Extracts of the African potato have long been believed to have anti-cancer properties. The aim of the current research was to isolate hypoxoside (HYP) from Hypoxis hemerocallidea (African potato) and synthesize the dimethyl (DMH) and decaacetyl (DAH) derivatives and to test their selective cytotoxicity on a model consisting of a normal (MCF10A) and premalignant, invasive breast epithelial cells (MCF10A-NeoT). Hypoxoside was extracted from the H. hemerocallidea corms using ethanol, purified using a C-18 reverse phase column and the compound examined by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry and found to be of high purity. This was also the case for the synthesized compounds. To assess possible selective effects (cytotoxicity) of derivatized and underivatized hypoxoside, effects on the metabolism of premalignant and normal cells were assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Effects on cell number (total counts) and cell death [trypan blue and propidium iodide (PI) staining for dead cells versus a lack of staining for live cells] were, thereafter, assessed. Imaging of live adherent cells was also carried out using acridine orange (AO) and PI for live and dead cells (respectively). Propidium iodide staining of detached cells was carried out for flow cytometric determination of cell death (PI indicating early apoptotic or late apoptotic/necrotic cells). After treatment of normal (MCF10A) breast epithelial cells and premalignant cHa-rastransfected (MCF10A-NeoT) derivative breast epithelial cells with HYP, DMH and the DAH derivative, the MTS assay and the Duncan‟s multiple range, analysis of variance (ANOVA) post hoc analysis of the MTS results revealed that only the 150 and 300 µM DAH derivative had a statistically significant effect on the metabolic activity of the abnormal cell line relative to the dimethyl sulfoxide (DMSO) and revealed no significant effect on the normal MCF- 10A cell line after treatment with any of the test compounds. Supravital PI staining of adherent cells seemed to indicate a far higher rate of induction of cell death in abnormal cells than evident in the MTS assay and the PI-based flow cytometry or the trypan blue exclusion assays and need re-investigating, though result trends were similar. Total cell counts, show that HYP and its derivatives appear to increase both cancer and normal cell proliferation significantly, except in the case of DAH at 150 and 300 μM in the MCF10A-NeoT, without affecting the MCF-10A cell line. The trypan blue method for detection of cell death, together with total cell counts, the Duncan‟s analysis of MTS results and a 24 hour exposure to test compounds, seems to constitute an optimal system for drug screening and indicates the statistically significant selective toxicity of the DAH compound at 150 and 300 μM in the MCF10A-NeoT, suggesting that the DAH derivative at 150 and 300 µM would have significant, selective therapeutic potential on Ras-related malignancies. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.

Health Locus of Control (HLOC) and other predictors of Quality of Life (QL) were examined for women with an initial versus recurrent breast cancer diagnosis. Twenty-eight women with an initial breast cancer (IBC) diagnoses and twenty-eight women with recurrent breast cancer (RBC) diagnoses were recruited from doctors' offices and cancer support groups. Correlational analyses were used to assess the relationships between variables. No significant differences were found between women with IBC and RBC on Psychological QL. Doctor HLOC and Psychological QL were related for women with RBC (r = .481, p = .01) and marginally so for women with IBC (r = .329, p = .09). A positive correlation was also found between Doctor HLOC and Functional QL for both women with IBC (r = .464, p = .01) and women with RBC (r = .390, p = .04). After controlling for stage of cancer, women with RBC reported higher Functional QL than did women with IBC. Advanced (stages III or IV) versus early (stages I or II) cancer stage related to lower Functional QL, controlling for initial versus recurrent diagnosis (r = -.283, p = .01). A marginally significant relationship was also found for cancer stage, regardless of initial versus recurrent diagnosis, with higher Overall QL for women with early stages of breast cancer (r = -.157, p = .09). No significant differences in Optimism or Overall QL were found between women with IBC versus RBC. No differences were found between married and single women. This research begins to explore differences in Quality of Life for women with a new versus a recurrent breast cancer diagnosis.

This dissertation refines knowledge synthesis from publicly accessible databases, based on the model of D.R. Swanson. Knowledge synthesis endeavors bring together two or more non-interactive literatures to create combinatorial research data on a specific topic. In this endeavor the biomedical literature was searched on the anti-neoplastic agent nordihydroguaiaretic acid (NDGA) for its potential role as a functional food in the chemoprevention of breast cancer. Bibliometric cocitation was utilized to identify complementary but non-interactive literatures in the disciplines of biomedicine and dietary science. The continuing specialization and fragmentation of the cancer literature degenerates the potential usefulness of cross-disciplinary research and information. As the biomedical sciences become more specialized the potential increases for isolation of discoveries and for failures to connect science to the needs of the people. Within the information science discipline several techniques are available to bridge the isolation between discoveries recorded in different sets of literatures. Electronic database searching with combinatorial keyword entries, syllogistic modeling and bibliometric author cocitation analysis are the principle techniques applied in this endeavor. The research questions are addressed to the absence or presence of human in vivo research on breast cancer with the potentially chemopreventative functional food NDGA. Utilizing a syllogistic model the literatures of functional foods, nordihydroguaiaretic acid and breast cancer were searched with designated combinatorial keywords. The documents retrieved were subjected to author cocitation analysis to demonstrate disjointness or connectivity of the two complementary literatures. The results demonstrated a possible preventative relationship between breast cancer in women and nordihydroguaiaretic acid, a phytochemical antioxidant and potential functional food. The results of this study are consistent with D.R. Swanson's pioneering work in knowledge synthesis. Swanson's methods can be used to identify non-interactive, disjoint literatures. Continuing support for his techniques has been demonstrated.

Breast microwave imaging (BMI) is a novel modality that complements current breast screening tools. Microwave radar imaging creates a radar cross-section (reflection) map of the breast. The difference in permittivity between healthy and malignant tissue is between 10-50%. This contrast is significantly higher than that obtained with x-rays and supports the use of microwave imaging for breast cancer diagnosis. Prior to widespread clinical use, some areas require further study. Firstly, the performance of three different antennas was carried out, to assess their suitability for a BMI system. Secondly, the sampling constraint of a circular scan geometry was studied and tested using experimental phantoms and these antennas. For accurate breast BMI reconstruction, the transmission speed of the radio waves inside the breast must be determined. The tissue composition of each patient is different, making this task challenging. This work presents an algorithm for wave speed estimation in different mediums. / February 2017

Mutations in BRCA1 and BRCA2, the first two breast cancer susceptibility genes identified, carry as much as an 85% lifetime risk of developing breast, ovarian or other cancers. Genetic testing for mutations in these two genes has recently become commercially available. There have been varying amounts of psychological distress noted among women with a family history of breast cancer. Distress has been observed to impact psychological functioning, activities of daily living, and the practice of breast cancer surveillance behaviors. Within the genetic screening process, psychological distress has been shown to impact the decision to undergo genetic screening, the comprehension and retention of risk assessment information, as well as affecting the subject following the receipt of the genetic test results. Little work has been done to examine predictors of distress within at risk subjects. This study examines psychological distress among 52 community women presenting for BRCA1 and BRCA2 genetic mutation testing. Predictors of distress included family cancer history, education, age, Ashkenazi ethnicity, and Internality and Powerful Others Health Locus of Control. Vulnerable sub-groups of patients include younger women, women with higher levels of education and women of Ashkenazi ethnicity.

This dissertation presents an ethnographic account of a socially diverse, public breast cancer clinic in Johannesburg. The findings of this qualitative research radically challenge the unproblematised and overdetermined use of the categories of race and gender in existing literature concerning this disease. The growing breast cancer epidemic in South Africa affects all demographic categories of women including young women. Yet, previous research frames this as a racialised and gendered crisis. Black women have been depicted as ignorant “problem patients” who resist biomedical treatment, and all women are described as having a particular relationship to their breasted bodies and a deep fear of mastectomy. Departing from these stereotypes, this ethnography reveals unanticipated data showing, firstly, that race, class, age and level of education did not determine women’s relationship to breast cancer and biomedicine. Secondly, socially diverse women commonly experienced breast cancer as a life-threatening disease that evoked confrontation with existential concerns regarding suffering, death, family, and faith. Due to these commonalities, an intimate and powerful sociality existed amongst women at this clinic. Thirdly, within this sociality, women accepted mastectomy as a necessity in creating a healthy body. Breastlessness was normalised and women generally were reluctant of breast reconstruction, thus destabilising the conceptual relationship between breasts and gender. This dissertation’s deconstruction of the use of hegemonic social categories is a significant intervention in a context where these categories are often viewed as absolute determinants of social and health phenomena, and therefore prompts more nuanced approaches to understanding experiences of illness in post-apartheid South Africa.

The purpose of this study is to investigate the changes of the pericardial dose at different respiratory phases and statuses in accelerated partial breast irradiation (APBI) using Cyberknife M6™ multileaf collimators (CK-MLC). Anonymous 6 female patient files with respiration gated four-dimensional computed tomography (4DCT) sets, and 6 left breast cancer cases with CT images in free-breathing (FB) and deep inhalation breath-hold (BH) were selected. One CT image set from each patient was planned for APBI in Accuray Multiplan™ 5.2, and respectively compared its pericardial dose with those from CT sets of other respiratory phases. All the comparable CT images were fused in the planning system according to the left chest wall, among which the lung gap anterior to the pericardium varies by the lung expansion. For the purpose of this study, the tumor volume was outlined in the media-lower quadrant of the left breast where this lung gap is relatively small. All the plans in this study met the requirements set by the National Surgical Adjuvant Breast and Bowel Project/Radiation Therapy Oncology Group (NSABP/RTOG), specifically protocol B-39/RTOG 0413. From the comparisons in this investigation, the mean relative pericardial dose of the BH CT group showed significant or 45% (p < 0.01) lower value than that of FB CT group. However, in FB 4DCT group, 3 of 6 cases indicated a meaningful reduction (p < 0.05) in 100% inhalation phase when compared with the mean dose over other phases. The inconsistent pericardial doses were displayed in FB 4DCT group due to minimal changes in the anterior lung gap of the pericardium, when the diaphragmatic breathing was dominant in those patients. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

After menopause, a woman's production of 17-estradiol, the predominant female sex hormone, declines. This change is associated with increased risk of osteoporosis/osteopenia and atraumatic bone fracture, cardiovascular disease, and breast and ovarian cancers. Phytoestrogens are non-steroidal compounds isolated from plants that have antagonistic, weak agonistic, or super-agonistic estrogenic effects in mammalian tissues; they have emerged as a potential therapeutic to alleviate post-menopausal symptoms. While some epidemiological evidence indicates that dietary consumption of phytoestrogens can alleviate post-menopausal health risks, other research suggests that phytoestrogens may not be completely safe. The research presented in this thesis indicates that a high concentration and sustained dose of phytoestrogens may be necessary to achieve antiestrogenic effects. MCF-7 cells, an estrogen-sensitive breast adenocarcinoma cell line, were used as a model system, and proliferating cell nuclear antigen (PCNA) was used as a marker of cell proliferation. Immunoblotting shows that genistein, a commercially purified phytoestrogen, promotes cell proliferation when administered for 24 hours, but may reduce proliferation when cells were treated for 48 hours. Genistein and estrogen have an additive effect on cells that were treated simultaneously with both hormones for 24 hours. In contrast, Promensilâ„¢, an over-the-counter phytoestrogen dietary supplement, was able to abolish expression of PCNA after 48 hours, and at high concentrations prevented estrogen-induced upregulation of PCNA after 48 hours. The clinical significance of these findings is that phytoestrogens may reduce the risk of breast cancer, but only after sustained high doses, which may be difficult if patient non-compliance is at issue. Additionally, because cell proliferation and not cell survival was investigated, we cannot say whether phytoestrogens are cytotoxic to breast cancer cells, only that they reduce proliferation.

The overall goal of this thesis was to determine whether optical tomographic imaging can be employed to predict treatment outcome in women with breast cancer (BC) who undergo neoadjuvant chemotherapy (NACT). NACT is widely applied as a standard treatment for patients with newly diagnosed operable invasive BC. Only about 13-30% of women have a response to this treatment. Furthermore, NACT is an expensive and toxic treatment that takes several months to completely administer. In order to know the response of the patient, physicians usually need to wait until the months of NACT has finished and the patient has undergo surgery in which they receive the pathology. If the long-term treatment response could be predicted early into the treatment regimen, the patient would be relieved of any unnecessary side effects and alternative treatments could be initiated. We have used a novel dynamic DOT system to study the effects of targeted NACT. Unlike X-ray imaging, which requires potentially harmful ionizing radiation, DOT can be applied without side effects, which is particularly important in the case of multiple imaging sessions to be performed over the course of treatment. We have tracked 40 subjects and imaged them at 6 different time points during their NACT. For this study, two different types of data were collected: static (single 3D image) and dynamic (3D movies). The combination of the data may be used to accurately determine the response of the patient. With non-invasive, non-ionizing DOT imaging we have been able to determine within two weeks if the patient will respond to treatment with an accuracy as high as 94.1%.

As a master regulator of the epithelial state, p63 is a family member of the well-known tumor suppressor p53. It has previously been connected to a cancer-associated process, epithelial-to-mesenchymal transition (EMT), and here we find that it can be regulated by oncogenes involved in breast tumorigenesis. Specifically, activated forms of PIK3CA and H-RAS are able to strongly repress expression of ∆Np63α, which is the major p63 isoform in epithelial cells. In mammary epithelial lines, this oncogene downregulation occurs at the transcriptional level, and complete repression occurs over the course of several days. As p63 is repressed, the cells undergo EMT and acquire the ability to invade individually through a 3D collagen matrix. Strikingly, even when p63 is suppressed but no oncogene action is present, these cells undergo a mesenchymal shift, suggesting the importance of this gene in maintaining the epithelial state. Furthermore, it is particularly interesting that p63 protein and RNA levels are often low in breast tumors. By connecting H-RAS and PIK3CA signaling to p63, it is hypothesized that such oncogene suppression could account for tumor progression in cases where p63 levels are low. Here, it is proposed that p63 acts in a tumor-suppressive manner, although it can be overcome by oncogenes leading to changes in differentiation state and migratory capability, therefore drastically affecting breast carcinogenesis.