Altered histone modifications are known to be observed in cancer cells. Acetylation of histone H4 (acetyl-H4) occurs reversibly on its amino-terminal end at four lysines positions 5, 8, 12 and 16 by Histone Acetyltransferase (HATs). Acetyl-H4 is responsible for a complex set of post-translational modifications that regulate the accessibility of DNA, transcription activation and DNA repair processes. Acetyl-H4 can also acetylate non-histone proteins which eventually control numerous cell signal pathways such as 53BP1, BRCA, AKT. Accumulated evidence showed that P13K, AKT controls the survival signaling pathway and is crucial in developing in drug resistance. This study investigates the global level of all lysine sites of acetyl-H4, its association with p-AKT as well as its prognostic significance in breast cancer. The expression levels of acetyl-H4 were assessed by immunohistochemistry on 102 cases of breast cancer from Queen Mary Hospital in Hong Kong using tissue microarray technology. Nuclear expression of acetyl-H4 was scored and SPSS used for statistical analysis. p-AKT expression data previously obtained in our laboratory (Chen et al.) was also retrieved for correlation with nuclear acetyl-H4 scores. Nuclear acetyl-H4 scores were analyzed for association with a) various clinico-pathological parameters, b) luminal subtypes (ER-and PR-positive), HER-2-positive and triple negative breast cancer, c) p-AKT in breast cancer and d) patient survival by Kaplan-Meier analysis and Cox-regression. By Pearson correlation test, we observed high acetyl-H4 expression was significantly associated with PR-positive breast cancer but not correlated with other clinical parameters and phenotypes of breast cancers (p>0.05). High acetyl-H4 expression was not correlated with p-AKT activity (p=0.84), although it showed inverse correlation with high nuclear p-AKT score. By Kaplan-Meier and Cox-regression analysis, high nuclear acetyl-H4 expression was significantly correlated with poor disease-specific survival in invasive ductal carcinoma (p=0.008 and 0.017 respectively). Multivariate Cox regression analysis confirmed high acetyl-H4 expression (p=0.047) when analyzed together with lymph node involvement (p=0.032) and T-stage (p=0.008) was an independent predictor of poor disease-specific survival in invasive ductal carcinoma. Our results suggest that high acetyl-H4 expression is significantly associated with PR-positive phenotype and lower disease-free survival. The expression of acetyl-H4 was not correlated with p-AKT. Acetyl-H4 may be a potential biomarker to predict poor disease-specific survival for invasive ductal carcinoma. Further investigation is needed for possible use as therapeutic targeting for breast cancer. / published_or_final_version / Pathology / Master / Master of Medical Sciences

In view of the increasing prevalence of female breast cancer in the global and local arenas, this disease has become a critical problem affecting women’s physical, psychological, spiritual and social conditions. With medical technology advancements, women can receive early diagnosis and effective treatment. However, maladjusted rehabilitation affects women’s long-term recovery. In order to improve women’s rehabilitation, more attention is being paid to breast cancer survivorship care after treatment. Therefore, how women experience and perceive breast cancer during the transition period is the important information for us to understand women’s breast cancer survivorship. The present study aims to explore how women perceive their breast cancer experiences during the transition period from a holistic perspective. This study adopted the qualitative inquiry approach. Movement-based focus group design was the present research design, in which dance/movement activities and group discussions were included. It is based on the belief that expressing through dance/movement enables an individual to reveal the experiences which have been stored in the body. Four focus groups were used, with a total of twenty recruited informants. Data collected from the focus group interviews included verbal (transcriptions) and non-verbal (writing/drawing and created body shapes) expressions. Interviews were transcribed verbatim and analyzed using the ATLAS.ti 7 qualitative data analysis software. The findings indicated that women's descriptions of their experiences during the transition period were associated with bodily, emotional, cognitive, spiritual, and self and social relational perspectives. Five domains (bodily, emotional, cognitive, spiritual and self and social relational experiences) were generated after data processing. Analysis of the contents in each domain reveals the body-mind-spirit connection. During this period, women consider their health and exercise to be important, they were relaxed and happy, they reflected more, they searched for purpose and meaning in life, and they appreciated developing relationships with others and self. Furthermore, the results showed that these women attained self-growth through their breast cancer experiences. Nevertheless, the self-growth areas and pace were different for each individual. The results also revealed that the non-verbal information (writing/drawings and created body shapes) enriched the women’s expression by illustrating their in-depth or hidden breast cancer experiences. The results provide practitioners with insight and direction into designing rehabilitation programmes for breast cancer survivors. Therefore, the contents of the programme include not only psychosocial aspects but also bodily, cognitive and spiritual perspectives. Furthermore, the present movement-based focus group demonstrated the use of non-verbal expressions, as well as dance/movement, to enhance communication. To conclude, this study sheds light on our understanding of women’s breast cancer experiences during the transition period, as well as on the use of the movement-based focus group research method. The present practice and experiences may contribute to qualitative research and psychosocial oncology research. Further research with larger sample size is recommended. The present methodology can also be extended to other cancer populations such as cervical cancer survivors. Furthermore, studies examining the additional benefits of using movement in focus group interview are also recommended. / published_or_final_version / Social Work and Social Administration / Master / Master of Philosophy

Background: The Gail Model is a statistical and risk assessment tool for women with given age and risk factors to estimate their probability that will develop invasive breast cancer. An accurate assessment of individual risk for developing breast cancer would be useful for health care providers to facilitate their risk communication with women at average risk and to make decision on taking chemoprevention for high-risk women in clinical practice. Currently, there are several validation studies of the Gail Model in western populations, however, model validity on Chinese people has not yet to be studied. Objective: To conduct a systematic review on the studies that validated the performance accuracy of the Gail model for predicting risk of developing breast cancer at population level and individual level. Methods and results: The literature search on the PubMed database and additional articles retrieved by hand searching reference lists. After applying the inclusion and exclusion criteria, a total of 11 studies met the criteria and finally include in the systematic review. Quality of review studies was assessed follow the STROBE checklist. The PRSMA guidelines were used to produce this review. Conclusions: The Gail model was validated in general American white women with annual screening. However, there is insufficient evidence to approve that the Gail model can be applied to Chinese women in China widely. / published_or_final_version / Public Health / Master / Master of Public Health

Objective: Breast cancer is the most common invasive cancer in women in the world. Benzo[a]pyrene (B[a]P), a carcinogenic component of cigarette smoke and grilled meat, was related to expression of enzymes involved in several epithelial malignancies including breast cancer. Understanding the association of exposure to B[a]P and breast cancer risks may inform potential disease preventive measures. The objective of this systematic review was to assess from epidemiological studies the relationship between the exposure to and the risks and development of breast cancer in humans. Study design: A systematic search using keywords in PubMed (1990-2014), CNKI (1994-2014) and Google Scholar databases was carried out to identify eligible epidemiological studies on the association between the exposure to B[alP and breast cancer risks published during 1990-2014. Results: Nine studies met the inclusion criteria and included in this review. All nine included studies used case-control design, with B[a]P exposure mainly proxied by benzo(a)pyrene diolepoxide (BPDE) and dietary consumption of B[a]P-rich food. Of these, seven found a significant positive association between B[a]P exposure and breast cancer risks, after adjustment for age, family history of breast cancer, smoking, ethnicity, alcohol use and parity in most studies. Discussion: Discuss the potential reason for inconsistence, the possible biological pathways explaining the role of B[a]P in the development of breast cancer, limitations of the studies and the public health implication from this review. Conclusion: A positive association between B[a]P exposure and breast cancer risks was suggestive from the systematic review. However given the limited number of studies included, further prospective cohort studies in humans as well as molecular/animal studies are warranted to explore the impact of B[a]P on the development of breast cancer to inform evidence based preventive measures against breast cancer. / published_or_final_version / Public Health / Master / Master of Public Health

VCP/p97 works as a segregase to extract the ubiquitylated proteins from protein complexes, lipid membranes and chromosomes, thereby promoting their degradation or recycling. VCP/p97 plays essential roles in ubiquitin-dependent proteasome degradation, ERAD, autophagy, endocytosis, reassembly of ER, Golgi and nuclear envelop, and cell cycle regulation. In ubiquitin dependent proteasome degradation pathway, VCP/p97, as a special ubiquitin binding-shuttle factor, is required for the successful cell cycle progression in regulating IκB, CDT-1, Aurora B, and CDC25A. Here, we studied the role of VCP/p97 in G1 to S phase transition in MCF-7 human breast cancer cells. We found that VCP/p97 knockdown or inhibition by DBeQ, a potent VCP/p97 inhibitor, decreased cell proliferating rates and reduced S phase cell percentages in asynchronized MCF-7 cells.VCP/p97 inhibition by DBeQ also arrested cells at G1 phase in synchronized MCF-7 cells. These data suggest that VCP/p97 is required for G0/G1 to S phase transition in MCF-7 cells. In addition, in either asynchronized or synchronized MCF-7 cells, VCP/p97 knockdown or DBeQ treatment resulted in the accumulation of p21 and p27, two CDK inhibitors. Moreover, p27, not p21, knockdown in MCF-7 cells rescued the defects of S phase entry caused by VCP/p97 knockdown or DBeQ treatment. Taken together, our results suggest that VCP/p97 regulates the timely degradation of p27 to promote G1 to S phase transition in MCF-7 cells. / published_or_final_version / Physiology / Master / Master of Philosophy

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The purpose of the study was to demonstrate that breast cancer related lymphoedema can be managed by means of Complete Decompression Therapy and consequently improve quality of life. An instrumental case study design was used. The target population was all women with breast cancer related lymphoedema living in Tshwane, the context of the study. The patient with the most severe breast cancer related lymphoedema treated by the researcher is presented. Mixed methods were used to gather data. The expected 60% limb volume reduction could not be achieved after 4 weeks of induction therapy. After 8.5 weeks of treatment, the limb volume reduced from the initial 3841 mL to 1639 mL, a 57.2% reduction. Patient compliance to compression therapy was a challenge and led to relapse extending the induction phase of treatment. Despite the prolonged treatment, the limb volume reduction improved the patient’s quality of life. The study demonstrated and confirmed that despite a degree of noncompliance, breast cancer related lymphoedema can be managed with Complete Decongestive Therapy which, in turn, improves the quality of life of women living with breast cancer.

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published_or_final_version / Medicine / Master / Doctor of Medicine