1063/1.3076894　
  70. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces a reduction of epididymal and ejaculated sperm number in rhesus monkeys.Reproductive Toxicology 28: 495-502, 2009.
  71. Inhibition of endostatin/collagen XVIII deteriorates left ventricular remodeling and heart failure in rat myocardial infarction. Circulation Journal, 74, 109-119, 2009.
  72. In utero and lactational exposure to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) induces disruption of glands of the prostate and fibrosis in rhesus monkeys. Reproductive Toxicology 29:317–322, 2010.
  73. High dose of ascorbic acid induces cell death in mesothelioma cells. Biochem Biophys Res Commun. 394:249-253, 2010.
  74. EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy. Cancer Cell Int. 13:19-27, 2013.
  75. Zebularine exerts its antiproliferative activity through S phase delay and cell death in human malignant mesothelioma cells. Bioscience Biotechnology and Biochemistry 82:1-6, 2018.
  76. Protamine may have anti-atherogenic potential by inhibiting the binding of oxidized-low density lipoprotein to LOX-1. Bioscience Biotechnology and Biochemistry 83:1094–1101, 2019.
  77. Cognitive-behavioral-based physical therapy for patients with severe lumbar spinal stenosis: a report of 38 cases. Journal of Biotechnology and Bioengineering 4:19-27, 2020.
  78. Loss of FYCO1 leads to cataract formation. Scientific Reports 11: 13771, 2021.

所属学会等

  • 米国がん学会
  • 日本がん転移学会
  • 日本生化学会
  • 日本薬学会
  • 日本臨床スポーツ医学会

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