title: Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer.
abstract: To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Onimaru
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Egami
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Junji
authors.initials: J
authors.lastname: Uchino
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D014162:Transfection; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D017500:Adenovirus E1A Proteins; D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D003841:Deoxycytidine; C509186:TERT protein, human; D019098:Telomerase; D000093542:Gemcitabine