GENE THERAPY FOR MALIGNANT BRAIN TUMORS USING HSV/EBV HYBRID AMPLICONS.

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14370433
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: KAGAWA UNIVERSITY(FACULTY OF MEDICINE) (2003); Okayama University (2002)
• Principal Investigator: TAMIYA Takashi KAGAWA UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (50252953)
• Co-Investigator(Kenkyū-buntansha): ONO Yasuhiro OKAYAMA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医歯学総合研究科, 講師 (40294409) ; MATSUMOTO Yoshihito KAGAWA UNIVERSITY, SCHOOL OF MEDICINE, LECTURE, 医学部, 講師 (80311827) ; KAWAI Nobuyuki KAGAWA UNIVERSITY, HOSPITAL, LECTURE, 医学部附属病院, 講師 (40294756) ; SUGIU Kenji OKAYAMA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部附属病院, 講師 ; TOTUNAGA Koiji OKAYAMA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT, 医学部附属病院, 講師
• Project Period (FY): 2002 – 2003
• Keywords: gene therapy / gene expression / glioma / Herpes virus vector / EB virus vector / Adenovirus vector / Cytosin deaminase gene

Research Abstract

Previously, we evaluated the therapeutic efficacy of the virus-mediated transduction of the chemosensitivity genes and prodrugs for malignant gliomas such as 5-fluorocytosine (5-FC)/cytosine deaminase (CD) gene therapy.
Firstly, we investigated the ability of radiation therapy to enhance 5-fluorocytosine (5-FC)/cytosine deaminase (CD) plus uracil phosphoribosyltransferase (UPRT) gene therapy in malignant gliomas. This combination therapy may be feasible for the treatment of gliomas, although the radiation dose and area should be reduced in order to prevent side effects (Cancer Gene Therapy 9 : 840-845, 2002).
Secondly, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9 (J of Neuro-Oncology 66 : 117-127, 2004).
Recently, we are making new HSV/EB hybrid-based amplicon vector system for transgene delivery and developing the use MRI for in vivo imaging of transgene expression employing engineered transferrin receptor.

Research Products

• [Publications] Kambara Y, Tamiya T, et al.: "Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes"Cancer Gene Therapy. 9. 840-845 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takeda M, Tamiya T, et al.: "Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas"Biochem Biophys Res Commun. 306. 812-818 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fujiwara K, Tamiya T, et al.: "Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor-secreting cells in a model of middle cerebral artery occlusion in rats."J Neurosurg. 99. 1053-1062 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kurozumi K, Tamiya T, et al.: "Apoptosis induction with 5-fluorocytosine/cytosine deaminase gene therapy for human malignant glioma cells mediated by adenovirus"Journal of Neuro-oncology. 66. 114-127 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kurozumi K, Tamiya T, et al.: "BDNF Gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model."Molecular Therapy. 9. 189-197 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kambara Y, Tamiya T, Ono Y, Ohtsuka S, Terada K, Adachi Y, Ichikawa T, Hamada H, Ohmoto T: "Combined radiation and gene therapy for brain tumors with adenovirus-mediated transfer of cytosine deaminase and uracil phosphoribosyltransferase genes"Cancer Gene Therapy. 9. 840-845 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeda M.Otsuka F, Suzuki J, Kishida M, Ogura T, Tamiya T, Makino H: "Involvement of activin/BMP system in development of human pituitary gonadotropinomas and nonfunctioning adenomas."Biochem Biophys Res Commun.. 306(4). 812-818 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujiwara K, Date I, Shingo T, Yoshida H, Kobayashi K, Takeuchi A, Yano A, Tamiya T, Ohmoto T: "Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor-secreting cells in a model of middle cerebral artery occlusion in rats."J.Neurosurg.. 99(6). 1053-1062 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kurozumi K, Tamiya T, Ono Y, Otsuka.S, Kambara H, Adachi Y, Ichikawa T, Hamada H, Ohmoto T: "Apoptosis induction with 5-fluorocytosine/cytosine deaminase gene therapy for human malignant glioma cells mediated by adenovirus"Journal of Neuro-oncology. 66. 117-127 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K, Honmou O, Houkin K, Date I, Hamada H: "BDNF Gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model."Molecular Therapy. 9. 189-197 (2004)
  • Description: 「研究成果報告書概要(欧文)」より