The diagnosis of cancer in early stages is an unmet clinical need, especially in view that current treatments for cancer cannot address metastatic disease. Cancer aberration processes are associated to an increase in the production of reactive oxygen species (ROS). Chemical probes that can specifically detect these species are potentially useful as medical diagnostics and research tools for cancer imaging. One of the aims of my thesis was the design and synthesis of the activatable fluorescent probes based on small molecule fluorophores modified with chemically reactive moieties. The activation of these moieties by defined targets (e.g. ROS) results in the activation of the fluorophore and subsequent emission of a fluorescent signal. Two libraries of fluorescence probes for the detection of ROS have been designed and synthesised: 1) hydrocyanine-based probes as silent fluorophores that can be activated with superoxide ions, 2) coumarin-based hydrogen peroxide probes with red-shifted fluorescent properties and different boronate activatable groups for hydrogen peroxide sensing. We have performed in vitro assays to evaluate the fluorescence response of our probes as well as experiments in relevant live cells to assess their application for detection of ROS in live cells with molecular resolution. Moreover, cancer cells also overexpress Epidermal Growth Factor Receptors (EGFR). Surface-enhanced Raman scattering (SERS) nanotags that can recognize specifically EGFR receptors in cells are promising tools for the enhanced diagnosis of cancer. Two near-infrared cyanine Raman reporters were synthesized with a carboxylic group that was conjugated to cysteamine for derivatization of gold nanoparticles (AuNPs). This work was performed in the CSIR-NIIST (Kerala, India), where I did a 3-month PhD placement. I conjugated the cyanine reporters to spherical AuNPs of 40 nm diameter, and measured their Raman intensity and stability. The best SERS nanotags were selected for encapsulation with PEG and subsequently derivatization with anti-EGFR-EP22 antibodies. In vitro characterization of the SERS nanotags was performed: SERS and absorbance spectra, electron microscopy images as well as SERS imaging experiments in A549 lung cancer cells.

Obstructive sleep apnea (OSA) occurs commonly in the U.S. population and is seen in both obese as well as non-obese individuals. OSA is a disease characterized by periodic upper airway collapse during sleep, which then results in either apnea, hypopnea, or both. The disorder leads to a variety of medical complications. Neuropsychiatric complications include daytime somnolence, cognitive dysfunction, and depression. Increased incidence of motor vehicle accidents has been documented in these patients and probably reflects disordered reflex mechanisms or excessive somnolence. More importantly, vascular disorders such as hypertension, stroke, congestive cardiac failure, arrhythmias, and atherosclerosis occur frequently in these patients. The lungs may be affected by pulmonary hypertension and worsening of asthma. Recent data from several laboratories demonstrate that obstructive sleep apnea is characterized by an inflammatory response. Cytokines are elaborated during the hypoxemic episodes leading to inflammatory responses as marked clinically by elevated C-reactive protein (CRP). As elevated CRP levels are considered markers of the acute phase response and characterize progression of vascular injury in coronary artery disease, it is likely that obstructive sleep apnea could lead to worsening of vasculopathy. Moreover, as inflammatory mechanisms regulate bronchial asthma, it is also likely that cytokines and superoxide radicals generated during hypoxemic episodes could exacerbate reactive airway disease. Patients with Cough, Obstructive sleep apnea, Rhinosinusitis, and Esophageal reflux clustered together can be categorized by the acronym, "CORE", syndrome. The purpose of this manuscript is to review the inflammatory responses that occur in patients with obstructive sleep apnea and relate them to the occurrence of cardiopulmonary disease.

Chan Fat-Yiu. / Thesis (M.Sc.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 85-93). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.4 / SUMMARY --- p.5 / ABBREVIATIONS --- p.9 / LIST OF TABLES --- p.11 / LIST OF FIGURES --- p.13 / Chapter CHAPTER I --- INTRODUCTION --- p.14 / Chapter 1.1 --- The Historical Aspects of C-Reaction Protein --- p.15 / Chapter 1.2 --- Biochemistry of CRP --- p.16 / Chapter 1.3 --- Physiology of CRP --- p.18 / Chapter 1.4 --- Current Clinical Applications of Serum CRP Assay --- p.19 / Chapter 1.5 --- Recent Findings of CRP --- p.21 / Chapter 1.5.1 --- Pathophysiology of atherosclerosis --- p.22 / Chapter 1.5.2 --- A nother atherogenic risk factor: hs- CRP --- p.26 / Chapter 1.5.3 --- Can hs-CRP replace other risk factors? --- p.30 / Chapter 1.5.4 --- Altering hs-CRP result in medication --- p.32 / Chapter 1.6 --- Methods of Measurement of CRP Concentration --- p.33 / Chapter 1.7 --- Analytical Considerations in the Measurement of hs-CRP --- p.34 / Chapter CHAPTER II --- OBJECTIVES AND SIGNIFICANCE --- p.36 / Chapter 2.1 --- Objectives --- p.37 / Chapter 2.2 --- Issues and Problems --- p.37 / Chapter 2.3 --- Significance and Value of this Study --- p.38 / Chapter CHAPTER III --- MA TERIALS AND METHODS I Setting up the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.39 / Chapter 3.1 --- Materials --- p.40 / Chapter 3.1.1 --- Reagents from Roche Diagnostics --- p.40 / Chapter 3.1.2 --- Reagents for the Beckman Coulter Array ® Analyzer --- p.40 / Chapter 3.1.3 --- In-house reagents --- p.41 / Chapter 3.2. --- Apparatus and Equipment --- p.41 / Chapter 3.2.1 --- Hitachi 911 Analyzer --- p.41 / Chapter 3.2.2 --- Beckman Coulter Array ® 360 Analyzer --- p.42 / Chapter 3.3 --- The Tina-quant a C-Reactive Protein (Latex) Ultrasensitive Assay --- p.42 / Chapter 3.3.1 --- Priniciple of the Dual-Radius Enhanced Latex (DuREL´ёØ) technology --- p.42 / Chapter 3.3.2 --- Assessment of Analytical Performance --- p.45 / Chapter CHAPTER IV --- MA TERIALS AND METHODS II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.48 / Chapter 4.1 --- Patient Recruitment --- p.49 / Chapter 4.2. --- Blood Specimens --- p.49 / Chapter 4.3 --- Assay Methods --- p.50 / Chapter 4.3.1 --- hs-CRP --- p.50 / Chapter 4.3.2 --- TC --- p.50 / Chapter 4.3.3 --- TG --- p.51 / Chapter 4.3.4 --- HDL-C --- p.51 / Chapter 4.3.5 --- LDL-C --- p.52 / Chapter 4.3.6 --- Apo A-1 --- p.52 / Chapter 4.3.7 --- Apo B --- p.53 / Chapter 4.3.8 --- Lp(a) --- p.53 / Chapter 4.4 --- Ultrasound measurement of carotid artery inter-media thickness --- p.53 / Chapter 4.5 --- Statistical analysis --- p.54 / Chapter CHAPTER V --- RESUTLSI Setting up the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.55 / Chapter 5.1 --- Imprecision --- p.56 / Chapter 5.2 --- Linearity --- p.56 / Chapter 5.3 --- Recovery --- p.56 / Chapter 5.4 --- Detection Limit --- p.57 / Chapter 5.5 --- Carry-over --- p.57 / Chapter CHAPTER VI --- RESULTS II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.63 / Chapter 6.1 --- Patient Recruitment --- p.64 / Chapter 6.2 --- Chinese chronic-renal-failure patients with AVD --- p.64 / Chapter 6.3 --- Chinese chronic-renal-failure patients with CVC --- p.65 / Chapter CHAPTER VII --- DISCUSSION I Performance of the serum hs-CRP assay on the Hitachi 911 Analyzer --- p.75 / Chapter 7.1 --- "Imprecision, Detection Limit, Linearity, and Recovery of hs-CRP Assay" --- p.76 / Chapter 7.1.1 --- Imprecision --- p.76 / Chapter 7.1.2 --- Detection Limit --- p.76 / Chapter 7.1.3 --- Linearity --- p.76 / Chapter 7.1.4 --- Recovery --- p.77 / Chapter 7.2 --- Overall Performance --- p.77 / Chapter CHAPTER VIII --- DISCUSSION II Serum hs-CRP in Chinese chronic-renal-failure patients with atherosclerotic vascular disease or cardiac valve calcification --- p.79 / Chapter 8.1 --- CAPD Patients --- p.80 / Chapter 8.2 --- Serum hs-CRP Concentration of AVD and CVC Patients --- p.81 / Chapter 8.3 --- Other risk factors in AVD and CVC Patients --- p.82 / Chapter 8.4 --- Conclusion --- p.83 / REFERENCES --- p.85