Cyclooxygenase 2 promoter-based replication-selective adenoviral vector for hypopharyngeal cancer.
OBJECTIVE
To explore the potential clinical application of the oncolytic activity of cyclooxygenase 2 (COX-2) promoter-based, conditional, replication-selective adenovirus vector for hypopharyngeal squamous cell carcinoma.


METHODS
In vivo study and retrospective study.


METHODS
Kobe University Hospital, Kobe, Japan.


METHODS
Expression of COX-2 in hypopharyngeal cancers treated at Kobe University Hospital was immunohistochemically investigated. In addition, nude mice bearing human hypopharyngeal cancer cells (H891) were used to analyze oncolytic activity of a conditional replication-selective adenovirus vector in which the expression of E1a, required for viral replication, is controlled by the COX-2 promoter Ad-COX2-E1a.


RESULTS
In vivo assays showed significant growth suppression in the murine hypopharyngeal model. Cyclooxygenase 2 expression was observed in 75.3% of hypopharyngeal cancers, especially in differentiated tumor cells (P = .001; r = 0.433).


CONCLUSIONS
In this study, we demonstrated the potential of oncolytic therapy using the COX-2-promoter based, conditional, replication-selective adenovirus for COX-2-expressing hypopharyngeal squamous cell carcinomas.
Nakagawa
Takahiro
T
Department of Otolaryngology-Head and Neck Surgery, Kobe University, Graduate School of Medicine, Kobe, Japan.
Tanaka
Hironori
H
Shirakawa
Toshiro
T
Gotoh
Akinobu
A
Hayashi
Yoshitake
Y
Hamada
Katsuyuki
K
Tsukuda
Mamoru
M
Nibu
Ken-ichi
K
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009374:Neoplasms, Experimental; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000235:genetics*
D004273:DNA, Neoplasm; D051546:Cyclooxygenase 2