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Life Sci ; 242: 117185, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862453


Colorectal cancer (CRC) is a multifactorial syndrome that drives to uncontrollable cell division, genetic alterations, and functional alteration. In the present work, we evaluated the immunomodulatory properties of P-mapa, a compound extracted from Aspergillus oryzae fungus, versus Fluorouracil (5-FU) treatment in chemically induced CRC. CRC was induced by DMH in F344 rats. Animals of treated groups receive weekly 15 mg/Kg of 5-FU or 5 mg/Kg of P-mapa, over 10 weeks. Tissues were stained for aberrant crypt foci (ACF) counting and histopathology evaluation, immunostained for TLR4 pathways and quantified for TNFα Cytokine assay. DMH was efficient to induce hyperplastic lesions and ACF. Both treatments reduced significantly ACF formation and tumor aggressiveness. Immunohistochemistry for TLR4 signaling reveals that both treatments had no effect over the TLR4-NFκB signaling pathway. On the other hand, both succeed in increase interferon signaling, with activation of the TRIF-IRF3 pathway and consequently inducing IFNγ synthesis. The present results show the immunomodulatory properties of P-mapa in chemically induced CRC model. P-mapa induced a significant increase in Type-I IFNs synthesis and subsequently immune cell recruitment, resulting in an increase of IFNγ concentration in colorectal mucosa and its inhibitory effects over tumoral growth. In this scenario, P-mapa showed an interesting antitumoral effect by inhibiting tumor growth.

Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Ácidos Linoleicos/uso terapêutico , Ácidos Oleicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Focos de Criptas Aberrantes/patologia , Animais , Biopolímeros/uso terapêutico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ensaio de Imunoadsorção Enzimática , Fluoruracila/uso terapêutico , Masculino , Ratos , Ratos Endogâmicos F344 , Fator de Necrose Tumoral alfa/metabolismo
Life Sci ; 237: 116895, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610204


To evaluate the effect of a probiotic on the aggressiveness of a chemically induced colorectal tumor in rats. Twenty-five male Fisher 344 rats, 250 g, provided with feed and water ad libitum, were randomly divided into 5 groups (5 rats/group): GControl, no treatment; GTumor, tumor induction; GTumor+5FU, tumor induction, 5-Fluorouracil applied; GTumor+Prob, induction of the tumor, supplemented with probiotic; GTumor+5-FU+Prob, tumor induction, 5-Fluorouracil applied, supplemented with probiotic. For tumor induction 20 mg/kg of 1,2-dimethylhydrazine was applied intraperitoneally over 4 weeks, followed by an interval of 15 days, and then repeated for a further 4 weeks. Five weeks after the final dose of the carcinogen, treatment was initiated with 5-Fluorouracil (15 mg/kg, intraperitoneally/week) and a commercial probiotic (1 × 109 CFU, daily/gavage). Data were analyzed by One Way Variance Analysis and means compared by Dunnett's test. GraphPad Prism statistical software was used. The histopathological analyzes were evaluated by the chi-square test. A 5% type-I error was considered statistically significant. Compared with the GTumor, the GTumor+Prob (p < 0.0373) and GTumor+5-FU+Prob (p < 0.0003) demonstrated an attenuated effect on the aggressiveness of the colorectal tumor, with a reduction in the count of Aberrant Crypt foci; and a lower percentage of malignant neoplastic lesions in the GTumor+Prob (40% low grade tubular adenoma, 40% carcinoma in situ, 20% low grade adenocarcinoma) and GTumor+5-FU+Prob (40% low grade tubular adenoma and 60% carcinoma in situ). Probiotic supplementation has the potential to decrease the formation of aberrant crypts and ameliorate tumor malignancy, enhancing the antitumor effect of 5-Fluorouracil chemotherapy in colic segments.

Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Dimetilidrazinas/toxicidade , Probióticos/administração & dosagem , Animais , Carcinógenos/toxicidade , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Masculino , Ratos , Ratos Endogâmicos F344