title: Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.
abstract: In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 10(10) , 1.0 × 10(11) , and 1.0 × 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199).
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ariyoshi
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sadahira
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Motoo
authors.initials: M
authors.lastname: Araki
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ebara
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
mesh_terms: D000368:Aged; D017209:Apoptosis; D001706:Biopsy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local; D011336:Probability; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000601:surgery* / Q000628:therapy*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D017430:Prostate-Specific Antigen
keywords: REIC/Dkk-3; gene therapy; localized prostate cancer; neoadjuvant therapy