MR Guided Pulsed High Intensity Focused Ultrasound Enhancement of Gene Therapy Combined with Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment.

摘要

This work aimed to test the hypothesis that MR guided pulsed HIFU exposures enhance gene delivery and increase the efficacy of gene therapy in inhibiting prostate cancer growth in vivo, particularly when combined with AD or RT. We developed techniques for the treatment of prostate tumor-bearing mice using a clinical MRgHIFU device. We performed animal studies for quantitative measurement of the doxorubicin concentration in HIFU treated prostate tumors to evaluate the optimal ultrasonic parameters derived from experiments using an acoustic phantom. We also performed experiments on the efficacy of MRgHIFU enhancement of docetaxel delivery combined with RT in inhibiting prostate tumor growth in vivo. We investigated the MRgHIFU effect on the enhancement of gene therapy using AS-MDM2 and bcl-2 in implanted prostate tumors in mice in vivo by measuring the protein expression level of MDM2, p53 and p21 using immunohistochemical staining and west blotting techniques. We also performed experiments on the efficacy of MRgHIFU enhancement of AS-MDM2 delivery in inhibiting prostate tumor growth in vivo. Our results show that MRgHIFU is safe and effective for the enhancement of drug delivery in prostate tumor.