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1.
BMC Surg ; 21(1): 329, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407789

RESUMO

BACKGROUND: Mediastinal lymph node metastases (MLNM) are not rare in thyroid cancer, but their treatment has not been extensively studied. This study aimed to explore the preliminary application of video mediastinoscopy-assisted superior mediastinal dissection in the diagnosis and treatment of thyroid carcinoma with mediastinal lymphadenopathy. MATERIALS AND METHODS: We retrospectively reviewed the clinical pathologic data and short-term outcomes of thyroid cancer patients with suspicious MLNM treated with video mediastinoscopy-assisted mediastinal dissection at our institution from 2017 to 2020. RESULTS: Nineteen patients were included: 14 with medullary thyroid carcinoma and five with papillary thyroid carcinoma. Superior mediastinal nodes were positive in nine (64.3%) patients with medullary thyroid carcinoma and in four (80.0%) patients with papillary carcinoma. No fatal bleeding occurred. There were three cases of temporary recurrent laryngeal nerve (RLN) palsy postoperatively, one of which was bilateral. Four patients had temporary hypocalcemia requiring supplementation, one had a chyle fistula, and one developed wound infection after the procedure. Postoperative serum molecular markers decreased in all patients. One patient died of cancer while the other 18 patients remained disease-free, with a median follow-up of 33 months. CONCLUSION: Video mediastinoscopy-assisted superior mediastinal dissection can be performed relatively safely in patients with suspicious MLNM. This diagnostic and therapeutic approach may help control locoregional recurrences.


Assuntos
Linfadenopatia , Neoplasias da Glândula Tireoide , Dissecação , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Mediastinoscopia , Esvaziamento Cervical , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
2.
Pan Afr Med J ; 38: 405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381549

RESUMO

Introduction: thyroid cancer (TC) is considered to have become the fastest growing cancer in terms of incidence worldwide. Despite literature reporting a prevalence of 5-10% in clinically identified thyroid nodules, Cameroon still has limited data on the profile of TCs in patients with Nodular Goitres (NGs). The Objective were to describe the epidemiological, diagnostic and therapeutic profiles of TCs in patients with nodular goitres at the Douala General Hospital (DGH). Methods: this was a retrospective cross-sectional analysis of patient records with diagnoses of NGs, over 11 years (2006 to 2016) at the DGH. Results: overall, 187 patients (mean age= 46.8±13.9 years, men=27 (14.4%)) were included; 43 (23%) cancers were identified. The most common histological type was papillary cancer (50%). Nodule size of >4cm and hypoechogenicity were independently associated with malignancy. Most patients presented with TNM stage II (47.4%) and well-differentiated cancers were considered to be predominantly at low-risk according to MACIS (55%) and AMES (74%) scores. Surgery was offered to 95.3% of patients. Conclusion: TCs are frequent in patients with NGs with papillary cancer dominating. A high index of suspicion should be held if a nodule is >4cm and/or is hypoechogenic. Prognostic studies are needed to describe the outcome of TCs in our setting.


Assuntos
Carcinoma Papilar/patologia , Bócio Nodular/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Camarões , Carcinoma Papilar/epidemiologia , Estudos Transversais , Feminino , Hospitais Gerais , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/epidemiologia , Adulto Jovem
3.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445474

RESUMO

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in ENT diseases are linked to the level of sex hormones. The sex hormone receptors are present on a wide variety of immune cells; therefore, it is evident that they play crucial roles in regulating the immune system and hence affect the disease progression of ENT diseases. In this review, we focus on how sex hormones, particularly estrogens, regulate ENT diseases, such as chronic rhinosinusitis, vocal fold polyps, thyroid cancer, Sjögren's syndrome, and head and neck cancers, from the perspectives of inflammatory responses and specialized proresolving mediator-driven resolution. This paper aims to clarify why considering sex differences in the field of basic and medical research on otolaryngology is a key component to successful therapy for both males and females in the future.


Assuntos
Estrogênios/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Inflamação/patologia , Rinite/patologia , Sinusite/patologia , Síndrome de Sjogren/patologia , Neoplasias da Glândula Tireoide/patologia , Animais , Progressão da Doença , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Inflamação/metabolismo , Otolaringologia , Rinite/metabolismo , Fatores Sexuais , Sinusite/metabolismo , Síndrome de Sjogren/metabolismo , Neoplasias da Glândula Tireoide/metabolismo
4.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445479

RESUMO

A spaceflight to the International Space Station (ISS) is a dream of many researchers. We had the chance to investigate the effect of real microgravity (CellBox-2 Space mission) on the transcriptome and proteome of FTC-133 human follicular thyroid cancer cells (TCC). The cells had been sent to the ISS by a Falcon 9 rocket of SpaceX CRS-13 from Cape Canaveral (United States) and cultured in six automated hardware units on the ISS before they were fixed and returned to Earth. Multicellular spheroids (MCS) were detectable in all spaceflight hardware units. The VCL, PXN, ITGB1, RELA, ERK1 and ERK2 mRNA levels were significantly downregulated after 5 days in space in adherently growing cells (AD) and MCS compared with ground controls (1g), whereas the MIK67 and SRC mRNA levels were both suppressed in MCS. By contrast, the ICAM1, COL1A1 and IL6 mRNA levels were significantly upregulated in AD cells compared with 1g and MCS. The protein secretion measured by multianalyte profiling technology and enzyme-linked immunosorbent assay (AngiogenesisMAP®, extracellular matrix proteins) was not significantly altered, with the exception of elevated angiopoietin 2. TCC in space formed MCS, and the response to microgravity was mainly anti-proliferative. We identified ERK/RELA as a major microgravity regulatory pathway.


Assuntos
Adenocarcinoma Folicular/patologia , Biomarcadores Tumorais/metabolismo , Proteoma/metabolismo , Esferoides Celulares/patologia , Neoplasias da Glândula Tireoide/patologia , Transcriptoma , Ausência de Peso , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteoma/análise , Voo Espacial , Esferoides Celulares/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
5.
Ann R Coll Surg Engl ; 103(8): e264-e265, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464554

RESUMO

Papillary carcinoma is the most common type of thyroid cancer, accounting for 80-90% of cases. Distant metastasis of papillary thyroid cancer is uncommon, but when it does occur, it is most commonly to the lungs, liver and bone. Bone metastases to the mandible are rarely reported. We present a 68-year-old man who was referred due to a right parotid mass. Appropriate imaging and biopsy revealed a thyroid malignancy with bone metastases. The patient subsequently underwent thyroidectomy, with histology revealing multifocal papillary carcinoma. Radioactive iodine treatment was then commenced to control the metastatic disease.


Assuntos
Neoplasias Mandibulares/secundário , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Neoplasias Mandibulares/diagnóstico , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia
6.
Medicine (Baltimore) ; 100(32): e26882, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397906

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) incidence has been increasing worldwide. Obesity, that is, having a high body mass index, is associated with the incidence of several cancers including colon, breast, esophageal, and kidney cancer. However, the association between obesity and the clinical features of PTC is still unknown. This study aimed to determine the impact of obesity on the clinical features of PTC. METHOD: A database search was conducted for articles published up to 2020 on obesity and clinical features of PTC. Data were extracted from articles that met the meta-analysis inclusion criteria. RESULTS: A total of 11 retrospective cohorts and 11,729 patients were included. Obesity was associated with the following variables in PTC patients: older age (difference in means = 1.95, 95% confidence interval [CI] 0.16-3.74, P = .03), male sex (odds ratio [OR] = 3.13, 95%CI 2.24-4.38, P < .00001), tumor size ≥1 cm (OR = 1.34, 95%CI 1.11-1.61, P < .002), multifocality (OR = 1.54, 95%CI 1.27-1.88, P < .0001), extrathyroidal extension (OR = 1.78, 95%CI 1.22-2.59, P = .003) and advanced tumor, node, metastasis stage (OR = 1.68, 95%CI 1.44-1.96, P < .00001). Preoperative serum thyroid-stimulating hormone level (difference in means  = 0.09, 95%CI 0.35-0.52, P = .70), Vascular invasion (OR = 0.84, 95%CI 0.56-1.26, P = .41), lymph node metastasis (OR = 1.07, 95%CI 0.87-1.32, P = .50), distant metastasis (OR = 1.14, 95%CI 0.64-2.04, P = .66), and recurrence (OR = 1.45, 95%CI 0.97-2.15, P = .07) were not associated with obesity. CONCLUSION: Obesity was associated with several poor clinicopathologic prognostic features: older age, male gender, tumor size ≥1 cm, extrathyroidal extension, multifocality, and advanced tumor/node/metastasis stage. However, thyroid-stimulating hormone level, vascular invasion, lymph node metastasis, distant metastasis, and recurrence were not associated with obesity in PTC.


Assuntos
Obesidade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Índice de Massa Corporal , Causalidade , Progressão da Doença , Humanos , Obesidade/diagnóstico , Obesidade/epidemiologia , Prognóstico , Medição de Risco , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia
7.
Biomed Res Int ; 2021: 6616826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337037

RESUMO

Objective: To evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of low-risk papillary thyroid microcarcinoma (PTMC). Methods: From June 2012 to May 2015, 105 patients with solitary, pathologically confirmed PTMC lesions were treated with ultrasound-guided PLA. Nodule location, nodule volume, thyroid function, and clinical symptoms were evaluated before ablation. Contrast-enhanced ultrasound (CEUS) was performed 1 h after treatment to evaluate whether the ablation was complete. Ultrasound examination was performed at 1, 3, 6, and 12 months after ablation and every 6 months thereafter to determine the size of the ablation area and search for recurrence in the thyroid parenchyma and lymph node metastasis. Thyroid function was examined before and 1 month after ablation. Fine needle aspiration biopsy was performed for any suspicious metastatic lymph nodes and recurrent lesions in the thyroid. Results: All 105 lesions were completely inactivated after one ablation, making the success rate for single ablation 100%. The average ablation time was 2.78 ± 1.05 min, and the average ablation energy was 505 ± 185 J. All patients could tolerate and complete the ablation. No serious complications occurred during the treatment; only minor side effects such as pain and local discomfort were reported. The volume reduction rates were -781.14 ± 653.29% at 1 h posttreatment and -268.65 ± 179.57%, -98.39 ± 76.58%, 36.78 ± 30.32%, 75.55 ± 21.81%, 96.79 ± 10.57%, and 100% at 1, 3, 6, 12, 18, and 24 months after ablation, respectively. This rate remained 100% at the later follow-up times. Overall, 28 (26.67%), 74 (70.48%), 96 (91.43%), and 103 (100%) were completely absorbed by 6, 12, 18, and 24 months after PLA. One patient developed another lesion 12 months after ablation, and two patients had central cervical lymph node metastasis 24 months after ablation. Conclusion: PLA is a safe and effective alternative clinical treatment for low-risk PTMC.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Terapia a Laser , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia , Adulto , Idoso , Carcinoma Papilar/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Fatores de Risco , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360599

RESUMO

Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20-5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/patologia , Adulto , Apoptose , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Prognóstico , Taxa de Sobrevida , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas
9.
Acta Cytol ; 65(5): 368-376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350849

RESUMO

INTRODUCTION: There are few studies on the role of puncture feeling in thyroid nodules during ultrasound-guided fine-needle aspiration cytology (US-FNAC), although it is expected to become a new predictive technique. We aimed to analyze the importance of puncture feeling in combination with US-FNAC and investigate whether it can be used as an indicator to predict the nature of thyroid nodules. MATERIALS AND METHODS: From January 1, 2018, to October 31, 2020, a total of 623 thyroid nodules were included. Puncture feeling was classified as "soft," "hard," or "hard with grittiness." The correlation between puncture feeling and postoperative pathology and the diagnostic value of FNAC combined with puncture feeling were analyzed, and the influence of thyroid nodule size on puncture feeling, FNAC, and FNAC combined with puncture feeling was studied. We further explored the correlation between puncture feeling and histopathology in Bethesda III and IV thyroid nodules. RESULTS: There was a significant correlation between puncture feeling and postoperative pathology (p < 0.001). The sensitivity, negative predictive value, and total coincidence rate of US-FNAC combined with puncture feeling for the diagnosis of thyroid nodules were higher than those of US-FNAC alone (96.1, 83.6, and 94.7% vs. 89.0, 65.5, and 89.7%, respectively). Thyroid nodule size was the influencing factor for puncture feeling, FNAC, and FNAC combined with puncture feeling (p < 0.05 for all). The area under the curve for puncture feeling, FNAC, and FNAC combined with puncture feeling for thyroid nodules of size ≤1 cm was greater than for modules of size >1 cm. Puncture feeling was of great value in diagnosing Bethesda III thyroid nodules (p < 0.001), and all Bethesda IV thyroid nodules had puncture feeling of soft. CONCLUSION: Puncture feeling is of great value during US-FNAC. "Hard" and "hard with grittiness" were indicators for malignancy, while "soft" indicated that the thyroid nodule was likely to be benign. The diagnostic value of US-FNAC combined with puncture feeling for thyroid nodules is higher than US-FNAC alone, especially when nodule size is ≤1 cm. Puncture feeling is of great value in predicting the nature of Bethesda III thyroid nodules.


Assuntos
Punções , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina/métodos , Citodiagnóstico/métodos , Técnicas Citológicas/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ultrassonografia/métodos
10.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360757

RESUMO

Thyroid cancer is the most common endocrine malignancy, and the characterization of the genetic alterations in coding-genes that drive thyroid cancer are well consolidated in MAPK signaling. In the context of non-coding RNAs, microRNAs (miRNAs) are small non-coding RNAs that, when deregulated, cooperate to promote tumorigenesis by targeting mRNAs, many of which are proto-oncogenes and tumor suppressors. In thyroid cancer, miR-146b-5p is the most overexpressed miRNA associated with tumor aggressiveness and progression, while the antisense blocking of miR-146b-5p results in anti-tumoral effect. Therefore, inactivating miR-146b has been considered as a promising strategy in thyroid cancer therapy. Here, we applied the CRISPR/Cas9n editing system to target the MIR146B gene in an aggressive anaplastic thyroid cancer (ATC) cell line. For that, we designed two single-guide RNAs cloned into plasmids to direct Cas9 nickase (Cas9n) to the genomic region of the pre-mir-146b structure to target miR-146b-5p and miR-146b-3p sequences. In this plasmidial strategy, we cotransfected pSp-Cas9n-miR-146b-GuideA-puromycin and pSp-Cas9n-miR-146b-GuideB-GFP plasmids in KTC2 cells and selected the puromycin resistant + GFP positive clones (KTC2-Cl). As a result, we observed that the ATC cell line KTC2-Cl1 showed a 60% decrease in the expression of miR-146b-5p compared to the control, also showing reduced cell viability, migration, colony formation, and blockage of tumor development in immunocompromised mice. The analysis of the MIR146B edited sequence shows a 5 nt deletion in the miR-146b-5p region and a 1 nt deletion in the miR-146b-3p region in KTC2-Cl1. Thus, we developed an effective CRISPR/Cas9n system to edit the MIR146B miRNA gene and reduce miR-146b-5p expression which constitutes a potential molecular tool for the investigation of miRNAs function in thyroid cancer.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Marcação de Genes , MicroRNAs , RNA Neoplásico , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Animais , Linhagem Celular , Movimento Celular/genética , Sobrevivência Celular/genética , Xenoenxertos , Humanos , Camundongos , MicroRNAs/biossíntese , MicroRNAs/genética , Transplante de Neoplasias , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
11.
Int J Mol Sci ; 22(14)2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34299284

RESUMO

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.


Assuntos
Quimiotaxia/fisiologia , Fatores de Transcrição Forkhead/genética , Macrófagos/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/metabolismo , Humanos , Técnicas In Vitro , Macrófagos/citologia , Camundongos , Camundongos Knockout , Ratos , Ratos Endogâmicos F344 , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
12.
Eur J Endocrinol ; 185(3): 431-439, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34260410

RESUMO

Objective: Thyroid disorders are common. Information on the long-term progression of morphologic disorders is scarce. The aim of this study was to describe the course of thyroid nodules and volume over a period of up to 10 years. Design and Methods: Data from the population-based Study of Health in Pomerania were used for longitudinal analysis of 10 years, on average. Billing data from the Association of Statutory Health Insurance Physicians were matched to the data to exclude participants with thyroid surgery, radioiodine therapy and thyroid carcinoma. Changes in the number and size of thyroid nodules and thyroid volume were observed using ultrasound. Results: A total of 1270 participants were included (53% female, median age at baseline 51 years). The proportion of subjects with at least one thyroid nodule increased from 34.9 to 47.5% after 10 years. The majority of participants had an unchanged or reduced number of nodules. About one-quarter had at least one nodule of size ≥ 1 cm. The proportion of participants with goitre increased from 35 to 37% after 10 years. Nevertheless, individual thyroid volume increased by < 1 mL (95% CI: 0.38-3.66) after adjusting for age and BMI irrespective of thyroid medication. Conclusion: Thyroid nodules and goitre are common. After 10 years, the number of nodules did not increase in about 70% of people. This proportion did not differ substantially when excluding people with thyroid medication. Thyroid volume increased slightly over the follow-up period. These changes do not seem clinically relevant. Our results support a more restrictive approach regarding follow-up diagnostics in asymptomatic patients with thyroid nodules or minimally enlarged thyroid.


Assuntos
Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adulto , Idoso , Feminino , Bócio/patologia , Humanos , Radioisótopos do Iodo/análise , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
14.
Eur J Endocrinol ; 185(3): 397-404, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34232125

RESUMO

Aim: The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. Patients and methods: We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after the end of therapy. Results: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural responses, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (P = 0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto's thyroiditis, vascular invasion, and extrathyroidal extension (P = 0.78, P = 0.77, P = 0.52, P = 0.19, P = 0.73, and P = 0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio = 6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (P = 0.02). Conclusion: Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.


Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Tireoidectomia , Resultado do Tratamento , Adulto Jovem
15.
Cytogenet Genome Res ; 161(5): 227-235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34311462

RESUMO

Inactivation of tumor suppressor genes, such as RAP1GAP, by hypermethylation of their regulatory region can give rise to thyroid tumors. The aim of this study was to investigate the expression of the RAP1GAP gene and the DNA methylation patterns of its CpG74a, CpG74b, and CpG24 in an Iranian population with differentiated thyroid cancer (DTC). In this study, 160 individuals who underwent thyroidectomy in the Tehran Erfan Hospital between 2018 and 2020 were selected. DNA methylation patterns of selected CpG islands (CpG74a, CpG74b, and CpG24) were determined using methylation-specific PCR. The mRNA expression and protein level of -RAP1GAP were also evaluated. SW1736 and B-CPAP cells were treated with 5-aza-2'-deoxycytidine (5-Aza) to demethylate these regions. The hypermethylation rates of CpG74a and CpG24 in DTC samples were significantly higher than in the control. The mRNA expression and protein level of -RAP1GAP were significantly decreased in the DTC group. In the DTC group, hypermethylation in CpG74a was correlated with decreasing RAP1GAP expression (R2: 0.34; p = 0.043). CpG74a with a specificity of 86.4% has significant prediction power to distinguish between DTC and normal thyroid tissues. Additionally, hypermethylation of CpG74a was significantly associated with higher tumor stages (stage III-IV: 77%; stage I-II: 23%; p = 0.012). Increasing expression of RAP1GAP after demethylation with 15 µM of 5-Aza was observed in both cell lines. These results indicate that DNA hypermethylation in CpG74a can be considered as an epigenetic biomarker in DTC.


Assuntos
Adenocarcinoma Folicular/genética , Carcinoma Papilar/genética , Metilação de DNA , DNA de Neoplasias/genética , Epigênese Genética , Proteínas Ativadoras de GTPase/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ilhas de CpG/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Decitabina/farmacologia , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos
16.
Biomolecules ; 11(6)2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207842

RESUMO

Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the parafollicular C-cells, which produces the hormone calcitonin. RET is a transmembrane receptor protein-tyrosine kinase, which is highly expressed in MTC. Our previous studies reported that cyclin-dependent kinase 5 (CDK5) plays a crucial role in cancer progression, including MTC. However, the role of CDK5 in GDNF-induced RET signaling in medullary thyroid cancer proliferation remains unknown. Here, we investigated RET activation and its biochemically interaction with CDK5 in GDNF-induced medullary thyroid cancer proliferation. Our results demonstrated that GDNF stimulated RET phosphorylation and thus subsequently resulted in CDK5 activation by its phosphorylation. Activated CDK5 further caused STAT3 activation by its specific phosphorylation at Ser727. Moreover, we also found that GDNF treatment enhanced ERK1/2 and EGR1 activity, which is involved in p35 activation. Interestingly, we identified for the first time that CDK5 physically interacted with RET protein in MTC. Overall, our results provide a new mechanism for medullary thyroid cancer cell proliferation, suggesting that targeting CDK5 may be a promising therapeutic candidate for human medullary thyroid cancer in the near future.


Assuntos
Quinase 5 Dependente de Ciclina/metabolismo , Proteínas Proto-Oncogênicas c-ret/metabolismo , Fator de Transcrição STAT3/metabolismo , Carcinoma Neuroendócrino/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Quinase 5 Dependente de Ciclina/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Fosforilação , Proteínas Proto-Oncogênicas c-ret/fisiologia , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT3/genética , Transdução de Sinais , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
17.
Biomed Res Int ; 2021: 9937742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307677

RESUMO

The aim of this study was to explore the correlation between ultrasound-guided fine-needle aspiration cytology(US-FNAC) combined with BRAF V600E mutation analysis and central neck lymph node metastasis in cN0 papillary thyroid cancer, so as to provide reliable molecular evidence to use it for preoperative evaluation, operation procedure design, and postoperative follow-up planning in clinic. Specimens were obtained from 250 patients with cN0 thyroid cancer (TI-RADS≥4a, highly suspected of PTC by US-FNAC) after bilateral thyroidectomy and central neck lymph node dissection with accessible postoperative pathologic results of PTC and central neck lymph nodes and used for cytological diagnosis by H&E stain and BRAF V600E mutation detection. Single-factor analysis showed that differences between the central neck lymph node metastasis and nonmetastasis groups were statistically significant in gender, BRAF V600E mutation, and extracapsular extension. Logistic multivariate regression analysis showed significant differences in gender, BRAF V600E mutation, and extracapsular extension. Positive BRAF V600E mutations by US-FNAC, extracapsular extension, and male gender are risk factors of central neck lymph node metastasis in cN0 PTC metastatic PTC to central neck lymph node. Patients with those factors should undergo prophylactic central neck lymph node dissection.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Metástase Linfática/genética , Pescoço/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Sequência de Bases , Análise Mutacional de DNA , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
18.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201607

RESUMO

BACKGROUND: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. METHODS: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. RESULTS: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. CONCLUSIONS: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.


Assuntos
Regulação Neoplásica da Expressão Gênica , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proteínas Supressoras de Tumor/genética , Apoptose/genética , Estudos de Casos e Controles , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Esferoides Celulares/patologia , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Proteínas Supressoras de Tumor/metabolismo
19.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204950

RESUMO

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, where V600EBRAF is a main oncogene. Here, we analyse the effect of V600EBRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition of V600EBRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show that V600EBRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells to V600EBRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects of V600EBRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy by V600EBRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targeting V600EBRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment of V600EBRAF-positive thyroid tumours.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Apoptose/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/farmacologia , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
20.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299334

RESUMO

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient's diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.


Assuntos
Biópsia Líquida/métodos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Vesículas Extracelulares/patologia , Humanos , Biópsia Líquida/tendências , Células Neoplásicas Circulantes/patologia , Prognóstico
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