東北大学加齢医学研究所 加齢医学研究拠点 | Institute of Development, Aging and Cancer, Tohoku University

研究活動

腫瘍循環研究分野

教授 医博 佐藤 靖史
准教授 医博 掘 勝義
助教 理博 鈴木 康弘
助教 理博 小林 美穂
博士研究員 医工博 堀江 佐知子 
腫瘍循環研究分野のホームページへ


  1. 研究分野紹介

    当研究分野のスタッフは、佐藤靖史教授、堀勝義准教授、鈴木康弘助教、小林美穂助教、堀江佐知子博士研究員であり、佐藤靖史教授、鈴木康弘助教、小林美穂助教、堀江佐知子博士研究員は血管新生の分子制御に関する研究を、堀勝義准教授は腫瘍血流制御による癌治療の基礎的研究を進めている。

  2. 研究プロジェクト
    1. 血管新生の分子制御に関する研究

      本研究は、血管内皮細胞のバイオロジーに関する基盤的研究と、その知見を基にしたトランスレーショナル研究の推進を目指ている。 我々は、血管新生の中心的な促進因子VEGFの刺激によって血管内皮細胞で発現誘導される遺伝子群の中から血管新生のnegative feedback 調節因子としての機能を果たすと考えられる新規血管新 生抑制因子Vasohibin-1(VASH-1)とそのホモログVasohibin-2(VASH-2)を単離・同定した。VASH-1は血管新生のみならずリンパ管新生に対して広いスペクトルムで抑制活性を有しており、このような活性を持つ内因性因子はVASH-1が初めてのものである。特に、癌の発育と遠隔転移は血管新生に、リンパ管新生はリンパ節転移に直結することから、VASH-1の癌治療への応用を目指している。これに対してVASH-2は、VASH-1と拮抗して血管新生を促進する因子である。血管新生モデルでの観察では、VASH-1は主に発芽領域よりも後方の血管内皮細胞に発現して血管新生を終息させるのに対し、VASH-2は、主に血管新生が活発な発芽領域に浸潤している骨髄由来CD11b陽性の単核球に発現して、発芽部位の血管新生を促進することが分かった。ところが、癌組織においては間質に浸潤する単核球のみならず癌細胞もVASH-2を発現し、腫瘍血管新生を介して癌の発育を促進するばかりか、がん細胞自身に作用してがん幹細胞としての特性獲得に関与する可能性のあること観察している。以上より、VASH-1の作用を増強するのみならず、VASH-2の作用を阻害することがより効果的な治療法となると考え、今後開発研究を進める。

    2. 腫瘍血流制御による癌治療の基礎的研究

      固形腫瘍の病態生理、特に腫瘍微小循環動態は癌の治療に密接に関連している。近年、コンブレタスタチン A-4(African bush willowから抽出された生薬)誘導体が選択的かつ 不可逆的な腫瘍血流遮断作用を有し、癌への栄養供給を断つことにより広範囲の腫瘍壊死を誘導することを示した。同時に、その微小循環メカニズムと壊死誘導のプロセスを解明した。現在、この基礎的所見に立脚した癌治療、およびDDSへの応用研究を進めている。

  図1
  図2

2001年以降の発表論文
原著論文
  1. Kosaka T, Miyazaki Y, Miyajima A, Mikami S, Hayashi Y, Tanaka N, Nagata H, Kikuchi E, Nakagawa K, Okada Y, Sato Y, Oya M. The prognostic significance of vasohibin-1 expression in patients with prostate cancer. Br J Cancer 2013 (in press).
  2. Kanomata N, Sato Y, Miyaji Y, Nagai A, Moriya T. Vasohibin-1 is a new predictor of disease-free survival in operated renal cell carcinoma patients. J. Clin. Pathol. 2013 [Epub ahead of print].
  3. Yazdani S, Miki Y, Tamaki K, Ono K, Iwabuchi E, Abe K, Suzuki T, Sato Y, Kondo T, Sasano H. Proliferation and maturation of intra-tumoral blood vessels in non-small cell lung cancer. Human Pathol. 2013 [Epub ahead of print].
  4. Onami H, Nagai N, Kaji H, Nishizawa M, Sato Y, Osumi N, Nakazawa T, Abe T. Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization. PLoS One 8, e58580, 2013.
  5. Koyanagi T, Saga Y, Takahashi Y, Suzuki Y, Suzuki M, Sato Y. Downregulation of vasohibin-2, a novel angiogenesis regulator, suppresses tumor growth by inhibiting angiogenesis in endometrial cancer cells. Oncol Lett. 5, 1058-1062, 2013.
  6. Xue X, Gao W, Sun B, Xu Y, Han B, Wang F, Zhang Y, Sun J, Wei J, Lu Z, Zhu Y, Sato Y, Sekido Y, Miao Y, Kondo Y. Vasohibin 2 is transcriptionally activated and promotes angiogenesis in hepatocellular carcinoma. Oncogene. 32, 1724-1734, 2013.
  7. Miyashita H, Watanabe T, Hayashi H, Suzuki Y, Nakamura T, Ito S, Ono M, Hoshikawa Y, Okada Y, Kondo T, Sato Y. Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1. PLoS One 7, e46459, 2012.
  8. Takahashi Y, Koyanagi T, Suzuki Y, Saga Y, Kanomata N, Moriya T, Suzuki M, Sato Y. Vasohibin-2 expressed in human serous ovarian adenocarcinoma accelerates tumor growth by promoting angiogenesis. Mol. Cancer Res. 10, 1135-1146, 2012.
  9. Miyazaki Y, Kosaka T, Mikami S, Kikuchi E, Tanaka N, Maeda T, Ishida M, Miyajima A, Nakagawa K, Okada Y, Sato Y, Oya M. The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma. Clin Cancer Res. 18, 4145-4153, 2012.
  10. Watanabe T, Okada Y, Hoshikawa Y, Eba S, Notsuda H, Watanabe Y, Ohishi H, Sato Y, Kondo T. A Potent Anti-angiogenic Factor, Vasohibin-1, Ameliorates Experimental Bronchiolitis Obliterans. Transplant Proc. 44: 1155-1157, 2012.
  11. Onami H, Nagai N, Machida S, Kumasaka N, Wakusawa R, Ishikawa Y, Sonoda H, Sato Y, Abe T. Reduction od laser-induced choroidal neovascularization by intravitreal vasohibin-1in monkey eyes. Retina. 2012 [Epub ahead of print].
  12. Ishikawa Y, Nagai N, Onami H, Kumasaka N, Wakusawa R, Sonoda H, Sato Y, Abe T. Vasohibin-1 and retinal pigment epithelium. Adv Exp Med Biol. 723, 305-310, 2012.
  13. Miyashita H, Suzuki H, Ohkuchi A, Sato Y. Mutual Balance between Vasohibin-1 and Soluble VEGFR-1 in Endothelial Cells. Pharmaceuticals 4, 1551-1577, 2011.
  14. Wakusawa R, Abe T, Sato H, Sonoda H, Sato M, Mitsuda Y, Takakura T, Fukushima T, Onami H, Nagai N, Ishikawa Y, Nishida K, Sato Y. Suppression of Choroidal Neovascularization by Vasohibin-1, Vascular Endothelium-derived Angiogenic Inhibitor. Invest Ophthalmol Vis Sci. 52, 3272-3280, 2011.
  15. Saito D, Maeshima Y, Nasu T, Yamasaki H, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Amelioration of renal alterations in obese type 2 diabetic mice by vasohibin-1, a negative feedback regulator of angiogenesis. Am. J. Phys - Renal Physiol. 300, F873-886, 2011.
  16. Yoshinaga K, Ito K, Moriya T, Nagase S, Takano T, Niikura H, Sasano H, Yaegashi N, Sato Y. Roles of intrinsic angiogenesis inhibitor, vasohibin, in cervical carcinomas. Cancer Sci. 102, 446-51. 2011.
  17. Bai X, Margariti A, Hu Y, Sato Y, Zeng L, Ivetic A, Habi O, Mason JC, Wang X, Xu Q. PKCδ-deficiency accelerates neointimal lesion of mouse injured artery involving delayed reendothelialization and vasohibin-1 accumulation. Arterioscler. Thromb. Vasc. Biol. 30, 2467-2474, 2010.
  18. Suzuki Y, Kobayashi M, Miyashita H, Ohta H, Sonoda H, Sato Y. Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion. J. Cell Sci. 123: 3094-4101, 2010.
  19. ZhouS-Y, Xie Z-I, Xiao O, Yang X-R, Heng BC, Sato, Y. Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1. Mol. Vision 16: 1389-1398, 2010.
  20. Yoshida T, Sato Y, Morita I, Abe M. Pigpen, a nuclear coiled body component protein is involved in angiogenesis. Cancer Sci. 101: 1170-1176, 2010.
  21. Tamaki K, Sasano H, Maruo Y, Takahashi Y, Miyashita M, Moriya T, Sato Y, Hirakawa H, Tamaki N, Watanabe M, Ishida T, Ohuchi N. Vasohibin-1 as a potential predictor of aggressive behavior of ductal carcinoma in situ of the breast. Cancer Sci. 2010 (Epub ahead of print).
  22. Heishi T, Hosaka T, Suzuki Y, Miyashita H, Oike Y, Takahashi T, Nakamura T, Arioka S, Mitsuda Y, Takakura T, Hojo K, Matsumoto M, Yamauchi C, Ohta H, Sonoda H, Sato Y. Endogenous angiogenesis inhibitor vasohibin1 exhibits a broad-spectrum anti-lymphangiogenic activity and suppresses lymph node metastasis. Am. J. Pathol. (Epub ahead of print).
  23. Miura S, Mitsui K, Heishi T, Shukunami C, Sekiguchi K, Kondo J, Sato Y, Hiraki Y. Impairment of VEGF-A-stimulated lamellipodial extensions and motility of vascular endothelial cells by Chondromodulin-I, a cartilage-derived angiogenesis inhibitor. Exp. Cell Res. 316: 775-788 2010.
  24. Komi Y, Sogabe Y, Ishibashi N, Sato Y, Moriwaki H, Shimokado K, Kojima S. Acyclic retinoid inhibits angiogenesis via suppressing MAPK pathway. Lab. Invest. 90: 52-60, 2010.
  25. Hori K, Nishihara M, Shiraishi K, Yokoyama M. The combretastatin derivative (Cderiv), a vascular disrupting agent, enables polymeric nanomicelles to accumulate in microtumors. J. Pharm. Sci. 99: 2914-2925, 2010.
  26. Hori K, Nishihara M, Yokoyama M. Vital microscopic analysis of polymeric micelle extravasation from tumor vessels: macromolecular delivery according to tumor vascular growth stage. J. Pharm. Sci. 99: 549-562, 2010.
  27. Miyake K, Nishida K, Kadota Y, Yamasaki H, Nasu T, Saitou D, Tanabe K, Sonoda H, Sato Y, Maeshima Y, Makino H. Inflammatory Cytokine-induced Expression of Vasohibin-1 by Rheumatoid Synovial Fibroblasts. Acta Med. Okayama 63: 349-358, 2009.
  28. Suzuki H, Ohkuchi A, Matsubara S, Takei Y, Murakami M, Shibuya M, Suzuki M, Sato Y. The effect of recombinant PlGF-2 on hypertension induced by full-length mouse sFlt-1 adenoviral vector in pregnant mice. Hypertension 54: 1129-1135, 2009.
  29. Lee HJ, Kim YS, Sato Y, Cho Y-J. RCAN1-4 knockdown attenuates cell growth through the inhibition of Ras signaling. FEBS Lett. 583: 2557-64, 2009.
  30. Nasu T, Maeshima Y, Kinomura M, Hirokoshi-Kawahara K, Tanabe K, Sugiyama H, Sonoda H, Sato Y, Makino H. Vasohibin-1, a negative feedback regulator of angiogenesis, ameliorates renal alterations in a mouse model of diabetic nephropathy. Diabetes 58: 2365-2375, 2009.
  31. Taniguchi K, Sasaki K, Watari K, Yasukawa H, Imaizumi T, Ayada T, Okamoto F, Ishizaki T, Kato R, Kohno R, Kimura H, Sato Y, Ono M, Yonemitsu Y, Yoshimura A. Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis. PLoS ONE. 4:e5467, 2009.
  32. Hosaka T, Kimura H, Heishi T, Suzuki Y, Miyashita H, Ohta H, Sonoda H, Moriya T, Suzuki S, Kondo T, Sato Y. Vasohibin-1 expressed in endothelium of tumor vessels regulates angiogenesis. Am. J. Pathol. 175: 430-439, 2009.
  33. Kimura H, Miyashita H, Suzuki Y, Kobayashi M, Watanabe K, Sonoda H, Ohta H, Fujiwara T, Shimosegawa T, Sato Y. Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis. Blood 113: 4810-4818, 2009.
  34. Naito H, Kidoya H, Sato Y, Takakura N. Induction and expression of anti-angiogenic vasohibins in the hematopoietic stem/progenitor cell population. J. Biochem. 145: 653-659, 2009.
  35. Nishida Y, Shibata K, Yamasaki M, Sato Y, Abe M. A possible role of vimentin on the cell surface for the activation of latent transforming growth factor-β. FEBS Lett. 583: 308–312, 2009.
  36. Sato H, Abe T, Wakusawa R, Asai N, Kunikata H, Ohta H, Sonoda H, Sato Y, Nishida K. Vitreous levels of vasohibin-1 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetologia 52:359-361, 2009.
  37. Lefter LP, Dima S, Sunamura M, Furukawa T, Sato Y, Abe M, Chivu M, Popescu I, Horii A. Transcriptional silencing of ETS-1 efficiently suppresses angiogenesis of pancreatic cancer. Cancer Gene Ther. 16:137-148, 2009.
  38. Tamaki K, Moriya T, Sato Y, Ishida T, Maruo Y, Yoshinaga K, Ohuchi N, Sasano H. Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis. Cancer Sci. 100: 88-94, 2009.
  39. Hori K, Furumoto S, Kubota K. Tumor blood flow interruption after radiotherapy strongly inhibits tumor regrowth. Cancer Sci. 99:1485-1491, 2008.
  40. Wakusawa R, Abe T, Sato H, Yoshida M, Kunikata H, Sato Y, Nishida K. Expression of vasohibin, an antiangiogenic factor, in human choroidal neovascular membranes. Am. J. Ophthalmol. 146: 235-243, 2008.
  41. Yoshinaga K, Ito K, Moriya T, Nagase S, Takano T, Niikura H, Yaegashi N, Sato Y. Vasohibin, a novel endothelium-derived angiogenesis inhibitor: its expression on endometrial carcinoma in relation to tumor vascularity. Cancer Sci. 99: 914-919, 2008.
  42. Suzuki T, Abe M, Miyashita H, Kobayashi T, Sato Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) affects RhoA activation in endothelial cells. J. Cell. Physiol. 211: 708-715, 2007.
  43. Saito A, Sugawara A, Uruno A, Kudo M, Kagechika H, Sato Y, Owada Y, Kondo H, Sato M, Kurabayashi M, Imaizumi M, Tsuchiya S, Ito S. All-trans retinoic acid induces in vitro angiogenesis via retinoic acid receptor: Possible involvement of paracrine effects of endogenous vascular endothelial growth factor signaling. Endocrinology 148: 1412-1423, 2007.
  44. Kim YS, Lee HJ, Cho KO, Kim SY, Sato Y, Cho Y.J. Down Syndrome Candidate Region 1 increases protein stability of IκBα: Implication for its anti-inflammatory effects. J. Biol. Chem. 281: 39051-39061, 2006.
  45. Nagasaka M, Kohzuki M, Fujii T, Kanno S, Kawamura T, Onodera H, Itoyama Y, Ichie M, Sato Y. Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle. Clin. Exp. Pharmacol. Physiol. 33: 623-627, 2006.
  46. Mizui M, Isaka Y, Takabatake Y, Sato Y, Kawach H, Shimizu F, Takahara S, Ito T, Imai E. Transcription factor ets-1 is essential for mesangial matrix remodeling. Kidney Int. 70: 298-305, 2006.
  47. Abe M, Sato Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is required for the development of vascular as well as hematopoietic system in embryoid bodies. Genes Cells 11: 719-729, 2006.
  48. Koizumi T, Abe M, Yamakuni T, Ohizumi Y, Hitotsuyanagi Y, Takeya K, Sato Y. Metronomic scheduling of a cyclic hexapeptide RA-VII for anti-angiogenesis, tumor vessel maturation, and anti-tumor activity. Cancer Sci. 97: 665-674, 2006.
  49. Yamashita H, Abe M, Watanabe K, Shimizu K, Moriya T, Sato A, Satomi S, Ohta H, Sonoda H, Sato Y. Vasohibin prevents arterial neointimal formation through angiogenesis inhibition. Biochem. Biophys. Res. Commun. 345: 919-925, 2006.
  50. Sonoda H, Ohta H, Watanabe K, Yamashita H, Kimura H, Sato Y. Multiple processing forms and their biological activities of a novel angiogenesis inhibitor vasohibin. Biochem. Biophys. Res. Commun. 342: 640-646, 2006.
  51. Shibuya T, Watanabe K, Yamashita H, Shimizu K, Miyashita H, Abe M, Moriya T, Ohta H, Sonoda H, Shimosegawa T, Tabayashi K, Sato Y. Isolation of vasohibin-2 as a sole homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin: a comparative study on their expressions. Arterioscler. Thromb. Vasc. Biol. 26: 1051-1057, 2006.
  52. Shen J, Yang X, Xiao WH, Hackett SF, Sato Y, Campochiaro PA. Vasohibin is Up-regulated by VEGF in the Retina and Suppresses VEGF receptor 2 and Retinal Neovascularization. FASEB J. 20: 723-725, 2006.
  53. Hori K. Antineoplastic strategy: irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062 (AC7700). Chemotherapy 51: 357-360, 2005.
  54. Miyashita H, Sato Y. Metallothionein1 is a downstream target of VEZF1 in endothelial cells and participates in the regulation of angiogenesis. Endothelium 12: 163-170, 2005.
  55. Cho Y-J, Abe M, Kim SY, Sato Y. Raf-1 is a binding partner of DSCR1. Arch. Biochem. Biophys. 439: 121-128, 2005.
  56. Shimizu K, Watanabe K, Yamashita H, Abe M, Yoshimatsu H, Ohta H, Sonoda H, Sato Y. Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells. Biochem. Biophys. Res. Commun. 327: 700-7006, 2005.
  57. Kanemura M, Abe M, Ueda M, Ueki M, Awaya A, Sato Y. MS-818 accelerates mobilization of endothelial progenitor cells and differentiation to endothelial cells. Endothelium 11: 221-230, 2004.
  58. Hori K, Saito S, Tamai M. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration. Int. J. Radiat. Oncol. Biol. Phys. 60: 1564-1571, 2004.
  59. Tanaka H, Terada Y, Kobayashi T, Okado T, Inoshita S, Kuwahara M, Seth A, Sato Y, Sasaki S. Expression and function of Ets-1 during experimental acute renal failure in rats. J. Am. Soc. Nephrol. 15: 3083-3092, 2004.
  60. Watanabe K, Hasegawa Y, Yamashita H, Shimizu K, Ding Y, Abe M, Ohta H, Imagawa K, Hojo K, Maki H, Sonoda H, Sato Y. Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis. J. Clin. Invest. 114: 884-886, 2004.
  61. Yamazaki T, Akada T, Niizeki O, Suzuki T, Miyashita H, Sato Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyses PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis. Blood 104: 2345-2352, 2004.
  62. Iizuka M, Abe M, Shiiba K, Sasaki I, Sato Y. Down syndrome candidate region 1 (DSCR1), a downstream target of VEGF in endothelial cells, regulates cell migration and angiogenesis via the functional interaction with integrin αvβ3. J. Vasc. Res. 41: 334-344, 2004.
  63. Hashiya N, Jo N, Aoki M, Matsumoto K, Nakamura T, Sato Y, Ogata N, Ogihara T, Kaneda Y, Morishita R. In vivo evidence of angiogenesis induced by transcription factor Ets-1. Ets-1 is located upstream of angiogenesis cascade. Circulation 109: 3035-3041, 2004.
  64. Hori K, Saito S. Induction of tumour blood flow stasis and necrosis a new function for epinephrine similar to that of combretastatin A-4 derivative AVE8062 (AC7700). Br. J. Cancer 90: 549-553, 2004.
  65. Hasegawa Y, Abe M, Yamazaki T, Niizeki O, Shiiba K, Sasaki I, Sato Y. Transcriptional regulation of humen angiopoietin-2 by transcription factor ETS-1. Biochem. Biophys. Res. Commun. 361: 52-58, 2004.
  66. Niizeki O, Miyashita H, Yamazaki T, Akada T, Abe M, Yoshida N, Watanabe T, Yoshimatsu H, Sato Y. Transcriptional regulation of angiogenesis-related puromycin-insensitive leucyl-specific aminopeptidase in endothelial cells. Arch. Biochem. Biophys. 424: 63-71, 2004.
  67. Watanabe D, Takagi H, Suzuma K, Suzuma I, Oh H, Ohashi H, Kemmochi S, Uemura A, Ojima T, Suganami E, Miyamoto N, Sato Y, Honda T. Transcription Factor Ets-1 Mediates Ischemia- and VEGF-dependent Retinal Neovascularization. Am. J. Pathol. 164: 1827-1835, 2004.
  68. Miyashita H, Kanemura M, Yamazaki T, Abe M, Sato Y. Vascular endothelial zinc finger 1 (Vezf1), an endothelium-specific transcription factor, plays an important role in angiogenesis: possible contribution of stathmin/OP18 as a downstream target gene. Arterioscler. Thromb. Vasc. Biol. 24: 878-884, 2004.
  69. Nakagawa T, Abe M, Yamazaki T, Miyashita H, Niwa H, Kokubun S, Sato Y. HEX acts as a negative regulator of angiogenesis by modulating the expression of angiogenesis-related gene in endothelial cells in vitro. Arterioscler. Thromb. Vasc. Biol. 23: 231-237, 2003.
  70. Hori K, Saito S, Sato Y, Akita H, Kawaguchi T, Sugiyama K, Sato H. Differential relationship between changes in tumour size and microcirculatory functions induced by therapy with an antivascular drug and with cytotoxic drugs: implications for evalustion of therapeutic efficacy ofAC7700 (AVE8062). Eur. J. Cancer 39: 1957-1966, 2003.
  71. Hori K, Saito S. Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br. J. Cancer 89:1334-1344, 2003.
  72. Abe M, Inoue D, Matsunaga K, Ohizumi Y, Ueda H, Asano T, Murakami M, Sato Y. Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibiting actin reorganization of endothelial cells. J. Cell. Physiol. 190: 109-116, 2002.
  73. Miyashita H, Yamazaki T, Akada T, Niizeki O, Ogawa M, Nishikawa S, Sato Y. A mouse orthologue of puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is expressed in endothelial cells and plays an important role in angiogenesis. Blood 99: 3241-3249, 2002.
  74. Abe M, Oda N, Shibata K, Yamasaki M, Sato Y. Augmented binding and activation of latent transforming growth factor-β by a tryptic fragment of latency associated peptide. Endothelium 9: 25-36, 2002.
  75. Akada T, Yamazaki T, Miyashita H, Niizeki O, Abe M, Sato A, Satomi S, Sato Y. Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial integrins. J. Cell. Physiol. 193: 253-262, 2002.
  76. Hori K, Saito S, Kubota K. A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs. Br. J. Cancer 86:1604-1614, 2002.
  77. Yashima R, Abe M, Tanaka K, Ueno H, Shitara K, Takenoshita S, Sato Y Heterogeneity of the signal transduction pathways for VEGF-induced MAPKs activation in human vascular endothelial cells. J. Cell. Physiol. 188: 201-210, 2001.
  78. Teruyama K, Abe M, Nakano T, Iwasaka-Yagi C, Takahashi S, Yamada S, Sato Y. Role of transcription factor Ets-1 in the apoptosis of human vascular endothelial cells. J. Cell. Physiol. 188: 243-252, 2001.
  79. Iwasaka-Yagi C, Abe M, Sato Y. TGF-β attenuates the transactivation activity of Ets-1 despite its induction via the inhibition of DNA binding. Tohoku J. Exp. Med. 193: 311-318, 2001.
  80. Terai Y, Abe M, Miyamoto K, Koike M, Yamasaki M, Ueda M, Ueki M, Sato Y. Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin αvβ3 on vascular endothelial cells. J. Cell. Physiol. 88: 394-402, 2001.
  81. Igarashi T, Abe M, Oikawa M, Nukiwa T, Sato Y. Retinoic Acids Repress the Expression of ETS-1. Tohoku J. Exp. Med. 194: 35-43, 2001.
  82. Teruyama K, Abe M, Nakano T, Takahashi S, Yamada S, Sato Y. Neuropilin-1 is a downstream target of transcription factor Ets-1 in human umbilical vein endothelial cells. FEBS Lett. 504: 1-4, 2001.
  83. Oikawa M, Abe M, Kurosawa H, Hida W, Shirato K, Sato Y. Hypoxia induces transcription factor ETS-1 via the activity of hypoxia inducible factor-1. Biochem. Biophys. Res. Commun. 289: 39-43, 2001.
  84. Sato Y, Teruyama K, Nakano T, Oda N, Abe M, Tanaka K, Iwasaka-Yagi C. Role of transcription factors in angiogenesis: Ets-1 promotes angiogenesis as well as endothelial apoptosis. Ann. N. Y. Acad. Sci. 947: 117-123, 2001.
  85. Abe M, Sato Y. cDNA microarray analysis of the gene expression profile of VEGF-induced human umbilical vein endothelial cells. Angiogenesis 4: 289-298, 2001.
  86. Hori K, Saito S, Sato Y, Kubota K. Stoppage of blood flow in 3-methyl- cholanthrene-induced autochthonous primary tumor due to a novel combretastatin A-4 derivative, AC7700, and its antitumor effect. Med. Sci. Monit. 7: 26-33, 2001.

総説

  1. Sato Y. Is Histone Deacetylase-9-MicroRNA-17~92 Cluster a Novel Axis for Angiogenesis Regulation? Arterioscler Thromb Vasc Biol. 33, 445-446, 2013.
  2. Sato Y. The Vasohibin Family: A Novel Family for Angiogenesis Regulation. J Biochem. 153, 5-11. 2013.
  3. Sato Y. The Vasohibin Family: Novel Regulators of Angiogenesis. Vascular Pharmacology 2012 [Epub ahead of print].
  4. Sato Y. Persistent vascular normalization as an alternative goal of anti-angiogenic cancer therapy. Cancer Sci. 102, 1253-1256, 2011.
  5. Sato, Y. Is Vasohibin-1 for more than angiogenesis inhibition? J. Biochem. 149, 229-230, 2011.
  6. Sato Y. The vasohibin family. Pharmaceuticals 3: 433-440, 2010.
  7. Sato Y. Delta-like 4 and vasohibin 1: two endothelium-produced negative regulators of angiogenesis with distinctive roles. Eur. Cytokine Netw. 20, 1-5, 2009.
  8. Sato Y. VEGFR1 for lymphangiogenesis: an alternative signaling pathway? Arterioscler. Thromb. Vasc. Biol. 28: 604-605, 2008.
  9. Sato Y, Sonoda H. The vasohibin family: a negative regulatory system of angiogenesis genetically programmed in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 27: 37-41, 2007.
  10. Sato Y. Update on endogenous inhibitors of angiogenesis. Endothelium 13: 147-155, 2006.
  11. Sato Y. Role of aminopeptidase in angiogenesis. Biol. Pharm. Bull. 27: 772-776, 2004.
  12. Sato Y. Neovascularization; its molecular mechanism and biology. Intern. Med. 42: 295-297, 2003.
  13. Sato Y. Molecular diagnosis of tunmor angiogenesis and anti-angiogenic cancer therapy. Int. J. Clin. Oncol. 8: 200-206, 2003.
  14. Sato Y. Aminopeptidase and angiogenesis. Endothelium 10: 287-290, 2003.
  15. Sato Y. Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct. Funct. 26: 19-24, 2001.

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