Adenovirus-Mediated p53 Gene Transfer to the Bile Duct by Direct Administration Into the Bile in a Rat Cholangitis Model1

An archaeal histone-like protein mediates efficient p53 gene transfer and facilitates its anti-cancer effect in vitro and in vivo

“…Many investigations and clinical trials using transfer of viral genes encoding wt-p53 had been performed. [22][23][24] Viral vectors, such as genetically engineered adenovirus, had been shown to be capable of gene delivery both in vitro and in vivo. However, they still suffered from some problems in clinical use.…”

Significance of Controlling Chronic Proliferative Cholangitis in the Treatment of Hepatolithiasis

“…Unfortunately, less attention has been paid to this relationship of refractory biliary infection with residual CPC and its role in postoperative stone recurrence. It is now recognized that, beyond the routine antibiotic treatment, additional therapeutic approaches are required for the subsequent treatment of residual CPC after choledochoscopic lithotomy; the goal is to interrupt this vicious cycle in which refractory biliary infection leads to stone recurrence [37][38][39]46]. Another point that needs to be emphasized is that the pathological structure of this kind of chronic proliferative inflammation is also a basis for hepatolithiasis-associated cholangiocarcinoma.…”

“…In the past, improvement of surgical skills in the treatment of hepatolithiasis received great attention while the connection between postoperative residual CPC and stone recurrence went unrecognized [5, 14–17, 35]. In recent years, with a deeper understanding of pathological changes in hepatolithiasis, more and more attention has been paid to the vicious cycle between intrahepatic calculi and CPC, a condition that is considered an important reason for the poor prognosis in hepatolithiasis patients [37–39]. Both the stone itself and the secondary biliary infection secondary to it can stimulate persistent hyperplasia in the biliary duct wall, leading to the occurrence of CPC and biliary stricture.…”

“…In fact, CPC is the key linkage in this vicious cycle [11–17, 40]. In this regard, ignorance of postoperative CPC treatment is responsible, at least in part, for the current poor prognosis in hepatolithiasis patients [37, 39, 41].…”

Oncolytic Gene Therapy Combined with Double Suicide Genes for Human Bile Duct Cancer in Nude Mouse Models

“…b-Galactosidase expression in bile duct epithelial cells was observed 3 d after the administration of HVJ-cationic liposomes containing pCAG-lacZ through the papilla of Vater in a rat model [1]. Intrabiliary administration of the adenovirus vector of the retinoblastoma (RB) gene [2] and the p53 gene [3] inhibited epithelial and fibrous tissue proliferation in a cholangitis model of rats. However, due to a lack of cancer specificity, the application of this method to the treatment of bile duct cancer is limited.…”