RESUMO
OBJECTIVE: Neurotrophin and neuropeptide pathways are emerging targets in cancer. Here we show that brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are present in colorectal cancer and that BDNF levels are increased in tumors compared to nontumor tissue. In addition, we investigate the role of BDNF in influencing the response of colorectal cancer cells to inhibition of gastrin-releasing peptide receptors (GRPR). METHODS: Fresh-frozen sporadic colorectal adenocarcinoma specimens and adjacent nonneoplastic tissue from 30 patients, as well as paraffin-embedded colorectal cancer samples from 21 patients, were used in this study. Cell proliferation and mRNA and protein levels were examined in HT-29 or SW620 cells treated with a GRPR antagonist, human recombinant BDNF (hrBDNF), a Trk antagonist K252a, or cetuximab. RESULTS: Expression of BDNF and TrkB was detected in tumor samples and cell lines. BDNF levels were higher in tumor samples compared to nonneoplastic tissue. BDNF expression and secretion were increased by GRPR blockade in HT-29 cells through a mechanism dependent on epidermal growth factor receptors. Treatment with hrBDNF prevented the effect of GRPR blockade on cell proliferation, whereas a Trk inhibitor reduced proliferation. CONCLUSIONS: BDNF and TrkB are present in colorectal cancer and might contribute to resistance to GRPR antagonists.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neoplasias Colorretais/metabolismo , Receptor trkB/metabolismo , Receptores da Bombesina/antagonistas & inibidores , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Fator Neurotrófico Derivado do Encéfalo/genética , Linhagem Celular Tumoral , Proliferação de Células , Cetuximab , Ensaio de Imunoadsorção Enzimática , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Expressão Gênica , Células HT29 , Humanos , RNA Mensageiro/análise , Receptor trkB/genética , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Acid mine drainage (AMD) represents a major problem in the mining industry worldwide due to the risk of water and soil pollution. Its active treatment involves the addition of alkaline reagents such as NaOH or Ca(OH)2 to increase the pH and precipitate the dissolved metals, although substantial amounts of dissolved ions might persists. Under a remediation approach, the aim of this work was to assess the chemical and physical characteristics of treated effluent and to evaluate its ecotoxicological effects on zebrafish (Danio rerio) embryonic and larval stages, through developmental, functional, morphological, and behavioral end-points. The studied AMD sample, highly associated with pyrite, presented high sulfate and dissolved metal ions content and was submitted to the following treatment conditions: NaOH - pH 7.0 and 8.7, and Ca(OH)2 - pH 7.0 and 8.7. All neutralizing treatments resulted in a satisfactory reduction of the metals concentration, with best results achieved using Ca(OH)2 at pH 8.7; although Mn and As still remained above or very near the discharge maximum limits according to Brazilian legislation. Therefore, an additional step was employed to Mn and As adsorption by algal biomass. Regarding in-vivo toxicological assays, no significant lethality was recorded in all treated AMD groups, although adverse effects were observed in all endpoints analyzed. Ca(OH)2 groups performed closer to control than NaOH-treated groups. The additional polishing stage treatment with the algae Scenesmus sp. allowed tenuous improvements in terms of removal of residual amounts of As and Mn but not in the toxicological characteristics of treated AMD.
Assuntos
Mineração , Poluentes Químicos da Água/química , Ácidos/química , Adsorção , Animais , Brasil , Ecotoxicologia , Concentração de Íons de Hidrogênio , Ferro , Metais/análise , Sulfatos , Sulfetos , Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologiaRESUMO
The protist Tritrichomonas foetus (Excavata, Parabasalia) is a parasite that causes bovine and feline trichomonosis. Bovine trichomonosis is a venereal disease that leads to abortion and reproductive problems in herds. Feline trichomonosis affects domestic cats. Here, we report the genome sequence of the T. foetus K strain, isolated in Brazil.