ETD Collection

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    Comparison of the risk factors and initial presenting symptoms to stage of disease in pancreatic ductal adenocarcinoma patients at Chris Hani Baragwanath Academic Hospital
    (2019) Lahoud, Nicola
    Background: Pancreatic adenocarcinoma (PDAC) is the second leading cause of death in the US amongst both sexes and patients often present with advanced disease. Where many studies have described the risk factors, symptoms, biochemistry and staging of the disease, none have assessed the risk factor profile and presenting symptoms according to the stage of the cancer in a black South African population. Objectives: To assess the initial risk factor profile, presenting symptoms and biochemistry according to stage in Black South African patients with diagnosed PDAC at Chris Hani Baragwanath Academic Hospital. Methods: A retrospective study including 71 patients with diagnosed PDAC from the Hepatobiliary unit database at CHBAH. We determined the TNM staging of each tumor from patient CT scans and correlated it to the demographic, biochemistry, risk factor and symptom data recorded in the patients file. Results: The study population had a mean (±SD) age at presentation of 59.9 (±10.8) years with a male predominance of 56.3% males. The majority of patients had stage 2 disease (35.2%). BMI and current smoking status differed significantly across the stages. The most common symptoms were abdominal pain (67.7%), jaundice (65.6%) and weight loss (50.8%), none of which were associated with PDAC stage. Lower platelet count, high GGT and elevated CA19-9 levels were significantly associated with advanced PDAC. Platelet count showed statistical significant in each T, N and M stage, respectively. Univariate logistic regression demonstrated that platelet count, CRP and CA19-9 values are significantly associated with metastasis. In a multivariate logistic regression model lower platelet count and increased CA 19-9 are independent predictors of metastatic disease in PDAC patients with 97% specificity and 83% PPV. Conclusion: Our data demonstrates that most risk factors or presenting symptoms show no association with PDAC stage, although it does illustrate the risk factors and clinical presentation that are prevalent in our population. Moreover, platelet count and CA19-9 are independent predictors of metastases in PDAC.
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    Evaluating the anti-proliferative effects of methanol and butanol extracts of lobostemon fruticosus on a pancreatic cancer cell line AsPC-1
    (2017) Blose, Malangu Sibusiso
    Cancer has become a problematic fatal disease in developing and industrialised countries with pancreatic cancer as the seventh leading cause of cancer-related deaths, with an average survival rate of less than 5%. Environmental risk factors associated with pancreatic cancer include smoking, obesity, diet, alcohol etc. Furthermore, pancreatic cancer is commonly diagnosed at a late stage where its response to current anti-cancer agents is poor. Consequently, with South Africa being a 3rd world country and the cost of chemotherapy being so high, this has led to us trying to identify new, cheaper therapeutics for cancer cells. A majority (80%) of the South African population relies on traditional medicines, hence in this study we aimed to assess Lobostemon fruticosus for anti-proliferative effects on pancreatic cancer cell line (AsPC-1). This was achieved by the use of methanol and butanol extracts of L. fruticosus to screen for induction of apoptosis and inhibition of cell proliferation. The plant was collected, dried, crushed and dissolved in butanol and methanol to obtain experimental extracts. Cytotoxicity of the plant on Aspc-1 was determined using MTT Assay, xCELLigence and cell cycle analysis. MRC-5 cell line was used as a positive control cell line. L. fruticosus extracts induced cell death at IC50 of 60µg/ml (methanol extract) and 50µg/ml (butanol extract) at 48hour treatments on AsPC-1 cell line. Western Blots showed that the methanol and butanol extracts of L. fruticosus led to slight upregulation of the apoptotic gene p53 in AsPC-1 cell line, which was further confirmed by FACS apoptosis detection. Cell cycle analysis further showed the plant extracts do promote cell cycle arrest. LC/MS of the extracts gave spectra of active compounds presumed to play a role in induction of apoptosis on the pancreatic cancer cell line. The data obtained implies that the methanol and butanol extracts of L. fruticosus does have, to a certain extent, growth inhibiting and apoptosis inducing potential on the pancreatic cancer cell line. KEYWORDS: Lobostemon fruticosus, Pancreatic Cancer, methanol extract, butanol extract, AsPC-1