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.
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