Anti-VEGF in malignant pleural effusion induced in experimental model in mice: histopathological evaluation

• Grant number: 16/06902-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2016
• End date: July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Lisete Ribeiro Teixeira
• Grantee: Gabriela Hidaka da Silva
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Malignant pleural effusion resulting from pleural metastasis of cancer like lung is a common clinical problem and with important repercussions. It is a manifestation of advanced or disseminated cancer without possibility of cure, low life expectancy, high morbidity and limited treatment to control the effusion, a practice that does not benefit all patients and does not modify the disease progression. Recent studies of pleural neoplasm in murine models properly reproducing the formation of effusion and pleural metastasis. Thus, in order to provide a better understanding of the pathophysiology of malignant pleural effusion resulting from lung adenocarcinoma, and to facilitate understanding of current therapies, we intend to evaluate the histopathological profile of intrapleural action of anti-VEGF in mice with pleural effusion induced by Lewis cells at different stages of the disease.C57BL/6 immunocompetent mice, a prototype that allows the implantation of specific lung adenocarcinoma cells called cells LLC (Lewis Lung Cancer) will used. The development of pleural cancer will be performed by intrapleural injection of 0.5 x 105 cancer cells (LLC) with different treatment strategies using anti-VEGF. Samples of visceral pleura and tumors will be stained with H&E, and evaluated qualitatively and semi-quantitatively for morphological indices as necrosis, neovascularization, and inflammatory infiltrate graded from 0 to 4 according to their extent and severity, as well as metastatic spread. Histological changes in the pericardium, diaphragm, lungs, kidneys, spleen and liver will also be graded from 0 to 4 according to their extent and severity. Samples of pleural tumors of untreated and treated animals will be submitted to immunohistochemical staining for identifying of factor VIII, CD34, EGF, VEGF, Ki67, PCNA and apoptosis (Tunel) evaluated in image analysis system.