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Intrapleural immunoterapy in experimental model of lung adenocarcinoma with KRAS mutation


Lung cancer is the leading cause of cancer related death. In the advanced stage of the disease most patients present pleural effusion, which increases morbidity. Pulmonary adenocarcinoma is the most frequent subtype, and approximately 25% of cases have mutations in the KRAS gene. However, an effective treatment for these patients is still a subject of research and several drugs are being tested. One promising treatment line is the use of immunotherapy with Nivolumab. The nivolumab, through the blockade of PD-1 receptors, aims to stimulate the immune system itself to recognize and destroy cancer cells more effectively. In the search for a better pathophysiological understanding that allows significant changes in the therapy of malignant effusion, secondary to lung adenocarcinoma, several experimental models of study have been developed without the pretension to define the cure (but with the perspective of improving its local control and its dissemination). OBJECTIVES: Better knowledge about the pathophysiology of malignant pleural effusion due to lung adenocarcinoma with Kras- mutated gene. We also will study the action of immunotherapy (nivolumab) associated or not with docetaxel intrapleural in an experimental model of malignant pleural effusion. METHODS: Malignant pleural effusion model will be induced by intrapleural injection of Lewis cells in C57BL/6 mice. After induction of neoplasia the animals will be treated with Nivolumab with or without the combination of Docetaxel. The survival curve, weight and mobility, pleural fluid volume, cytological biochemical and immunological parameters as well as tumor gene expression will be analyzed. (AU)

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