Studies on biomarkers of Malignant Pleural Mesothelioma to determine their value in assessing a targeted cancer therapeutic.

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Copyright: Armstrong, Luke
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Abstract
Mesothelioma is a cancer of the pleural cavity in the lungs. The prognosis for people who develop this type of cancer is incredibly low, with survival rates of less than 18 months for nearly all patients. Chemotherapy so far has not improved the quality of life significantly for mesothelioma patients. This means new methods of treating the disease are required. The EnGeneIC Dream Vector™ (EDV) is a 400nm bacterially derived nanocell which can be loaded with either chemotherapeutic drugs or genetic material and targeted with bispecific proteins to target cancer cells directly and deliver the treatment specifically to these cells. For malignant pleural mesothelioma, a miR-16 mimic RNA molecule was loaded into the EDVs in order to prevent cell proliferation and promote apoptosis. In this study, several non-invasive methods were investigated to determine their value as markers pre and post EDV treatment in mesothelioma. First, circulating tumour cells (CTCs) were extracted from the whole blood samples of mesothelioma patients for diagnostic purposes based on their concentration. To corroborate this data, the biomarker mesothelin was also quantified from serum samples of these patients as well as in tissue culture experiments. Additionally, macrophages from tumour microenvironments in murine models of mesothelioma were isolated and identified based on their cell surface receptors. Methods for the identification of different classes of macrophage were developed to monitor their concentrations in the tumour microenvironment pre and post EDV treatment. This study found no significant results for the change in CTC concentrations of mesothelioma patients or the differentiation of macrophages. Surprisingly, a significant increase in mesothelin levels of cultured mesothelioma cells occurred when cell death was achieved. The trend in the patients matched this increase but was not significant.
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Author(s)
Armstrong, Luke
Supervisor(s)
Marquis, Christopher
MacDiarmid, Jennifer
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Publication Year
2016
Resource Type
Thesis
Degree Type
Masters Thesis
UNSW Faculty
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