Abstract | OBJECTIVE: METHODS: Initial experiments evaluated whether icodextrin would adversely affect replication of a clinical grade infectivity enhanced conditionally replicative adenovirus (Delta24-RGD). Virus was added to prepared blinded solutions of PBS or icodextrin (20%) and then evaluated in vitro in various human ovarian cancer cell lines (SKOV3.ip1, PA-1, and Hey) and in vivo in a SKOV3.ip1 human ovarian cancer IP murine model. Viral replication was measured by detecting adenovirus E4 gene levels utilizing QRT-PCR. Survival was subsequently evaluated in a separate SKOV3.ip1 ovarian cancer IP murine model. Cohorts of mice were treated in blinded fashion with PBS alone, icodextrin alone, PBS+Delta24-RGD, or icodextrin+Delta24-RGD. Survival data were plotted on Kaplan-Meier curve and statistical calculations performed using the log-rank test. RESULTS: There was no adverse affect of icodextrin on vector replication in the ovarian cancer cell lines nor murine model tumor samples evaluated. Median survival in the IP treated animal cohorts was 23 days for the PBS group, 40 days for the icodextrin group, 65 days for the PBS+Delta24-RGD group, and 105 days for icodextrin+Delta24-RGD (p=0.023). Of note, 5 of the 10 mice in the icodextrin+Delta24-RGD group were alive at the end of the study period, all without evidence of tumor (120 days). CONCLUSIONS:
|
Authors | Rodney P Rocconi, Michael T Numnum, Zeng B Zhu, Baogen Lu, Minghui Wang, Angel A Rivera, Mariam Stoff-Khalili, Ronald D Alvarez, David T Curiel, Sharmila Makhija |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 103
Issue 3
Pg. 985-9
(Dec 2006)
ISSN: 0090-8258 [Print] United States |
PMID | 16857247
(Publication Type: Journal Article)
|
Chemical References |
- Dialysis Solutions
- Glucans
- Icodextrin
- Glucose
|
Topics |
- Animals
- Dialysis Solutions
(administration & dosage, therapeutic use)
- Disease Models, Animal
- Female
- Genetic Therapy
- Glucans
(administration & dosage, therapeutic use)
- Glucose
(administration & dosage, therapeutic use)
- Icodextrin
- Infusions, Parenteral
- Mice
- Ovarian Neoplasms
(pathology, therapy)
|