Browsing by Author "Olivier, Daniel Wilhelm"

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    The age-old problem of pollution, its role in endocrine disruption and the current analytical technologies that can be employed to monitor and assess waste water treatment plants
    (Stellenbosch : Stellenbosch University, 2017-03) Olivier, Daniel Wilhelm; Wolfaardt, Gideon M.; Swart, Pieter; Stellenbosch University. Faculty of Science. Dept. of Biochemistry.
    ENGLISH ABSTRACT: Water scarcity is a global problem and pollution of this valuable resource is a growing concern. South Africa is no exception. As part of an on-going study aimed at developing decentralized water treatment systems based on biomimicry design, this project aimed to evaluate and optimize analytical methods that can be used to evaluate the efficiency of these systems in removing compounds with endocrine disrupting properties. In addition, this project also aimed to show the possible consequences if pollutants are not removed by investigating the effects of a number of endocrine disrupting chemicals in combination with one another and in combination with natural human hormones. This should provide a more realistic view of how a combination of pollutants that typically end up in the environment due to pollution can adversely affect organisms, and by extension, the ecosystem. It should also contribute to our understanding of how common pollutants that gets applied on the skin as personal care products (PCPs) can possibly influence human health and be linked to diseases such as breast cancer. The first aim resulted in a method that can be used to isolate, identify and quantify 11 endocrine disrupting chemicals (3 hormones, 1 synthetic hormone analog, 4 PCPs, 2 plasticizers and 1 anticonvulsant) and one human indicator. The method uses solid phase extraction to isolate compounds, dansyl chloride derivatization of compounds to enhance mass spectrometry detection and a novel super-critical fluid chromatography system, called an ultra-performance convergence chromatography (UPC2) system, coupled to tandem mass spectrometry for detection and quantification of each compound. This method can be used to evaluate the removal efficiency of waste water treatment systems. However, method validation revealed additional optimization and simplification should be considered. The second aim yielded data that showed the combined effect four common PCP pollutants as either being additive, antagonistic or synergistic. The data highlights how these PCPs can possibly interfere with the endocrine system of humans and animals if used as PCPs or are found in environment as pollutants. Finally, the data also suggest how common PCPs can influence diseases such as breast cancer.
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    An investigation into the role of Serum amyloid A in breast cancer
    (Stellenbosch : Stellenbosch University, 2021-12) Olivier, Daniel Wilhelm; Engelbrecht, Anna-Mart; Pretorius, Etheresia; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Cancer remains a global challenge that affects many lives. To this extent, much research has gone into understanding this disease and the factors that contribute to it. Over the past 40 years, an accumulation of data have shown the presence of the acute phase protein, serum amyloid a (SAA), in the blood of cancer patients, tumors and cells associated with tumors. Moreover, it seems that SAA levels also correlate with disease progression. As such, SAA was investigated as a contributing factor to cancer and its role therein. To date, only in a few publications exist where a role for SAA in triple-negative breast cancer (TNBC) have been investigated, apart from reporting its omnipresence in cancer patients. Moreover, many investigations to date have neglected, or was unable, to distinguish between the various SAA isoforms found in humans and mice. As such, no coherent role for each isoform have been established. Additionally, some studies have used recombinant SAA proteins, which have been questioned for various reasons discussed in this dissertation. Therefore, the aim of this study was to address some of the above shortfalls, in addition to establishing a role for SAA in cancer. Here, the role of the acute phase SAA isoforms, SAA1 and SAA2, were investigated, which are secreted in response to tissue injury or inflammation in models of TNBC. In vitro, a role for SAA1 was investigated through RNA interference, whereby the SAA1 gene was knocked down. Data showed that SAA1 is essential for healthy epithelial functioning, but also in the cancer cells. However, whereas SAA1 knockdown in an epithelial cell line (MCF12A) induced characteristics associated with cell death inhibition and cell repair, knockdown in the two TNBC cell lines (MDA-MB-231 and HCC70) induced characteristics of mitotic catastrophe and also caused decreased migration in these cells. Subsequently, an in vivo model was considered wherein TNBC tumors were induced in mice genetically wild-type for SAA1/2 (WT), and mice deficient in SAA1/2 (SAADKO). Here, results showed that tumor induction in SAADKO mice elicited an inflammatory response opposite to WT mice. Molecular analysis of WT and SAADKO tumors further revealed that SAADKO tumors showed signs of inhibition of apoptosis, but a high level of DNA repair, in addition to characteristic associated with lower metastatic potential, when compared to WT tumors. Histological analysis subsequently revealed that SAADKO tumors also had less necrosis. Combinedly, this data suggests that SAADKO tumors are less aggressive, leading to the conclusion that SAA1/2 contributes to cancer progression as a chronic inflammatory mediator. Therefore, SAA could potentially serve as a therapeutic target in the future.
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    An investigation into the role of Serum amyloid A in breast cancer
    (Stellenbosch : Stellenbosch University, 2021-04) Olivier, Daniel Wilhelm; Engelbrecht, Anna-Mart; Pretorius, Etheresia; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Cancer remains a global challenge that affects many lives. To this extent, much research has gone into understanding this disease and the factors that contribute to it. Over the past 40 years, an accumulation of data have shown the presence of the acute phase protein, serum amyloid a (SAA), in the blood of cancer patients, tumors and cells associated with tumors. Moreover, it seems that SAA levels also correlate with disease progression. As such, SAA was investigated as a contributing factor to cancer and its role therein. To date, only in a few publications exist where a role for SAA in triple-negative breast cancer (TNBC) have been investigated, apart from reporting its omnipresence in cancer patients. Moreover, many investigations to date have neglected, or was unable, to distinguish between the various SAA isoforms found in humans and mice. As such, no coherent role for each isoform have been established. Additionally, some studies have used recombinant SAA proteins, which have been questioned for various reasons discussed in this dissertation. Therefore, the aim of this study was to address some of the above shortfalls, in addition to establishing a role for SAA in cancer. Here, the role of the acute phase SAA isoforms, SAA1 and SAA2, were investigated, which are secreted in response to tissue injury or inflammation in models of TNBC. In vitro, a role for SAA1 was investigated through RNA interference, whereby the SAA1 gene was knocked down. Data showed that SAA1 is essential for healthy epithelial functioning, but also in the cancer cells. However, whereas SAA1 knockdown in an epithelial cell line (MCF12A) induced characteristics associated with cell death inhibition and cell repair, knockdown in the two TNBC cell lines (MDA-MB-231 and HCC70) induced characteristics of mitotic catastrophe and also caused decreased migration in these cells. Subsequently, an in vivo model was considered wherein TNBC tumors were induced in mice genetically wild-type for SAA1/2 (WT), and mice deficient in SAA1/2 (SAADKO). Here, results showed that tumor induction in SAADKO mice elicited an inflammatory response opposite to WT mice. Molecular analysis of WT and SAADKO tumors further revealed that SAADKO tumors showed signs of inhibition of apoptosis, but a high level of DNA repair, in addition to characteristic associated with lower metastatic potential, when compared to WT tumors. Histological analysis subsequently revealed that SAADKO tumors also had less necrosis. Combinedly, this data suggests that SAADKO tumors are less aggressive, leading to the conclusion that SAA1/2 contributes to cancer progression as a chronic inflammatory mediator. Therefore, SAA could potentially serve as a therapeutic target in the future.