Antitunor effect of carcinoma cells transduced with herpes simplex virus - thymidine kinase by gancyclovir and radiation

BACKGROUND: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. METHODS: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. RESULTS: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X 10(6) CFU/ml . After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. CONCLUSIONS: The result s suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

A Case of Hemobilia Associated with Spontaneous Gallbladder Hemorrhage / 대한소화기내시경학회지

Hemobilia is a hemorrhage into the biliary tract that may follow trauma (including surgical and percutaneous techniques in hepatobiliary system), aneurysms of the hepatic artery (and its branch), tumors of the biliary tract, hepatoma, inflammation, liver abscess, and gallstone disease. But, a case has not been reported involving of hemobilia associated with gallbladder hemorrhage without obvious predisposing factors or causes. A 62-year-old woman was admitted to Kyunghee Medical Center due to intermittent nausea, and right upper quadrant pain for 2 days before admission. She had no history of abdominal trauma. On the second and third day of her stay, she experienced melena of which the amount was about 300 ml. Abdominal ultrasonography revealed a gallbladder with a 8 mm sized cystic lesion attached to the fundus. Computed tomographic (CT) evaluation of the abdomen demonstrated a highly enhanced 7~8 mm sized nodular mass in the lumen of the gallbladder. The gallbladder, cystic duct, and CBD were dilated due to the filling of blood clots or sludge material. An ERCP was performed and bleeding from the papilla of Vater was confirmed. Subsequently, emergent laparoscopic cholecystectomy was conducted. Pathologic evaluation revealed a grayish-red gallbladder that had a ruptured vessel. The ruptured vessel showed a severe hypertrophic state but there was no evidence of vasculitis, aneurysm, arterio-venous malformation, or malignancy. The case is here in reported of hemobilia associated with spontaneous gallbladder hemorrhage.