systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses系统性与潜在regulatable溶瘤腺病毒治疗宫颈癌.pdfVIP

Systemic Therapy for Cervical Cancer with Potentially Regulatable Oncolytic Adenoviruses Anna Kanerva1,2, Sergio Lavilla-Alonso1,3, Mari Raki1,3, Lotta Kangasniemi1,3, Gerd J. Bauerschmitz1,3,4, 5 ¨ 6 7 1,3 Koichi Takayama , Ari Ristimaki , Renee A. Desmond , Akseli Hemminki * 1 Cancer Gene Therapy Group, Molecular Cancer Biology Program and Transplantation Laboratory and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland, 2 Department of Obstetrics and Gynecology, Helsinki University Central Hospital (HUCH), Helsinki, Finland, 3 Transplantation Laboratory, HUSLAB, Helsinki University Central Hospital (HUCH), Helsinki, Finland, 4 Department of Obstetrics and Gynecology, Heinrich-Heine University, Duesseldorf, Germany, 5 Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan, 6 Department of Pathology, HUSLAB, Helsinki University Central Hospital (HUCH), and Genome- Scale Biology Program, University of Helsinki, Helsinki, Finland, 7 Comprehensive Cancer Center, Biostatistics and Bioinformatics Unit, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the cyclooxygenase-2 (Cox-2) or vascular endothelial growth factor (VEGF) promoter for controlling replication. Anti-inflammatory agents can lower Cox-2 protein levels and therefore we hypothesized that also the promoter might be affe