Eradication of Therapy-resistant Human Prostate Tumors Using an Ultrasound-guided Site-specific Cancer Terminator Virus Delivery Approach (Articolo in rivista)

Type
Label
  • Eradication of Therapy-resistant Human Prostate Tumors Using an Ultrasound-guided Site-specific Cancer Terminator Virus Delivery Approach (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Greco A; Di Benedetto A; Howard CM; Kelly S; Nande R; Dementieva Y; Miranda M; Brunetti A; Salvatore M; Claudio L; Sarkar D; Dent P; Curiel DT; Fisher PB; Claudio PP (2010)
    Eradication of Therapy-resistant Human Prostate Tumors Using an Ultrasound-guided Site-specific Cancer Terminator Virus Delivery Approach
    in Molecular therapy (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Greco A; Di Benedetto A; Howard CM; Kelly S; Nande R; Dementieva Y; Miranda M; Brunetti A; Salvatore M; Claudio L; Sarkar D; Dent P; Curiel DT; Fisher PB; Claudio PP (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Marshall Univ, Joan C Edwards Sch Med, Dept Surg, Dept Biochem & Microbiol, Huntington, WV 25755 USA 2. Univ Naples Federico 2, Dept Biomorphol & Funct Sci, Naples, Italy 3. IRCCS SDN Fdn, Naples, Italy 4. CEINGE Adv Biotechnol Scarl, Naples, Italy 5. Univ Aquila, Fac Sci, Dept Basic & Appl Biol, I-67100 Laquila, Italy 6. Marshall Univ, Dept Orthoped Surg, Huntington, WV USA 7. Marshall Univ, Dept Math, Huntington, WV USA 8. Fdn Senatore Pascale, NCI, Dept Urol, Naples, Italy 9. Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Dept Human & Mol Genet,VCU Inst Mol Med, Richmond, VA USA 10. Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, VCU Inst Mol Med,Dept Biochem & Mol Biol, Richmond, VA USA 11. Univ Alabama, Dept Med, Div Human Gene Therapy, Birmingham, AL 35294 USA 12. Univ Alabama, Dept Pathol, Div Human Gene Therapy, Birmingham, AL 35294 USA 13. Univ Alabama, Dept Surg, Div Human Gene Therapy, Birmingham, AL 35294 USA 14. Univ Alabama, Gene Therapy Ctr, Div Human Gene Therapy, Birmingham, AL 35294 USA 15. Marshall Univ, Joan C Edwards Sch Med, Dept Surg, Huntington, WV USA (literal)
Titolo
  • Eradication of Therapy-resistant Human Prostate Tumors Using an Ultrasound-guided Site-specific Cancer Terminator Virus Delivery Approach (literal)
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 (microbubbles-MBs) 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. (literal)
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