RGD Reference Report - Adenovirus-mediated soluble FLT-1 gene therapy for ovarian carcinoma. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Adenovirus-mediated soluble FLT-1 gene therapy for ovarian carcinoma.

Authors: Mahasreshti, PJ  Navarro, JG  Kataram, M  Wang, MH  Carey, D  Siegal, GP  Barnes, MN  Nettelbeck, DM  Alvarez, RD  Hemminki, A  Curiel, DT 
Citation: Mahasreshti PJ, etal., Clin Cancer Res. 2001 Jul;7(7):2057-66.
RGD ID: 2301254
Pubmed: PMID:11448924   (View Abstract at PubMed)

PURPOSE: We hypothesized that adenovirus-mediated soluble fms-like tyrosine kinase receptor (sFLT-1) gene therapy can inhibit the ovarian tumor growth and increase survival of mice in the context of ovarian carcinoma. EXPERIMENTAL DESIGN: We constructed an infectivity-enhanced recombinant adenovirus (AdRGDGFPsFLT-1) expressing soluble FLT-1 and green fluorescent protein (GFP). An adenovirus AdRGDGFP expressing GFP alone was used as control. The functional validation of adenovirus-mediated sFLT-1 was determined by an in vitro human umbilical vein endothelial cell proliferation inhibition assay. To evaluate the therapeutic potential of adenovirus-expressed sFLT-1 to inhibit the growth of ovarian tumors and to increase the survival duration of mice with ovarian tumors, two tumor models were used. First, SKOV3.ip1 ovarian carcinoma cells were infected ex vivo with either AdRGDGFPsFLT-1 or AdRGDGFP or uninfected and then inoculated s.c. into BALB/c nude mice, and tumor growth was monitored. Second, SKOV3.ip1 cells were inoculated i.p. into CB17 SCID mice and then treated with two doses of either AdRGDGFPsFLT-1 or AdRGDGFP or with PBS on days 1 and 14 after inoculation of cells, and the survival duration was monitored. RESULTS: Treatment with adenovirus-expressed sFLT-1 significantly inhibited the proliferation of human umbilical vein endothelial cells. The s.c. tumor nodules in mice derived from cells infected with AdRGDGFPsFLT-1 were significantly smaller than those infected with either AdRGDGFP or uninfected. In addition, i.p. administration of the AdRGDGFPsFLT-1 resulted in a significant increase in the survival times of mice compared with AdRGDGFP- or PBS-treated mice. CONCLUSIONS: Our results suggest that adenovirus-mediated sFLT-1 gene therapy can effectively inhibit ovarian tumor growth and increase survival in a murine model of ovarian carcinoma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ovarian Neoplasms  IMP 2301254 RGD 
Ovarian Neoplasms  ISOFLT1 (Homo sapiens)2301254; 2301254 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt1  (Fms related receptor tyrosine kinase 1)

Genes (Mus musculus)
Flt1  (FMS-like tyrosine kinase 1)

Genes (Homo sapiens)
FLT1  (fms related receptor tyrosine kinase 1)


Additional Information