Angiogenesis and microcirculation of human mesothelioma xenografts assessed by intravital microscopy


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A Master's thesis.
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Master (thesis) (master)
Angiogenesis and microcirculation of human mesothelioma xenografts assessed by intravital microscopy
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Université de Lausanne, Faculté de biologie et médecine
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Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor whose principal risk factor is asbestos exposure. Its incidence varies worldwide and is around 20 per million in Europe (1). It is expected that this number will double within the next 20 years (2), will reach a peak in 2015‐2020, and that the predicted number of deaths over the next 40 years will be of 250'000 in Europe (3), becoming a major health problem on a worldwide scale (4).
Despite different therapeutic strategies (multimodal treatment including surgery, chemotherapy and radiotherapy) (1, 5), the survival of patients suffering of MPM is still unsatisfactory. Therefore new treatment options, especially targeted therapies, are currently investigated. Antiangiogenic agents seem to be promising (4). Indeed, it has been shown that the prognosis in MPM is related to angiogenesis (6‐8). High levels of VEGF and increased microvessel density are associated with poor outcome (6, 9). Furthermore, the highest VEGF levels of any solid tumor patients are found in mesothelioma patients (10, 11). Several antiangiogenic agents have already been tested in vitro, in vivo, or in clinical trials (11). To our knowledge, their effects on tumor angiogenesis and microcirculation have not yet been observed in vivo.
This study was undertaken in order to develop and standardize a new animal model for MPM, which may serve as tool for assessment of antivascular therapies directed against MPM. We evaluated tumor angiogenesis in human mesothelioma xenografts qualitatively and quantitatively during 14 days in a rodent model using a dorsal skinfold chamber (DSFC) technique and intravital microscopy (IVM), a recognized method for analysis of tumor architecture and vasculature (12). IVM permits repeated non‐invasive
microscopic studies of living tissue using trans‐ and epi‐illumination microscopy.
Usually, the obtained images have to be analyzed using a sophisticated technical set‐up in order to describe microcirculatory characteristics. In this study, our aim was to simplify the qualitative and quantitative evaluation of the microcirculation and to establish an easy and reproducible model for assessment of tumor angiogenesis in MPM. Therefore, we adapted a well‐established and simple clinical scoring system initially
developed for the assessment of microcircular pertubations in critical ill patients.
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21/06/2012 11:29
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20/08/2019 16:48
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