Human Thyroglobulin

Background: prophylactic central neck dissection (pCND) is a subject of discussion for papillary thyroid carcinoma T1-2 N0, our study proves that pCND should be recommended as it is associated with less postoperative residual tumour with increasing recurrence-free survival. Objective: The primary endpoint is the recurrence free survival, study exclusively compares the outcome of surgical ablation with and without CND in PTC T1-2N0. Another endpoint is whether patients with residual disease, need to receive repeated radioactive iodine ablation or completion surgery. Subject and method: A Randomized controlled trial multi-centre study, assigned the patients into two arms, Group I was the control arm underwent total thyroidectomy only, whereas the other arm, included Total thyroidectomy and central neck dissection. Univariate and multivariate analysis was performed to declare risk group for recurrence. Recurrence Free Survival was the main issue of the study and calcu- lated as the time elapsed from the date of surgery to the date of relapse; patients with residual and uTg 0.2-2 ng/ml received radio-active iodine (RAI) therapy versus completion surgery. Results: Loco-regional recurrence cases were found more in male patients aged more than 45 years old. Size of the primary tumour and the extent of surgery was a signi ficant factor for RFS, patients with PCND in group II, had lower loco-regional recurrence and longer RFS, mean RFS was 25 months with (95%CI) is (23.61-26.38 months). Recurrence was high in the controlled group 38.1%. Conclusion: N0 patients will bene fit by total thyroidectomy and pCND. pCND is recommended to de- creases the residual tumour, increase the RFS. Completion surgery versus RAI for postoperative recur- rence needs more number of patients. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objective: It has been demonstrated that the transcription factors TAZ (transcriptional coactivator with PDZ-binding motif), paired box gene 8 (PAX8), and NK2 homeobox 1 (NKX2-1) are coexpressed in the nucleus of thyroid cells. Furthermore, TAZ is known to enhance the transcriptional activity of PAX8 and NKX2-1 as well as the key thyroid-specific gene, thyroglobulin (TG), suggesting a critical role for TAZ in the control of thyroid cell speciation. We previously reported that the small molecule ethacridine, identified as a TAZ activator, was able to induce thyroid-specific transcription in endodermal cells differentiated from human embryonic stem (hES) cells using activin A. Since transcription factors are epigenetically regulated in cell differentiation, we investigated the epigenetic changes in the promoter regions of these key transcription factors during in vitro differentiation of hES cells into thyrocytes. Methods: We initially profiled chromatin accessibility using the technique of Assay for Transposase Accessible Chromatin sequencing (ATAC-seq), and then examined DNA methylation and histone acetylation in the promoter regions of the three selected thyroid transcription factors and the thyroid-specific genes during hES cell differentiation. Results: ATAC-seq analysis showed enriched chromatin accessibility of TAZ, NKX2-1, and PAX8 after exposure to activin A and ethacridine. There were no methylation changes found in the NKX2-1, PAX8, and TAZ promoters by bisulfite sequencing. In contrast, acetylation of histone H4, specifically acetylation of lysine 16, was observed in each of the promoters when measured by chromatin immunoprecipitation polymerase chain reaction assays, which correlated with the activity and expression of NKX2-1 and PAX8 as well as sodium/iodide symporter, thyroid stimulating hormone receptor, and TG genes. Conclusions: These results indicate that ethacridine treatment of activin A-derived endodermal hES cells leads to enhanced chromatin accessibility, which, in turn, allows histone H4 acetylation in the regulation of active genes for speciation of thyroid follicular cells from hES cells.