M.Sc.

Magister Artium (Psychology) - MA(Psych) / The aim of this study is to explore the role of communication between the physician and women with breast cancer, and to examine women’s coping mechanisms from diagnosis through the management of the illness to its resolution. A qualitative methodology was utilised, with purposive sampling of participants from a public hospital in the Western Cape. A semi-structured interview was used to gather the data, after which a thematic analysis was conducted. The findings reveal the information exchange between physician and patient was clear, direct and understandable. Furthermore, the participants coped by accessing and using support from family and friends, by recourse to spirituality and prayer (bargaining with God, questioning of God), and by developing a positive attitude, with hope for recovery and acceptance. There were also emotional and psychological reactions from women in the sample when they received their diagnoses. This study may provide valuable insights into the experiences of women with stages I to III of breast cancer

Small molecules are powerful tools to probe biological systems and cure diseases. In the scope of this dissertation, small molecules were applied to study three distinct disease models: cancer, Sedaghatian-type spondylometaphyseal dysplasia (SSMD), and COVID-19. First, encouraged by the recently reported vulnerability of drug-resistant, metastatic cancers to GPX4 (Glutathione Peroxidase 4) inhibition, we examined the basis for nanomolar potency of proof-of-concept GPX4 inhibitors, which revealed an unexpected allosteric binding site. Through hierarchical screening of a lead-optimized compound library, we identified novel small molecules binding to this allosteric site. Second, a homozygous point mutation in the GPX4 gene was identified in three living patients with SSMD. With a structure-based analysis and cell models of the patient-derived variant, we found that the missense variant significantly changed the protein structure and caused substantial loss of enzymatic function. Proposed proof-of-concept treatments were subsequentially validated in patient fibroblasts. Our further structural investigation into the origin of the reduced enzymatic activity revealed a key residue modulating GPX4 enzymatic function. We also found that the variant alters the degradation of GPX4, unveiling the native degradation mechanism of GPX4 protein. Third, driven by the recent urgent need for COVID-19 antiviral therapeutics, we utilized the conservation of 3CL protease substrate-binding pockets across coronaviruses to identify four structurally divergent lead compounds that inhibit SARS-CoV-2 3CL protease. With structure-based optimization, we ultimately identified drug-like compounds with < 10 nM potency for inhibiting the SARS-CoV-2 3CL protease and blocking SARS-CoV-2 replication in human cells.

Thesis (M. Sc. (Biochemistry)) -- University of Limpopo, 2019 / Cervical cancer is the fourth most common cancer in females, and the seventh of all cancer types in both genders, with an estimated 500,000 new cases each year. As with liver cancer, a large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers. About 90% of cervical cases are associated with human papillomavirus (HPV) as a causative agent and this virus is frequently transmitted through sexual contact involving exchange of fluids (Walboomers et al., 1997). Due to the ineffectiveness, undesirable side effects and costly treatment for the disease the current study was aimed at determining the anti-proliferative effects of extracts of selected medicinal plants for their anticancer activity on HeLa cell line invitro. In order to accomplish the outcome of this research study, medicinal plants (Toona cilliata, Seriphium plumosum and Schkuhria pinnata) from Limpopo Province (South Africa) with history of traditional use on cervical cancer-associated patients were selected. The Toona cilliata plant leaves were collected from Tzaneen, area while Seriphium plumosum and Schkuhria pinnata leaves were collected from Mankweng area. The dried leaves were grounded into powder and extracted using acetone. Thereafter, extracted leaf materials of selected plants were subjected to fingerprint profiling using TLC silicon coated plates immersed in tanks with different mobile phases (TEA, CEF and EMW) of various increasing polarities since. The plates were sprayed with vanillin/H2SO4, dried and visualised under UV light. Scavenging ability of the plant extracts was determined through investigating the presence of antioxidant activities using 0.2% of the 2,2- diphenyl-1- picrylhydrazyl (DPPH) indicator. The quantitative presence of total phenolic and flavonoids contents was also determined using garlic and quercetin as standards, respectively. Quantitative antioxidant scavenging activities were also determined and ascorbic acid was used as a positive control. This was followed by quantitative determination of ferric reducing power and thereafter the EC50 values of the extracts were determined by linear regression. Cell proliferation or viability was determined using the 3[4, 5 dimethylthiazol-2-yl]-2-5 diphenyltetrazolium (MTT) assay with actinomycin as a xv positive control and untreated cells as the negative control. Apoptotic effects of the extracts were determined using the Annexin V Fluos staining kit. This was followed by determining whether apoptosis was calcium dependent or independent using a calorimetric assay. In comparing the acetone extract yield per 10 g leaves of plants, Toona cilliata leaves exhibited the highest yield followed by Seriphium plumosum and with the least yield from Schkuhria pinnata. The finger print profile showed the prominent separation and was achieved from all the plants when using the non-polar TEA solvent. All plants were shown to contain extracts with varying levels of antioxidant activity especially when using CEF and EMW mobile phases. When evaluating the total phenolic and flavonoids contents all plant extracts exhibited presence of phenolic compounds with high presence observed in Seriphium plumosum and Toona cilliata. Extracts from Seriphium plumosum and Toona cilliata showed to have higher concentrations of phytochemicals that may be of a benefit in antioxidant activities as compared to Schkuhria pinnata in relation to the positive control and a similar trend were observed in the ferric reducing power assay. Extracts from Seriphium plumosum were shown to have the best IC50 scavenging values followed by Toona cilliata and Schkuhria pinnata respectively. All the plants exhibited free radical scavenging abilities with Seriphium plumosum shown to possess higher activities in comparison with the positive control. All the plants exhibited a dose-dependent cytotoxicity activity against the HeLa cervical cell line. Evidence of induced apoptotic activity was observed in HeLa cells when using extracts from Seriphium plumosum and Toona cilliata. Induction of apoptosis by plant extracts was shown to be calcium dependent as there was a decrease in calcium concentration with a decrease in the number of viable cells. In conclusion, the leaf extracts from Toona cilliata, Seriphium plumosum and Schkuhria pinnata contain compounds of various polarities with freeradical, antioxidant and anti-cancerous activities that may be beneficial if further studies are conducted to identify chemical compounds that may inhibit anticervical cancer activities.

The goal of our research was to find a cancer treatment that was both effective and cancer specific, sparing immune and normal tissues. We evaluated the efficacy of a combinatorial treatment using the glycolytic inhibitor 3-bromopyruvate and the fatty acid metabolism inhibitor fenofibrate in cancer, immune and normal tissue cells lines. Treatment of the human breast cancer MCF-7 with 3-bromopyruvate and fenofibrate resulted in increased cell death and decreased colony formation. In the immune cells known as peripheral blood mononuclear cells our combinatorial treatment displayed less toxicity than the traditional chemotherapy doxorubicin. Our combinatorial treatment displayed greater toxicity than doxorubicin towards an established breast cell line MCF- 10A, described in the literature as representing normal breast cells. We have shown for the first time a synergistic relationship between 3-bromopyruvate and fenofibrate. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

In this research we aimed to investigate the anti-proliferative properties of three South African plants: Kedrostis foetidissima, Euphorbia mauritanica and Elytropappus rhinocerotis against breast cancer cells. This was done on the basis of their documented ethno-medicinal use against cancer and other ailments. The plant extracts were screened for cytotoxicity and pro-apoptotic activity against two breast cancer cell lines MCF-7 and YMB-1. With an IC50 ~ 100 μg/ml, K. foetidissima was the only extract that exhibited significant cytotoxicity on both cell lines, whilst E. mauritanica was cytotoxic to MCF-7 cells only. The cytotoxicity assay was followed by the Annexin-V detection assay to evaluate the occurrence of apoptosis. The results observed suggested that K. foetidissima was inducing significant apoptosis on both YMB-1 and MCF-7 cells, whilst E. mauritanica was inducing significant apoptosis on MCF-7 cells. Since both K. foetidissima and E. mauritanica crude extracts induced apoptosis to MCF-7 cells, they were selected for gene expression studies on MCF-7 using real-time PCR. This was done with the aim of investigating if these extracts were having an effect on the tumour suppressors p53 and RBBP6, which were shown in previous studies to be deregulated in up to 50% of cancers. From the real-time PCR data we observed no changes in the expression levels of these genes following treatment with the herbal extracts. This may suggest that these plants have an effect on other components of the apoptotic pathway other than the tumour suppressors p53 and RBBP6. The antiproliferative activity observed whilst treating these particular cell lines with K. foetidissima and E. mauritanica suggests that these South African herbal plants present themselves as potential future cancer therapeutic agents; however, further studies on these herbal plants need to be performed to validate these results. KEYWORDS: Apoptosis Breast cancer Euphorbia mauritanica Kedrostis foetidissima p53

With the rising rates of heart disease incidents in the United States and the increase in lung cancer deaths as well, many individuals suffer and get their treatments compromised due to these diseases. Especially considering that many lung cancer and heart disease patients are over 70 years of age, treatment options and success rates drop significantly. Due to this, a great concern is raised for patients with co-existing heart disease and lung cancer. This was a case-control study that assessed lung cancer treatment options and success rates for patients with co-existing heart disease. We used research papers that discussed lung cancer treatment success in patients with heart disease to gather data on the subject. Furthermore, we used the 2020 NHIS to gather demographic data on the interviewed adults who answered the questions regarding lung cancer and heart disease. At the start, we hypothesized that there wasn’t going to be a high success rate for lung cancer treatment in patients with heart disease due to the invasive nature of the treatment available. We found that most patients with pre-existing heart disease that sought lung cancer treatment had their condition worsened due to severe invasive treatments such as chemotherapy and radiotherapy. In most surgical lung cancer treatment options, patients with pre-existing heart disease were more likely to die after the operation than patients without pre-existing heart disease. Currently and in future times, it’s more likely to find individuals with both diseases due to the rising culture which endorses poor habits in eating, alcohol consumption, smoking, and the utilization of drugs. Understanding the difficulty and dangers that are found in current treatment options for heart disease patients suffering from lung cancer will allow for innovation and improvement in treating such patients.

Cancer is a leading cause of death in the United States and the world. Based on the literature, the side effects of prolonged use of cancer treatment pose a threat to the patient's treatment compliance and efficacy. This study aims to determine the extent to which calorie restriction and fasting can improve the efficacy of cancer treatments, tolerability of cancer treatments, and compliance with cancer treatments through a systematic review. The search for studies involved the use of key terms and extenders based on population, intervention, comparator, outcomes, and study designs (PICOS) framework including participants receiving cancer treatment, dietary interventions, and cancer treatment outcomes. All search results were uploaded to Covidence® software and two independent blinded reviewers screened the studies, and three independent reviewers extracted the data. Studies were first screened based on the title and abstract, and then they were screened based on the full text. If the synthesized data had similar characteristics and there were enough studies available, then the meta-analysis would be performed. While Riedinger et al., Voss et al., and de Groot et al. did not find any significant difference in treatment efficacy between fasting and control groups, the earlier study done by de Groot et al. showed that the effects of fasting can show significant improvement in decreasing the amount of DNA damage in noncancerous cells. Regarding the effects of fasting and calorie restriction on patient tolerability when receiving chemotherapy or radiotherapy, all studies covering the effect demonstrate a trend suggesting that there is no significant difference between the dietary intervention groups and control groups. Overall, there is not enough information from these studies to conclude the effect of fasting on treatment compliance.

Gliomas are aggressive glial cell tumors that are nearly impossible to treat successfully, yielding strikingly low survival rates for patients. Glioblastomas, the most severe type of gliomas, have even poorer prognoses. In the past decade, new literature has shown that H19, a long non-coding RNA (lncRNA), is not only highly expressed in human gliomas, but that it plays several important roles in glioma progression and can even impede certain treatment measures. H19 directly and indirectly promotes several features of glioma cells including their survival, growth, migration, invasion, metastasis – essentially every stage of glioma development – and even stemness. Simply knocking down H19, in vitro, hampered every single one of these features to some degree. High H19 levels have also been linked to a lack of response to temozolomide and radiation treatments, two of the main therapeutic methods currently used to target gliomas. In vivo observations also followed this pattern of high H19 levels correlating with glioma tumorigenicity. So far, due to the accumulation of such findings, H19 has already become valued as both a prognostic and theragnostic marker. However, having seen how damaging H19 knockdown is to gliomas, there is no reason the role of H19 should be limited to that of an indicator; rather, the proto-oncogenic lncRNA should be viewed as a potential therapeutic target. Moreover, given that high H19 expression is an attribute unique to the human embryo stage, any instances of upregulation are typically oncogenic in nature, making H19 an ideal target for cancer therapy. Thus, targeting H19 in glioma patients should be integrated into existing treatment plans as this will obstruct glioma tumorigenesis, improve responsiveness to other therapies, and is not likely to impede normal biological functions.

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