Acute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic... Show moreAcute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic defense against pathogens as well as pathologies including autoimmunity and cancer. A major mechanism through which neutrophils contribute to health and disease is oxidative burst, which involves rapid release of reactive oxygen species (ROS) generated by a chemical reaction network catalyzed by enzymes including NADPH oxidase and myeloperoxidase (MPO). Due to the involvement of neutrophil-derived reactive oxygen species in many diseases and importance of NADPH oxidase and MPO-mediated reactions in progression and treatment of myeloid leukemia, monitoring this process and modulating it by pharmacological interventions is of great interest. In this work, we have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor ROS production in neutrophil-like HL60 myeloid leukemia cells. Suppression of ROS was achieved by several drug candidates that target different parts of the reaction pathway. Our results show that UPE can report on ROS production as well as suppression by pharmacological inhibitors. We find that UPE is primarily generated by MPO catalyzed reaction and thus will be affected when an upstream reaction is pharmacologically modulated. Show less
In recent decades, the use of a systems-based view of life has provided key insight into fundamental processes with respect to biology. In life sciences, important paradigm shifts are the way in... Show moreIn recent decades, the use of a systems-based view of life has provided key insight into fundamental processes with respect to biology. In life sciences, important paradigm shifts are the way in which we approach health and disease. Although modern medicine has traditionally emphasized pathology and acute conditions, our current understanding is that different interventions are needed for treating and preventing chronic disease. To design better interventions, new diagnostic tools are urgently needed in order to create new opportunities for achieving personalized health and medicine. The focus in diagnosis is, therefore, shifting from measuring single biomarkers such as glucose and cholesterol to creating complex maps of the dynamic patterns underlying regulatory processes. Moreover, the notion of "health" is viewed in a holistic context using biochemistry as a basis and then expanding this basis to include the psycho-social environment, including the individual's worldview. In the field of diagnostics, a highly promising new tool has recently emerged based on ultra-weak photon emission from biological systems, including all living cells. The aim of this thesis was to explore the applications of UPE and correlate it with biochemistry in order to obtain a deeper understanding of the processes that occur in living systems. Show less
Rossetto Burgos, R.C.; Zhang, W.; Wijk, E.P.A. van.; Hankemeier, T.; Ramautar, R.; Greef, J. van der 2017
