title: A combinatory use of adenoviruses expressing melanoma differentiation-associated gene-7 and replication-competent adenoviruses produces synergistic effects on pancreatic carcinoma cells.
abstract: Type 5 adenoviruses expressing mda-7 gene (Ad-mda-7) induced cell death in various kinds of human tumors, but pancreatic carcinoma cells were relatively resistant to Ad-mda-7-mediated cytotoxicity. We then examined whether infection of Ad-mda-7 together with replication-competent Ad produced combinatory cytotoxic effects. We prepared replication-competent Ad, defective of the E1B55kDa gene or activated by a transcriptional regulatory region of the midkine or the survivin gene of which the expression was up-regulated in human tumors. Type 5 Ad bearing the exogenous regulatory region were further modified by replacing the fiber-knob region with that of type 35 Ad. Pancreatic carcinoma cells were infected with replication-incompetent Ad-mda-7 and the replication-competent Ad. Combinatory effects were examined with the CalcuSyn software and cell cycle analyses. Ad-mda-7 and the replication-competent Ad achieved cytotoxicity to pancreatic carcinoma. A combinatory use of Ad-mda-7 and either Ad defective of the E1B55kDa gene or Ad activated by the regulatory region produced synergistic cytotoxic effects. Cell cycle analyses demonstrated that the combination increased sub-G1 populations. These data collectively suggest that expression of MDA-7 augments cytotoxicity of replication-competent Ad and achieves adjuvant effects on Ad-mediated cell death.
authors.affiliation: Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.|Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Boya
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan.|Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan.
authors.forename: Hongdan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China.|Cell Therapy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Quanhai
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Thoracic Diseases, Chiba Cancer Center, Chiba, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shingyoji
authors.affiliation: Department of Thoracic Diseases, Chiba Cancer Center, Chiba, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Surgery, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. mtagawa@chiba-cc.jp.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan. mtagawa@chiba-cc.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D000099180:Interleukin-24
keywords: Cytotoxicity; MDA-7; Pancreatic carcinoma; Replication-competent adenovirus