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.

Treating the entire person

[Excerpt] A critical case from a Portuguese hospital reveals how the ultimate healthcare customer, the patient, is a complete system, not a jumble of parts. (...) The lean production philosophy has made inroads into service sectors, including medical care in the United Kingdom and the United States. Unfortunately, numerous medical organizations in those two countries and the rest of the world treat patients like they are made up of parts, not as a whole system. This leads to disjointed handoffs, bottlenecks in information flow that delay treatment, and sending the patient back and forth from department to department. The following case in Portugal shows how most of the world’s health systems still suffer from functional silos and how waste is all over the place. In this case, the missing links in communication between doctors, nurses, auxiliary staff, the patient and her family led to the patient’s death. Adopting lean healthcare with its proven tools would be a solution to many of the problems described. When a patient dies in a hospital, the family often is told that the doctors did everything they could. Normally, that is the case, as healthcare providers – doctors, nurses, auxiliary staff, therapists – do their best with the system they have.

Effects of fermentation residues on the melt processability and thermomechanical degradation of PHBV produced from cheese whey using mixed microbial cultures

"Available online 28 March 2016"

In-line rheo-optical microstructural characterization of complex polymer systems

Tese de Doutoramento em Ciência e Engenharia de Polímeros e Compósitos.