Targeting lactate transport suppresses in vivo breast tumour growth

Background: Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as “Warburg effect”. Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. Results: The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. Conclusions: This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

Osteoblast, fibroblast and in vivo biological response to poly(vinylidene fluoride) based composite materials

Electroactivematerials can be taken to advantage for the development of sensors and actuators as well as for novel tissue engineering strategies. Composites based on poly(vinylidenefluoride),PVDF,have been evaluated with respect to their biological response. Cell viability and proliferation were performed in vitro both with Mesenchymal Stem Cells differentiated to osteoblasts and Human Fibroblast Foreskin 1. In vivo tests were also performed using 6-week-old C57Bl/6 mice. It was concluded that zeolite and clay composites are biocompatible materials promoting cell response and not showing in vivo pro-inflammatory effects which renders both of them attractive for biological applications and tissue engineering, opening interesting perspectives to development of scaffolds from these composites. Ferrite and silver nanoparticle composites decrease osteoblast cell viability and carbon nanotubes decrease fibroblast viability. Further, carbon nanotube composites result in a significant increase in local vascularization accompanied an increase of inflammatory markers after implantation.

Collecting system percutaneous access using real-time tracking sensors: first pig model in vivo experience

Purpose: Precise needle puncture of the renal collecting system is an essential but challenging step for successful percutaneous nephrolithotomy. We evaluated the efficiency of a new real-time electromagnetic tracking system for in vivo kidney puncture. Materials and Methods: Six anesthetized female pigs underwent ureterorenoscopy to place a catheter with an electromagnetic tracking sensor into the desired puncture site and ascertain puncture success. A tracked needle with a similar electromagnetic tracking sensor was subsequently navigated into the sensor in the catheter. Four punctures were performed by each of 2 surgeons in each pig, including 1 each in the kidney, middle ureter, and right and left sides. Outcome measurements were the number of attempts and the time needed to evaluate the virtual trajectory and perform percutaneous puncture. Results: A total of 24 punctures were easily performed without complication. Surgeons required more time to evaluate the trajectory during ureteral than kidney puncture (median 15 seconds, range 14 to 18 vs 13, range 11 to 16, p ¼ 0.1). Median renal and ureteral puncture time was 19 (range 14 to 45) and 51 seconds (range 45 to 67), respectively (p ¼ 0.003). Two attempts were needed to achieve a successful ureteral puncture. The technique requires the presence of a renal stone for testing. Conclusions: The proposed electromagnetic tracking solution for renal collecting system puncture proved to be highly accurate, simple and quick. This method might represent a paradigm shift in percutaneous kidney access techniques

Collecting system percutaneous access using real-time tracking sensors: first pig model in vivo experience

Purpose: Precise needle puncture of the renal collecting system is an essential but challenging step for successful percutaneous nephrolithotomy. We evaluated the efficiency of a new real-time electromagnetic tracking system for in vivo kidney puncture. Materials and Methods: Six anesthetized female pigs underwent ureterorenoscopy to place a catheter with an electromagnetic tracking sensor into the desired puncture site and ascertain puncture success. A tracked needle with a similar electromagnetic tracking sensor was subsequently navigated into the sensor in the catheter. Four punctures were performed by each of 2 surgeons in each pig, including 1 each in the kidney, middle ureter, and right and left sides. Outcome measurements were the number of attempts and the time needed to evaluate the virtual trajectory and perform percutaneous puncture. Results: A total of 24 punctures were easily performed without complication. Surgeons required more time to evaluate the trajectory during ureteral than kidney puncture (median 15 seconds, range 14 to 18 vs 13, range 11 to 16, p ¼ 0.1). Median renal and ureteral puncture time was 19 (range 14 to 45) and 51 seconds (range 45 to 67), respectively (p ¼ 0.003). Two attempts were needed to achieve a successful ureteral puncture. The technique requires the presence of a renal stone for testing. Conclusions: The proposed electromagnetic tracking solution for renal collecting system puncture proved to be highly accurate, simple and quick. This method might represent a paradigm shift in percutaneous kidney access techniques.