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Influence of pleural disease progression in pleurodesis' result in mouse

Grant number: 15/03960-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2016
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Ricardo Mingarini Terra
Grantee:Carolina Reis Bonizzio
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Pleural effusion is the accumulation of fluid between the pleura that covers the thoracic cavity, and is a frequent clinical entity, with over fifty etiologies and different types of presentation in medical practice, requires different approaches and treatments of clinical or thoracic surgeons. Malignant pleural effusion is defined by the presence of neoplastic cells in the liquid, or effusion with affected pleura, diagnosed by biopsy. Among all known causes, the malignant pleural effusion is the type of effusion that has more been gaining importance due to the increase in its incidence. This has occurred due to improvement in clinical standards of treatment related to cancer and therefore the emergence of a greater amount of complications related to this type of disease. US old statistics already presented a significant number of over 1,000,000 new cases of pleural effusion / year, and of these, about 200,000 are associated with malignancy, being that the expectations described in the current studies would be an increase of 5% per year in these data. In consequence of the increasing number of cases and therefore need of treatment, pleurodesis has become the procedure of choice in cases of symptomatic neoplastic pleural effusion which also fulfill the eligibility criteria: pleural effusion in cancer cells, KPS greater than 40 , improvement of symptoms with the procedure, lung expansion after emptying the liquid and besides that, present recurrent effusion. Following these criteria, we can with pleurodesis eradicate liquid, improve lung function, and hence the quality of life of patients. Objectives: 1- Study if evolution of pleural neoplasm is associated with the outcome of pleurodesis. 2- Study if the progression of the pleural neoplastic disease affects the safety of pleurodesis by observing the spread of talc, lung and systemic inflammation. Methods: Two hundred C57BL/6 mouses will be used, which is an immunocompetent mouse prototype that allows the implant specific lung adenocarcinoma cells called LLC (Lewis Lung Cancer) from the cell bank American Type Culture Collection (ATCC, USA). In total, 10 thousand LLC cells will be injected into each animal's pleura. The animals will be sex, weight and age similar and will have free access to water and proper nutrition. They will be divided into 2 subgroups: GCa Group or Cancer Group - group of animals with pleural neoplasm; GSFI Group or Saline Group - group of animals without pleural neoplasm, in which will be injected in only saline, for the purpose of violating the pleural space. These groups will be divided according to the time of pleural disease or instillation of Saline 0.9%: Gca D3 Group -Cancer Group with 3 days of disease, GSFI D3 Group - Saline Group with 3 days of instillation, Gca D7 Group - Cancer Group with 7 days of disease, GSFI D7 Group - Saline Group with 7 days of instillation. At last, they will again be subdivided according to the date of euthanasia in relation to pleurodesis time (24 hours or 8 days). In two cancer subgroups (GcaD3 and GcaD7) 3 animals will be sacrificed on the day of pleurodesis, which will serve as controls and will be tested for the presence and quantification of disease in the pleura. For that, we will use the same standardization of pleural tissue histologic section to be described next: we will research the point of maximum amount of grouped neoplastic cells and quantify its greatest extent, from the pleural elastic lamina by the end of the conglomerate cellular. Additionally, 5 animals sacrificed on the 8th day after pleurodesis in GCaD3, GCaD7, GSFI D3 and GSFiD7 groups will have the lungs, kidneys, liver and spleen investigated in histological sections for the dissemination of talc particles We will proceed with the analyses of the collected data.

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