Usefulness of repeated direct intratumoral gene transfer using hemagglutinating virus of Japan-liposome method for cytosine deaminase suicide gene therapy.
To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.
Kanyama
H
H
Department of Surgery II, Osaka University Medical School, Suita, Japan. h-kan@qf6.s0-net.nc.jp
Tomita
N
N
Yamano
T
T
Aihara
T
T
Miyoshi
Y
Y
Ohue
M
M
Sekimoto
M
M
Sakita
I
I
Tamaki
Y
Y
Kaneda
Y
Y
Senter
P D
PD
Monden
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D043525:Cytosine Deaminase; D005240:Feasibility Studies; D005260:Female; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology; D005472:Fluorouracil / Q000493:pharmacokinetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D015552:Injections, Intralesional; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009700:Nucleoside Deaminases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018108:Respirovirus / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D012333:RNA, Messenger; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil