Submitted in fulfilment of the requirements for the Degree Philosophiae Doctor in Health Sciences, Durban University of Technology, 2017. / Background Cancer is a global concern because it affects and kills millions of people worldwide. In South Africa, patients frequently move between traditional health practitioners and radiation oncologists to seek cure of cancer, yet these health practitioners do not communicate with each other. Consequently, the treatment is often disrupted and imcomplete therefore compromising the survival of patients. The future of the health system in effective treatment of patients with cancer is dependent on health practitioners’ changing fundamentally in their co-operative practice. The aim of this study was to explore the practice of traditional health practitioners in the treatment of patients with cancer in order to describe a viable co-operative practice between them and radiation oncologists and ultimately develop traditional health practitioners as a component in the health system in the treatment of patients with cancer. Methods An exploratory descriptive qualitative study using an interpretive phenomenological approach was employed to collect data from 28 traditional health practitioners and four radiation oncologists in KwaZulu-Natal utilising snowball and stratified purposive samplings for the former and latter, respectively. Semi-structured face-to-face and group interviews were employed to collect primary data from traditional health practitioners and data from the radiation oncologists were collected through face-to-face and email interviews. Data were transcribed verbatim and analysed using framework analysis. Results It emerged that the referral of patients, in addition to external conditions, individual attributes, trusting attitudes of participants as well as organisational dynamics and philosophy of practice, were the main categories used by participants in their understanding of co-operative practice in KwaZulu-Natal. The patient is the main player in the co-operation between parties, and coordinates the health practitioners’ activities during treatment. Effective co-operative practice is time consuming and requires commitment, co-operation and training of the participants. Conclusion Considering the problems associated with treatment of cancer when patients move freely between the traditional health practitioners and radiation oncologists, resulting in interruptions in treatment, co-operative practice between the two health practitioners is paramount. The development of traditional health practitioners could result in extending their role in the management of cancer and therefore increasing the accessibility of cancer services. It follows that a workable practice between traditional health practitioners and radiation oncologists in the treatment of patients with cancer could be an inclusive health system where the parties work in parallel with the patient being the main actor in the collaboration. There should be a healthy relationship between all those involved in the collaboration in order to facilitate referral of patients between the health practitioners. / D

It has been estimated that between 3000 and 4000 plant species are used for their medicinal properties throughout South Africa, with approximately 27 million South Africans making use of traditional medicines. Of this 27 million, 3 million South Africans rely on traditional medicine as their primary source of health care. Of the 250 000 to 500 000 known plant species, very few have been investigated for their pharmacological qualities, and compounds of significant medicinal value may still remain undiscovered in many plant species. The aims of this study included investigating the antimicrobial properties of Geranium incanum and Artemisia afra, both plants traditionally used for their medicinal properties, and comparing the antimicrobial activity of the latter to that of Artemisia absinthium, as well as investigating the anticancer properties of G. incanum and A. afra, and comparing the anticancer activity of the latter to that of A. absinthium. Infusions, aqueous-, methanol- and acetone extracts of the three plants were prepared and used for anticancer and antimicrobial screening. Plant specimens used to prepare extracts for antimicrobial activity were collected and extracted over three seasons, while extracts used for anticancer screening were prepared from plants collected during the summer only. Considerable variation existed in the percentage crude extract yields obtained when different extractants were used, while the season in which the plants were harvested and extracted also appeared to play a significant role in the amount of extract obtained. The plant extracts were screened for antimicrobial activity against various strains of Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus, using an agar dilution method. G. incanum and A. afra possessed activity for C. albicans, while all three plants showed activity for S. aureus and B. cereus. Activity was largely dependent on the extraction method used. iii The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to screen for anticancer activity of the respective extracts, at varying concentrations, against MCF-7 (human breast adenocarcinoma) cells, HT-29 (human colonic adenocarcinoma) cells and HeLa (human cervical cancer) cells. All of the extracts showed cytotoxic activity in all three cell lines to varying extents, depending on the extract used and cell line screened. The acetone extract of A. afra proved to be the most effective inhibitor with the lowest IC50 (2.65 ± 1.05 μg/ml) having been shown in MCF-7 cells. A. afra and A. absinthium showed similar inhibitory patterns, with the methanol- and acetone extracts having been the most potent inhibitors of each of the respective cell lines in general. Fluorescence microscopy employing 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) and propidium iodide (PI) staining indicated that the acetone extract of A. afra induces apoptosis in MCF-7 cells as apposed to necrosis, and the results were comparable to those obtained for cells exposed to cisplatin. Screening of the A. afra acetone extract for toxicity in normal human cells using the CellTiter-Blue® assay indicated the extract to be toxic to peripheral blood mononuclear cells (PBMC’s) at concentrations comparable to that for MCF-7 cells, while cell cycle analysis of MCF-7 cells exposed to the A. afra acetone extract indicated the extract’s ability to induce apoptosis comparable to that of cisplatin, with the extract exerting its activity at a point during or just prior to the S phase of the cell cycle.

Thesis (M. A. (Nursing Science)) -- University of Limpopo, 2021 / Background: Mastectomy is one of the treatments for breast cancer. It causes a change in the appearance of the breast thus causing a major effect on women’s self‑image and a decreased sense of femininity that can lead to anxiety and depression to such an extent that they avoid visiting public places. The study explored and described experiences of women who had undergone mastectomy at Mankweng Hospital, Limpopo Province, South Africa. Study design: This study used a phenomenological approach to perform a qualitative, exploratory, descriptive, and contextual research. Using a non-probability purposive sample of about 15 women who had undergone mastectomy in Mankweng hospital. Data were gathered through semi-structured interviews. The semi-structured interviews' audio recordings were transcribed verbatim. Seven steps procedure for data analysis using Colaizzi method was used to interpret the data. Results: The most challenging experience by women who had undergone mastectomy defined as a feeling of being disabled, anxious, relieved, acceptance, and financial constraints. Conclusion: Strategies to address the challenges faced by women who had undergone mastectomy has been developed to assist them with coping mechanism post mastectomy and living a normal life. Key concepts: Breast Cancer, Mastectomy, Women

In the twenty-first century, advances in synthetic biology and molecular tools to implement programmable behavior into microbes have fueled significant efforts to develop microbial-based therapeutics. Bacteria and viruses have been explored independently for their ability to replicate and induce cytotoxic effects in cancer cells selectively. This dissertation aims to co-opt the anti-tumor capabilities of gram-negative Salmonella enterica subspecies enterica serotype Typhimurium (referred to as Salmonella typhimurium moving forward) and picornaviruses (small RNA viruses with positive sense genomes) to develop a potent, single bacterial-viral consortium- based system to treat solid tumors.I first describe our efforts to co-opt S. typhimurium’s natural internalization into hosts and intracellular space-sensing to deliver self-amplifying picornaviral RNA. Protein effectors that promote intracellular survival of S. typhimurium within the Salmonella-Containing-Vacuole (SCV) are transcribed by Salmonella Pathogenicity Island-2 (SPI-2) promoters, which turn on after sensing the intracellular pH, ion concentrations, and oxidative stressors. These effectors are then translocated into the host’s cytoplasm by a needle apparatus that connects the SCV and cytoplasm, which is also transcribed by SPI-2 promoters. By using the SPI-2 promoter PsseA to drive the expression of fluorescent reporters and membrane-disrupting proteins (eukaryotic and prokaryotic), efficient escape of Salmonella-produced proteins into tumor-host cells was established. RNA delivery into host cells was also made possible by a secondary SPI-2 promoter, PsseJ, which transcribes RNA polymerase T7 (T7), which then transcribes a T7-promoter-driven Poliovirus replicon or full-length Senecavirus A (SVA). Inoculation of this engineered S. typhimurium strain on a panel of cancer cell lines identified the system’s ability to deliver viral replicons and full-length viruses in a small cell cancer cell line, H446. In a murine model, S. typhimurium delivery of SVA was then shown to clear xenografted H446 tumors. Motivated by the possibility of delivering other picornaviral species with similar anti-tumor properties, but documented healthy tissue cytotoxicity, S. typhimurium was further engineered to control SVA viral spread. By driving Tobacco Etch Virus (TEV) protease expression via a second SseA promoter, and replacing a natural cleavage site on SVA with the TEV-cleavage domain, we demonstrate TEV-dependent SVA spread in H446 cells. I conclude with efforts on engineering TEV-dependent-SVA transgene expression to confer greater antitumor properties. Interferon-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to attenuate H446 growth in vitro. Expression of interferon-gamma off SVA would produce a direct selective pressure against viral replication and virion production. However, a fusion of human GM-CSF to Nano-Luciferase protein on the TEV-dependent SVA genome maintained luminescent signals, GM-CSF activity, and TEV-dependent spread, providing a framework to survey anti-tumor properties of SVA-transgenes. Furthermore, I address our development of syngeneic models for Salmonella-mediated delivery of SVA, an important step towards clinical applications of the system as immunocompetent models more closely correlate to immunocompetent patient populations. SVA’s efficient entry and replication in neuroendocrine-derived tissue identified murine neuroblastoma N1E-115 cells as a suitable cell line for SVA cytotoxicity studies. However, the ability of these cells to support bacterial-viral superinfections is unknown. Here, we show that Salmonella-mediated launch of SVA leads to viral spread that can attenuate heterologous hind flank tumor growth and improve their survival along with mice engrafted with orthotopic intracranial brain tumors.

Submitted in complete fulfillment for the Degree of Master of Technology: Biotechnology, Durban University of Technology, 2012. / Recently our understanding of cancer has advanced in the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. It is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anti-cancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis, such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit. Plants have a long history in cancer treatment. More than 3000 species have been known for their anti-cancer potential. Over 60% of currently used anti-cancer agents are derived in one way or another from higher plants. Indeed, compounds derived from natural sources, including plants, have played, and continue to play, a dominant role in the discovery of leads for the development of conventional drugs for the treatment of most human diseases especially cancer. Thus the aim of this study was to investigate if Centella asiatica and Elytropappus rhinocerotis possess anti-cancer potential and determine the effect on the modulation of apoptosis. In South Africa C. asiatica is known anecdotally to treat various forms of cancers and E. rhinocerotis is known to treat colic and diarrhoea. The anti-cancer activity of C. asiatica has been studied in some parts India but E. rhinocerotis has not been investigated. This study was conducted using polarity guided fractionation (aqueous, ethanolic, methanolic and hexane), thereafter these extracts were tested for their toxicity on a colon cancer cell line (CaCO-2) and on normal cells vi (PBMC). Subsequently, the most active extract was used to isolate the active fraction. The fraction that displayed toxicity on the CaCO-2 cells were further investigated for their ability to induce apoptosis by observing the morphological effects and DNA changes using acridine orange-ethidium bromide staining. Apoptosis was confirmed using Annexin V- PI staining. Nuclear effects were studied by DNA fragmentation and by agarose gel electrophoresis. Nuclear fragmentation was studied by flow cytometry using bromodeoxyuridine (BrDU). Pro-apoptotic changes were determined with Caspase III enzyme levels using flow cytometry. The results were compared to the effect of a known anti-carinogen - Taxol. The anti-oxidant activity was also evaluated for the different extracts. The ethanolic extracts of both C. asiatica and E. rhinocerotis showed more than 100% radical scavenging activity. The methanolic extract (125 μg/ml -500 μg/ml) showed cytotoxicity on the CaCO-2 cells and a proliferative effect on the PBMC. Apoptosis was confirmed in the methanolic extract for both plants and was therefore used to carry forth this study. This included early apoptotic changes observed by the morphological study i.e., membrane blebbing, nuclear condensation and the presence of apoptotic bodies, in both C. asiatica and E. rhinocerotis fractions demonstrated more non-viable apoptotic cells than the methanolic extracts. Late changes of apoptosis were also found as indicated by DNA laddering and a positive outcome with BrDU. Both the active fractions from C. asiatica and E. rhinocerotis showed more DNA laddering and active caspase III than the methanolic extract. These features indicate that C. asiatica and E. rhinocerotis cause apoptotic death of colon cancer cells CaC0-2. In conclusion, there was a significant increase in apoptosis of CaCO-2 cells with little alteration of PBMC in the presence of the methanolic extract of C. asiatica and E. rhinocerotis. The semipure fractions resulted in changes related to late apoptosis. The results suggest that C. asiatica and E. rhinocerotis induces apoptosis in CaCO-2 cells which is an important step in elucidating the underlying molecular mechanism for anti-tumour activity.

The purpose of this study was to investigate the effects of music and imagery versus imagery only interventions on inducing relaxation and reducing nausea and emesis in cancer patients undergoing chemotherapy treatment. Specifically, this study explored an adaptation of the Bonny Method of Guided Imagery and Music (BMGIM). Approximately 280 patients were interviewed, 43 began data collection procedures, and 20 of these individuals completed the study. Three dependent measures (heart rate, nausea, and emesis) were collected both before and after each of six intervention sessions. Experimental treatment conditions were guided imagery with music (MI) or without music (IO), alternated across the sessions. As part of the experimental treatment, participants were also encouraged to listen to music at home, i.e., to listen twice daily to CD recordings for relaxation. One recording contained a script for relaxation with music in the background, and the other contained only a script for relaxation. Moreover, after the fourth and sixth week of being in the study, the participants responded to a satisfaction survey on their perception on the benefits of MI and IO intervention. A follow-up telephone interview was conducted with each participant nine days after completion of the study. Regression analysis was used to examine factors relating to the frequency of nausea and emesis as well as heart rate. A Pearson correlation coefficient was used to examine the relationship between the extent to which patients utilized the CD for relaxation at home and the amount of improvement experienced. Descriptive analyses were employed to examine participants' responses to their perceptions of the benefits of imagery only and music with imagery interventions (i.e., to the Participant Satisfaction Survey). Results indicated a statistically significant decrease on post-heart rate for MI as well as for IO interventions. There were no statistically significant differences in heart rate, nausea, or emesis between the two experimental interventions. However, there was a significant decrease in the frequency of nausea and emesis over time, i.e., across the six-weeks of treatment. The Pearson correlation indicated no significant relationship between the times participants listened to the CD and the outcomes of nausea and emesis. Self-reports from the participants indicated that the guided imagery with music, both within the experimental intervention sessions as well as at home, seemed to be very beneficial in inducing relaxation for these particular cancer patients.

A qualitative research design and an ethno-nursing research method were used to identify cultural factors influencing Xhosa women's health seeking behaviours associated with breast lumps. Focus group interviews were conducted to obtain data. The research results revealed that these Xhosa women with breast lumps did not disclose some cultural factors which influenced their health seeking behaviours associated breast lumps. Registered nurses, sharing the same culture and language as the Xhosa women, revealed that Xhosa women with breast lumps sought treatment from traditional healers, prior to seeking medical care from the hospital and/or clinics. When they arrive at the hospital/clinics the breast lumps have often progressed to advanced ulcerated breast cancer, with poor prognoses and poor treatment outcomes. Xhosa women lacked knowledge about the management of breast lumps. Health promotion efforts should address this issue at Primary Health Care services in the Eastern Cape. / Health Studies / M.A. (Health Studies)

A qualitative research design and an ethno-nursing research method were used to identify cultural factors influencing Xhosa women's health seeking behaviours associated with breast lumps. Focus group interviews were conducted to obtain data. The research results revealed that these Xhosa women with breast lumps did not disclose some cultural factors which influenced their health seeking behaviours associated breast lumps. Registered nurses, sharing the same culture and language as the Xhosa women, revealed that Xhosa women with breast lumps sought treatment from traditional healers, prior to seeking medical care from the hospital and/or clinics. When they arrive at the hospital/clinics the breast lumps have often progressed to advanced ulcerated breast cancer, with poor prognoses and poor treatment outcomes. Xhosa women lacked knowledge about the management of breast lumps. Health promotion efforts should address this issue at Primary Health Care services in the Eastern Cape. / Health Studies / M.A. (Health Studies)