[Adenovirus-mediated double suicide gene therapy for experimental bladder carcinoma].
OBJECTIVE
To evaluate the feasibility and efficacy of cytocine deaminase-thymidine kinase (CD-TK) fusion double suicide gene therapy using adenovirus mediated CD-TK gene and green fluorescent rotein (GFP) gene combined with ganciclovir(GCV) or 5-flourocytosine(5-FC) in a murine subcutaneous bladder carcinoma model.


METHODS
A replication defective adenovirus vector containing CD-TK gene was used. Subcutaneous tumors were established in syngenic C57BL/6 female mice with 1 x 10(6) Mb49 cells. Intratumoral injection of AdCD-TK (1.58 x 10(8) PFU, qd x days) in combination with GCV (40 mg.kg(-1).d(-1), ip, qd x 10 days) or 5-FC (400 mg.kg(-1).d(-1), ip, qd x 10 days) was administered in vivo for the determination of treatment efficacy in separate controlled experiments.


RESULTS
In vivo experiments demonstrated that the mean volume of tumor in the group of AdCD-TK/GCV(326.58+/-109.56 mm(3)), AdCD-TK/5-FC (235.33+/-62.94 mm(3)) and AdCD-TK/(GCV+5-FC) (23.58+/-6.78 mm(3)) was reduced significantly compared with that of control group (993.51+/-158.32 mm(3)) (P=0.00), the mean volume of tumor in the group of AdCD-TK/(GCV+5-FC) was significantly less than that in the group of AdCD-TK/GCV or AdCD-TK/5-FC (P=0.04). Tumor necrosis was revealed by histomorphology compared with control animals.


CONCLUSIONS
Adenovirus mediated CD-TK double suicide gene combining with GCV or 5-FC could provide an effective therapy in an experimental murine bladder carcinoma by significantly inhibiting tumor growth. The treatment efficacy of AdCD-TK combining GCV and 5-FC was superior to that of AdCD-TK combining GCV or AdCD-TK combining 5-FC.
Tan
Wan-long
WL
Department of Urologic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. twl@fimmu.com
Xie
Yi
Y
Wu
Yuan-dong
YD
Zhu
Wen-hui
WH
Zheng
Shao-bin
SB
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism; D003673:Defective Viruses / Q000235:genetics; D005260:Female; D005437:Flucytosine / Q000494:pharmacology / Q000627:therapeutic use; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir