@article{279163f7f1814799b51acd25c411c9be,
title = "Eradication of therapy-resistant human prostate tumors using an ultrasound-guided site-specific cancer terminator virus delivery approach",
abstract = "Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation-associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x L. However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major challenge for gene therapy is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubblesMBs) are viable candidates for gene delivery/therapy. Here, we show that MB/Ad.mda-7 complexes targeted to DU-145 cells using US dramatically reduced tumor burden in xenografted nude mice. Additionally, US-guided MB/CTV delivery completely eradicated not only targeted DU-145/Bcl-x L-therapy-resistant tumors, but also nontargeted distant tumors (established in the opposite flank), thereby implementing a cure. These findings highlight potential therapeutic applications of this novel image-guided gene therapy technology for advanced PC patients with metastatic disease.",
author = "Adelaide Greco and {Di Benedetto}, Altomare and Howard, {Candace M.} and Sarah Kelly and Rounak Nande and Yulia Dementieva and Michele Miranda and Arturo Brunetti and Marco Salvatore and Luigi Claudio and Devanand Sarkar and Paul Dent and Curiel, {David T.} and Fisher, {Paul B.} and Claudio, {Pier P.}",
note = "Funding Information: We gratefully acknowledge the Marshall University Biochemistry and Microbiology & Surgery Departments for their support. This study was supported in part by the awards number CA131395 and CA140024 from the National Cancer Institute, and in part by NIH-COBRE 5P20RR020180, WV-INBRE 5P20RR016477, and the Cell Differentiation and Development Center (CDDC), Marshall University (to P.P.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institute of Health. We also acknowledge support from: the Goldhirsh Foundation and the Dana Foundation (to D.S.); NIH grants P01 CA104177, R01 CA35675, and R01 CA097318 (to P.B.F.); the Samuel Waxman Cancer Research Foundation (to P.B.F.); and the National Foundation for Cancer Research (NFCR) (to P.B.F.). S.K. is the recipient of a fellowship from WV NASA Space Grant Consortium. We also gratefully acknowledge SonoSite, Inc. for loaning the Micro-Maxx, SonoSite ultrasound portable platform and Targeson, Inc. for the custom synthesis of the ultrasound contrast agent that were used in this study. D.S. is a Harrison Endowed Scholar in Cancer Research, VCU Massey Cancer Center. P.B.F. holds the Thelma Newmeyer Corman Chair in Cancer Research, VCU Massey Cancer Center.",
year = "2010",
month = feb,
doi = "10.1038/mt.2009.252",
language = "English",
volume = "18",
pages = "295--306",
journal = "Molecular Therapy",
issn = "1525-0016",
number = "2",
}