No description available.

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2007. / "A dissertation in pharmaceutical science and chemistry." Advisor: Simon H. Friedman. Typescript. Vita. Description based on contents viewed July 16, 2008; title from "catalog record" of the print edition. Includes bibliographical references (leaves 206-220). Online version of the print edition.

Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. Johannesburg, 2013 / Cancer is a hypernym used to describe a group of diseases characterised by the uninhibited growth and spread of abnormal cells in the body. An estimated 7.6 million annual deaths are attributed to the disease while 12.7 million new cases are reported every year. The severity of this disease demonstrates the urgent requirement of novel anti-cancer therapeutic agents. The non-integrin laminin receptor, here designated the 37 kDa/67 kDa laminin receptor (LRP/LR), is a multifunctional protein located on the surface, in the cytoplasm, in the perinuclear compartment and in the nucleus of cells. While this receptor is imperative for normal cellular functioning, it has also been implicated in many diseases – it serves as a cell surface receptor for numerous viruses, infectious prion proteins as well as certain respiratory tract pathogens. Additionally, LRP/LR has been found to have some involvement in zoonotic diseases and those involving neurodegeneration, such as Alzheimer’s disease. Most importantly for this study, LRP/LR has been implicated in cancer progression, where it was found to be overexpressed on the surface of various cancer cell lines, this overexpression correlating to increased metastasis. The aim of this study was to investigate the effect of the siRNA-mediated downregulation of LRP expression on the viability of tumorigenic lung and cervical cancer cells (A549 and HeLa, respectively). The cell surface LRP/LR and total LRP levels were investigated using flow cytometry and western blotting, respectively, in A549 and HeLa cells, the results revealing high percentages of both cell lines expressing LRP/LR on their surface. Additionally, A549 and HeLa cells express similar total levels LRP. The transfectability of these cells was confirmed and siRNA-LAMR1 was shown to significantly downregulate LRP expression (80% and 60% in A549 and HeLa cells, respectively). MTT assays revealed that the significant 13% and 18% reduction in cellular viability in A549 and HeLa cells, respectively, was as a consequence of LRP downregulation. This reduction in cellular viability was found to be a consequence of induced apoptosis (identified by the visualisation of the loss in nuclear integrity, as well as the significantly increased activity of the apoptosis-associated protein caspase- 3) and inhibited cellular proliferation in the aforementioned cells. These findings suggest that siRNA targeting LRP mRNA may act as a potential alternative therapeutic tool for the teatment of cancer.

published_or_final_version / abstract / Microbiology / Master / Master of Philosophy

published_or_final_version / Computer Science / Master / Master of Philosophy

No description available.

No description available.

published_or_final_version / Pathology / Master / Master of Philosophy

Nasopharyngeal carcinoma (NPC) is squamous cell carcinoma derived from the epithelial layer of nasopharynx. The incidence is high in Southern China and South-east Asia. In Hong Kong, the prevalent of NPC subtype is undifferentiated NPC and is in close association with Epstein-Barr virus (EBV). MicroRNAs (miRNAs) are small non-coding RNAs. They play vital roles in regulating gene expression at post-transcriptional level. EBV also expresses viral miRNAs but the function remains unclear. In NPC diagnosis and monitoring, circulating EBV DNA level has been commonly used. However, in some cases, EBV DNA is below the detection threshold in the plasma of NPC patients making it impossible to be used in continuous monitoring of the patients. This study aimed to evaluate whether miRNAs (both NPC-derived and EBV-derived miRNAs) could be used as candidate circulating markers for disease monitoring. Candidate gene approach was used to select suitable circulating miRNA markers for NPC patients. Four candidate miRNAs including miR-21, miR-1301, miRBART7 and miR-BART22 were examined. The expression levels were first validated in paired NPC tissues and normal counterparts. Furthermore, circulating miRNA levels were evaluated in the plasma of NPC and normal individuals. To examine the changes of miRNA in response to radiotherapy, changes of circulating miRNA were monitored in 13 NPC patients before and after radiotherapy. In addition, functional assay in cell proliferation was performed to validate the potential role of the candidate miRNA in the pathogenesis of undifferentiated NPC. Of the 4 candidate miRNAs, miR-BART7 was consistently over-expressed in both tumor tissues and plasma samples of NPC. In addition, circulating miRBART7 was also detected in NPC patients in case of the plasma EBV DNA levels below the detection threshold. In response to radiotherapy, 10 of 13 (76.92%) patients had decreasing circulating miR-BART7 in the plasma samples collected at 3 month after radiotherapy. Furthermore, introducing miR-BART7 mimics into the undifferentiated NPC cell line HONE1 and normal nasopharyngeal-derived epithelial cell cultures NP69 and NP460 resulted in significant increases in cell proliferation rates of all the 3 cell lines. To summarize, miR-BART7 expression was significantly higher in NPC patients as a potential oncogenic miRNA. Evaluating the miR-BART7 levels is a possible screening approach in NPC diagnosis and post-treatment monitoring. The oncogenic role of miR-BART7 in the development of undifferentiated NPC deserves further investigation. / published_or_final_version / Surgery / Master / Master of Philosophy