Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac... Show moreSerum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed. Show less
In cells, proteins are continuously synthesized and degraded to control protein levels and thereby regulate a wide variety of biochemical processes. The proteasome is the main cellular degradation... Show moreIn cells, proteins are continuously synthesized and degraded to control protein levels and thereby regulate a wide variety of biochemical processes. The proteasome is the main cellular degradation machinery, responsible for the degradation of key proteins involved in the regulation of a wide range of cellular processes, including quality control, cell cycle progression, cell differentiation, signal transduction and apoptosis. Inhibition of the proteasome causes disruption of many regulatory processes, eventually leading to cell death. The observation that many cancer cells are more sensitive to proteasome inhibition than normal cells has led to the development of several proteasome inhibitors for the treatment of cancer. Proteasome activity in its broadest sense is the central theme of this thesis. The development and characterization of different chemical proteasome activity probes that can be used to study proteasome activity in a wide range of tissue types using a variety of assays are described. Subsequently, these probes are used to assess the effects of different proteasome inhibitors in preclinical and clinical studies and to purify proteasome and characterize its activity and composition. Finally, the molecular mechanism of proteasomal antigen splicing is studied. Show less
The first half of this thesis describes the synthesis of several conformationally restricted alkylated and bicyclic sugar amino acids (SAAs). The second half of the thesis describes the application... Show moreThe first half of this thesis describes the synthesis of several conformationally restricted alkylated and bicyclic sugar amino acids (SAAs). The second half of the thesis describes the application of the SAAs and their intermediates presented in the first half, as components of tools applied for the probing of biological systems. Show less
