Bianca Ribeiro de Souza , Gabriela Oliveira , Giovana Leme , Ianny Brum Reis , Felippe Augusto Tossini Cabral , Juliane Lima Baggio de Paula , Daniel Henrique da Silva Santos , Claudia Ronca Felizzola , Nelson Durán , Michael Anglesio , Wagner José Fávaro
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引用次数: 0
Abstract
Aims
The term ovarian carcinoma (OC) refers to a heterogeneous collection of five distinct diseases known as histotypes. While histotype-specific treatment is still a clinical challenge in OC, well-characterized models are required for testing new therapeutic strategies. We employed OncoTherad® (MRB-CFI-1), an interferon (IFN-γ)-stimulating nano-immunotherapy mediated by Toll-like receptors (TLR) 2/4, in association or not with Erythropoietin (EPO) in a chemically-induced ovarian cancer model. Besides characterization of the therapies effects, we also assessed whether the animal model was representative of human OC by providing histotype classification.
Main methods
Thirty-five Fischer rats were distributed into five groups: Control (Sham surgery); Cancer (7,12-dimethylbenzoanthracene – DMBA injection in the ovarian bursa, 1.25 mg/kg); OncoTherad® (20 mg/kg intraperitoneal); EPO (8.4 µg/kg intraperitoneal); and OncoTherad+EPO (same doses). Ovaries were formalin-fixed into paraffin-embedded blocks. TLR pathway and the inflammatory response profile were evaluated by immunohistochemistry (IHC). After DNA extraction and tissue microarray construction, we assessed typical gene mutations directly (Sanger sequencing) or indirectly (IHC surrogates) and examined biomarkers of different OC histotypes.
Key findings
OC induction decreased TLR2, TLR4, and proinflammatory cytokines. OncoTherad® alone or associated with EPO modulated the OC microenvironment to a cytotoxic immune profile through stimulation of the TLR4-mediated non-canonical pathway. EPO stimulated TLR2-mediated canonical pathway and notably increased Tregs.
Significance
The features analyzed favored interpretation of our DMBA-induced tumor model as predominantly low-grade, serous carcinoma-like, in which treatments with OncoTherad® and EPO showed immunomodulatory properties related to the reduction of ovarian lesions.
期刊介绍：
Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.
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