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Suppression of proliferative cholangitis in a rat model with direct adenovirus‐mediated retinoblastoma gene transfer to the biliary tract
Author(s) -
Terao Ryuta,
Honda Kazuo,
Hatano Etsuro,
Uehara Tetsuya,
Yamamoto Masayuki,
Yamaoka Yoshio
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280301
Subject(s) - hepatolithiasis , biliary tract , genetic enhancement , bile duct , adenoviridae , immunohistochemistry , medicine , cancer research , transfection , ampulla of vater , pathology , biology , hepatectomy , carcinoma , gene , surgery , biochemistry , resection
Abstract Proliferative cholangitis (PC) associated with hepatolithiasis develops the stricture of main bile ducts, and is the main cause of residual and/or recurrent stones after repeated treatments for hepatolithiasis. The aim of this study was to inhibit PC using the cytostatic gene therapy with direct adenovirus‐mediated retinoblastoma (Rb) gene transfer to the biliary tract. PC was induced by introducing a fine nylon thread into the bile duct in a rat model. The adenovirus vector encoding a nonphosphorylatable, constitutively active form of retinoblastoma gene product (AdRb) was administered directly into the biliary tract. The adenovirus vector encoding β‐galactosidase (AdlacZ) was also given as a control. The bile duct wall thickness and 5′‐bromodeoxyuridine (BrdU) labeling index were compared among uninfected, AdlacZ‐infected, and AdRb‐infected PC rats. The Rb expression in the bile duct was detected using reverse‐transcription polymerase chain reaction (RT‐PCR) and immunohistochemical study. AdRb‐infected bile ducts showed inhibition of the epithelial and fibrous tissue proliferation and the peribiliary gland hyperplasia, resulting in a significant reduction of wall thickness compared with uninfected and AdlacZ‐infected ones. The BrdU labeling index was 4.87% ± 3.06% in the AdRb‐infected bile ducts, while those of uninfected and AdlacZ‐infected ones were 15.48% ± 4.61% and 11.72% ± 1.23%, respectively ( P < .05). In conclusion, our cytostatic gene therapy approach using direct Rb gene transfer into the biliary tract suppressed PC in a rat model and may offer an effective therapeutic option for reducing recurrences following treatments against hepatolithiasis.