Evaluation of cellular and inflammatory changes and profile of pleural mesothelial and/or neoplastic cells exposed to talc used for pleurodesis

• Grant number: 13/13295-9
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Milena Marques Pagliarelli Acencio
• Grantee: Milena Marques Pagliarelli Acencio
• 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
• Associated researchers: Evaldo Marchi ; Francisco Vargas Suso ; Leila Antonangelo ; Lisete Ribeiro Teixeira

Abstract

Lung cancer is a leading cause of death due to cancer worldwide. In advanced stages of the disease patients may present with pleural effusion, dyspnea and decreased quality of life, and talc pleurodesis for definitive obliteration of the pleural space is indicated. The pleural mesothelial cell (PMC) plays a central role in the modulation of pleural aggression and the response to pleurodesis may vary according to tumor burden and the pleural local inflammatory response. It is speculated that in tumors with high tumor burden there is greater chance of pleurodesis failure. In contrast, it is attributed to the talc used for pleurodesis a potent role in inducing inflammation which may contribute to the increased pleurodesis efficacy. This study aims to determine the profile of the acute inflammatory response to talc used for pleurodesis in culture models of normal PMC or neoplastic cells. For this purpose, cultured human PMC extracted from transudative effusions and cultured lung adenocarcinoma cells (Lewis Lung Cells - LLC) will be exposed to 48 mm/cm2 of talc for 48 hours. Culture plates will be divided into groups with different tumor loads: 100% PMC (control), 100% LLC, 25% PMC + 75% LLC, 50% PMC + 50% LLC and 75% PMC + 25% LLC. The acute inflammatory response will be evaluated by the production of lactate dehydrogenase (LDH) and the cytokines IL-6, IL-1b, TNF-a, IL-10 and sTNFRI, along with the values of cellular apoptosis and necrosis. From these results we intend to infer if a high amount of pleural cancer can interfere with the local inflammatory response and the induction of apoptosis, and if talc used for pleurodesis contributes to accelerate and enhance inflammation despite the large tumor burden. These findings may help to clarify aspects observed in clinical practice, as the control of neoplastic effusion with intrapleural instillation of talc used for pleurodesis, or pleurodesis failure that occurs in patients with advanced malignancy. (AU)