THE ESTABLISHMENT OF JAPAN-ORIGINAL GENE THERAPY BY ANTI-TUMOR ANGIOGENESIS USING DECOY GENE.

• Project/Area Number: 20390478
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Shimane University
• Principal Investigator: ISHIBASHI Hiroaki 島根大学, 医学部, 准教授 (90254630)
• Co-Investigator(Kenkyū-buntansha): SEKINE Joji 島根大学, 医学部, 教授 (20236095) ; NARIAI Yoshiki 島根大学, 医学部, 講師 (60333465) ; KONNDOU Seiji 島根大学, 医学部, 講師 (10432634)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 実験腫瘍学 / 血管新生 / 悪性新生物 / 遺伝子治療 / 口腔がん / 口腔癌

Research Abstract

The conditioned media(CM) harvested from human pulmonary squamous cell carcinoma(QG56), pulmonary small cell carcinoma(QG90) and gastric adenocarcinoma(MKN28) cultivated under hypoxic conditions(3% O2), enhanced the angiogenic activity in vitro more than those obtained under normoxic cultivation(20% O2). The total length of the tube structures formed by bovine capillary endothelial cells(BCEs) in the CM cultured at 3% O2 was about 1. 5(QG56 and MKN28) or 1. 9(QG90) times longer than that at 20% O2. Tube formation was diminished by the preincubation of CM with anti-basic fibroblast growth factor(bFGF) IgG. After performing the fractionations of the CM and the crude extracts of cell lysates cultured using a heparin-Sepharose column, the mitogenic activity in the CM from all cancer cells at 3% O2 was about 2 times higher than that in the CM at 20% O2, while it decreased in the cell lysates at 3% O2 to about 40% of those at 20% O2. This mitogenic activity of BCEs in the CM from all cancer cells was almost totally suppressed by anti-basic fibroblast growth factor(bFGF) IgG, but not with anti-vascular endothelial growth factor(VEGF) IgG. These results suggest that the hypoxic condition is an important cause for tumor angiogenesis by bFGF or bFGF-like molecule(s) derived from tumor cells.

Research Products

• [Journal Article] Oral symptoms including dental erosion in gastroesophageal reflux disease are associated with decreased salivary flow volume and swallowing function (2012)
  • Author(s): Yoshikawa H, et al.
  • Journal Title: Journal of Gastroenterology Volume: 27 Pages: 124-128
  • Peer Reviewed
• [Journal Article] A pediatric case of unicystic ameloblastoma treated with conservative suegery leading to eruption of the impacted permanent teeth (2011)
  • Author(s): Kanno T, Ishibashi H, Sukegawa S, Tsunematsu K, Nakamura S, Mano S, Sekine J, Furuki Y
  • Journal Title: Hospital Dentistry and Oral-Maxillofacial Surgery Volume: 23(2) Pages: 129-132
• [Journal Article] A fish bone in the tongue : a report of a case (2010)
  • Author(s): Nariai Y, Yanai C, Kondo S, Ishibashi H, Egawa M, Kitagaki H, Sekine J
  • Journal Title: Asian J Oral Maxillofac Surg 22 Pages: 30-32
• [Journal Article] Our approach for early detection of oral cancer using smear cytology. (2010)
  • Author(s): Kikuchi M, Ishibashi H, Kondo S, Fujihara S, Karino M, Tatsumi H, Yoshino A, Enomoto Y, Nariai Y, Sekine J
  • Journal Title: Journal of the Korean Association of Oral and Maxillofacial Surgeons 36 Supplement No.1 Pages: 315-316
• [Journal Article] Use of TCP plates in condylar fracture osteosynthesis. (2010)
  • Author(s): Yanai C, Nariai Y, Kondo S, Tatsumi H, Ishibashi H, Sekine J
  • Journal Title: International Proceedings of 20th Congress of the European Association of Cranio-Maxillo-Facial Surgery. Pages: 35-37
• [Journal Article] Our approach for early detection of oral cancer using smear cytology (2010)
  • Author(s): Kikuchi M, Ishibashi H, et al
  • Journal Title: Korean Association of Oral and Maxillofacial Surgeons Volume: 36 Pages: 315-316
• [Journal Article] A fish bone in the tongue (2010)
  • Author(s): Nariai Y, Yanai C, Kondo S, Ishibashi H, et al.
  • Journal Title: Asian J Oral Maxillofac Surg Volume: 22 Pages: 30-32
  • Peer Reviewed
• [Journal Article] Autocrine loop between vascular endothelial growth factor(VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangio-genesis in oral squamoid cancer cells (2009)
  • Author(s): Matsuura M, Onimaru M, Yonemitsu Y, Suzuki H, Nakano T, Ishibashi H, Shirasuna K, Sueishi K
  • Journal Title: Am J Pathology Volume: 174 Pages: 361-368
• [Journal Article] Management of tongue squamous cell carcinoma in pregnant women : Report of two Patients (2009)
  • Author(s): Kondo S, Ishibashi H, Nariai Y, Kato T, Enomoto Y, Karino M, Sekine J
  • Journal Title: Asian J Oral Maxillofac Surg Volume: 21 Pages: 129-132
• [Journal Article] Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells. (2009)
  • Author(s): Matsuura M, Onimaru M, Yonemitsu Y, Suzuki H, Nakano T, Ishibashi H, Shirasuna K, Sueishi K
  • Journal Title: Am J Pathology 174 Pages: 361-368
• [Journal Article] Management of tongue squamous cell carcinoma in pregnant women : Report of two Patients. (2009)
  • Author(s): Kondo S, Ishibashi H, Nariai Y, Kato T, Enomoto Y, Karino M, Sekine J
  • Journal Title: Asian J Oral Maxillofac Surg 21 Pages: 129-132
• [Journal Article] Feasible technique for the prediction of lymph node involvement in squamous cell carcinoma of the tongue by nuclear morphometric analysis. (2009)
  • Author(s): Karino M, Ishibashi H, Fujihara S, Watanabe M, Ichiba Y, Nariai Y, Kondo S, Sekine J
  • Journal Title: Proceedings of the 19th International Conference on Oral and Maxillofacial Surgery 38(5) Pages: 426-426
• [Journal Article] Feasible technique for the prediction of lymph node involvement in squamous cell carcinoma of the tongue by nuclear morphometric analysis. (2009)
  • Author(s): Karino M, Ishibashi H, Fujihara S, Watanabe M, Ichiba Y, Nariai Y, Kondo S, Sekine J
  • Journal Title: The 55th Annual Congress of the Japan Section, Proceedings 36
• [Journal Article] Our surgical management of odontogenic tumor. (2009)
  • Author(s): Higashi T, Ishibashi H, Kato T, Karino M, Yoshino A, Nariai Y, Kondo S, Yanai C, Sekine J
  • Journal Title: The International College of Surgeons, The 55th Annual Congress of the Japan Section, Proceedings 37
• [Journal Article] Autocrine loop between vascular endothelial growth factor(VEGF)-C and VEGF Receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells. (2009)
  • Author(s): Matsuura M, Onimaru M, Yonemitsu Y, Suzuki H, Nakano T, Ishibashi H, et al.
  • Journal Title: American Journal of Pathology 175(4) Pages: 1709-1721
  • Peer Reviewed
• [Journal Article] Study on feasibility of cervical lymphnode metastasis in squamous cell carcinoma. (2008)
  • Author(s): Karino M., Ishibashi H., et al.
  • Journal Title: Proc Int Oral Cancer 3 Pages: 89-90
  • Peer Reviewed
• [Journal Article] A case of a mucous retention cyst on the soft palate in one-year-old boy. (2008)
  • Author(s): Ninomiya T., Yuneyoshi T., et al.
  • Journal Title: Pediatric Oral and Maxillofacial Surgery 18(1) Pages: 21-24
  • Peer Reviewed
• [Presentation] 「Novel gene therapy」Newly regulation strategy against tumor angiogenesis and chemosensitivity using decoy system (2011)
  • Author(s): Ishibashi, H. Koike, H. Hideshima, K. Karino, M. Tunematsu, K, Sekine J
  • Organizer: 4th Internatinal Conference of Advanced Digital Technology in Head and Neck reconstruction
  • Place of Presentation: Freiburg
  • Year and Date: 2011-05-05
• [Presentation] Newly gene therapy for temporomandibular joint arthritis by in vitro cis-transelement decoy against TNF α-induced NF-kB activation (2011)
  • Author(s): Ishibashi H, et al.
  • Organizer: 4^<th> Advanced Digital Conference
  • Place of Presentation: Freiburg, Germany(招待講演)
  • Year and Date: 2011-05-05
• [Remarks]
  • URL: http://www.med.shimane-u.ac.jp/oral/