Project description:These experiments have systematically assessed the potential utility of transcriptomic endpoints as enhancements to the guaiacol assay. Previously, we demonstrated that benzophenone-2, benzophenone, perfluorooctane sulfonate, bisphenol A bis ether, and vinclozolin decreased TPO activity, and that dibutyl phthalate, carbaryl, dibenzo(a,h)anthracene, benzo(a)pyrene, and methylmercury increased TPO activity. In this study, we used human oligonucleotide chips to examine changes in the gene expression profile of FTC-238 human follicular thyroid carcinoma cells expressing human recombinant TPO, after exposure of the cells to TPO activity-disrupting agents.
Project description:These experiments have systematically assessed the potential utility of transcriptomic endpoints as enhancements to the guaiacol assay. Previously, we demonstrated that benzophenone-2, benzophenone, perfluorooctane sulfonate, bisphenol A bis ether, and vinclozolin decreased TPO activity, and that dibutyl phthalate, carbaryl, dibenzo(a,h)anthracene, benzo(a)pyrene, and methylmercury increased TPO activity. In this study, we used human oligonucleotide chips to examine changes in the gene expression profile of FTC-238 human follicular thyroid carcinoma cells expressing human recombinant TPO, after exposure of the cells to TPO activity-disrupting agents. FTC-238/hrTPO/RSK008 cells were seeded and after incubation for 24 h at 37C, the cells were treated with non-toxic dose for 48 h. And after total RNA isolation, gene expression analysis was conducted using a 8x60-k or 4x44-k whole human genome microarray. Labeling and hybridization were performed using a FairPlay microarray labeling kit, followed by the coupling of Cy3 (controls) or Cy5 (treated samples) dye. The hybridized slides were scanned using a GenePix 4000B microarray scanner, and the images were analyzed using GenePix 4.1 software to obtain gene expression ratios. The fluorescence intensity of each spot was calculated by local median background subtraction. We then used the robust scatter-plot smoother LOWESS function to perform intensity-dependent normalization of gene expression. Scatter-plot analysis was performed using Microsoft Excel 2000. A significance analysis of microarray (SAM) was performed for genes with significant changes in expression.
Project description:Discrimination between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) prior to surgery remains a major challenge in clinical practice. To evaluate the feasibility of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs for non-invasive detection of FTC. The diagnostic properties of sEV long RNAs, cell-free long RNAs, sEV miRNAs, and cell-free miRNAs were compared for the detection of FTC.
Project description:The transcriptomic dose-dependent response of rat immortalized thyrocytes to two thyroid disrupting chemicals was investigated by RNA-seq experiment. PCCl3 cells were exposed for one week to different doses of ethylenethiourea (ETU) and chlorpyrifos (CPF) and to their combinations.
Project description:We investigated the effects of thyroid hormone disruptions on gene expression in juvenile mice liver to develop a stronger understanding of the mechanisms by which thyroid disrupting chemicals impair development. Gene expression was examined by hybridization of hepatic RNA to Agilent mouse microarrays for hyper-, hypo-, hypo-replacement (hypo+) and euthyroid animals. Keywords: Toxicogenomics, biomarkers of thyroid disruptors
Project description:Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for the differential diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples.
Project description:Well-differentiated tumours (WDT) of the thyroid gland can be difficult to diagnose. Focal nuclear clearing can be suggestive of a papillary thyroid carcinoma (PTC), while questionable vascular or capsular penetration may raise the possibility of diagnosis of a follicular thyroid carcinoma (FTC). The recently proposed term “thyroid tumours of uncertain malignant potential” (TT-UMP) defines cases showing inconclusive morphological evidence of malignancy. We use microRNA (miRNA) expression profiling to analyze 42 well differentiated thyroid tumours including 7 follicular tumours of uncertain malignant potential (FT-UMP), 6 well differentiated tumours of uncertain malignant potential (WDT-UMP), 7 follicular thyroid adenomas (FTA), 5 follicular variant of papillary thyroid carcinoma (FV-PTC) 6 follicular thyroid carcinoma (FTC), and 11 conventional papillary thyroid carcinoma (C-PTC) with 6 C-PTC mutated for BRAFV600E (C-PTC-mut) and 5 not mutated: wild type (C-PTC-wt). Comparison of these 13 tumours of uncertain malignant potential (7 FT-UMP and 6 WDT-UMP) with those obtained from 16 PTC (11 C-PTC and 5 FV-PTC), 6 FTC and 7 FTA is performed in order to clarify the relationships between TT-UMP and the morphologically well characterized categories of thyroid tumours (i.e. C-PTC, FV-PTC, FTC and FTA). In first, each pathological sample (“L” for Lesional tissue) is compared with its matched control (“S” for Safe tissue) for the 42 patients (84 miRNA microarray slides). This control was taken from the same patient at a large distance from the tumour. Secondly, the perilesional tissue from the same patients but 2 (1 PTC and 1 adenoma, without enough RNA left) is compared to normal thyroid tissue (safe tissue reference) obtained from a patient who underwent total thyroidectomy for a laryngeal carcinoma that partially invaded the thyroid gland, to search for microRNA signatures of perilesional tissues (80 miRNA microarray slides).Experiments is performed with a miRNA microarray, referenced in GEO under the accession number GPL4717 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4717).
Project description:Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas (FTC and PTC, respectively). Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied a label-free quantitative mass spectrometry analysis to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma.