RESUMO
The malignancy that most affects the endocrine system is thyroid neoplasm, with an increasing incidence over the years. The most prevalent histological type of the carcinomas that affect the thyroid gland is papillary carcinoma with a prevalence of 80 % worldwide. The current diagnostic methodology may present inconclusive results, emphasizing the need for new effective and sensitive techniques to aid the diagnosis. For this, it is necessary to understand molecular and protein mechanisms in the identification of diagnostic and predictive markers in the lesions. The Cyclin A1 protein, encoded by the CCNA1 gene, is an important cell cycle regulator, belonging to the MAPK/ERK signaling pathway directly involved with thyroid cancer. The aim of this study was to evaluate the CCNA1 gene and Cyclin A1 protein expression in papillary thyroid carcinoma, follicular thyroid carcinoma, and benign thyroid lesions, by real time quantitative PCR and immunohistochemistry analysis, respectively, to verify their roles as potential diagnostic and predictive markers to future applications in the clinical routine. Overexpression of CCNA1 gene was observed in the papillary carcinoma group compared to the normal group (Pâ¯=â¯0.0023), benign lesions (Pâ¯=â¯0.0011), colloid goiter (Pâ¯=â¯0.0124), and follicular carcinoma (Pâ¯=â¯0.0063). No differential expression was observed in the papillary primary tumor group from negative lymph nodes compared with the one from positive lymph nodes (Pâ¯=â¯0.3818). Although an increased expression of Cyclin A1 was observed in the PTC group compared to the other one in the IHC analysis, no significant difference was observed (Fisher's exact Test). A Cyclin A1 overexpression was detected with weak to mid-moderate immunoreactivity in the benign group (kâ¯=â¯0.56), (score 1.5); mid-moderate to moderate in the goiter group (kâ¯=â¯0.58); weak in the FTC group (kâ¯=â¯0.33); and mid-moderate to moderate in the PTC group (kâ¯=â¯0.48). Due to the small sample size in the IHC analysis and to the fact that not all RNA is translated into protein, the diagnostic potential of Cyclin A1 could not be assessed. However, these findings highlight the potential of the CCNA1 gene as a diagnostic marker for papillary thyroid carcinoma.
Assuntos
Adenocarcinoma Folicular/genética , Biomarcadores Tumorais/genética , Ciclina A1/genética , Neoplasias/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Adulto , Biomarcadores Tumorais/metabolismo , Ciclina A1/metabolismo , Diagnóstico Diferencial , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Linfonodos/metabolismo , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/patologia , Neoplasias/cirurgia , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Carga TumoralRESUMO
Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4'-dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies.