Pathogenesis of thyroid cancer

2011 ◽  
pp. 600-609
Author(s):  
Dan Mihailescu ◽  
Arthur B Schneider ◽  
Leon Fogelfeld
Keyword(s):  
Thyroid Cancer ◽  
Molecular Biology ◽  
Chernobyl Accident ◽  
Epidemiological Studies ◽  
Thyroid Cell ◽  
Tumour Suppressor Genes ◽  
Thyroid Cells ◽  
Suppressor Genes ◽  
The Third ◽  
Biological Studies

Both epidemiological and molecular biological studies have been used to understand the origins of thyroid cancer. Epidemiological studies have been used to identify factors that predispose to thyroid cancer. That is principally how we know that exposure to radiation leads to thyroid cancer (see Chapter 3.2.5). In fact, radiation is the only environmental factor for which the proof is incontrovertible. Molecular biological studies, reviewed in the second part of this chapter, have been used to investigate the events within thyroid cells that are initiated by predisposing factors, e.g. radiation, and lead, by one or multiple steps, to transformation and cancer. These studies have focused on cancer-related genes, particularly proto-oncogenes and tumour suppressor genes, and have led to the identification of potential therapeutic agents. They have also focused on the cellular pathways and processes, including epigenetic changes and microRNA expression, which accompany transformation of the thyroid cell. Epidemiology and molecular biology have interacted productively in the studies that have followed the Chernobyl accident. This interaction is described in the third part of this chapter in which the mutations found in radiation-related thyroid cancers are reviewed.

Integration of Clinical and Genomic Data for Decision Support in Cancer

2008 ◽  
pp. 768-776
Author(s):  
Yorgos Goletsis ◽  
Themis P. Exarchos ◽  
Nikolaos Giannakeas ◽  
Markos G. Tsipouras ◽  
Dimitrios I. Fotiadis
Keyword(s):  
Decision Support ◽  
Molecular Biology ◽  
Early Diagnosis ◽  
Clinical Data ◽  
Support System ◽  
Genomic Data ◽  
Biological Information ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Cancer Diseases

In this article, we address decision support for cancer by exploiting clinical data and identifying mutations on tumour suppressor genes. The goal is to perform data integration between medicine and molecular biology by developing a framework where clinical and genomic features are appropriately combined in order to handle cancer diseases. The constitution of such a decision support system is based on (a) cancer clinical data and (b) biological information that is derived from genomic sources. Through this integration, real time conclusions can be drawn for early diagnosis, staging and more effective cancer treatment.

Integration of Clinical and Genomic Data for Decision Support in Cancer

2011 ◽  
pp. 412-421 ◽  
Author(s):  
Yorgos Goletsis ◽  
Themis P. Exarchos ◽  
Nikolaos Giannakeas ◽  
Markos G. Tsipouras ◽  
Dimitrios I. Fotiadis
Keyword(s):  
Decision Support ◽  
Molecular Biology ◽  
Early Diagnosis ◽  
Clinical Data ◽  
Support System ◽  
Genomic Data ◽  
Biological Information ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Cancer Diseases

In this article, we address decision support for cancer by exploiting clinical data and identifying mutations on tumour suppressor genes. The goal is to perform data integration between medicine and molecular biology by developing a framework where clinical and genomic features are appropriately combined in order to handle cancer diseases. The constitution of such a decision support system is based on (a) cancer clinical data and (b) biological information that is derived from genomic sources. Through this integration, real time conclusions can be drawn for early diagnosis, staging and more effective cancer treatment.

scholarly journals Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

2007 ◽  
Vol 51 (5) ◽  
pp. 701-712 ◽  
Author(s):  
Meyer Knobel ◽  
Geraldo Medeiros-Neto
Keyword(s):  
Thyroid Cancer ◽  
Iodine Deficiency ◽  
Animal Experiments ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Iodine Intake ◽  
Thyroid Cell ◽  
Predisposing Factor ◽  
Iodine Prophylaxis ◽  
Iodine Excess

Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. In conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

Thyroid Cancer in Ukraine After the Chernobyl Accident: Incidence, Pathology, Treatment, and Molecular Biology

2009 ◽  
pp. 305-316 ◽  
Author(s):  
Mykola Tronko ◽  
Tetyana Bogdanova ◽  
Ilya Likhtarev ◽  
Ihor Komisarenko ◽  
Andriy Kovalenko ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Molecular Biology ◽  
Chernobyl Accident

scholarly journals AXL Is a Novel Predictive Factor and Therapeutic Target for Radioactive Iodine Refractory Thyroid Cancer

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 785 ◽  
Author(s):  
Francesca Collina ◽  
Lucia La Sala ◽  
Federica Liotti ◽  
Nella Prevete ◽  
Elvira La Mantia ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Braf V600e ◽  
Specific Gene ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Viral Oncogene ◽  
Rat Thyroid ◽  
Viral Oncogene Homolog

Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.

scholarly journals miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

2014 ◽  
Vol 21 (4) ◽  
pp. 517-531 ◽  
Author(s):  
Myriem Boufraqech ◽  
Lisa Zhang ◽  
Meenu Jain ◽  
Dhaval Patel ◽  
Ryan Ellis ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Needle Aspiration ◽  
Cancer Growth ◽  
Akt Pathway ◽  
Thyroid Cell ◽  
Differentiation Markers ◽  
Thyroid Cells ◽  
Thyroid Cancer Cell Lines ◽  
And Function

The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targetedAKT3.In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

scholarly journals Radiation Exposure to the Thyroid After the Chernobyl Accident

2021 ◽  
Vol 11 ◽  
Author(s):  
Vladimir Drozdovitch
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Gland ◽  
Radiation Exposure ◽  
Chernobyl Accident ◽  
Epidemiological Studies ◽  
Thyroid Diseases ◽  
Exposure Pathways ◽  
Population Average ◽  
Thyroid Dose ◽  
Cleanup Workers

IntroductionThe Chernobyl accident resulted in a considerable release of radioactivity to the atmosphere, particularly of Iodine-131 (131I), with the greatest contamination occurring in Belarus, Ukraine, and western part of Russia.Material and MethodsIncrease in thyroid cancer and other thyroid diseases incidence in population exposed to Chernobyl fallout in these counties was the major health effect of the accident. Therefore, a lot of attention was paid to the thyroid doses, mainly, the 131I intake during two months after the accident. This paper reviews thyroid doses, both the individual for the subjects of radiation epidemiological studies and population-average doses. Exposure to 131I intake and other exposure pathways to population of affected regions and the Chernobyl cleanup workers (liquidators) are considered.ResultsIndividual thyroid doses due to 131I intake varied up to 42 Gy and depended on the age of the person, the region where a person was exposed, and their cow’s milk consumption habits. Population-average thyroid doses among children of youngest age reached up to 0.75 Gy in the most contaminated area, the Gomel Oblast, in Belarus. Intake of 131I was the main pathway of exposure to the thyroid gland; its mean contribution to the thyroid dose in affected regions was more than 90%. The mean thyroid dose from inhalation of 131I for early Chernobyl cleanup workers was estimated to be 0.18 Gy. Individual thyroid doses due to different exposure pathways varied among 1,137 cleanup workers included in the epidemiological studies up to 9 Gy. Uncertainties associated with dose estimates, in terms of mean geometric standard deviation of individual stochastic doses, varied in range from 1.6 for doses based on individual-radiation measurements to 2.6 for “modelled” doses.ConclusionThe 131I was the most radiologically important radionuclide that resulted in radiation exposure to the thyroid gland and cause an increase in the of rate of thyroid cancer and other thyroid diseases in population exposed after the Chernobyl accident.

scholarly journals Thyroid tumor cells-fibroblasts crosstalk: role of extracellular vesicles

2020 ◽  
Vol 9 (6) ◽  
pp. 506-518 ◽  
Author(s):  
Rocío del Carmen Bravo-Miana ◽  
Ana Belén Della Vedova ◽  
Ana Lucía De Paul ◽  
María Mónica Remedi ◽  
María Laura Guantay ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Tumor Stroma ◽  
Thyroid Tumor ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Cd147 Expression

Tumor-stroma crosstalk leads to a tumor-promoting microenvironment. In this milieu, extracellular vesicles (EVs) are protagonists in cell-cell communication. Despite thyroid cancer being the most common endocrine malignancy, the contribution of the tumor microenvironment to thyroid cancer progression is still largely underexplored. We focused on the role of thyroid tumor cell-fibroblast interaction and EVs as mediators of tumor-stroma interplay, in the promotion of thyroid tumor aggressiveness. Thyroid tumor (TPC-1, 8505c) or non-tumor thyroid cells (NThyOri) were co-cultured with human fibroblasts (Fb). Thyroid cell migration was investigated by the wound-healing assay and actin-network staining. Cell-CD147 expression was characterized by flow cytometry. EVs, obtained by ultracentrifugation of conditioned media (CMs), were characterized by transmission electron-microscopy and CD81 and CD147 expression. Metalloproteinases (MMPs) were evaluated by zymography in CMs. A migratory phenotype was triggered in thyroid tumor cells treated with CMs from Fb or from Fb-thyroid tumor cell co-cultures. Fb-thyroid cell co-cultures induced the secretion of proMMP9 and proMMP2 and led to a significant MMP2 activation in CMs. Fb, thyroid cells and Fb-thyroid cell co-cultures released EVs, and remarkably, EVs released by Fb-thyroid tumor cell co-cultures induced the secretion of proMMP2 and the expression of MMP2 from normal Fb. A significant CD147 expression was demonstrated in Fb-thyroid tumor cell-derived EVs. These findings reveal the role of Fb and thyroid tumor cell-Fb interaction in the promotion of a microenvironment suitable for thyroid tumor progression. Moreover, they highlight, for the first time, the role of thyroid tumor cell-Fb interaction in the production of specialized EVs.

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