Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

The pancreas is a very inaccessible organ situated in the retroperitoneal space. Study of its physiology and function was first confined to animals, where it was possible to construct a pancreatic fistula and thus collect pure pancreatic juice. In addition, pancreatic tissue from animals was also obtainable relatively easily. Early attempts to study the pancreas in man was restricted to patients with pancreatic fistulae, usually the result of surgical procedures. These investigations were on the whole unsatisfactory as the conditions of the experiment were not truly physiological and the juice soon became contaminated and infected. Another method employed later used the intraduodenal tube to collect duodenal contents. The aspirate consisted of a mixture of gastric acid and contents, duodenal juice, bile and succus entericus. Various meals were used to stimulate the pancreatic secretion. Other authors have emphasized the importance of preventing contamination of duodenal contents with gastric juice, and by inserting a second tube or double lumen tube to aspirate the acid from the stomach this was attained. Meal stimulation was now no longer possible so that various drugs and later the two hormones, secretin and pancreozymin, were used to stimulate pancreatic secretion. These two hormones very soon completely replaced any other method of pancreatic simulation. The intravenous injection or infusion of secretin and/or pancreozymin is, however, not a physiological procedure. The initial enthusiasm aroused by this method was tempered due to the varied results obtained by different workers. More recently, Lund has used the test meal to stimulate pancreatic secretion. This technique has been replicated by numerous authors, with promising results reported by all. These reports are characterized by the varied nature of the test meal used, the different position of the intraduodenal tube, the type of suction employed, the period of collection, the length of the test and the type of enzymes estimated. The purpose of the present study is to investigate the physiological responses to the test meal, to define its value in the investigation of pancreatic function and to try and standardise the procedure to obtain optimal pancreatic stimulation.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirement for the degree of Master of Science in Epidemiology and Biostatistics. November 2017. / Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a devastating diagnosis for anyone as it is associated with a global mortality rate of about 4%, and has few therapeutic interventions that prolong survival as compared to other cancers. Frequent epidemiological reports on PDAC are available in the developed countries, but in South Africa, there is a paucity of epidemiological data on this aggressive cancer. Understanding risk factors will help to assess and develop relevant interventions for asymptomatic high-risk patient populations. Aim: To investigate and explore how various risk factors were associated with PDAC at two public academic hospitals in Johannesburg between 2013 and 2015. Method: This was a secondary unmatched case-control study to assess risk factors for developing PDAC at two public academic hospitals, namely the Chris Hani Baragwanath Academic Hospital (CHBAH) and the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). All cases of PDAC were histologically and/or cytologically confirmed. All participants were >18 years of age, including 139 cases and 139 controls. Data exported from REDCap database included patient demographics and social and medical histories. Proportions used the chi-square test and bivariate logistic regression estimated ORs between individual variables and PDAC. Multivariate logistic regression analysis investigated all possible confounders present in the data. The likelihood ratio test with a p-value of <0.20 was accepted to assimilate data fitting into the model. Results: Eighty two percent of the study population was black. The 50-59 age group accounted for 37% of the cases. Multiple logistic regressions showed the following odds ratios 95% CI and p-values for ages (i) 20-29 [0.11(0.11-1.00) p=0.05] and (ii) 50-59 [2.63(1.03-6.70) p=0.04]. As for diet, the following odds were observed (i) high white meat [0.18(0.04-0.86) p=0.03], (ii) low fish intake [2.17(1.06-4.45) p=0.03], (iii) low consumption of fried food [0.48(0.23-1.00) p=0.05] and (iv) high consumption of vegetables [0.17(0.05-0.61) p=0.007]. In terms of occupation, general workers had the following likelihood [1.79(0.93-3.45) p=0.08] of developing PDAC. Conclusion: Being 50-69 years of age and employed for longer periods than the general norm, was positively associated with PDAC. Additionally, increased consumption of vegetables and white meat was protective against PDAC, whilst a low intake of fish increased PDAC risk. Keywords: Pancreatic cancer, risk factors, epidemiology and case-control. / LG2018

A Thesis submitted to the Faculty of Health Sciences, University of Witwatersrand, in fulfilment of the requirements for the degree of Doctor of philosophy. Johannesburg, 2017. / Pancreatic cancer (PDAC) is a deadly type of cancer with almost an equal amount of new cases and deaths observed yearly. It accounts for about 7% of cancer related deaths worldwide with less than 5% of PDAC patients living up to 5 years. The lack of specific and sensitive diagnostic tests is strongly responsible for this poor statistic. The discovery of differentially expressed genes and proteins associated with PDAC is crucial to elucidating this condition and may lead to biomarker finding and further understanding of the disease. This in turn may lead to improved diagnostic tests for early diagnosis. The aim of this study was to identify novel potential biomarkers for PDAC. [No abstract provided. Information taken from summary] / MT2017

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer death in Western countries. The PDAC tumour microenvironment (TME) is characterized by a dense stromal reaction, consisting of many cell types including fibroblasts and immune cells. The chemokine receptor, CX3CR1 forms a high-affinity axis with its unique ligand CX3CL1 and is expressed on monocytes, macrophages and T cells. CX3CR1 is also present on pancreatic malignant cells, where it has been associated with metastasis formation. The aim of my project is to investigate the role of CX3CR1 in the progression and development of pancreatic cancer in a genetically engineered mouse model of PDAC, the CX3CR1GFP/GFPLSL-KRASG12D/+LSL-Trp53R172H/+Pdx1-Cre (CKPC) mouse. In these mice, the CX3CR1 protein is not functional but they express GFP. I have found that the absence of CX3CR1 in KPC mice has no effect in their lifespan and response to chemotherapy. Comparison of the immune infiltrate of the tumours revealed that the lack of CX3CR1 causes a significant decrease in T cells and a possible increase in myeloid cells in CKPC mice compared to KPC mice. Expression analysis of several inflammatory cytokines in the TME showed a significant difference in IL-10 between KPC and CKPC mice. There was also a significant increase in levels of, CX3CL1, both locally and in the plasma. Finally, we performed RNA-seq on KPC and CKPC tumours. My analysis revealed 607 differentially-expressed genes, some of which encoded other chemokines or protein regulating the immune system. In particular, I observed the upregulation of Cxcl10 and Cxcl12, and the downregulation of Gata3 and S100a4, which could explain the decrease in T cells in the TME of CKPC mice. In conclusion, although the lack of CX3CR1 modifies the TME in this genetic model of PDAC, these changes do not affect the lifespan or the response to chemotherapy.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

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