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Study of the effect of 15-DEOXI-D12,14-PROSTAGLANDIN J2 on the expression of peroxiredoxins I and IV in estabilished plasmocitomas in immunudefficient mice

Grant number: 14/18607-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2015
Effective date (End): May 31, 2016
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Ana Paula Dias Demasi
Grantee:João Pedro Greggo
Home Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil

Abstract

Multiple myeloma (MM) is a progressive and incurable neoplasm of plasma cells, usually accompanied by constant production of a single type of immunoglobulin. This production overloads the processing machinery of the endoplasmic reticulum, causing accumulation of unfolded proteins and increased reactive oxygen species (ROS). Cellular defense systems specific for these forms of stress have been exploited as therapeutic targets for the MM. It has been shown that 15-Deoxy-D12,14-prostaglandin J2 (15d-PGJ2) has potent anticancer activity, and ROS formation has been proposed as its mechanism of action. Peroxiredoxins (Prxs) constitute a family of abundant enzymes that can act in the elimination of ROS or as molecular chaperones. PrxI, located in the cytoplasm, is the most abundant isoform, whereas PrxIV is distributed in the endoplasmic reticulum. By quantitative PCR and immunohistochemistry, this project is aimed to study the effect of 15d-PGJ2 in the expression of peroxiredoxins I and IV in fragments of plasmacytomas developed from xenografts of human MM cells in immunodeficient mice. We believe that this study may contribute to the better understanding of the defense mechanisms of MM cells and to identify potential therapeutic targets.

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