Open AccessSuicide Gene Therapy for Chemically Induced Rat Bladder Tumor Entailing Instillation of Adenoviral Vectors
Author(s) -
Akasaka Shuji,
Suzuki Satoru,
Shimizu Hiroyuki,
Igarashi Takehito,
Akimoto Masao,
Shimada Takashi
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01131.x
Subject(s) - genetic enhancement , suicide gene , bladder cancer , ganciclovir , medicine , adenoviridae , cancer research , transitional cell carcinoma , in vivo , viral vector , pathology , vacuolization , cancer , immunology , biology , gene , virus , biochemistry , microbiology and biotechnology , human cytomegalovirus , recombinant dna
The efficacy of an in vivo gene therapy protocol making use of an adenoviral vector in the treatment of bladder cancer was examined. Bladder tumors were induced in rats by oral administration of BBN (N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine). Histologically, such tumors resemble those seen in human bladder cancer, and the cells can be selectively transduced using adenoviral vectors. The therapeutic protocol thus entailed instillation of an adenoviral vector containing the HSV‐tk suicide gene into rat bladder followed by a regimen of intraperitoneal ganciclovir (GCV) injections. Histological examination after a short‐term GCV regimen (3 days) revealed marked vacuolization of the tumor cells. Moreover, TUNEL assays showed that the cytotoxic reaction was mediated by apopto‐sis. Following a long‐term GCV regimen (14 days), tumor growth was significantly inhibited and glandular metaplasia was observed. This is the first report demonstrating the efficacy of in vivo suicide gene therapy in a chemically induced transitional cell carcinoma like that seen in most human bladder cancer. Intravesical instillation is already a well established clinical technique. Our findings indicate that now there is a strong potential for its incorporation into new and useful gene therapies aimed at the treatment of human bladder cancer.