2002 Fiscal Year Final Research Report Summary
SCCA1 distal promoter for gene therapy of cervical intraepithelial neoplsia
| Project/Area Number |
13671724
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Ehime University |
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Principal Investigator |
HAMADA Katsuyuki Ehime University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (90172973)
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| Project Period (FY) |
2001 – 2002
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| Keywords | squamous cell carcinoma / IN / cervical cancer / gene therapy / p53 / SCCA1 / promoter / adenovirus |
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| Research Abstract |
Cervical intraepithelial neoplasia (CIN) has been increased for these 10-20 years especially in the young ages with 15-30 years, although advanced cervical cancer has been decreased for these 10-20 years. It has been strongly suggested that cervical cancer is developed by the infection of human papillomaivurs (HPV) and is infected in 90% of patients with HPV. CIN is treated by photodynamic therapy (PDT), laser treatment, cornization, but these treatment still nave some problems concerning treatment effect and steriligy. Therefore, a new method should be established for the treatment of CIN in young ages to be needed for sterility. SCCA1 gene was originally cloned from cervical cancer tissue and was expressed in cervical cancer tissue and normal squamous tissue in the cervix. In this study, we cloned and sequenced SCCA1 promoter, and characterized the promoter activity of SCCA1 promoter. To use for the determination of tissue specific promoter activity, we established cell lines of mild dysplasia, moderate dysplasia, severe dyplasia, and CIS. The proximal promoter of 500-bp upstream SCCA1 transcriptional start site was activated in invasive cervical cancer, and the distal promoter of 3.7-kb upstream SCCA1 transcriptional start site was activated in CIN cell lines. This distal promoter was introduced into adenoviru to express p53 to develop Adenovirus-SCCA1-3.7-p53 in order to determine growth inhibitory effect of this vector in invasive cervical cancer and CIN cell lines. Adenovirus-SCCA1-3.7-p53 induced strong apoptic changes especially in CIN but not in invasive cervical cancer, furthermore, showed strong growth inhibitory effect especially in CIN but not in invasive cervical cancer. From these results, it is suggested that distal promoter indroduced adenovirus vector (Adenovirus-SCCA1-3.7-p53) has the potential to treat CIN.
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Research Products
(6 results)
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[Publications] Hamada, K., Kohno, S., Iwamoto, M., Yokota, H., Okada, M., et al.: "Identification of the Human IAI.3B promoter element and its use in the construction of a replication-selective adenovirus for ovarian cancer therapy"Cancer Research. 63. 2506-2512 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hamada, K., Kohno, S., Iwamoto, M., Yokota, H., Okada, M., et al.: "Identification of the Human IAI.3B promoter element and its use in the construction of a replication-selective adenovirus for ovarian cancer therapy"Cancer Research. (in print).
Description
「研究成果報告書概要(欧文)」より
