Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger cell death. In this study, we compared the relative sensitivity of different human tumor models and normal tissues to calcium electroporation. Plasma membrane Ca-ATPase (PMCA) protein expression was confirmed in all cancer cell lines and normal primary dermal fibroblasts studied. In all tumor types tested, calcium electroporation effectively induced necrosis, with a range of sensitivities observed (36%-88%) 2 days after treatment. Necrosis was induced using calcium concentrations of 100-500 mmol/L and injection volumes 20%-80% of tumor volume. Notably, only limited effects were seen in normal tissue. Calcium content increased >7-fold in tumor and skin tissue after calcium electroporation but decreased in skin tissue 4 hours after treatment to levels comparable with untreated controls, whereas calcium content endured at high levels in tumor tissue. Mechanistic experiments indicated that calcium influx was similar in fibroblasts and cancer cells. However, we observed decreased PMCA expression in cancer cells compared with fibroblasts, offering a potential explanation for the different calcium content in tumor cells versus normal tissues. Overall, our results suggest that calcium electroporation can elicit a rapid and selective necrosis of solid tumors, with limited deleterious effects on surrounding normal tissues..

Background:The mechanism coupling substrate binding to transport in neurotransmitter: sodium symporters (NSSs) is poorly understood. Significance: The data add to our mechanistic understanding of Na ϩ -coupled transport across lipid bilayers.

Thirty-six patients (21 male, 15 female) with ductal pancreatic cancer were treated with the long-acting synthetic luteinizing hormone releasing hormone (LH-RH) analogue buserelin. All patients had advanced tumor stages (stage 11: 7 patients; stage 111: 11 patients; stage IV: 18 patients). A monthly follow-up including clinical status, computed tomography scan, or ultrasonography and the tumor markers carcinoembryonic antigen (CEA) and H carbohydrate antigen 19-9 (CA19-9) was camed out. There were no severe side effects apart from impotency in men and hot flashes and outbreaks of perspiration in three patients. No partial or complete remission was seen. Twenty-six patients showed tumor progression with a median survival time of 4 months (range 0.5-1 1 months). In 10 patients a "no change" evaluation with a median survival time of 10 months (range 8-17 months) was registered. In only two of these patients there was no increase in the serum tumor markers CA19-9 and CEA during this time. In conclusion, LH-RH analogue treatment cannot be recommended in this selected group of patients suffering from advanced tumor stages of pancreatic cancer.

Here, we bind the sodium dependent amino acid transporter on nitrilotriacetic acid/polyethylene glycol functionalized gold sensors in detergents and perform a detergent-lipid exchange with phosphatidylcholine. We characterize the LeuT structure in the adsorbed film by magnetic contrast neutron reflection using the predicted model from molecular dynamic simulations.