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1.
Exp Oncol ; 41(4): 342-345, 2019 12.
Article in English | MEDLINE | ID: mdl-31868336

ABSTRACT

The aim of the work was to carry out an immunocytochemical (ICC) study of thyroid peroxidase (TPO) and thyroglobulin (Tg) expression in the punctates of the radioiodine (RI) refractory and RI uptake metastases of thyroid papillary carcinoma (PTC), on the basis of which it is possible to develop new methods of preoperative prediction of RI resistance and RI therapy efficiency for thyroid papillary carcinoma metastases. MATERIALS AND METHODS: The ICC research was carried out on a fine needle aspiration biopsy material of 104 metastases that were found after thyroidectomy and RI therapy, i.e. in postoperative period (79 - radioiodine-refractory metastases, 25 - radioiodine-uptake metastases). The ICC analysis of TPO and Tg expression in PTC was performed with the use of monoclonal antibodies against TPO and Tg. RESULTS: RI-refractory (RIRM) and RI-uptake metastases of PTC significantly differ by the percentage of cells expressing TPO and Tg (p < 0.05, and p < 0.05 respectively). The effectiveness of RI therapy was different for patients with different percentages of TPO-positive cells. CONCLUSION: A statistically significant difference was demonstrated in the expression of TPO in a punctates of RI-resistant and RI-sensitive metastatic TPC, based on which a new method for preoperative prediction of RI resistance and RI therapy efficiency was developed. It was shown that ICC determination of Tg expression in metastases is effective in preoperative monitoring of RI resistance of PTC if the part of Tg-positive cells in punctates is lower than 56%. The comprehensive study of the ICC profile of thyrocytes in RI-uptake metastases punctates allows us to develop a personified approach to prediction, monitoring and therapy of patients with PTC.


Subject(s)
Thyroid Cancer, Papillary/pathology , Thyroid Epithelial Cells/pathology , Thyroid Neoplasms/pathology , Adolescent , Adult , Child , Female , Humans , Iodide Peroxidase/analysis , Iodine Radioisotopes/therapeutic use , Male , Thyroglobulin/analysis , Thyroid Cancer, Papillary/radiotherapy , Thyroid Epithelial Cells/radiation effects , Thyroid Neoplasms/radiotherapy , Young Adult
2.
PLoS One ; 13(7): e0197911, 2018.
Article in English | MEDLINE | ID: mdl-30001320

ABSTRACT

High-throughput gene expression analysis is increasingly used in radiation research for discovery of damage-related or absorbed dose-dependent biomarkers. In tissue samples, cell type-specific responses can be masked in expression data due to mixed cell populations which can preclude biomarker discovery. In this study, we deconvolved microarray data from thyroid tissue in order to assess possible bias from mixed cell type data. Transcript expression data [GSE66303] from mouse thyroid that received 5.9 Gy from 131I over 24 h (or 0 Gy from mock treatment) were deconvolved by cell frequency of follicular cells and C-cells using csSAM and R and processed with Nexus Expression. Literature-based signature genes were used to assess the relative impact from ionizing radiation (IR) or thyroid hormones (TH). Regulation of cellular functions was inferred by enriched biological processes according to Gene Ontology terms. We found that deconvolution increased the detection rate of significantly regulated transcripts including the biomarker candidate family of kallikrein transcripts. Detection of IR-associated and TH-responding signature genes was also increased in deconvolved data, while the dominating trend of TH-responding genes was reproduced. Importantly, responses in biological processes for DNA integrity, gene expression integrity, and cellular stress were not detected in convoluted data-which was in disagreement with expected dose-response relationships-but upon deconvolution in follicular cells and C-cells. In conclusion, previously reported trends of 131I-induced transcriptional responses in thyroid were reproduced with deconvolved data and usually with a higher detection rate. Deconvolution also resolved an issue with detecting damage and stress responses in enriched data, and may reduce false negatives in other contexts as well. These findings indicate that deconvolution can optimize microarray data analysis of heterogeneous sample material for biomarker screening or other clinical applications.


Subject(s)
Neuroendocrine Cells/radiation effects , RNA, Messenger/genetics , Thyroid Epithelial Cells/radiation effects , Thyroid Gland/radiation effects , Tissue Array Analysis/methods , Transcriptome , Animals , Beta Particles/adverse effects , Female , Gamma Rays/adverse effects , Gene Expression Regulation , Gene Ontology , Iodine Radioisotopes , Mice , Mice, Nude , Molecular Sequence Annotation , Neuroendocrine Cells/cytology , Neuroendocrine Cells/metabolism , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Thyroid Epithelial Cells/cytology , Thyroid Epithelial Cells/metabolism , Thyroid Gland/cytology , Thyroid Gland/metabolism , Thyroid Hormones/metabolism , Thyroid Hormones/pharmacology
3.
Probl Radiac Med Radiobiol ; 22: 172-183, 2017 Dec.
Article in English, Ukrainian | MEDLINE | ID: mdl-29286504

ABSTRACT

OBJECTIVE: to investigate morphological changes in the primary thyroid cell culture of rat infants whose parents were prenatally exposed by radioisotope iodine 131. MATERIALS AND METHODS: obtaining and culturing of thyroid tissue primary cell cultures of newborn rats, cytological (receipt and analysis of cell cultures agents for optical microscopy), biophysical (flow cytometry), statistics. RESULTS: It was shown that cells in thyroid primary culture of offspring rats prenatally exposed by radioisotopes of iodine 131 signs of destructive degenerative changes were observed mostly when animals of both sexes were irra diated. Increased number of two and three nuclear cells and induction of ring like cells is an evidence of signifi cant genotoxic violation and points to the genome instability in offspring of animals exposed by radioisotope iodine 131. CONCLUSIONS: Analysis and quantitative morphological parameters of cells in thyroid primary culture of newborn rats whose parents were exposed prenatally by radioisotopes of iodine 131 showed that upon exposure to radiation thy roid undergoes destructive changes at the cellular level and, even in the second generation of offspring, leads to disruption of its functions.


Subject(s)
Iodine Radioisotopes/adverse effects , Micronuclei, Chromosome-Defective/radiation effects , Prenatal Exposure Delayed Effects/pathology , Radiation Exposure/adverse effects , Thyroid Epithelial Cells/radiation effects , Thyroid Gland/radiation effects , Animals , Animals, Newborn , Female , Genomic Instability/radiation effects , Male , Maternal Exposure/adverse effects , Micronucleus Tests , Paternal Exposure/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Primary Cell Culture , Rats , Rats, Wistar , Thyroid Epithelial Cells/pathology , Thyroid Epithelial Cells/ultrastructure , Thyroid Gland/pathology , Thyroid Gland/ultrastructure
4.
Int. j. morphol ; 34(2): 498-502, June 2016. ilus
Article in Spanish | LILACS | ID: lil-787028

ABSTRACT

Diez ratas Sprague Dawley de 4 meses de vida y peso aproximado de 250 g fueron divididas en dos grupos de 5 animales cada uno, el grupo A se mantuvo como control y los animales del grupo B recibieron estimulaciones con láser infrarrojo en la tiroides con dosis de 16 J/cm2 durante 15 días consecutivos. Posteriormente las ratas fueron sacrificadas, se extrajeron las respectivas tiroides siendo procesadas para microscopía óptica y se obtuvieron placas histológicas y micrografías de tiroides con aumentos finales de hasta 1000X, las cuales fueron sometidas a estudios morfométricos para determinar en 100 células foliculares: número, áreas y perímetro tanto celular como nuclear, además de disposición coloidal y presencia de vasos sanguíneos. El análisis de los resultados entre las 100 células foliculares pertenecientes a tiroides normal y estimulada revela que existen marcadas diferencias en todos los componentes analizados los que se podría traducir en distintas funcionalidades en el metabolismo de las respectivas glándulas.


Ten 4-month-old Sprague Dawley rats weighing approximately 250 g were divided into two groups of 5 animals each. Group A was the control and the animals in group B received thyroid stimulation with infrared laser in a dose of 16 J/cm2 for 15 consecutive days. Subsequently, rats were euthanized and thyroids were removed and processed for optical microscopy. From both cell types thyroid histological slides and micrographs were obtained with final increases of 400 and 1000X. Morphometric analysis determined the number, areas and cell perimeter as well as colloidal dispersion and presence of blood vessels in 100 follicular cells. Analysis of the results among the 100 follicular cells belonging to normal and stimulated thyroids revealed marked differences in all the analyzed components, which could translate into different functionalities in the metabolism of the respective glands.


Subject(s)
Animals , Rats , Infrared Rays , Lasers , Thyroid Epithelial Cells/radiation effects , Thyroid Epithelial Cells/ultrastructure , Microscopy , Rats, Wistar , Thyroid Gland/radiation effects , Thyroid Gland/ultrastructure
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