M. Tech. / AIM: To determine the efficacy of Astragalus membranaceous tincture at maintaining the circulating white blood cell count (WBC) and absolute neutrophil count (ANC) of breast cancer patients receiving chemotherapy. METHODS: This is an open-label study with an active control group. Both the study and control group consisted of fifteen participants. The participants in the study group each received ten millilitres of Astragalus membranaceous 1:2 tincture daily for the duration of their course of chemotherapy. RESULTS: The overall decrease in the WBC and ANC in the control was 4.9 and 3.13 parts per billion per litre, respectively. The study group showed an overall decrease of 2.7 and 1.9 parts per billion per litre, respectively. The average overall reduction in chemotherapy dose was 4.79 percent in the study group and 20.21 percent in the control. In all of the analyses p > 0.05. The small sample size, poor patient compliance and skewed distribution of the variables hindered the reliability of the results. CONCLUSION: The positive effects observed in the study group cannot be extrapolated to the entire population, however further research is strongly motivated.

>Magister Scientiae - MSc / Breast cancer is responsible for a large portion of cancer-related deaths. Worldwide, incidence is increasing. Routinely-used treatments for breast cancer are invasive and are associated with a range of side-effects which may affect quality of life. Fucoidan, a marine bioactive compound, found primarily in brown seaweed, has various medicinal qualities. Among its bioactivities studied, it has potent anticancer activity. Despite numerous studies, the mechanism of action of fucoidan on cancer cells remains unclear. This project aims to shed light on the mechanism of action of fucoidan by studying its effect on the MCF7 breast cancer cell proteome. The IC50 obtained for fucoidan treated MCF7 cells was 0.2 mg/ml. Decrease in expression of XIAP and phosphorylation of ERK1/2 was observed, indicating a decrease in inhibition of apoptosis and increased sensitivity to apoptosis, respectively. Literature reports activation of several caspases, including caspase-3, in various cell lines after to fucoidan treatment. Taken together, with data from the current study it can be said that fucoidan treatment led to cell death by apoptosis. SILAC analysis identified over 2000 proteins with more than 1700 at 95% confidence. STRING analysis of enriched proteins revealed 19 cell death related proteins. However, SILAC results were ambiguous with regards to differential protein regulation and should be repeated with lower electrospray ionization flow rates, pairwise and single sample runs, and validation with Western blot analysis of various apoptosis related proteins and biochemical assays. / National Research Foundation

Prognostic indicators, measured at diagnosis, are important in breast cancer. They help clinicians select optimal treatment, provide rational bases for stratification of treatment trials and assist analysis of response to treatment. Univariate statistical survival curves have identified many such indicators. However, they do not explain why some patients, classified as favoured by one or other factor(s), experience early treatment failure, nor why a substantial number with unfavourable signs remain recurrence-free many years later. This study was undertaken to identify independent prognostic factors with the use of multivariate regression. A Cox proportional hazards model of disease-specific survival was based on 1184 primary breast cancer patients referred to the Cancer Control Agency of B.C. between 1975 and 1981 (median follow-up 60 months). Significant univariate associations with overall survival were found for estrogen receptor concentration ([ER]), axillary nodal status (NO, Nl-3, N4+), clinical stage (TNM I, II, III, IV), histologic differentiation and confluent tumor necrosis (minimal, marked). These factors were assessed at primary diagnosis. A subset of 859 patients with complete data on these variables and also histologic type, menopausal status, age, tumor size and treatment was used to fit the multivariate model. Nodal status was the most important independent factor but three others, TNM stage, [ER] and tumor necrosis, were needed to make adequate predictions. A derived Hazard Index defined risk groups with 8-fold variation in survival. Five-year predicted survival ranged from 36% (N4+, loge[ER]=0, marked necrosis) to 96% (NO, loge[ER]=6, no necrosis) with TNM I and 0% to 70% for the same categories in TNM IV. This wide variation occurred across all stages. Study of post-recurrence survival (369 patients) yielded a model with only three independent predictors: [ER], nodal status and tumor necrosis. Survival - overall, recurrence-free and post-recurrent - is predictable by modelling a few factors measureable at diagnosis. Use of ER concentration, rather than the more common ER status (+ or -), greatly strengthens the model. Presence of ER was also shown to be increasingly important as 'protective', attenuating the effect of other factors, as risk of mortality increases. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Oestrogen receptor (ER) mutations have been identified for both ERα and ERβ in previous studies. The effects of the deletion variants due to splice mutations on clinical parameters, prognosis and treatment were examined in 61 breast carcinoma patients and 13 control samples from elective reduction mammoplasty procedures, respectively. RNA extracted from fine needle aspirates (FNAs) of breast tissue was reverse transcribed and using nested PCR and sequence analysis the presence of these variants elucidated. Using Χ2 and Fisher’s exact tests their significance with respect to clinical parameters such as tumour size, nodal involvement, stage, presence or absence of metastases, menstrual status and hormone responsiveness was examined. Kaplan-Meier survival analysis was also determined. The T-47D breast cancer cell line was cloned with two clones being selected for further analysis, namely TCA3 (hormone sensitive) and TCC1 (hormone resistant). These clones were treated for ten passages with oestrogen metabolites, 17-β- oestradiol and oestriol; oestrogen precursors, androstenedione and cholesterol; an anti-oestrogen, 4-hydroxy-tamoxifen; and the aromatase inhibitor aminoglutethimide, respectively. RNA was extracted from the cells initially and after the tenth passage and the ERα and ERβ exon profiles were examined using RT-PCR and sequence analysis. After the tenth passage hormone response tests were performed every 24 hours (up to 96 hours) with cell number being determined using the MTT assay. The results indicate that ERα and ERβ variants do not have any affect with respect to menstrual status and nodal involvement (N). Expression of ERα2 and ERα4 are required by the mouse monoclonal antibody (DAKO ® Clone 1D5) in the immunocytochemical assay used for the recognition of the protein in order to assess ER status and therefore show significance. ERαΔ2 and, contrary to previous investigations, the variant ERαΔ3 were not found to play a role in tumourigenesis. ERαΔ5 was observed to be more prevalent in ERα-positive patients and was usually co-expressed with the complete ERα5 indicating heterodimerization. ERαΔ5 showed no significance with respect to progression of disease or response to hormone treatment. An increase in the ratio of ERαΔ4: wild-type ERα4 indicated an increase in metastatic potential of diseased tissue. ERα4 and ERαΔ4 heterodimers were present in both T-47D clones and after 10 passages the TCA3 clone grown in 10-8M aminoglutethimide indicated a complete loss of ERα4 without altering hormone responsiveness. These results suggest that ERαΔ4 may play a role in progression of disease but not in the acquisition of tamoxifen resistance. ERαΔ6 was observed in 15% of patients but not in the T-47D clones or the control samples. An increase in the expression of ERαΔ6 among patient samples significantly increased their metastatic potential (p=0.018). ERαΔ6 was also observed as significant with respect to stage of disease (p=0.023) indicating the possible relevance of ERαΔ6 in progression of the disease. ERαΔ7 was the most frequently observed variant and did not show any significance with regard to any of the clinical parameters examined. The presence of ERαΔ7 did not show significance with regard to hormone response in vivo but in vitro the presence of this variant, expressed as a heterodimer with the wild-type ERα7, conferred greater sensitivity to tamoxifen in the tamoxifen resistant clone TCC1. Multiple exon deletions of ERα were also observed. The two more significant multiple deletion variants were those involving ERαΔ4, namely, ERαΔ2-ERαΔ6 and ERαΔ4-ERαΔ6. The multiple variant ERαΔ4-ERαΔ6 may be involved in tumour progression. ERβ variants were not examined in as much detail as ERα variants due to insufficient material available for analysis. The two domains, the DNA binding domain and the ligand binding domain, of ERβ were analyzed in a few of the patients and in the T-47D clones. They were not found to be significant with respect to the clinical parameters investigated and the ERβ profiles of the TCA3 and TCC1 clones remained unchanged after 10 passages under varying growth conditions.

Thesis (MPH.) -- University of Limpopo, 2020 / Breast milk contains antibodies that help babies to fight off viruses and bacteria, thus, breastfeeding lowers the baby's risk of having asthma or allergies. Babies who are breastfed exclusively for the first 6 months, without any formula, have fewer ear infections, respiratory illnesses, and bouts of diarrhoea. Dwarsloop Community Health Centre (CHC) has low rates of exclusive breastfeeding (EFB), despite many efforts to increase this practice. The purpose of the study is to evaluate, understand, describe, explore and explain the factors contributing to poor exclusive breastfeeding among mothers at Dwarsloop Community Health Centre (CHC). Methods: The proposed study was conducted using a quantitative research method. Data was collected using self-administered, structured questionnaires, with close-ended questions. The sample in this study was drawn from mothers of infants 0-6 months attending the child health clinic at Dwarsloop CHC during the period of data collection. A sample of 92 mothers was selected for the study. Result: The highest proportion of the mothers had poor exclusive breastfeeding practice (73%). compared to good exclusive breastfeeding practice (27%). Factors associated with poor exclusive breastfeeding practice include experience of breast problems ( 77%), mothers who were embarrassed to breast feed in public (52%), mothers who were supported by their partners ( 39%), mothers who believe that their child was satisfied with breast milk only ( 49%) and mothers who were HIV-positive ( 54%). Conclusions: Although EBF is the correct method for infant feeding, mothers still find it difficult to maintain the practice for up to 6 months. Interventions emphasizing practical education should be targeted at addressing factors associated with poor EBF.

Although there are hereditary risk factors strongly associated with breast cancer, only a small percentage of breast tumors can be attributed to these. Instead, it is believed that 85-90% of breast cancers are primarily of environmental origin. Polycylic aryl hydrocarbons (PAHs) are environmental carcinogens derived from combustion including fossil fuels. PAHs bind to a cellular aryl hydrocarbon receptor (AhR) that mediates downstream events leading to cellular transformation. Previous work in our laboratory used the prototypical PAH 7,12-dimethylbenz[a]anthracene (DMBA) to form tumors in mouse mammary glands that had constitutive AhR activation, increased Wnt signaling, and strong induction of the CK2 subunit CK2α (Currier, Solomon et al. 2005). Wnt, an important developmental pathway, is implicated in several cancers (Dominguez, Sonenshein et al. 2009). CK2 is a highly promiscuous, constitutively active serine/threonine kinase that is over-expressed in every cancer that has been examined for its presence (Meggio and Pinna 2003). Data from the DMBA-induced mouse tumors demonstrated that these factors may be involved in carcinogen-induced breast cancer, but their role in tumor development is uncertain. The hypothesis underlying this project was that CK2 and the Wnt pathway would be involved in early changes in mouse mammary and liver tissues in animals exposed to DMBA. We used qPCR, Western blotting, and immunohistochemistry to look at changes in Wnt pathway components and known Wnt-dependent genes, and CK2 subunits in mammary and liver tissues one and two weeks after DMBA exposure. Liver tissue was analyzed along with mammary gland tissue because the liver is the site of DMBA metabolism. Our results showed no change in liver or mammary gland morphology at these time points. There was induction of the AhR gene targets cyp1a1 and cyp1b1 in liver tissue but not in mammary gland. Liver also had evidence of Wnt pathway activation. Mammary glands did not have a strong AhR response but did show Wnt induction at two weeks post-exposure, suggesting that DMBA was affecting the liver before the mammary glands. CK2α had an unexpected early decrease in protein expression at one week in liver, which at two weeks resolved to the same levels as control tissue. In mammary glands, CK2α expression levels were the same as control at one week and decreased at two weeks, again suggesting a slower response than liver. Interestingly, CK2β was markedly overexpressed in mammary glands at the two week time-point. These results suggest there is a role for both Wnt and CK2 in early DMBA-generated tissue changes. It is still unclear if these pathways are separately affected by DMBA or if one initiates the other. Further experimentation, possibly in cell culture using inhibitors and siRNA, are called for to better understand these findings.

No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences