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1.
United European Gastroenterol J ; 6(3): 349-357, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29774148

RESUMO

BACKGROUND: Eosinophilic esophagitis (EoE) is an antigen-driven disease mediated by an abnormal immune Th2 response. OBJECTIVE: The objective of this article is to investigate genes associated with regulating immune responses leading to disease susceptibility. METHODS: Twenty-seven tag single nucleotide polymorphisms (tSNPs) selected in five candidate genes (TLR3, TLR4, FOXP3, FLG and TSLP) were genotyped in 218 EoE patients and 376 controls. Skin prick tests were carried out in EoE patients with a panel of 17 aeroallergens and 22 plant- and animal-derived foods. RESULTS: Five tSNPs located in the TSLP locus and one tSNP located in the TLR3 locus were significantly associated with EoE. The interactions between TLR3 and TSLP loci were analyzed. TLR3+/TSLP- and TLR3-/TSLP+ individuals showed a significantly reduced susceptibility to EoE compared to TLR3-/TSLP- individuals (OR = 0.66, p = 0.036 and OR = 0.23, p = 0.00014, respectively). Likewise, TLR3+/TSLP+ individuals showed the most decreased susceptibility of developing EoE (OR = 0.16, p = 0.0001). However, the interaction gain attributed to the combination of both genes was negative (IG = -4.52%), which indicated redundancy or independent effect. Additionally, TLR3 locus was found to be associated with aeroallergen and food sensitization in EoE patients (OR = 9.67, pc = 0.025 and OR = 0.53, pc = 0.048, respectively). CONCLUSION: TLR3 constitutes a novel genetic susceptibility locus for developing EoE, and the effects would be independent of TSLP.

2.
BMC Cancer ; 14: 656, 2014 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-25197016

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). METHODS: We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed. RESULTS: Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1). CONCLUSIONS: MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , MicroRNAs/genética , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida , Resultado do Tratamento
3.
Eur J Gastroenterol Hepatol ; 21(10): 1161-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19357520

RESUMO

OBJECTIVES: Analysis of the incidence rate and the evolution of duodenal and stomach polyps in our familial adenomatous polyposis (FAP) patients, the suitability of the surveillance method and the cancer-preventing treatment applied and the analysis of the complications arising from each procedure employed. MATERIALS AND METHODS: Twenty-nine patients diagnosed with FAP underwent study and endoscopic surveillance of the upper digestive tract. Front-view and side-view endoscopies were used. Papillary biopsies were performed even when the papilla were macroscopically normal. The Spigelman classification was used to determine the seriousness of the condition and to establish the surveillance and treatment intervals. RESULTS: Duodenal and/or papillary polyps were presented by 79.3% of the patients. Endoscopic polypectomy was performed in 13 patients with duodenal polyps. Endoscopic polypectomies for the papilla were performed in all patients. One patient required a cephalic duodenopancreatectomy and another endoscopic ampullectomy. The condition did not become cancerous in any of the patients who underwent surveillance. We report two complications arising from treatment: one postpolypectomy haemorrhage and one stenosis of the biliary-enteric anastomosis after cephalic duodenopancreatectomy. CONCLUSION: Our study shows a high incidence rate of duodenal polyps in FAP patients. A minute examination of the duodenum and papilla is necessary, using side-view endoscopes and duodenal papilla biopsies even when papilla appears to be normal. None of the patients having completed the surveillance and the prescribed treatment developed cancer and all have a low Spigelman score. This method, therefore, seems to be adequate for the treatment and surveillance of duodenal polyps.


Assuntos
Polipose Adenomatosa do Colo/patologia , Neoplasias Duodenais/patologia , Neoplasias Gástricas/patologia , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Adulto , Progressão da Doença , Neoplasias Duodenais/cirurgia , Endoscopia Gastrointestinal/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Prospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Adulto Jovem
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