Abstract
Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes.
Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.
Keywords: Retinoblastoma, RB, p130, p53, tumor suppressor gene, microbubbles, ultrasound, systemic targeted viral gene delivery, radiation, external beam radiation, apoptosis induction, prostate cancer.
Current Gene Therapy
Title:Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer
Volume: 13 Issue: 3
Author(s): Rounak Nande, Adelaide Greco, Michael S. Gossman, Jeffrey P. Lopez, Luigi Claudio, Marco Salvatore, Arturo Brunetti, James Denvir, Candace M. Howard and Pier Paolo Claudio
Affiliation:
Keywords: Retinoblastoma, RB, p130, p53, tumor suppressor gene, microbubbles, ultrasound, systemic targeted viral gene delivery, radiation, external beam radiation, apoptosis induction, prostate cancer.
Abstract: Combining radiation therapy and direct intratumoral (IT) injection of adenoviral vectors has been explored as a means to enhance the therapeutic potential of gene transfer. A major challenge for gene transfer is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles) are viable candidates to enhance targeted delivery of systemically administered genes.
Here we show that p53, pRB, and p130 gene transfer mediated by US cavitation of microbubbles at the tumor site resulted in targeted gene transduction and increased reduction in tumor growth compared to DU-145 prostate cancer cell xenografts treated intratumorally with adenovirus (Ad) or radiation alone. Microbubble-assisted/US-mediated Ad.p53 and Ad.RB treated tumors showed significant reduction in tumor volume compared to Ad.p130 treated tumors (p<0.05). Additionally, US mediated microbubble delivery of p53 and RB combined with external beam radiation resulted in the most profound tumor reduction in DU-145 xenografted nude mice (p<0.05) compared to radiation alone. These findings highlight the potential therapeutic applications of this novel image-guided gene transfer technology in combination with external beam radiation for prostate cancer patients with therapy resistant disease.
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Cite this article as:
Nande Rounak, Greco Adelaide, Gossman Michael S., Lopez Jeffrey P., Claudio Luigi, Salvatore Marco, Brunetti Arturo, Denvir James, Howard Candace M. and Claudio Pier Paolo, Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer, Current Gene Therapy 2013; 13 (3) . https://dx.doi.org/10.2174/1566523211313030001
DOI https://dx.doi.org/10.2174/1566523211313030001 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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