ABSTRACT
Objective To compare the efficacy and safety of E1B gene-deleted adenovirus (H101)and ethanol in treating advanced pancreatic carcinomas by intratumoral injection combined with intravenous gemcitabine.Methods We constructed an orthotopic nude mouse model of pancreatic carcinoma through cancer cell injection into pancreas.A total of 54 nude mice were randomly allocated to 6 groups to accept H101,ethanol or saline (control) intratumoral injection,combined with or without intravenous gemcitabiein.The animals were sacrificed 4 weeks after the treatment and the pancreatic tumors were collected to determine the size,existence of metastasis,distribution of virus by indirect immunofluorescence and apoptosis in tumor by TUNEL and electron microscope.Results All mice completed the scheduled treatment,while 3 died in 48 hours after ethanol injection resulting in a mortality of 16.7％ (3/18).On the contrary,no mice died in the adenovirus injcction group.The average tumor size in group of H101 intratumoral injection combined with intravenous gemcitabie was significant smaller than that in group of saline injection with or without systemic gemcitabie (P =0.008,0.040,respectively).Similar differences were observed between ethanol intratumoral injection and control groups (P =0.012,0.041).Meanwhile,the H101 was absent in all the other organs except the pancreas,which meant that the selectivity of the H101 was tremcndous.The virus combine gemcitabie group had higher apoptosis rate in tumor (83.2 ± 35.7) ％,determined by TUNEL.Conclusion E1B gene-deleted adenovirus intratumral injection in combination with intravenous gemcitabine treating pancreatic carcinomas is efficient and safe,in spite of its lower effectiveness than ethanol.
ABSTRACT
Objective To investigate the effect of MHC class Ⅱ transactivator( MHC Ⅱ TA ) on MHC Ⅱ expression of human and rat pancreatic cancer cell line CaPanC-2 and PanC-02. Methods The recombinant adenovirus (Ad-C Ⅱ TA) was transfected into the CaPanC-2 cell and the PanC-02 cell, then it was cultured for 24, 48, 72 h. The C Ⅱ TA mRNA expressions were assayed by Real Time PCR and CⅡ TA protein expressions were determined by Western blotting. The percentage of positive expression cells of MHC Ⅱ were measured by flow cytometry. Results The C Ⅱ TA mRNA expressions of CaPanC-2 cell at 24, 48, 72 h were 16769 ± 6455, 261568 ±348850 and 834816 ±97783 folds higher than that of control group (P <0.05). The CⅡTA mRNA expressions of PanC-02 was 548546 ± 87755, 1242684 ± 624888 and 1401647 ± 726145 folds higher than that of control group ( P <0.05). CⅡ TA protein was not expressed in CaPanC-2 cell and PanC-02 cell. After transfection for 48 h, the CⅡ TA protein expressions of CaPanC-2 and PanC-02 were 0.746 ± 0.499 and 0.631 ±0.244. The percentage of positive expression cells of MHC Ⅱ in CaPanC-2 cells after 24, 48, 72 h were (8.1±0.3)%, (18.9±0.3)%, (78.5±0.90%, which were significantly higher than that in control group [ ( 7.0 ± 0.1)% , P < 0.01 . The percentage of positive expression cells of MHC Ⅱ in PanC - 0 2 were (5.1 ±0.2)% , (37.3 ±2.0)% , (68.8 ±2.2)%, which were significantly higher than that in control group [ (2.2 ±0.2)% , P <0.01). Conclusions Transfection of Ad-C Ⅱ TA could increase the expression of CⅡTA and MHC Ⅱ molecules of pancreatic tumor cells in vitro.