1,721,452 research outputs found
The role of blood protein biomarkers in the management of malignant pleural mesothelioma.
No full textProgression free survival rate at 9 and 18 weeks predict overall survival in patients with malignant pleural mesothelioma: an individual patient pooled analysis of 10 European Organisation for Research and Treatment of Cancer Lung Cancer Group studies and an independent study validation
No full textIl gouerno della caualleria leggiera Español
No full textObra perteneciente al Fondo Antiguo de la Biblioteca de la USA
Monocyte-derived dendritic cells in lung cancer : from partner in crime to therapeutic option
No full text
Investigation of immune checkpoint blockade as novel treatment strategy for malignant pleural mesothelioma
No full textAbstract: Malignant pleural mesothelioma (MPM) is a highly aggressive and nearly always fatal cancer that is in most afflicted patients causally associated with a previous, mostly professional, asbestos exposure.1 The highest incidence rates, around 30 cases per million inhabitants, are reported for Australia, Belgium and the UK2,3. Although preventive measures to limit asbestos use and exposure have been around for several decades, the incidence of MPM is still expected to increase over the next decade due to the long latency (20 up to 40 years) between asbestos exposure and MPM development and because asbestos is still being used in developing countries4 4. The prognosis of patients diagnosed with MPM remains dismal with an untreated median overall survival of only 9-12 months and a 5-year survival rate of less than 5%4,5, due to its aggressive nature, its diagnostic delay and extended stage at presentation4,6. Chemotherapy consisting of a combination of a platinum compound and a folate antimetabolite, either pemetrexed or raltitrexed, have a significant but limited impact on overall survival7,8. Palliative platinum-antifolate chemotherapy results in a median overall survival of about 1 y compared with the 8\u2013 10 months observed for chemotherapy-na\uefve patients7,9,10. Therefore, new therapeutic strategies are needed to complement the limited armamentarium against MPM6. The observation that the immune system can recognize and eliminate tumors is the impetus of the fast-growing research domain of tumor immunology and immunotherapy. For MPM specifically, the development of immunotherapy is supported by the recent knowledge that our immune system plays a critical role in its pathogenesis and in protection against MPM6,11,12. Immunotherapy of cancer has entered a new and exciting phase because of the discovery of immune checkpoint (ICP) receptors. In this doctoral thesis we investigated immune checkpoint blockade (ICPB) as novel treatment strategy for MPM. First of all, I focused on the tumor microenvironment and the ICP expression profile of tissue samples and effusions from MPM patients. The obtained results showed that ICPs are expressed in mesothelioma patient samples and identified TIM-3 and LAG-3 as promising new targets13,14. In vitro, we showed that (combined) ICPB might offer new opportunities to improve mesothelioma patient prognosis which is confirmed by preliminary in vivo data that show a survival benefit for mice treated with PD-L1 monotherapy and its combination with LAG-3 blockade. Further research will aim to unveil the working mechanisms of ICPB and the investigation of other treatments for advantageous combination strategies
Volatile biomarkers for malignant pleural mesothelioma : from discovery to translation and validation
No full textAbstract: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-induced thoracic cancer, with a very poor prognosis. As MPM is usually diagnosed in an advanced stage, it is believed that patient survival can be improved by early detection. Analysis of volatile organic compounds (VOCs) in exhaled breath has emerged as a new, innovative approach to this end. Although different studies have shown the potential of VOCs as non-invasive biomarkers for MPM, clinical implementation has been hampered by a lack of independent validation and limited knowledge about the underlying biochemical origin. The overall aim of this PhD was to contribute to these necessary next steps, building further on the discovery studies that were previously conducted by our research group. Part II of this thesis covered the results of the biological translation in vitro, which aimed to gain insights into the biological origin of VOCs. The first study characterized the VOCs in the headspace of different MPM and lung cancer cell lines. Comparative analysis identified VOC profiles that were able to differentiate between the different cell types, suggesting the existence of tumor- and subtype-specific VOCs. Despite these interesting results, limited correlations with exhaled VOCs of MPM patients were observed, which was hypothesized to be the consequence of the difference in oxygen levels between in vivo and standard in vitro conditions. Therefore, we investigated in a second study the influence of in vivo-like hypoxic cell culture conditions on the VOC profile generated by MPM cells. The headspace VOC profiles of MPM cells cultured under both normoxic (21% O2) and hypoxic (1% O2) conditions were compared, revealing significant alterations in many VOCs upon hypoxic exposure. This study thus demonstrated the importance of hypoxic cell culture conditions in VOC research, as it better simulates the in vivo situation and has been shown to significantly impact the VOC profile. Part III of this thesis was related to the results of the external validation of a previously developed breath VOC-based prediction model for MPM. This external validation revealed poor predictive performance of the original model in the validation cohort, which could substantially be improved by updating the model. This was reflected by a high sensitivity and NPV, demonstrating the model\u2019s potential for screening purposes. However, its predictive performance should be reconfirmed in a new cohort. Although this doctoral research has yielded interesting findings, further studies are clearly warranted before a ready-to-use breath test can be implemented in practice
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