title: Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.
abstract: We studied the effect of suicide gene therapy using an adenovirus vector expressing the cytosine deaminase (CD) gene combined with irradiation therapy (chemo-radio-gene therapy) for human colorectal cancer cells. Since serum CEA levels are elevated in patients with some malignant tumors including colorectal cancer, we applied the CEA promoter to chemo-radio-gene therapy, expecting tumor-specific expression of the CD gene. In in vitro study, we succeeded in selective expression of the target CD gene and growth inhibition in only CEA-producing tumor cells; Further the inhibitory effect was enhanced by combination with radiation therapy in an irradiation dose-dependent manner. In addition, in in vivo study, a significant growth inhibition was observed in chemo-radio-gene therapy in comparison with radiation therapy alone or suicide gene therapy alone. Thus, we suggest that tumor-specific chemo-radio-gene therapy may be a useful strategy for human colorectal cancer.
authors.affiliation: 1st Department of Surgery, Nara Medical University, Kashihara, Japan. mu42724@naramed-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.forename: F
authors.initials: F
authors.lastname: Koyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: K
authors.initials: K
authors.lastname: Kamada
authors.forename: A
authors.initials: A
authors.lastname: Naito
authors.forename: S
authors.initials: S
authors.lastname: Hirao
authors.forename: T
authors.initials: T
authors.lastname: Mukogawa
authors.forename: H
authors.initials: H
authors.lastname: Hamada
authors.forename: Y
authors.initials: Y
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009700:Nucleoside Deaminases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil