Syn3 provides high levels of intravesical adenoviral-mediated gene transfer for gene therapy of genetically altered urothelium and superficial bladder cancer.
Using our model to grow superficial human bladder cancer in the mouse bladder, we have found that the polyamide compound, Syn3, when injected intravesically for 1 hour at 1 mg/mL on two consecutive days, markedly increases rAd-beta-gal intravesical gene transfer and expression. This enhanced transgene expression was much greater than obtain by the use of 22% ethanol, which had previously been shown to increase intravesical adenoviral gene transfer, whereas little or no gene expression was seen with exposure to only rAd-beta-gal. beta-Galactosidase staining was seen in virtually every normal urothelial and superficial tumor cell present, including tumors that express little or no coxsackie-adenovirus receptors when Syn3 was present. High adenoviral-mediated gene transfer was also documented in the pig bladder using Syn3 in a similar protocol. Therefore, Syn3 may overcome the limitations of adequate intravesical adenoviral-mediated gene transfer and, when combined with an appropriate adenoviral-mediated gene, could offer an effective approach to the treatment of superficial bladder cancer and perhaps even genetically altered precursor lesions.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Motoyuki
M
Yamashita
Charles J
CJ
Rosser
Jain-Hua
JH
Zhou
Xin-Qiao
XQ
Zhang
Robert J
RJ
Connor
Heidrun
H
Engler
Daniel C
DC
Maneval
Takashi
T
Karashima
Bogdan A
BA
Czerniak
Colin P N
CP
Dinney
William F
WF
Benedict
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002793:Cholic Acids / Q000008:administration & dosage*; D004187:Disaccharides / Q000008:administration & dosage*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D013552:Swine; D014162:Transfection; D014407:Tumor Cells, Cultured; D019459:Urothelium / Q000378:metabolism*
D002793:Cholic Acids; D004187:Disaccharides; C525256:Syn3 compound