EGFR mutations in non small cell lung cancer patients in South Africa

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Internal Medicine / Medical Oncology. Johannesburg 1st September 2014Introduction: Tyrosine kinase inhibitors and EGFR mutations has changed the treatment approach to lung cancer globally. This retrospective study will look at factors associated with EGFR mutations and define the EGFR mutation rate in South Africa. Methods: Retrospective record review from NSCLC patients in South Africa who were tested for EGFR mutations at Lancet Laboratories during 1st September 2009 to 30th June 2012. Chi-squared test was used to determine association with categorical variables. Kaplan- Meier survival analysis was done for OS and PFS between EGFR mutation positive and negative patients. Cox proportional hazards were used for subgroup analysis. Treatment practices and response were described. Results: 170 lung cancer samples were evaluable for EGFR mutation and 37 were EGFR mutation positive (21.8%). There were 22 (59.5%) exon 19 deletions, 11 (29.7%) L858R mutations, two G719X mutations, one S768I mutation and one exon 20 insertion. The median age was 63 (range 27-85). There were more females (55.6%) than males (44.4%) sent for mutation testing. Most patients were whites (71%), followed by blacks (18.3%), and other race (10.7%). 85% of all NSCLC samples tested were adenocarcinoma. None of the squamous cell carcinoma tested was positive for EGFR mutation. Smoking status was inversely proportional to EGFR mutation status (p<0.001). Over 60% patients received chemotherapy first and second line and responses decreased with each line of chemotherapy. Median PFS and OS were not different between the EGFR mutation positive and negative groups (6.85 versus 6.8 months; HR 1.6; 95% CI 0.70-3.65; p=0.2543 and 11.5 versus 12.9 months; HR 0.70; 95% CI 0.28-1.75; p=0.44, respectively). On multivariate analysis, only non-white race was associated with decrease in OS (HR 6.66; 95% CI 2.31-19.19; p=0.0004). Conclusion: EGFR mutation rate in South African lung cancer patients was 21.8%. 89% of all EGFR mutations were either exon 19 deletions or L858R point mutations. Most EGFR mutations were associated with adenocarcinoma of the lung in non-smokers. These findings were consistent with current literature in western countries. Treatment practice remained chemotherapy based, with few patients receiving EGFR TKIs. Efforts should be made to prioritized targeted treatment approach in lung cancer in South Africa

Regulating the sale of first-hand residential properties in Hong Kong : a study of policy and administrative dynamics

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Effect of a Chinese herbal tonic, 'watermelon frost', in preventing vocal fatigue

Also available in print."A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2006."Thesis (B.Sc)--University of Hong Kong, 2006.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use

Combining CD4 recovery and CD4: CD8 ratio restoration as an indicator for evaluating the outcome of continued antiretroviral therapy: an observational cohort study

Immune recovery following highly active antiretroviral therapy (HAART) is commonly assessed by the degree of CD4 reconstitution alone. In this study, we aimed to assess immune recovery by incorporating both CD4 count and CD4:CD8 ratio

Decreased brain-expressed X-linked 4 (BEX4) expression promotes growth of oral squamous cell carcinoma

© 2016 Gao et al.Background: Brain-expressed X-linked (BEX) 4 is a member of BEX family. The functional role of BEX4 in oral squamous cell carcinoma (OSCC) remains unknown. Methods: Expression level of BEX family members (BEX1-5) in OSCC tissues and the paired normal epithelial were examined. Functions of epigenetic changes (DNA methylation and histone modifications) on BEX4 suppression in OSCC were examined by zebularine and trichostatin A (TSA) treatment on OSCC cell lines. Lentivector containing full-length BEX4 was used to generate OSCC cell lines with stable BEX4 expression. Effects of BEX4 expression on OSCC proliferation were monitored with xCELLigence RTCA real-time cell analyzer. BEX4-overexpressing CAL27 was implanted into nude mice to evaluate the effects on tumor growth in vivo. The signaling pathways regulated by BEX4 in OSCC was explored using human whole-transcript expression microarray. Results: Among the 5 BEX family members, BEX1 and BEX4 showed significant down-regulation in OSCC (P < 0.001). BEX3, in comparison, was overexpressed in the primary tumor. BEX4 expression in OSCC cell lines was re-activated after zebularine and TSA treatment. High BEX4 expression could suppress proliferation of OSCC in vitro. Subcutaneous tumor volume of BEX4-overexpressing CAL27 was remarkably reduced in nude mice. Microarray experiment showed that S100A family members (S100A7, S100A7A, S100A8, S100A9 & S100A12) might be the downstream targets of BEX4 in OSCC. Conclusions: BEX4 functions as tumor suppressor by inhibiting proliferation and growth of oral cancer. Decreased BEX4 contributes to the increased proliferative propensity of OSCC.published_or_final_versio

Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive–behavioural therapy-based psychoeducation and usual care. Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms

Public healthcare financing and provision in Hong Kong : a public-private partnership approach

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio