title: Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy.
abstract: Little is known concerning promoters or gene therapy specific for malignant glioma. To explore the potential use of midkine promoter in gene therapy for malignant glioma, we constructed a midkine promoter-based conditionally replicating adenovirus (Ad-MK). Midkine was overexpressed in malignant glioma tissues but cyclooxygenase-2 was not. The midkine promoter activity of the 600-bp fragment was 2 orders of magnitude higher in midkine-positive glioma cells than in midkine-negative primary normal brain cells. Ad-MK showed strong oncolytic effects in midkine-positive glioma cells but did not exhibit cytotoxicity in midkine-negative primary normal brain cells. The cell-killing effect was evident in E3-intact Ad-MK more than in E3-deleted Ad-MK. In an animal experiment, Ad-MK completely eradicated midkine-positive glioma xenografts. These findings indicate that midkine promoter-based conditionally replicative adenovirus might be a promising new modality of gene therapy for malignant glioma.
authors.affiliation: Department of Neurosurgery, Ehime University School of Medicine, Shitsukawa, Shigenobu, Onsen-gun, Ehime 791-0295, Japan. kouno@m.ehime-u.ac.jp
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Kou
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hamada
authors.forename: Hironobu
authors.initials: H
authors.lastname: Harada
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nagato
authors.forename: Koji
authors.initials: K
authors.lastname: Furukawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000601:surgery*; D002470:Cell Survival; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008565:Membrane Proteins; D000078792:Midkine; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012016:Reference Values
chemical_list: D016207:Cytokines; D017931:DNA Primers; D008565:Membrane Proteins; D000078792:Midkine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases