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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16503


    Title: A novel targeting modality for renal cell carcinoma: human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D
    Authors: 謝嘉玲;Hsieh, Chia-Ling
    Contributors: 生物科技學系
    Keywords: adenoviral vectors;gene therapy;osteocalcin promoter;renal cell carcinoma;vitamin C;vitamin D3
    Date: 2010-11
    Issue Date: 2012-11-23 17:13:57 (UTC+8)
    Abstract: "Background
    Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone-like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin-regulatable hOC promoter for RCC-specific transcriptional targeting, and examined the anti-tumor effect of vitamins C and D3 with hOC-based adenoviral vectors towards RCC.

    Methods
    Real-time reverse transcriptase-polymerase chain reaction measured OC expression induced by vitamins C and D3, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC-cytotoxic effects of concomitant vitamins and hOC promoter-based adenoviral vectors, Ad-hOC-TK and Ad-hOC-E1, were evaluated in both cell culture and a xenograft murine model.

    Results
    We found that high doses of vitamin C induced H2O2-dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D3 treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co-administrated Ad-hOC-E1.

    Conclusions
    The results obtained in the present study demonstrate that vitamins C and D3 synergized with the anti-tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy. Copyright © 2010 John Wiley & Sons, Ltd."
    Relation: JOURNAL OF GENE MEDICINE
    Appears in Collections:[生物科技學系] 期刊論文

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