Colorectal cancer has a 9.8% cumulative incidence rate, making it the third most common cancer in the Western world. Despite a 50-60% response rate in patients to current cancer therapies, drug resistance and tumour relapse remain a concern. While current therapies reduce the tumour mass, they possibly fail to eradicate a unique population of pluripotent tumour resident cells. These cells, known as cancer stem cells, may have similar properties of self-renewal and proliferation to embryonic and adult stem cells, as they also express a number of key pluripotent transcription factors, including amongst others, NANOG, OCT3/4 and SOX2. Furthermore, since discreet groups of such stem cells are proposed to essentially drive tumourigenesis, they present as potential novel targets for cancer therapy. This study aimed to isolate a putative CSC population from the advanced colon adenocarcinoma cell lines HT29 and DLD1 and to assess the therapeutic effects of the epigenetic drugs Valproic acid and Zebularine on pluripotent gene expression.

by Chan Chi Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 119-137). / Chapter SECTION 1 --- INTRODUCTION / Chapter 1.1 --- Overview on lipids --- p.2 / Chapter 1.1.1 --- Definition and Classification of Lipids --- p.2 / Chapter 1.1.2 --- Lipoproteins and Apolipoproteins --- p.4 / Chapter 1.1.3 --- Outline of Lipoprotein Metabolism --- p.9 / Chapter 1.1.4 --- LDL Metabolism --- p.12 / Chapter 1.2 --- Dyslipidaemia and Cardiovascular Disease (CVD) --- p.16 / Chapter 1.2.1 --- Definition --- p.16 / Chapter 1.2.2 --- Dyslipidaemia and CAD --- p.16 / Chapter 1.2.3 --- Dyslipidaemia in Non-Insulin Dependent Diabetes Millitus Patients --- p.18 / Chapter 1.2.4 --- Claasification of Dyslipidaemia --- p.24 / Chapter 1.2.5 --- Causes of Hyperlipidaemia --- p.26 / Chapter 1.3 --- Dyslipidaemia and Atherosclerosis --- p.29 / Chapter 1.3.1 --- Pathogenesis of Atherosclerosis --- p.29 / Chapter 1.3.2 --- Mechanism of Atherogenesis --- p.31 / Chapter 1.3.3 --- Intrinsic Roles of LDL in Atherogenesis --- p.33 / Chapter (1) --- LDL Oxidizability --- p.33 / Chapter (2) --- LDL Particle Size Heterogeneity --- p.39 / Chapter 1.4 --- Management of Dyslipidaemia --- p.42 / Chapter 1.5 --- Aims of This Study --- p.49 / Chapter SECTION 2 --- MATERIALS AND METHODS / Chapter 2.1 --- Materials --- p.52 / Chapter 2.1.1 --- Patients and Controls --- p.52 / Chapter 2.1.2 --- Drug Administration Trials --- p.54 / Chapter 2.1.3 --- Blood Samples --- p.55 / Chapter 2.1.4 --- Biochemicals --- p.56 / Chapter 2.1.5 --- Solutions and Buffers --- p.56 / Chapter 2.1.6 --- Apparatus and Equipment --- p.60 / Chapter 2.2 --- Methods --- p.62 / Chapter 2.2.1 --- General Clinical Biochemistry Tests --- p.62 / Chapter 2.2.2 --- Apolipoprotein Assays --- p.62 / Chapter 2.2.3 --- Ultracentrifugation of LDL Fraction --- p.63 / Chapter 2.2.4 --- De-Salting of LDL Fraction --- p.64 / Chapter 2.2.5 --- Qualitative Determination of LDL-Cholesterol and Protein Fractions --- p.64 / Chapter 2.2.6 --- In Vitro Assessment of LDL Oxidizability --- p.65 / Chapter 2.2.7 --- Electrophoretic Gel Pattern of LDL Fraction During In Vitro Oxidizability --- p.65 / Chapter 2.2.8 --- Study of LDL Particle Size --- p.66 / Chapter 2.2.9 --- Statistical Analysis --- p.67 / Chapter SECTION 3 --- RESULTS / Chapter 3.1 --- Quantitative Determination and Standardization of LDL Fractions --- p.69 / Chapter 3.2 --- In Vitro Assessment of LDL Oxidizability --- p.72 / Chapter 3.3 --- Electrophoretic Patterns of LDL during In Vitro Oxidizability --- p.72 / Chapter 3.4 --- LDL Sizing --- p.73 / Chapter 3.5 --- "Correlations of Triglycerides Concentration, LDL Particle Size and Oxidizability" --- p.76 / Chapter 3.6 --- Diabetes Millitus --- p.83 / Chapter 3.6.1 --- NIDDM Patients & Controls --- p.83 / Chapter 3.6.2 --- Effect of Drug Treatment on Serum Lipid-Lipoprotein- Apolipoprotein Profile --- p.86 / Chapter 3.7 --- Hypertriglyceridaemic Patients --- p.90 / Chapter 3.7.1 --- Patients & Controls --- p.90 / Chapter 3.7.2 --- Bezafibrate Treatment --- p.91 / Chapter 3.8 --- CAD Patients --- p.97 / Chapter 3.8.1 --- CAD Patients & Controls --- p.97 / Chapter SECTION 4 --- DISCUSSION / Chapter 4.1 --- Patients and Controls --- p.101 / Chapter 4.2 --- Ultracentrifugation of LDL Fractions --- p.102 / Chapter 4.3 --- In Vitro LDL Oxidizability --- p.103 / Chapter 4.4 --- "Association of TG, LDL Oxidizability and Particle Size" --- p.105 / Chapter 4.5 --- LDL Sizing --- p.106 / Chapter 4.6 --- Comparsion of Patients and Controls in Lipid-Lipoprotein- Apolipoprotein Profiles --- p.107 / Chapter 4.7 --- The Effect of Lovastatin and Acipimox on NIDDM Patients --- p.111 / Chapter 4.8 --- The Effect of Bezafibrate on Hypertriglyceridaemic Patients --- p.114 / Chapter SECTION 5 --- CONCLUSION --- p.116 / References --- p.119 / Appendices --- p.138

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A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand In partial fulfilment of the requirements for the degree of Master of Science in medicine (Pharmaceutical affairs) Johannesburg, 1998 / Despite the availability of highly effective treatment regimens for tuberculosis, cure rates remain low for tuberculosis mainly due to patient non-compliance which results in the occurrence of multi drug resistance tuberculosis. To avoid the problem of further creation and propagation of multi drug-resistant tuberculosis, patients should be given fixed-dose combinations of anti-tubercular drugs whenever self-administration of drugs iJ permitted. During this study, an anti-tuberculosis extemporaneous powder for suspension was optimized in order to formulate a fixed combination of rifampicin. isoniazid, pyrazinamide and ethambutol hydrochloride as a powder to be ' . constituted with water by the patient prior to administration. Once an effective manufacturing method was established, different suspending agents were evaluated by their influence on powder flow properties and sedimentation volume on the powder blends. Sodium starch glycollate was chosen as the suspending agent of choice because as the concentration of sodium starch glycollate was increased, the powder flow properties of the powder blends improved. The sedimentation volume also. increased with the increasing concentration of sodium starch glycollate in the powder blends. A suitable flavour and colour was also determined to increase the acceptability of the preparation to the patient. Liquorice flavour was the most acceptable in terms of colour and flavour. An evaluation of the dissolution characteristics of the extemporaneous powder for suspension was also conducted in comparison to the dissolution profiles from commercially available tablet dosage forms. The dissolution rates from the powder tor suspension for rifampicin, isoniazid and pyrazinamide was faster than from the commercially available tablet dosage form, while the dissolution race of ethambutol HCl from the powder closely resembles the dissolution profile from the Rolab-Ethambutol HCIR tablet dosage form Therefore. a fixed combination powder for suspension was achieved and with its ease of administration would increase the compliance amongst tuberculosis patients. and increase therapeutic outcomes. / MT2017

After declining for many years, the incidence of tuberculosis (TB) is on the increase again. With TB resurgence there is also resistance of some TB strains to the commonly used TB drugs. This condition is kno wn as multi-drug resistance tuberculosis (MDR TB). Among all factors that increase TB and MDR TB, treatment compliance and completion is the greatest challenge. MDR TB is mainly caused by poor adherence to TB treatment by either the patient or the prescriber. In order to improve patient adherence to treatment. Directly Observed Therapy (DOT) has been implemented in many countries including South Africa. DOT means that each consumption of TB drugs by the patient is observed by a reliable person. Even with DOT in place, many patients still do not adhere to the prescribed treatment. This study aimed at determining from health workers the following: • Problems experienced by the health workers when giving treatment to TB patients, • causes for non-adherence to TB treatment, and • what could be done to make DOT more effective. A questionnaire was used to gather information. Ail clinics rendering TB services in Gauteng were considered in this study. Two questionnaires were sent to each of the 138 participating clinics and had to be completed by any two health workers involved in the treatment of TB patients. Only 69 of the 276 questionnaires sent, were returned completed (25%). Information gathered from the questionnaires revealed that patients seen at TB clinics in Gauteng came from various residential areas including townships, suburban rural and informal settlement. The Pearson chi squared test showed that there was no association between the percentage of patients who completed treatment and the number of patients seen at a clinic, or between the percentage of patients who completed treatment and the working hours at a particular clinic. The main cause of non-compliance shown by the results of this study was that patients discontinued treatment as soon as they felt better. Other causes of non-compliance mentioned by health workers included patient denial of having TB, ignorance, long treatment periods and many drugs that were to be taken during treatment. Health workers revealed that the main problem experienced in giving treatment to TB patients was that of deiaulting. The majority of these respondents suggested education as one way of making DOT more effective. In terms o f this study, it can be concluded that education on TB at various levels namely the patient, the health care worker and the community, is recommended. Education on the disease TB and its optimal treatment will improve patient compliance, decrease defaulting in delivering TB drugs to patients and make DOT more effective.

Thesis (M.Pharm.)--University of the Witwatersrand, Faculty of Health Sciences, 2011.