Historically, the Nuu-chah-nulth People of Vancouver Island passed down knowledge and skills utilizing methods analogous with traditional Indigenous pedagogies around the world. These traditional teaching and assessment methods of the Nuu-chah-nulth have ensured the successful transfer of important physical, mental, cultural and spiritual knowledge over thousands of years. Within these pedagogies, assessment and evaluation is integral and inclusive, achieved through authentic and holistic means. Conversely, contemporary assessment in the post-secondary realm, despite endeavours to integrate formative assessment more frequently, tends toward a summative end result. The historical traditional assessment methods of the Nuu-chah-nulth exemplify holistic values and are illustrated through the concept of heshook-ish-tsawalk, or ‘everything is connected’. This dissertation argues that there are insights to be gleaned from identifying these assessment and evaluation methods, and in bringing them forward into contemporary pedagogy. Through a series of in-depth interviews, the researcher examined the learning and teaching understandings and experiences of several Nuu-chah-nulth Elders and cultural experts. Interviews took place within the homes of the Elders, and care was taken to ensure representation across a wide range of Nuu-chah-nulth territory. Augmenting these interviews, the researcher examined translated recordings of past Nuu-chah-nulth Elders while reflecting on her personal experiences as a Nuu-chah-nulth person. These personal experiences were analyzed through a self-study style examination of her own journey through education, and her recollections of traditional and contemporary assessment practice. Significant themes emerged from the collected data, including the overarching importance of time, relationships, echoing, and demonstration in historical Nuu-chah-nulth assessment. These themes fit naturally within a circular medicine wheel framework, which effectively illuminates the holistic and connected nature of an Indigenous pedagogy. This study concludes that these themes hold significant importance for contemporary assessment practice. / Graduate

Chan Shun Wan. / "August 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 217-235). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The Mackenzie River Delta is an ecologically rich freshwater environment in Canada’s Northwest Territories. It is vulnerable to multiple stressors such as climate change, resource development activities (oil and natural gas) and upstream-downstream linkages related to extraction activities in the southern part of the Mackenzie River watershed. Resultant socio-ecological impacts affect fishing livelihoods, which represent a significant component of the country food system and ways of life for Inuvialuit (Inuit of the Western Arctic), whose Settlement Area overlaps with the Delta. This thesis analyzes the implications of socio-ecological changes in the Mackenzie River Delta for Inuvialuit fishing livelihoods and the country food system, drawing from Local and Traditional Knowledge. In collaboration with the Fisheries Joint Management Committee in the Inuvialuit Settlement Region, the westernmost Inuit region in Canada, I undertook a participatory-qualitative research, while also drawing on relevant literature and complementary data. Using 28 semi-structured interviews about changes in the Mackenzie River Delta and the importance of fishing livelihoods, results indicated that fishing livelihoods are essential contributors to the Inuvialuit food system, as well as cultural practices surrounding fishing as an activity. Moreover, some results imply the importance of previously ignored species for food security, such as burbot and inconnu, which receive limited attention in other studies. Key findings also indicate that multiple environmental changes are occurring in the Delta, including lower water levels, increasing land erosion, decreasing fish populations, and changes in Delta-reliant wildlife populations (e.g. more beavers), warmer water temperatures, poorer fish quality (e.g. softer flesh, parasites), thinner ice, climate variability, and an escalating cost of living. These changes affect primarily fishing access and raise important concerns about the safety of fish consumption for human health. Ultimately, limited access and declining fish quality have a negative impact on food security, given the key role of fish in the country food system and the importance of socio-cultural dimensions such as fishing knowledge and skills, and sharing practices.

This thesis explores the notion of social enterprise in Greece. In particular it investigates how non-profits incorporate social enterprise in an environment facing a severe financial and social crisis. The study is done through a participatory and reflective research approach that allows the emergence of enriched results. The review of the existing literature in this area revealed that despite the lack of a universal definition, the concept of social enterprise has generally been viewed positively and has raised the expectations for social and economic transformation. Policy makers expect social enterprises to become a lever out of the crisis of reducing state funding and contribute to financial and social change. Until recently, the common assumption was that social enterprises emerge bottom-up and constitute the most ethical option of social welfare services provision after the failure of the state and the markets to provide for society. Hence, non-profits were encouraged to adopt entrepreneurial techniques to support their social purpose as a way out of the financial problems they are facing. The great interest on the effect of 'social enterprise' on the traditional non-profit sector comes from the peculiarity of the Greek case with the top-down enforcement of the concept coupled with a history of corruption in civil society. Even though researchers following a more critical stance towards social enterprises challenge the underlying assumptions of this new concept and raise awareness about its negative impacts, in Greece the 'social economy' and 'social enterprise' concepts are used as 'silver bullets' by policy makers. Wishing to follow this critical tradition, I proceeded with an in-depth case study drawing upon participant observation and reflective methods. In locating my research in an active non-profit organisation in Athens, I intended that my findings could be extended to similar organisations. This thesis found that in Greece, the top-down implementation of the concept allowed non-profits to incidentally adopt this rhetoric in order to ensure their long-term survival and then in turn influence the way society makes sense of social enterprises. The institutional environment further hinders the growth of the sector as it directs the social enterprises and non-profits towards public procurement making and any other alternative seems impossible. Lastly, based on the above findings, I conclude that social economy despite its infancy faces the risk of corruption. Hence, I suggest that policy makers' support, rather than guide, social enterprises to allow them to achieve their full potential. Future research and practice need to focus on raising awareness for the social economy and assessing social impact as a way to improve transparency and gain the trust of society.

by Lee Kin Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 214-225). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vii / ABSTRACT IN CHINESE --- p.ix / LIST OF FIGURES --- p.xi / LIST OF TABLES --- p.xv / CONTENTS --- p.xvi / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Cordyceps --- p.2 / Chapter 1.1.1 --- Pharmacological Functions of Cordyceps --- p.5 / Chapter 1.1.1.1 --- Anti-tumor Activities --- p.5 / Chapter 1.1.1.2 --- Immunomodulatory Activities --- p.7 / Chapter 1.1.1.3 --- Hepatic Functions --- p.9 / Chapter 1.1.1.4 --- Cardiovascular Functions --- p.10 / Chapter 1.1.1.5 --- Renal Functions --- p.10 / Chapter 1.2 --- Biological Activities of Cordycepin --- p.12 / Chapter 1.2.1 --- Inhibition of RNA Synthesis --- p.12 / Chapter 1.2.2 --- Disruption of Microtubule Network --- p.12 / Chapter 1.2.3 --- Inhibition of Nucleic Acid Methylation --- p.13 / Chapter 1.2.4 --- Enhancement of Cell Differentiation --- p.13 / Chapter 1.2.5 --- Anti-tumor Activity --- p.13 / Chapter 1.2.6 --- Anti-fungal Activity --- p.14 / Chapter 1.3 --- Hepatocellular Carcinoma --- p.16 / Chapter 1.3.1 --- Incidence and Risk Factor of Hepatocellular Carcinoma --- p.16 / Chapter 1.3.2 --- Treatment of Hepatocellular Carcinoma --- p.16 / Chapter 1.3.2.1 --- Hepatic Resection --- p.16 / Chapter 1.3.2.2 --- Liver Transplantation --- p.17 / Chapter 1.3.2.3 --- Non-surgical Therapeutic Modalities for Hepatocellular Carcinoma --- p.17 / Chapter 1.3.3 --- Human Hepatocellular Carcinoma Cell Lines --- p.20 / Chapter 1.3.3.1 --- Human Hepatocellular Carcinoma Cell Line HepG2 --- p.20 / Chapter 1.3.3.2 --- Multidrug Resistant Human Hepatocellular Carcinoma Cell Line R-HepG2 --- p.20 / Chapter 1.4 --- Multidrug Resistance of Tumor Cells --- p.22 / Chapter 1.4.1 --- Multidrug Resistance Mediated by P-Glycoprotein --- p.22 / Chapter 1.4.1.1 --- Location and Structure of P-Glycoprotein --- p.22 / Chapter 1.4.1.2 --- Substrates of P-Glycoprotein --- p.23 / Chapter 1.4.1.3 --- Mechanism of Action of P-Glycoprotein --- p.23 / Chapter 1.4.2 --- Reversal of Multidrug Resistance by Chemosensitizers --- p.24 / Chapter 1.5 --- Leukemia / Chapter 1.5.1 --- Acute Myeloid Leukemia --- p.28 / Chapter 1.5.2 --- Acute Promyelocytic Leukemia and Treatment --- p.28 / Chapter 1.5.3 --- Human Promyelocytic Leukemia Cell Lines --- p.30 / Chapter 1.5.3.1 --- HL-60 --- p.30 / Chapter 1.5.3.2 --- NB-4 --- p.30 / Chapter 1.6 --- Objectives of Study --- p.33 / Chapter 1.6.1 --- Study of Biological Activities of Cordyceps militaris --- p.33 / Chapter 1.6.2 --- Study of Anti-tumor Activity of Cordycepin --- p.33 / Chapter CHAPTER 2: --- MATERIALS AND METHODS --- p.34 / Chapter 2.1 --- Materials --- p.35 / Chapter 2.1.1 --- Animal --- p.35 / Chapter 2.1.2 --- Cell Culture --- p.35 / Chapter 2.1.2.1 --- Cell Lines --- p.35 / Chapter 2.1.2.2 --- Cell Culture Media --- p.37 / Chapter 2.1.2.3 --- Buffers and other Reagents --- p.38 / Chapter 2.1.3 --- Reagents and Buffers for Different Assays --- p.40 / Chapter 2.1.3.1 --- Reagents and Buffers for Flow Cytometry --- p.40 / Chapter 2.1.3.2 --- Reagents and Buffers for DNA Fragmentation Assay --- p.40 / Chapter 2.1.3.3 --- Reagents and Buffers for Western Blot Analysis --- p.42 / Chapter 2.1.3.4 --- Reagents and Buffers for Caspases Activities --- p.46 / Chapter 2.1.3.5 --- Reagents and Buffers for Cell Surface Marker (CD3，CD4 and CD8) Staining --- p.48 / Chapter 2.1.3.6 --- Reagents and Buffers for Cytokine Determination --- p.49 / Chapter 2.2 --- Methods --- p.50 / Chapter 2.2.1 --- Preparation of Water Extract of Cordyceps militaris --- p.50 / Chapter 2.2.2 --- MTT Assay --- p.50 / Chapter 2.2.3 --- In Vivo Anti-tumor Study --- p.51 / Chapter 2.2.4 --- Preparation of Splenic Lymphocytes --- p.51 / Chapter 2.2.5 --- Lymphoproliferation Test --- p.51 / Chapter 2.2.6 --- "Cell Surface Marker (CD3, CD4 and CD8) Staining" --- p.52 / Chapter 2.2.7 --- Measurement of Cytokine Production by ELISA --- p.53 / Chapter 2.2.8 --- In Vivo Study of the Toxicity of WECM --- p.54 / Chapter 2.2.9 --- Cell Cycle Analysis --- p.55 / Chapter 2.2.10 --- DNA Fragmentation Assay --- p.56 / Chapter 2.2.11 --- Cell Morphology Study --- p.57 / Chapter 2.2.12 --- Detection of Apoptotic Cells with Annexin V-FITC/PI --- p.57 / Chapter 2.2.13 --- Detection of Mitochondrial Membrane Potential by JC-1 Fluorescent Dye --- p.58 / Chapter 2.2.14 --- Simultaneous Detection of Mitochondrial Membrane Potential and Intracellular Hydrogen Peroxide --- p.58 / Chapter 2.2.15 --- Western Blot Analysis --- p.59 / Chapter 2.2.15.1 --- Total Protein Extraction --- p.59 / Chapter 2.2.15.2 --- Determination of Protein Amount --- p.59 / Chapter 2.2.15.3 --- SDS Polyacrylamide Gel Electrophoresis --- p.60 / Chapter 2.2.15.4 --- Electroblotting of Protein --- p.61 / Chapter 2.2.15.5 --- Probing of Proteins with Antibodies --- p.61 / Chapter 2.2.15.6 --- Enhanced Chemiluminescence (ECL) Assay --- p.64 / Chapter 2.2.15.7 --- Extraction of Cytosolic Protein --- p.64 / Chapter 2.2.16 --- Determination of Caspases Enzymatic Activity --- p.65 / Chapter 2.2.16.1 --- Extraction of Proteins --- p.65 / Chapter 2.2.16.2 --- Determination of Caspase-3 Activity --- p.65 / Chapter 2.2.16.3 --- Determination of Caspase-8 Activity --- p.66 / Chapter 2.2.16.4 --- Determination of Caspase-9 Activity --- p.67 / Chapter 2.2.17 --- Hemolysis Assay --- p.69 / Chapter 2.2.18 --- Measurement of Intracellular Doxorubicin Accumulation --- p.69 / Chapter CHAPTER 3: --- ANTI-TUMOR AND IMMUNO- MODULATORY EFFECTS OF cordyceps militaris --- p.71 / Chapter 3.1 --- In Vitro Anti-tumor Study of Water Extract of Cordyceps militaris (WECM) --- p.72 / Chapter 3.2 --- In Vitro Study of Immunomodulatory Effect of WECM --- p.78 / Chapter 3.3 --- In Vivo Anti-tumor Study of WECM --- p.80 / Chapter 3.4 --- Anti-tumor Effect of WECM Mediated by Stimulating T-cell Proliferation --- p.83 / Chapter 3.5 --- Toxicity Studies of WECM --- p.92 / Chapter CHAPTER 4: --- ANTI-PROLIFERATIVE EFFECT OF THE ACTIVE COMPONENTS OF cordyceps militaris --- p.97 / Chapter 4.1 --- "Anti-proliferative Study of D-mannitol, Adenosine and Cordycepin (3'deoxyadenosine)" --- p.98 / Chapter 4.2 --- Anti-proliferative Study of Doxorubicin --- p.105 / Chapter 4.3 --- Accumulation of Doxorubicin in HepG2 and R-HepG2 Cells --- p.109 / Chapter 4.4 --- Cytotoxicity Study of Cordycepin and Doxorubicin on Normal Liver Cells --- p.114 / Chapter 4.5 --- Hemolytic Study of Cordycepin --- p.116 / Chapter CHAPTER 5: --- MECHANISTIC STUDY OF CORDYCEPIN IN THE INDUCTION OF APOPTOSIS IN LEUKEMIA CELLS --- p.118 / Chapter 5.1 --- Cell Cycle Analysis of Leukemia Cells --- p.119 / Chapter 5.2 --- Hallmarks of Apoptosis --- p.123 / Chapter 5.2.1 --- Induction of Phosphatidylserine Externalization in Leukemia Cells by Cordycepin --- p.123 / Chapter 5.2.2 --- Induction of DNA Fragmentation in Leukemia Cells by Cordycepin --- p.127 / Chapter 5.2.3 --- Morphological Changes in Leukemia Cells Induced by Cordycepin --- p.130 / Chapter 5.2.4 --- Caspase-3 Activation in Leukemia Cells Induced by Cordycepin --- p.133 / Chapter 5.3 --- Study of the Underlying Mechanisms of Cordycepin-induced Apoptosis in Leukemia Cells --- p.140 / Chapter 5.3.1 --- Induction of Mitochondrial Membrane Depolarization in Leukemia Cells --- p.140 / Chapter 5.3.2 --- Elevation of Intracellular Hydrogen Peroxide Level in Cordycepin-treated Leukemia Cells --- p.144 / Chapter 5.3.3 --- Induction of Cytochrome c Release from Mitochondria of Leukemia Cells --- p.148 / Chapter 5.3.4 --- Caspase-9 Activation in Leukemia Cells Induced by Cordycepin --- p.150 / Chapter 5.3.5 --- Involvement of Bcl-2 Family Members in Cordycepin-induced Apoptosis --- p.153 / Chapter 5.3.6 --- Involvement of Death Receptor Pathway in Cordycepin-induced Apoptosis in Leukemia Cells --- p.159 / Chapter CHAPTER 6: --- MECHANISTIC STUDY OF CORDYCEPIN IN THE INDUCTION OF CELL CYCLE ARREST IN HEPATOCELLULAR CARCINOMA CELLS --- p.164 / Chapter 6.1 --- Cell Cycle Analysis of Hepatocellular Carcinoma Cells --- p.165 / Chapter 6.2 --- Expression of Cell Cycle Regulatory Proteins in Cordycepin-treated Hepatocellular Carcinoma Cells --- p.170 / Chapter 6.3 --- Increased Expression of p21 in Cordycepin-treated Hepatocellular Carcinoma Cells --- p.176 / Chapter 6.4 --- Involvement of p53 in G2/M Phase Arrest of the Cell Cycle in Hepatocellular Carcinoma Cells --- p.178 / Chapter 6.5 --- Induction of Apoptosis in Cordycepin-treated R-HepG2 cells --- p.180 / Chapter CHAPTER 7: --- DISCUSSION --- p.185 / Chapter 7.1 --- In Vitro and In Vivo Studies in the Biological Activities of WECM --- p.186 / Chapter 7.2 --- Induction of Apoptosis in Leukemia Cells by Cordycepin --- p.192 / Chapter 7.3 --- Induction of Cell Cycle Arrest in Hepatocellular Carcinoma Cells by Cordycepin --- p.202 / Chapter CHAPTER 8: --- CONCLUSION AND FUTURE PERSPECTIVES --- p.210 / REFERENCES --- p.214

Sephton, Carmen Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 127-144). / Abstracts in English and Chinese. / Chapter A. --- Acknowledgement --- p.ii / Chapter B. --- Abstract in English --- p.iii / Chapter C. --- Abstract in Chinese --- p.v / Chapter D. --- Table of Contents --- p.vii / Chapter E. --- List of Abbreviations --- p.xii / Chapter D. --- Table of Contents / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Basic background of TCM --- p.3 / Chapter 1.2 --- Choosing TCM Over Western Medication --- p.6 / Chapter 1.3 --- TCM Clinical Trials --- p.7 / Chapter 1.4 --- Evidence Based Medicine and Good Clinical Practice --- p.11 / Chapter 1.5 --- Outline of ICH GCP guidelines used for evaluation --- p.15 / Chapter 2. --- Aim and Objectives --- p.18 / Chapter 3. --- Method --- p.19 / Chapter 3.1 --- Rational for choosing the two studies for comparison --- p.21 / Chapter 3.2 --- Literature Search --- p.25 / Chapter 4. --- Method - Traditional Chinese Medicine clinical trial --- p.27 / Chapter 4.1 --- Protocol Development --- p.27 / Chapter 4.2 --- Consent Form Development --- p.28 / Chapter 4.3 --- Ethics Committee Submission and Approval --- p.29 / Chapter 4.4 --- Case Report Form Development --- p.29 / Chapter 4.5 --- Investigator Folder Development --- p.32 / Chapter 4.6 --- GCP Documentation Collection and Development --- p.33 / Chapter 4.6.1 --- Curriculum Vitae Collection --- p.33 / Chapter 4.6.2 --- Site Personnel Log --- p.34 / Chapter 4.6.3 --- Subject Screening Log --- p.34 / Chapter 4.6.4 --- Subject Identification Code List --- p.35 / Chapter 4.6.5 --- Subject Enrolment Log --- p.35 / Chapter 4.7 --- Medication --- p.36 / Chapter 4.7.1 --- Capsules --- p.36 / Chapter 4.7.2 --- Randomisation Code --- p.39 / Chapter 4.7.3 --- Labelling of Study Medication --- p.40 / Chapter 4.7.4 --- Storage --- p.40 / Chapter 4.7.5 --- Drug Accountability --- p.40 / Chapter 4.8 --- Investigator Brochure --- p.41 / Chapter 4.9 --- Monitoring --- p.41 / Chapter 5. --- Method - Western medication clinical trial --- p.42 / Chapter 5.1 --- Protocol Development --- p.42 / Chapter 5.2 --- Consent Form Development --- p.43 / Chapter 5.3 --- Ethics Committee Submission and Approval --- p.43 / Chapter 5.4 --- Case Report Form Development --- p.43 / Chapter 5.5 --- Investigator Folder Development --- p.44 / Chapter 5.6 --- GCP Documentation Collection and Development --- p.44 / Chapter 5.6.1 --- Curriculum Vitae Collection --- p.44 / Chapter 5.6.2 --- Site Personnel Log --- p.45 / Chapter 5.6.3 --- Subject Screening Log --- p.45 / Chapter 5.6.4 --- Subject Identification Code List --- p.45 / Chapter 5.6.5 --- Subject Enrolment Log --- p.45 / Chapter 5.7 --- Medication --- p.46 / Chapter 5.7.1 --- Tablets --- p.46 / Chapter 5.7.2 --- Randomisation Code --- p.46 / Chapter 5.7.3 --- Labelling of Study Medication --- p.47 / Chapter 5.7.4 --- Storage --- p.47 / Chapter 5.7.5 --- Drug Accountability --- p.48 / Chapter 5.8 --- Investigator Brochure --- p.48 / Chapter 5.9 --- Monitoring --- p.48 / Chapter 6. --- Results & Discussion --- p.49 / Chapter 6.1 --- Protocol Development --- p.49 / Chapter 6.2 --- Consent Form Development --- p.59 / Chapter 6.3 --- Case Report Form Development --- p.65 / Chapter 6.4 --- Ethics Committee --- p.67 / Chapter 6.5 --- Investigator Folder Development --- p.68 / Chapter 6.6 --- GCP Documentation --- p.68 / Chapter 6.7 --- Medication --- p.69 / Chapter 6.7.1 --- Study Medication --- p.69 / Chapter 6.7.2 --- Randomisation Code and Code Break Envelops --- p.71 / Chapter 6.7.3 --- Labelling --- p.71 / Chapter 6.7.4 --- Storage --- p.73 / Chapter 6.8 --- Investigator Brochure (IB) --- p.73 / Chapter 6.9 --- Monitoring Visits --- p.75 / Chapter 6.9.1 --- Source document verification --- p.76 / Chapter 6.10 --- Results of Literature Search --- p.80 / Chapter 7. --- Discussion --- p.95 / Chapter 7.1 --- Discussion on the implementation of GCP in the two clinical trials evaluated --- p.95 / Chapter 7.2 --- Role and Importance of the Study Monitor & Results of Source Document Verification --- p.99 / Chapter 7.3 --- Blinding & randomisation procedures --- p.103 / Chapter 7.4 --- Good clinical Practice & TCM clinical trials --- p.103 / Chapter 7.5 --- Performing Literature Search in Preparation for TCM Clinical Trials --- p.110 / Chapter 7.6 --- Standardisation of Herbs and GMP Issues --- p.112 / Chapter 7.7 --- TCM Medical Practitioner (Investigator) Selection --- p.116 / Chapter 7.8 --- Method of Diagnosis --- p.117 / Chapter 7.9 --- Randomisation & Blind Assessment (placebo or control treatment) --- p.118 / Chapter 7.10 --- Adverse Events in TCM Clinical Trials --- p.122 / Chapter 7.11 --- Other Issues or Considerations & Future Work to be Performed at the CPSU --- p.122 / Chapter 8. --- Conclusion --- p.125 / Chapter 9. --- Reference List --- p.127 / Chapter 10. --- Appendices --- p.145

Wang Xin Ning. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 201-236). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Liu Ming Ju. / "June 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Chai, Stella. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 108-126). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 論文摘要 --- p.iii / ACKNOWLEDGEMENTS --- p.v / PATENT AND PUBLICAION --- p.vii / CONFERENCE ABSTRACTS AND PRESENTATIONS --- p.viii / AWARDS --- p.ix / ABBREVIATIONS --- p.x / LIST OF TABLES --- p.xii / LIST OF FIGURES --- p.xiv / TABLE OF CONTENT --- p.xviii / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- Multidrug resistance (MDR) --- p.1 / Chapter 1.1.1 --- Cancer --- p.1 / Chapter 1.1.2 --- Mechanisms of MDR in cancer --- p.1 / Chapter 1.1.2.1 --- Drug entry --- p.3 / Chapter 1.1.2.2 --- Drug metabolism --- p.3 / Chapter 1.1.2.3 --- Drug sequestration --- p.4 / Chapter 1.1.2.4 --- Mechanisms activated after nuclear entry --- p.5 / Chapter 1.1.2.5 --- Evasion of drug-induced apoptosis --- p.5 / Chapter 1.1.3 --- Approaches in treating MDR --- p.5 / Chapter 1.1.3.1 --- Overcoming MDR by inhibiting transporters --- p.6 / Chapter 1.1.3.2 --- Overcoming MDR by altering signaling pathway --- p.6 / Chapter 1.1.4 --- ATP Binding Cassette (ABC) Transporters --- p.7 / Chapter 1.1.4.1 --- P-glycoprotein (P-gp) --- p.7 / Chapter 1.1.4.2 --- Multidrug resistance-associated protein 1 (MRP 1) --- p.9 / Chapter 1.1.4.3 --- Breast cancer resistant protein (BCRP) --- p.10 / Chapter 1.1.4.4 --- ABC drug transporters and drug absorption --- p.11 / Chapter 1.2 --- The Use of Traditional Chinese Medicine (TCM) in circumventing P-gp-mediated MDR --- p.12 / Chapter 1.2.1 --- Active ingredients in TCM - Alkaloid --- p.12 / Chapter 1.2.2 --- Active ingredients in TCM - Saponin --- p.14 / Chapter 1.2.3 --- Active ingredients in TCM - Flavonoid --- p.15 / Chapter 1.2.4 --- Active ingredients in TCM - Others --- p.17 / Chapter 1.3 --- Polyoxypregnane compounds (POPs) --- p.17 / Chapter 1.3.1 --- Characterization --- p.17 / Chapter 1.3.2 --- POPs isolated from M. tenacissima --- p.18 / Chapter 1.4 --- Objectives of Current Study --- p.22 / Chapter CHAPTER 2. --- EFFECTS OF POLYOXYPREGNANE COMPOUNDS ON VIABILITY AND PROLIFERATION OF HUMAN RESISTANT CANCER CELLS --- p.24 / Chapter 2.1 --- Materials and Methods --- p.25 / Chapter 2.1.1 --- "Chemicals, Materials and Reagents" --- p.25 / Chapter 2.1.2 --- Methods --- p.26 / Chapter 2.1.2.1 --- Cell Lines and Cell Culture --- p.26 / Chapter 2.1.2.2 --- Preparation of POPs --- p.27 / Chapter 2.1.2.3 --- Sulforhodamine B assay --- p.27 / Chapter 2.1.2.4 --- Statistical analysis --- p.29 / Chapter 2.2 --- Results --- p.29 / Chapter 2.2.1 --- Effects of POPs on the viability of parental SW620 and P-gp-overexpressing resistant SW620/Ad300 cells --- p.29 / Chapter 2.2.2 --- Effects of POPs on the viability of parental MCF-7 and MRP1-overexpressing resistant MCF-7/VP cells --- p.33 / Chapter 2.2.3 --- Effects of POPs on the viability of parental MCF-7 and ABCG2-overexpressing resistant MCF-7/FLV1000 cells --- p.37 / Chapter 2.3 --- Discussion --- p.41 / Chapter 2.3.1 --- Structure activity relationship (SAR) --- p.43 / Chapter 2.3.2 --- Nine compounds relating to P-gp-mediated MDR --- p.46 / Chapter CHAPTER 3. --- MECHANISM OF NINE SELECTED POPS IN MODULATING P-GP-MEDIATED MDR --- p.49 / Chapter 3.1 --- Materials and Methods --- p.49 / Chapter 3.1.1 --- "Chemicals, Materials and Reagents" --- p.49 / Chapter 3.1.2 --- Methods --- p.53 / Chapter 3.1.2.1 --- Cell Lines and Cell Culture --- p.53 / Chapter 3.1.2.2 --- Extraction of nine POPs from M. tenacissima --- p.54 / Chapter 3.1.2.3 --- Sulforhodamine B (SRB) assay --- p.55 / Chapter 3.1.2.4 --- Flow cytometry assay --- p.55 / Chapter 3.1.2.5 --- P-gp ATPase assay --- p.56 / Chapter 3.1.2.6 --- Immuno-blot/Western blot analysis --- p.58 / Chapter 3.1.2.7 --- Reverse transcription and quantitative real-time PCR --- p.59 / Chapter 3.1.2.8 --- Statistical analysis --- p.60 / Chapter 3.2 --- Results --- p.60 / Chapter 3.2.1 --- Effects of nine selected POPs on the viability of sensitive human breast cancer MCF-7 cells --- p.60 / Chapter 3.2.2 --- Effects of nine selected POPs on the viability of MDR 1 -transfected HEK1 MDR1 cell line and its control vector transfected cell line HEK293 pcDNA3 --- p.61 / Chapter 3.2.3 --- Effects of nine selected POPs in inhibiting efflux of P-gp substrate --- p.64 / Chapter 3.2.4 --- Effects of nine selected POPs in modulating P-gp ATPase activity --- p.68 / Chapter 3.2.5 --- Effects of nine selected POPs in regulating P-gp protein expression --- p.69 / Chapter 3.2.6 --- MDR1 mRNA expression in various cell lines --- p.72 / Chapter 3.3 --- Discussion --- p.72 / Chapter 3.3.1 --- Effective POPs are targeting specifically P-gp overexpression --- p.73 / Chapter 3.3.2 --- Mechanistic understanding the circumvention of MDR by the effective POPs --- p.74 / Chapter 3.3.2.1 --- Relative potency for the reversal of P-gp-mediated MDR --- p.75 / Chapter 3.3.2.2 --- Inhibition of P-gp-mediated drug efflux across cell membrane by the effective POPs --- p.75 / Chapter 3.3.2.3 --- Stimulation of ATPase by the effective POPs --- p.76 / Chapter 3.3.2.4 --- No effect of POPs on the alteration of P-gp expression --- p.77 / Chapter 3.3.2.5 --- An overall summary of the mechanism of MDR reversal by the effective POPs --- p.78 / Chapter 3.3.3 --- Implication in drug disposition and drug-drug interactions --- p.79 / Chapter 3.3.4 --- Additional information for the structure activity relationship (SAR) --- p.80 / Chapter CHAPTER 4. --- EFFECTS OF CRUDE EXTRACT AND THREE MAJOR POLYOXYPREGNANES (POPS) OF MARS DEN I A TENACISSIMA --- p.81 / Chapter 4.1 --- Materials and Methods --- p.82 / Chapter 4.1.1 --- "Chemicals, Materials and Reagents" --- p.82 / Chapter 4.1.2 --- Methods --- p.82 / Chapter 4.1.2.1 --- "Preparation of M. tenacissima extract, artificial mixture and three fractions" --- p.82 / Chapter 4.1.2.2 --- Sulforhodamine B assay --- p.85 / Chapter 4.1.2.3 --- "Biotransformation study of POP68, POP69 and POP70" --- p.85 / Chapter 4.1.2.4 --- HPLC-MS analysis --- p.86 / Chapter 4.1.2.5 --- Animal care and housing conditions --- p.87 / Chapter 4.1.2.6 --- Toxicity studies of fraction 2 in mice --- p.88 / Chapter 4.1.2.7 --- Statistical analysis --- p.89 / Chapter 4.2 --- Results --- p.89 / Chapter 4.2.1 --- "Effects of crude extract, artificial mixture on the viability of sensitive human breast cancer MCF-7 cells" --- p.89 / Chapter 4.2.2 --- "Effects of crude extract, artificial mixture on the viability of sensitive SW620 and P-gp-overexpressing resistant SW620/Ad300 cells" --- p.90 / Chapter 4.2.3 --- "Metabolites of POP68, POP69 and POP70 after incubation with human intestinal microbiota" --- p.91 / Chapter 4.2.4 --- Toxicity of fraction 2 in mice --- p.94 / Chapter 4.3 --- Discussion --- p.98 / Chapter CHAPTER 5. --- FINAL DISCUSSION AND CONCLUSIONS --- p.105 / REFERENCES --- p.108

Orientador: Reynúncio Napoleão de Lima. / Banca: Francisco Cabral de Alambert Junior / Banca: Alexandre Luiz Mate / Resumo: Na presente pesquisa proponho a reflexão sobre a presença de manifestações da cultura popular tradicional como o bumba-meu-boi, o circo, a literatura oral e de cordel, nas obras do grupo Teatro Popular União e Olho Vivo, como elementos estruturais na abordagem de temas de relevância social, tais como greves, conflitos de classe, étnicos e religiosos, alienação. São tomados como base os textos O Evangelho segundo Zebedeu, 1970 e Bumba, meu queixada, 1978; obras representativas dos mais de 40 anos de atividades do grupo nas periferias de São Paulo. Discuto questões significativas para subsidiar o interesse sobre o conceito e prática do Teatro Popular postulado pelo grupo, estabelecendo nexos entre cultura popular tradicional, teatro popular e consciência crítica. Além disso, são abordados aspectos como as formas de produção artística, envolvendo o público ao qual se destina, os locais das apresentações e os elementos que caracterizam a formação do grupo. A atividade do TUOV é uma alternativa significativa de resistência à cultura de massa e o capitalismo pós-moderno, por socializar conhecimento e difundir práticas humanísticas com sua arte teatral. O grupo tem organização semelhante aos grupos de cultura tradicional das comunidades, em que o popular é entendido no sentido de participar da criação, manutenção e divulgação da obra artística. / Abstract: In this research I propose a reflection on the presence of manifestations of popular culture like the traditional bumba-meu-boi, the circus, oral literature and cordel literature, in the works of the group Teatro Popular União e Olho Vivo, as structural elements in addressing issues of social relevance, such as strikes, conflicts of class, ethnics and religious, alienation. Are taken as base the texts O Evangelho segundo Zebedeu, 1970 and Bumba, meu queixada, 1978; representative works of more than 40 years of activities of the group in the outskirts of São Paulo. I discuss significant issues to subsidize the interest on the concept and practice of the Popular Theater postulated by the group, establishing linkages between traditional popular culture, popular theater and critical conscience. Furthermore, are approached aspects such as forms of artistic production, involving the public wich is intended, the locations of the presentations and the elements that characterize the formation of the group. The activity of TUOV is a significant alternative to resistance to culture of mass and post-modern capitalism, for socializing knowledge and disseminate humanistic practices with their theater art. The group is organized similarly to groups of traditional culture of the communities, in which the popular is understood in the sense of participate of the creation, maintenance and dissemination of artistic work. / Mestre