ABSTRACT
Objective To investigate the influence of m4-1BBL on the anti-tumor effects induced by truncated human prostate specific membrane antigen (tPSMA) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL (pDC316-tPSMA-IRES-m4-1BBL), pDC316-tPSMA and pDC316 were constructed. C57BL/6 mice were vaccinated in the quadriceps femoris, respectively. The CTL activity of spleen cells from the immunized mice against prostate cancer RM-1-tPSMA was detected by CCK-8 kit in vitro. The tumor growth was then observed. Results The target cell specific cytotoxicity rate induced by pDC316-tPSMA-IRES-m4-1BBL was 42.6%, compared to 24.8% in the pDC316-tPSMA group and 10.8% in the pDC316 group. The difference was significant (P<0.05). The volume of tumor in the pDC316 group was 2657.4mm3 7 d after vaccination, compared to 1334.5 mm3 in the pDC316-tPSMA group, 9 d after vaccination. In the pDC316-tPSMA-IRES-m4-1BBL group, the tumor volume was 445.8 mm3, 12d after vaccination. The difference was significant (P<0.05). Conclusion Gene vaccines co-expressing tPSMA gene and m4-1BBL gene could significantly enhance anti-prostate cancer effects in mice.
ABSTRACT
Objective To investigate the effects of isehemic postconditioning (IPO) on the acute renal ischemia/reperfusion (I/R) injury in dogs. Methods Fifteen adult male mongrel dogs were randomly divided into three groups with 5 animals in each group. In sham operation group (S), after the dogs were anesthetized, the midline laparotomy was made and right nephrectomy was performed;In I/R group, animals were subjected to the similar surgical procedures, except that the left renal vessels were clamped; In IPO group, the IPO was induced by 6 cycles of reperfusion (30 s) and ischemia (30 s) after 60 min renal ischemia before reperfusion completely. Blood samples were obtained for determination of blood creatinine (Cr) and urea nitrogen (BUN) concentrations before operation and at 24, 48 and 72 h after operation. The dogs were killed at the thirdday after operation and left kidneys were removed for determination of SOD activity and MDA and MPO concentrations.The apoptosis in the nephridial tissue was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and apoptotic index (AI) was calculated. The changes of renal tissue were examined by a microscope. Results Blood Cr and BUN concentrations in I/R group, IPO group and S group were decreased in turn after operation (P<0. 05). MDA and MPO concentrations were decreased significantly, SOD activity was significantly increased and AI was decreased significantly in IPO group as compared with I/R group at 72 h after operation (P<0. 05). Microscopic examination showed that there was no renal injury in S group and renal I/R resulted in tubular necrosis, medullary hemorrhage congestion and proteinaceous casts in I/R group. The renal I/R injury was significantly attenuated by IPO. In S group, IPO group and I/R group the renal AI was 2. 7 ±1.3, 28. 4 ± 6. 2 and 15.4±4. 1 respectively (P<0. 05). Conclusion IPO can attenuate renal damage induced by I/R by inhibiting oxidative stress and apoptosis and decreasing inflammation.