thyroid tumors
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Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 357
Author(s):  
Caitlin E. M. Thornton ◽  
Jingzhu Hao ◽  
Prasanna P. Tamarapu ◽  
Iñigo Landa

Hotspot mutations in the TERT (telomerase reverse transcriptase) gene are key determinants of thyroid cancer progression. TERT promoter mutations (TPM) create de novo consensus binding sites for the ETS (“E26 transformation specific”) family of transcription factors. In this study, we systematically knocked down each of the 20 ETS factors expressed in thyroid tumors and screened their effects on TERT expression in seven thyroid cancer cell lines with defined TPM status. We observed that, unlike in other TPM-carrying cancers such as glioblastomas, ETS factor GABPA does not unambiguously regulate transcription from the TERT mutant promoter in thyroid specimens. In fact, multiple members of the ETS family impact TERT expression, and they typically do so in a mutation-independent manner. In addition, we observe that partial inhibition of MAPK, a central pathway in thyroid cancer transformation, is more effective at suppressing TERT transcription in the absence of TPMs. Taken together, our results show a more complex scenario of TERT regulation in thyroid cancers compared with other lineages and suggest that compensatory mechanisms by ETS and other regulators likely exist and advocate for the need for a more comprehensive understanding of the mechanisms of TERT deregulation in thyroid tumors before eventually exploring TPM-specific therapeutic strategies.


2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Huirong Wang ◽  
Yousheng Jiang ◽  
Jiayi Song ◽  
Huiwen Liang ◽  
Yuan Liu ◽  
...  

Abstract Background The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. Methods A case–control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. Results Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose–response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). Conclusions Perchlorate can increase the risk of PTC in a non-linear dose–response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.


2021 ◽  
Author(s):  
Caitlin E.M. Thornton ◽  
Jingzhu Hao ◽  
Prasanna P. Tamarapu ◽  
Iñigo Landa

AbstractHotspot mutations in the TERT (telomerase reverse transcriptase) gene are key determinants of thyroid cancer progression. TERT promoter mutations (TPM) create de novo consensus binding sites for the ETS (“E26 transforming sequence”) family of transcription factors. In this study, we systematically knocked down each of the 20 ETS factors expressed in thyroid tumors and screened their effects on TERT expression in seven thyroid cancer cell lines with defined TPM status. We observed that, unlike in other TPM-carrying cancers such as glioblastomas, ETS factor GABPA does not unambiguously regulate transcription from the TERT mutant promoter in thyroid specimens. In fact, multiple members of the ETS family impact TERT expression, and they typically do so in a mutation-independent manner. In addition, we observe that partial inhibition of MAPK, a central pathway in thyroid cancer transformation, is more effective at suppressing TERT transcription in the absence of TPMs. Taken together, our results show a more complex scenario of TERT regulation in thyroid cancers compared to other lineages, suggest that compensatory mechanisms by ETS and other regulators likely exist and advocate for the need of a more comprehensive understanding of the mechanisms of TERT deregulation in thyroid tumors before eventually exploring TPM-specific therapeutic strategies.Graphical Abstract


PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009941
Author(s):  
Alex Doan ◽  
Julia Arand ◽  
Diana Gong ◽  
Alexandros P. Drainas ◽  
Yan Ting Shue ◽  
...  

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Qing Wan ◽  
Peng Cao ◽  
Jing Liu

In recent years, the incidence of thyroid cancer (TC) patients has gradually increased, and it ranks first among all endocrine tumors. TC has no obvious characteristics at the initial stage of onset. Thyroid tumors (TT) have formed when they are discovered, and they are easy to see when they are diagnosed. The disease is confused, so it is necessary to rely on imaging methods for tumor diagnosis. Contrast-enhanced ultrasound (CEUS), as the most commonly used imaging method in current clinical testing, is simple, safe, highly sensitive, can accurately display tumor conditions, and has high clinical value in the judgment of TC tumors. This article uses meta-analysis to select 63 published studies on CEUS to determine benign and malignant (BAM) TT to analyze and explore its clinical application value. This article understands the analysis of BAM TT and its diagnostic methods, clarifies the diagnostic efficiency of CEUS for TT, imaging methods, and imaging characteristics, and uses statistical analysis to analyze its heterogeneity. In this paper, the meta-analysis of CEUS in judging BAM TT is mainly based on references. The sensitivity, specificity, and difference of CEUS in diagnosing BAM TT are analyzed. Real-time elastography (RTE) is the comparison experiment object, and CEUS is used to compare the diagnostic efficiency, pathological results, and diagnostic efficiency of thyroid nodules in CEUS mode. The results of the study show that the nodule with higher diagnostic sensitivity is the echo feature, with a sensitivity of 97.73%, followed by the halo feature, with a sensitivity of 86.36%. In terms of diagnostic specificity, the boundary feature is the most specific. The specificity is 89.47%. In the judgment of BAM tumor nodules, the most obvious difference is the echo feature, which is as high as 14.09, followed by the acoustic halo feature, and the difference is 10.65.


2021 ◽  
Vol 5 (5) ◽  
pp. 47-51
Author(s):  
Minghan Yang ◽  
Yaming Ji ◽  
Jinku Zhang

With the progress of science and technology as well as the development of ultrasound technology, more and more thyroid tumors have been found. Follicular tumor is one of the most common thyroid tumors, but borderline follicular tumors are relatively rare. At present, the diagnosis of borderline follicular thyroid tumor is unclear prior to surgery, and it is difficult to identify in frozen section or even conventional section. In order to effectively improve the diagnostic sensitivity and specificity of borderline follicular thyroid tumor, this paper summarizes the new WHO (World Health Organization) classification of borderline follicular thyroid tumor along with diagnostic methods, including clinical fine needle aspiration cytology, histopathology, and molecular biology, and reviews the research progress.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mutsumi Matsuu-Matsuyama ◽  
Kazuko Shichijo ◽  
Katsuya Matsuda ◽  
Nariaki Fujimoto ◽  
Hisayoshi Kondo ◽  
...  

AbstractChildhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis.


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