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Item Comprehensive analysis of molecular characteristics between primary and breast-derived metastatic ovarian cancer(AME Publishing Company, 2025-03-30) Long J; Liu B; Li J; Ji X; Zhu N; Zhuang X; Wang H; Li L; Chen Y; Li X; Zhao SBackground: The molecular basis for the disparities between primary ovarian cancer (POC) and ovarian cancer secondary to breast cancer (OCSTBC) remains poorly understood. This study aimed to explore the different characteristics between them through genomic analysis. Methods: We performed differentially expressed genes (DEGs) analysis between POC (n=96) and OCSTBC (n=44) groups with transcriptome data and revealed the enriched biological pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Hallmark gene sets between these two groups. Then, the Microenvironment Cell Populations (MCP)-counter and Cell-type Identification by Estimating Relative Subsets of RNA Transcript (CIBERSORT) algorithms were applied to evaluate the immune infiltration in tumor microenvironment (TME) between them. Finally, we performed the association analysis within single nucleotide polymorphism (SNP) data and obtained some meaningful SNPs and candidate genes for further transcriptomic analysis. Results: We identified a total of 13 cancer-related genes including GATA3, FOXA1, CCND1, and TTK between POC (n=96) and OCSTBC (n=44) groups with DEGs analysis. Integrated analysis revealed more significant immune-enriched pathways in the POC than in the OCSTBC group. Most immune cells had higher infiltration abundance in POC, except M2 macrophages, which was higher in OCSTBC. In SNP analysis, four SNP regions (8q12.1, 11q21, 11q24.3, and 17q25.3) were found to be significantly correlated with phenotypes (POC/OCSTBC), and importantly, some new susceptibility genes such as ETS1, CWC15, and XKR4 were revealed to potentially be associated with distinction between POC and OCSTBC. Conclusions: Our study provides a systematic molecular characteristic between POC and OCSTBC and suggests a pressing need to develop some specific therapeutic strategies in certain types of ovarian cancer.Item 'People who are together with me' : the personal social networks of women living with breast cancer in the lower southern region of Thailand : a dissertation presented in fulfilment of the requirements for the degree of Doctor of Philosophy in Nursing at Massey University, Palmerston North, New Zealand(Massey University, 2015) Purinthrapibal, ShutiwanLiving with breast cancer is a complex, long, and changeable journey. Due to my personal experiences of breast cancer in my family, and (breast) cancer clubs being promoted in the Thai health policy to support cancer care, this study’s aim was to explore the experiences of the personal social networks of women living with breast cancer in the lower southern region of Thailand. A qualitative collective case study approach was used to purposively examine eleven personal networks, comprising eleven women with a breast cancer diagnosis and their significant network members. Data were collected during eleven months of fieldwork, through interviews, (participatory) observation, and network mapping. Analysis of the longitudinal data revealed that personal social networks were identified as the ‘people who are together with me’. These people were predominantly family and they were held together by family relationships and feelings of ข้อง /Khong/ (the Thai southern dialect that means a combined feeling of ‘attachment’ and ‘concern or worry about’). Throughout the breast cancer journeys in the lower southern region of Thailand, an ongoing interplay between the contextual factors related to the breast cancer disease and its treatment, the health system, and normal life resulted in four unique patterns of living with breast cancer. These were: i) living with mature networks; ii) living with complexities in family circumstances; iii) living with complexities in the management of the breast cancer, and family circumstances; and iv) for some women, having a long-term involvement with a breast cancer club. Through cross case analysis, five core characteristics of networks emerged. These characteristics were the: i) interplay between support, supporters, and relationships; ii) hierarchies of member significance; iii) different degrees of relationships and feelings of ข้อง /Khong/; iv) fluidity of networks; and v) network life cycle. These characteristics were underpinned by criteria related to the disease, relationships, and cultural differences. These study findings have important implications for nursing, especially related to the nursing of people with long-term conditions such as breast cancer. First, personal social networks can form part of the health care team; second, family and family relationships are important and impact on both the women‘s support needs and access to resources; third complexities in clinical management of the disease as well as complexities in family circumstances have a high impact on the support needs and ability of the network to provide the necessary support; fourth, an involvement of non-family members in the core supporter group of a network is a significant sign of difficulties in family support provision; fifth, it is crucial that nurses understand the nature of networks; and sixth, there are considerable individual differences of needs for formal network support (cancer clubs) related to perceptions of needs, preferences for types of support, and barriers to participation. These findings provide an in-depth examination of the women‘s personal social networks, and their functions and actions in providing support for women that extended past coping with their breast cancer and its treatment into also supporting the women to meet their responsibilities within their everyday lives. While most personal social networks were resourceful and supportive, gaps in support emerged over time in some networks. Consideration of personal social networks would enable more opportunities for nurses to individualise care to the social and cultural contexts of women‘s lives and their specific support needs.Item Deciding treatment options for breast cancer : a grounded theory of the women's perspective : a thesis submitted in partial fulfilment of the requirements for the degree of Master of Arts in Nursing, Massey University(Massey University, 2000) Harwood, LynnFallowfield and Hall (1991, p. 387) state: "Coping with the diagnosis and treatment of breast cancer is problematic for both the women with the disease and their doctors who must treat it". A variety of surgical techniques and types of adjuvant therapy are now available. As well as advances in medical and surgical care, marked cultural changes have also occurred in western health care over the past 30 years, with increasing concern for individual autonomy and consumer rights. Increasing emphasis is now placed on the provision of information to patients and on their participation in decision making about their prospective treatment. Questions remain, however, as to whether patients benefit from being offered choice, and evidence is currently limited. The aim of the present study was to discover the women's perspective on having to make choices regarding their preferred treatment options for breast cancer. The Glaserian (after Barney Glaser) school of grounded theory was chosen as the research method. Fourteen participants were recruited. Each woman participated in a loosely structured interview lasting 1-1 1/2 hours, which was taped and transcribed. Together these interviews became the data for analysis. Substantive codes and theoretical categories were developed from this data and finally a conceptual framework was constructed. Three main categories were identified. These were: • Detecting a cancer - the crisis evolves. • Discerning value priorities. • Reaching a point of salience and commitment to choice. The over-arching or core category identified was "Unifying 'the self' with treatment choices". It was identified in the present study that freedom of choice is part of the life project of 'choosing oneself'. The self is not a ready-made being but an existent always in the process of becoming, or as Macquarrie (1972, p. 145) states: "A unitary self as distinct from a series of unconnected acts". Women made their choices based on their past, their present life situation and their projection, for themselves, of their future. These decisions were made within the context of provisionality versus permanence; a diagnosis of cancer brought with it a renewed awareness life's uncertainty and also one's mortality.Item The role of HP1α and HP1β in breast cancer progression : a thesis presented to Massey University in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry at Massey University, Palmerston North, New Zealand(Massey University, 2012) Campbell, Tahnee MareeBreast cancer is the foremost cause of cancer-related deaths in New Zealand women. Metastasis of breast tumours increases the likelihood of fatality of the disease as treatment becomes more difficult and the tumours may interfere with the function of multiple organ systems. Consequently, the identification of biomarkers that may indicate the potential for a tumour to become metastatic are of great importance and may allow for the selection of more targeted treatment regimes. Heterochromatin Protein 1 (HP1) is a chromatin associating protein that facilitates heterochromatic spreading through its interaction with trimethylated H3K9. There are three HP1 isoforms found in mammals, HP1α, HP1β and HP1γ, each with differing functions and chromatin localisation patterns. Previous research has demonstrated that deregulation of either HP1α or HP1β expression occurs in several types of cancers. Both increases and decreases in HP1α expression have been reported in breast tumour samples, with a decrease in HP1α associated with breast metastases. However, what role loss of HP1α may have in promoting a metastatic phenotype is unclear, and any contribution of HP1β to this process is also explored. This thesis examined the roles of HP1α and HP1β in breast cancer progression through the creation of breast cancer cell lines with knock-down of either HP1α or HP1β. These cell lines were characterised for changes in proliferation, cell cycle profile, global chromatin compaction, invasive potential and anchorage independence. Though no changes were observed in the majority of these characteristics, a novel role for HP1β as a potential suppressor of anchorage independence was identified. Additionally, it was found that HP1α may act to enhance anchorage independence. This information could help to further knowledge of how breast cancer cells proceed towards metastasis, and provide new avenues of research into the potential for levels of HP1α or HP1β to be used as biomarkers for breast cancer progression.Item Ethnic and socioeconomic inequalities in breast cancer survival : a thesis by publications presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Epidemiology, Massey University, Wellington, New Zealand(Massey University, 2010) McKenzie, Fiona; McKenzie, FionaThere are likely to be many contributing factors to inequalities in cancer survival. The most commonly theorised are: differences in access to cancer care, screening, diagnosis, quality of care and treatment; biological differences; lifestyle/behavioural differences; and differences in comorbidities. To investigate explanations for inequalities in survival for women with breast cancer, a conceptual model was used to illustrate potential pathways, and studies conducted to isolate which pathways could explain ethnic and socioeconomic differences in survival. The substantive body of this work comprises a systematic review, and analyses of datasets from England and New Zealand. Firstly, breast cancer survival differences between ethnic minority and majority groups are reviewed to examine the relationship between social determinants and behavioural factors. Secondly, inequalities by socioeconomic position (SEP) in screen-detected breast cancer survival in the South West of England are presented to examine social determinants and healthcare systems. Next, prognostic factors for New Zealand women with breast cancer by ethnicity and SEP are presented to examine the relationship between social determinants and biological factors. Finally, two separate analyses examine the relationship between ethnicity and SEP respectively, and biological factors and healthcare systems, as determinants of breast cancer survival in New Zealand. SEP was found to explain a sizeable proportion of ethnic inequalities in breast cancer survival; however other factors were also identified as important. The largest contributors to ethnic inequalities appear to be factors associated with access to timely healthcare. There are considerable SEP inequalities in breast cancer survival, which are independent of ethnicity. A large proportion of the observed deprivation-gap in breast cancer survival can be accounted for by early detection. Efforts to eliminate inequalities in breast cancer survival should focus on increasing attendance at breast screening for women of lower SEP. However efforts should also be made to ensure equal access through the secondary care system to address the attenuated survival inequalities that remained even among screen-detected women. Both timely access to and through healthcare will likely have an important impact on ethnic survival disparities. Biological tumour differences, which indicate breast cancer subtype, do not appear to explain survival inequalities, between women of different ethnicity or different SEP.Item An investigation into the regulation of the topoisomerase IIα promoter in breast cancer cells exposed to doxorubicin : a thesis presented to Massey University in partial fulfillment of the requirement for the degree of Doctor of Philosophy in Biochemistry(Massey University, 2003) Allen, Kirsty AnnChemotherapeutic drugs, such as doxorubicin, are some of the most effective agents for the treatment of breast cancer. Acquired resistance to these drugs often develops, however, and may preclude effective treatment. Such resistance is multifactorial in origin, but may include down-regulation of topoisomerase IIα (topo IIα) - an essential enzyme involved in normal DNA metabolism and a target for some of the anticancer drugs. A reduction in the levels of this enzyme is thought to reduce DNA damage induced by the drug-topo IIα complex and so increases the chances of survival. The mechanisms involved in this down-regulation and the development of resistance to doxorubicin are the focus of this study. Stable breast cancer cell lines, containing deletion constructs of the topo IIα promoter linked to the hGH reporter gene, were exposed to doxorubicin and both the reporter and endogenous gene expression were analysed in the surviving cells. It was shown that the reporter and endogenous topo IIα gene expression in the cell line containing the full length topo IIα promoter construct was no longer correlated in the surviving cells negating the use of this experimental system. Instead the endogenous expression of topo IIα and putative regulatory factors were investigated. Data suggest that specific cell lines show a down-regulation in the levels of the topo IIα protein. These changes were not due to changes in cellular proliferation rates, cell cycle profile or promoter sequence. Selected cell lines were analysed for changes in the relative amounts of specific transcription factors with putative roles in topo IIα gene regulation and for the expression of proteins proposed to have a role in the development of drug resistance. In specific cell lines, a reduction in topo IIα protein levels correlated with alterations in the relative amounts of NF-YA and/or Sp1. It was shown that the drug efflux pumps MDR1 and MRP1, as well as the heat shock factor Hsp70 were not involved in the survival of cells that were exposed to the drug. In vivo footprinting was attempted to detect changes in the in vivo binding of proteins to the topo IIα promoter after short term drug exposure.