TY - JOUR
T1 - A novel suicide gene therapy targeting the overexpression of eukaryotic initiation factor 4E improves survival in a rat peritoneal carcinomatosis model
AU - Byrnes, Kerry
AU - Li, Benjamin D.L.
AU - Holm, Neal
AU - Li, Jie
AU - Okadata, Yoshi
AU - De Benedetti, Arrigo
AU - Nedeljkovic-Kurepa, A.
AU - Mathis, James Michael
AU - Chu, Quyen D.
PY - 2007/8/1
Y1 - 2007/8/1
N2 - Background: Eukaryotic Initiation Factor 4E (eIF4E) is pivotal in translating mRNAs with complex 5′ un-translated regions (UTRs). A target-specific gene therapy was developed by splicing a complex 5′UTR upstream of the herpes simplex virus thymidine kinase (TK) gene in an adenovirus vector (Ad-HSV-UTK). Translation of the suicide TK gene is restricted to cells that overexpress eIF4E. We investigated the efficacy of this novel therapy in a rat peritoneal carcinomatosis (PC) model. Methods: A PC model was developed by implanting a syngeneic 0.25 cm3 tumor into Fisher 344 rats' omentum. Rats were grouped as follow: No surgery (Ø CS), cytoreductive surgery alone (CS), and CS + Ad-HSV-UTK + gancyclovir (GCV). 109 Ad-HSV-UTK was injected intraperitoneally (i.p.) and GCV (50 mg/kg) was administered i.p. every other day, beginning on postoperative day 2. The Kaplan-Meier survival method and log-rank test were statistical tests used. Results: Treated rats had a significantly longer median and overall survival than the Ø CS and CS groups (P = .012). The median survivals for the treated rats, Ø CS, CS were 18 days, 9 days, and 11 days, respectively. Conclusions: Treatment with a novel suicide gene therapy following cytoreductive surgery prolonged survival in a rat peritoneal carcinomatosis model.
AB - Background: Eukaryotic Initiation Factor 4E (eIF4E) is pivotal in translating mRNAs with complex 5′ un-translated regions (UTRs). A target-specific gene therapy was developed by splicing a complex 5′UTR upstream of the herpes simplex virus thymidine kinase (TK) gene in an adenovirus vector (Ad-HSV-UTK). Translation of the suicide TK gene is restricted to cells that overexpress eIF4E. We investigated the efficacy of this novel therapy in a rat peritoneal carcinomatosis (PC) model. Methods: A PC model was developed by implanting a syngeneic 0.25 cm3 tumor into Fisher 344 rats' omentum. Rats were grouped as follow: No surgery (Ø CS), cytoreductive surgery alone (CS), and CS + Ad-HSV-UTK + gancyclovir (GCV). 109 Ad-HSV-UTK was injected intraperitoneally (i.p.) and GCV (50 mg/kg) was administered i.p. every other day, beginning on postoperative day 2. The Kaplan-Meier survival method and log-rank test were statistical tests used. Results: Treated rats had a significantly longer median and overall survival than the Ø CS and CS groups (P = .012). The median survivals for the treated rats, Ø CS, CS were 18 days, 9 days, and 11 days, respectively. Conclusions: Treatment with a novel suicide gene therapy following cytoreductive surgery prolonged survival in a rat peritoneal carcinomatosis model.
UR - http://www.scopus.com/inward/record.url?scp=34547569976&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2007.04.009
DO - 10.1016/j.surg.2007.04.009
M3 - Article
C2 - 17689695
AN - SCOPUS:34547569976
VL - 142
SP - 270
EP - 275
JO - Surgery (United States)
JF - Surgery (United States)
SN - 0039-6060
IS - 2
ER -