Effect of vitamin E succinate as a differentiation agent on the efficacy of 5-ALA-PDT on prostate cancer cells in culture

 Photodynamic Therapy (PDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) has been considered as a new method for treating neoplasms. However, ALA-PDT is suboptimal for thick tumors. Searching for new approaches, we investigated the effect of adding differentiation therapy (DT) with Vitamin E succinate (VES) to PDT in human prostate LN-CaP-FGC10 cancer cells in vitro. The purpose of DT was to reverse the lack of differentiation in cancer cells and to enhance the effectiveness of ALA- dependent PDT.Three groups of cells were grown on RPMI1640 culture medium supplemented with 10% FBS. The cells included: ALA-PDT cells, which received 0.3 mM ALA for 4 hours at dark, and exposed to 532 nm, 50 mW Nd-YAG laser beam for 3 min; DT+ALA-PDT cells, which received 6 µg/ml VES for 24, 48 and 72 hours, followed by the addition of 0.3 mM ALA for 4 h and exposure to Nd-YAG laser beam for 3 min; control cells which were untreated. After 24 h, the percentage of cell viability was determined by MTT assay. Accumulation of PpIX was measured by spectrophotometry and fluorescent microscopy. Mechanism of induced cell death was investigated via Hoechst staining. The combination of both factors (VES and 5-ALA) lead to a significant increase in cell death after 72 h. Induction of differentiation augmented PpIX accumulation in cells treated with ALA. Elevated intracellular PpIX levels resulted in an enhanced lethal photodynamic sensitization of VES plus ALA-treated cells after 72 h. Apoptotic cell death by both ALA-PDT and VES-ALA-PDT was confirmed by Hoechst staining. Our data suggest that VES used in combination with 5-ALA may provide a new combinatorial approach for treating certain cancers.

Evaluation of the modified HTK solution in pancreas transplantationdAn experimental model

One of the great challenges in pancreas transplantation is the ischemia reperfusion injury. It is mentioned that free oxygen and/or nitrogen radicals play a prominent role in this phase. To minimize this problem, a modified histidineetryptophan eketoglutarate (HTK) solution that contains modified antioxidants has been developed. Our aim was to evaluate this solution in improving the viability of the pancreas in comparison with standard HTK and University of Wisconsin (UW) solutions in a porcine model of pancreas transplantation

Evaluation of the modified HTK solution in pancreas transplantation—An experimental model

One of the great challenges in pancreas transplantation is the ischemia reperfusion injury. It is mentioned that free oxygen and/or nitrogen radicals play a prominent role in this phase. To minimize this problem, a modified histidine–tryptophan–ketoglutarate (HTK) solution that contains modified antioxidants has been developed. Our aim was to evaluate this solution in improving the viability of the pancreas in comparison with standard HTK and University of Wisconsin (UW) solutions in a porcine model of pancreas transplantation. Twenty-three Landrace pigs were divided into three identical groups. After a 10-hour preservation time at 4°C, the pancreas was implanted in the organs of the recipients in a standardized manner. Serum parameters were assessed prior to and after implantation on the 1st postoperative day, 3rd postoperative day, and 7th postoperative day. Furthermore, three biopsies were taken: prior to and after reperfusion, and on Day 7 to assess the grafts. An analysis of serum glucose among the three groups showed no significant differences. Evaluation of the insulin levels showed no significant difference between the modified and standard HTK groups, however, differences between HTK and UW were significant (p = 0.004 in favor of UW solutions). The histopathological results showed a trend of a higher grade of rejection of pancreas tissue in the UW group compared to both HTK groups. The modified HTK solution could preserve the pancreas for the preservation of the graft with similar results to those observed for standard solutions without any significant difference. The trend showed that the pathological finding in the UW group was not as good as that in the modified HTK and standard HTK groups