ABSTRACT
A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC.
ABSTRACT
A Dietilnitrosamina (DEN), uma substância reconhecidamente hepatotóxica e carcinogênica, foiutilizada na indução da necrose hepática centrolobular em ratos isogênicos Lewis divididos em 5 grupos de 5 animais. O objetivo deste estudo foi avaliar o efeito quimiopreventivo da epigalocatequina-3-galato (EGCG), de Camellia sinensis (chá verde) no tratamento da hepatotoxicidade celular induzida pela DEN. Foi mensurada a concentração sérica da alanina aminotransferase (ALT) e aspartato aminotransferase(AST) dos diferentes grupos experimentais. No ensaio bioquímico para AST e ALT, houve diferença significativa entre os valores médios do grupo controle (163±70,32) comparado ao grupo DEN (1631±1039,44), sugerindo que a DEN influencia na função hepática. Entretanto, não houve diferença significativa entre o grupo DEN e o tratado com epigalocatequina. A lactato desidrogenase (LDH) éconsiderada um marcador bioquímico comum para avaliação da progressão tumoral, e em relação ao LDH, as amostras não apresentaram diferenças significativas entre o grupo DEN (1385,5±43,13) e DEN + EGCG 150mg ou DEN + EGCG 200mg 1537,5±1010,45). Neste trabalho foi demonstrado que a epigalocatequina nas concentrações de 150 e 200 mg/Kg não induziram alterações hepáticas e também não foi possível verificar nenhuma quimioproteção pela EGCG em animais inicialmente tratados comDEN durante 24 horas. Sendo assim, novos experimentos com diferentes concentrações de EGCG sãonecessários para comprovar seu possível efeito quimioprotetor.
Diethylnitrosamine (DEN), a known hepatotoxic and carcinogenic substance, was used in the induction of centrilobular hepatic necrosis in isogenic Lewis rats divided into 5 groups with 5 animals. The aim of this study was to evaluate the chemopreventive effect of epigallocatechin-3-gallate (EGCG)from Camellia sinensis (green tea) in the treatment of cellular hepatotoxicity induced by DEN. It was measured the serum concentration of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the different experimental groups. In the biochemistry assay for AST and ALT, there was significant difference between median values of control group (163±70.32) compared to DEN group(1631±1039.44), suggesting that DEN influences on hepatic function. However, there was no significant difference between DEN group to that treated with epigallocatechin. Lactate dehydrogenase (LDH) is considered a common biochemical marker for evaluation of tumor progression, and regarding LDH,the samples presented no significant differences between the DEN group (1385.5±43.13) and DEN + EGCG 150mg or DEN + EGCG 200mg (1537.5± 1010.45). In this work it was demonstrated that epigallocatechin concentrations of 150 and 200 mg/kg did not induce liver alterations and though was not verified any chemoprotective effect by EGCG in animals initially treated with DEN for 24 hours. Moreover, new experiments with different concentrations of EGCG are needed to verify its possiblechemoprotector effect.