Background: Nasopharyngeal carcinoma (NPC) is a common malignancy in South Asia and North Africa. In recent years, NPC incidence is dramatically decreasing which cannot be explained by the current etiological factors. Moreover, milk consumption is promising as factor to be investigated and showed declining trend in worldwide. To our knowledge, there are no population level studies to examine the association between NPC and milk & dairy products consumption. Objective: The objective of this study was to investigate the relationship between NPC incidence and per capita consumption of milk at the population level. Methods: These were two types of ecological studies (cross-sectional and longitudinal ecological study). NPC incidence data were collected from Cancer Incidence in Five Continents Vol. IX (1998-2002) and several population-based cancer registries. Data of per capita consumption of milk & dairy were obtained from Food Agriculture Organization (FAO). Results: In cross-sectional ecological study, age-standardized incidence rate (ASIR) of NPC is negatively associated with per capita consumption of milk & dairy products in 48 countries/ regions from 1961 to 2009. Moreover, in one-way sensitivity analysis, the result was consistent with the above. In longitudinal ecological study from around 1980 to 2009, ASIR of NPC (both genders) was negatively correlated with milk consumption per capita in Hong Kong and Singapore. The ASIR of NPC (both genders) was decreased with per capita consumption of milk from around 40 to 140 kg/capita/year in Hong Kong and Singapore. Further, such negative associations were found statistically significantly between NPC and milk consumption in Hong Kong after adjusting for HDI. Conclusion: Our study provided information on the protective association between NPC and milk & dairy products. Our ecological study shows that higher per capita consumption of milk & dairy products is associated with a lower risk of NPC development. However, our finding need to future confirm since there are major limitations on data and methods. Further research is needed for confirmation of the link between milk consumption and NPC. / published_or_final_version / Public Health / Master / Master of Public Health

Nasopharyngeal cancer (NPC) is more common in the Southern China region than the rest of the world. Radiation therapy (RT) is the contemporary and standard treatment for nasopharyngeal cancer. Chronic complications arise from RT including hearing loss, xerostomia, trismus and dysphagia. Previous research has shown that dysphagia is prevalent in irradiated NPC patients. Radiation therapy techniques have improved in the last decade with the emergence of Intensity Modulated Radiation Therapy (IMRT), which allows more precise radiation beams directed at the tumor. In turn, it should also allow greater sparing of surrounding structures that are vital for preservation of swallowing function. This study was designed to investigate the difference in the degree of swallowing function preservation in two groups of irradiated NPC patients: the conventional RT and the IMRT group. Thirty patients with NPC who received RT from 1998 to 2006 in Queen Mary Hospital, Hong Kong were randomly recruited during the period from January to December 2011. Participant’s swallowing competence and its effect on the quality of life was assessed by videofluoroscopic swallowing study (VFSS) and by the MD Anderson Dysphagia Inventory, respectively. In comparison of swallowing performance with VFSS between the two groups, only one measure (Duration of Laryngeal Elevation) out of 13 showed significant difference on thin liquid and congee diet. Results from the MDADI did not show significant difference between the two groups. From the results, it was concluded that IMRT only resulted in subtle improvement in preserving the swallowing function as compared to conventional RT. One possibility is the subject self-compensation of their swallowing impairments that led to functionally similar performance despite their differences in the anatomy and physiology. Swallowing is a highly complex body function and no single parameter can be used to accurately quantify and characterize one’s swallowing function. The interaction between the anatomical and physiological impairments resulted from radiation therapy and the compensatory mechanism could not be clearly explained with this study. Future research could adopt a longitudinal approach such that the changes in NPC patients who received radiation therapy can be better understood. / published_or_final_version / Speech and Hearing Sciences / Master / Master of Philosophy

Nasopharyngeal carcinoma (NPC) has distinctive ethnic and geographic distributions, with the highest incidence in Southern China. Epstein-Barr virus (EBV) infection, non-viral environmental risk factors, and host genetics contribute to the development of NPC. In our previous studies, Fibulin-2 (FBLN2), located at chromosome 3p25.1, has been identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC) by using a chromosome 3 NotI genomic microarray screen, followed by functional assays. FBLN2 belongs to the fibulin family of extracellular matrix glycoproteins. It encodes a large protein consisting of cysteinerich and cysteine-free segments, three anaphylatoxin (AT) modules, a series of cbEGFlike repeated, and a fibulin module. Although FBLN2 was also identified as a candidate TSG in other cancers, its molecular characterization is still largely unknown. In the present study, lentiviral constitutive and inducible transgene expression systems, fluorescent protein labelling and reporter systems, and shRNA-mediated knockdown system were optimized and established for studies in NPC. With the use of lentiviral systems, the FBLN2-mediated signaling pathways and the functions of FBLN2-related p65 signaling pathway were revealed. Lentiviral pWPI-FBLN2 infected HONE1, HK1, and C666 cell lines consistently reduced p65 phosphorylation at serine S536. Also, FBLN2 was shown to inactivate RhoA and Cdc42, resulting in decreased stress fiber and filopodia formation. Full-length and truncated FBLN2 fragments, with the exception of anaphylatoxin module, reduced phosphorylation of p65 as well as suppressed HUVEC tube formation. The p65 pathway was then chosen for in-depth studies. Inactivation of p65 by p65 stable knockdown and IκBα super repressor overexpression showed reduced cell migration, invasion, angiogenesis, in vitro cell growth, and in vivo tumor growth. In contrast, overexpression of wild type p65 and phospho-mimic S536E p65 promotes cell migration, invasion, angiogenesis, in vitro cell growth, and cell cycle progression. Molecular studies suggested that tumorassociated angiogenesis is regulated by p65 through expression of pro-angiogenic factors and the p65 activity controls epithelial-to-mesenchymal transition (EMT)-like properties in NPC. Western blotting and qPCR analyses showed that inactivation of p65 reduced expression of pro-angiogenic factors and mesenchymal markers. Overexpression of p65 induced expression of pro-angiogenic factors and mesenchymal markers as well as enhanced EMT-like properties. The elimination of the p65 feedback mechanism by IκBα knockdown largely induced expression of pro-angiogenic factors and mesenchymal markers, as well as changes in cell morphology. In conclusion, these results suggest that FBLN2 suppresses tumor growth, tumor-associated angiogenesis, migration, and invasion through the regulation of Erk1/2, p65, and Rho GTPase pathways. The important roles of the p65 pathway in angiogenesis and EMT were also revealed. These findings provide a strategic new insight into the understanding of mechanistic role of FBLN2 in NPC and provide a better understanding for the molecular genetic basis of NPC tumorigenesis. / published_or_final_version / Clinical Oncology / Doctoral / Doctor of Philosophy

published_or_final_version / Microbiology / Master / Master of Philosophy

published_or_final_version / Anatomy / Master / Master of Philosophy

published_or_final_version / Radiation Oncology / Master / Master of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available in print.

Thesis (M. D.)--University of Hong Kong, 2007. / Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 66-80) Also available in print.