Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor that was previously classified as an encapsulated follicular variant of papillary thyroid carcinoma, necessitating a new classification as it was recognized that encapsulated tumors without invasion have an indolent behavior, and may be over-treated if classified as a type of cancer. Definition of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): A noninvasive neoplasm that arises from the thyroid follicular cells (cells that normally make thyroid hormone), showing a predominantly follicular growth pattern and with nuclear features of papillary thyroid carcinoma. There are several specific inclusion and exclusion criteria (see below). When these are met, this tumor has an extremely low malignant potential. Abbreviations: NIFTP: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features EFVPTC: Encapsulated follicular variant of ...
TY - JOUR. T1 - Comprehensive genetic characterization of human thyroid cancer cell lines. T2 - A validated panel for preclinical studies. AU - Landa, Iñigo. AU - Pozdeyev, Nikita. AU - Korch, Christopher. AU - Marlow, Laura A.. AU - Smallridge, Robert Christian. AU - Copland, John A III. AU - Henderson, Ying C.. AU - Lai, Stephen Y.. AU - Clayman, Gary L.. AU - Onoda, Naoyoshi. AU - Tan, Aik Choon. AU - Garcia-Rendueles, Maria E.R.. AU - Knauf, Jeffrey A.. AU - Haugen, Bryan R.. AU - Fagin, James A.. AU - Schweppe, Rebecca E.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Purpose: Thyroid cancer cell lines are valuable models but have been neglected in pancancer genomic studies. Moreover, their misidentification has been a significant problem. We aim to provide a validated dataset for thyroid cancer researchers. Experimental Design: We performed next-generation sequencing (NGS) and analyzed the transcriptome of 60 authenticated thyroid cell lines and compared our findings with the known genomic defects ...
Mutation of the BRAF gene is common in thyroid cancer. Follicular variant of papillary thyroid carcinoma is a variant of papillary thyroid carcinoma that has created continuous diagnostic controversies among pathologists. The aims of this study are to (1) investigate whether follicular variant of papillary thyroid carcinoma has a different pattern of BRAF mutation than conventional papillary thyroid carcinoma in a large cohort of patients with typical features of follicular variant of papillary thyroid carcinoma and (2) to study the relationship of clinicopathological features of papillary thyroid carcinomas with BRAF mutation. Tissue blocks from 76 patients with diagnostic features of papillary thyroid carcinomas (40 with conventional type and 36 with follicular variant) were included in the study. From these, DNA was extracted and BRAF V600E mutations were detected by polymerase chain reaction followed by restriction enzyme digestion and sequencing of exon 15. Analysis of the data indicated ...
Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. These findings suggest that glycerol is
TY - JOUR. T1 - Involvement of cysteine-rich protein 61 in the epidermal growth factor-induced migration of human anaplastic thyroid cancer cells. AU - Chin, Li Han. AU - Hsu, Sung Po. AU - Zhong, Wen-Bin. AU - Liang, Yu Chih. PY - 2016. Y1 - 2016. N2 - Anaplastic thyroid cancer (ATC) is among the most aggressive types of malignant cancer. Epidermal growth factor (EGF) plays a crucial role in the pathogenesis of ATC, and patients with thyroid carcinoma typically exhibit increased cysteine-rich protein 61 (Cyr61). In this study, we found that EGF treatment induced cell migration, stress fiber formation, Cyr61 mRNA and protein expressions, and Cyr61 protein secretion in ATC cells. The recombinant Cyr61 protein significantly induced cell migration; however, inhibition of Cyr61 activity by a Cyr61-specific antibody abrogated EGF-induced cell migration. EGF treatment also affected epithelial-to-mesenchymal transition (EMT)-related marker protein expression, as evidenced by an increase in vimentin and ...
An individual with 2 first-degree relatives who have or have had non-medullary thyroid cancer or a documented diagnosis of non-medullary thyroid cancer and one living relative with documented non-medullary thyroid cancer. (Note: as this is a familial study, subjects do not need to present with the disease.). OR. Any member of an affected family. (Note: for this study, an affected family is defined as a family having 2 or more 1st degree relatives with a documented diagnosis of FNMTC.). ...
Department of Internal Medicine 4, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan. Zinc at concentrations of 150, microM or higher induced necrosis as well as apoptosis in thyroid cancer cell lines. Necrosis was induced by zinc in a dose-dependent manner, whereas apoptosis did not increase at higher concentrations of zinc. The expression of the antiapoptotic protein phosphorylated Bad was markedly increased, whereas the expression of the proapoptotic proteins Bax and Bad decreased following Zn(2+) exposure. Zn(2+) induced rapid degradation of IkappaB, and an increase in the binding of nuclear transcription factor-kappaB (NF-kappaB). These observations indicate that antiapoptotic pathways were activated in thyroid cancer cells following exposure to Zn(2+). This may be a self-defence mechanism against apoptosis and may underlie the general resistance of thyroid cancer cells to apoptotic stimuli. Zinc may be a potential cytotoxic agent for the treatment of ...
|i|Background.|/i| Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis. |i|Aim.|/i| The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma. |i|Methods.|/i| A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed. |i|Results.|/i| Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis. |i|Conclusions.|/i| Tumor located in upper
Anaplastic thyroid carcinoma is fatal if unresectable. However, improved survival has been reported after gross total resection and multimodality therapy. In this report, we describe the contrast-enhanced high-resolution CT characteristics of anaplastic thyroid carcinoma in 57 patients. Anaplastic thyroid carcinoma presented as a large neck mass with necrosis in 82% of cases. The tumors demonstrated common extrathyroidal extension (91%). Sixty-two percent of tumors demonstrated calcification. Visceral space invasion involved the esophagus (62%), trachea (57%), and larynx (29%). Carotid artery encasement was present in 42%, and 43% involved the internal jugular vein. Sixty-three percent had lateral compartment lymphadenopathy; 58% of these nodes were necrotic, and 11% were cystic. No metastatic nodes had calcification. Central compartment lymphadenopathy was seen in 56% of cases, and lateral retropharyngeal lymphadenopathy was detected in 12%. Knowledge of these imaging features aids in guiding ...
Introduction: We report an unusual case of adenocarcinoma of lung metachronous with stage IVA papillary thyroid carcinoma. The two tumors are morphologically similar; and the later presence of lung mass could clinically masquerade as metastatic thyroid carcinoma. We discuss the challenges in clinical, imaging and pathologic diagnosis. Case Report: A 64-year-old non-smoking female had a thyroidectomy and neck lymph node dissection for a stage IVA tumor with pathologic findings of one 2 mm microcarcinoma of left thyroid and six positive cervical lymph nodes. The post-surgical I131 whole body scan was negative and thyroglobulin is suppressed and stable (<1 ng/ml). One year later, she developed a ground glass and part-solid mass in the superior segment of left lower lobe of lung. The mass slowly grew increasing in size from 2.4 cm to 3.3 cm over 3 years. Biopsy of the lung lesion reveals morphologic features of nuclear inclusions and papillae similar to the previously diagnosed thyroid carcinoma. However,
A collision tumor involving a tracheal sarcomatoid carcinoma and a papillary thyroid carcinoma has never been reported in the literature. A 78-year-old female presented with a large neck mass and hoarseness. A fine needle aspiration demonstrated papillary thyroid carcinoma. Imaging revealed a right thyroid mass invading into the tracheal lumen with bulky ipsilateral lymphadenopathy. The patient underwent a total thyroidectomy, tracheal resection, and central and right neck dissections. Pathology demonstrated a tracheal sarcomatoid carcinoma invading the right thyroid, which had multifocal papillary thyroid carcinoma with central and lateral neck metastases. The patient subsequently received adjuvant chemoradiotherapy and radioactive iodine. We present a case of a tracheal sarcomatoid carcinoma colliding with a papillary thyroid cancer. Treatment modalities should address the most aggressive tumor, while being tailored to clinical picture, tumor histology, and patient preferences.
Introduction: The commonest metastases to the thyroid are from renal cell carcinomas (RCC) and 23 48% of all thyroid metastases are RCCs. They may occur many years after RCC excision, the longest reported latent period being 20 years. Sunitinib (SUN), a multiple targeted anti-cancer drug, is increasingly used for RCC therapy but may cause thyroid dysfunction in some usually hypothyroidism. We report a patient who presented with thyroid metastases 21 years after RCC excision, who developed biphasic thyroid dysfunction during SUN therapy.. Case presentation: A 76-year-old woman who had a nephrectomy for RCC 21 years before, and was on no relevant medication, presented with an enlarging right thyroid nodule. She had a thyroid lobectomy following inadequate FNAC of the nodule. Histology revealed metastatic clear cell renal carcinoma. CT scans revealed possible pancreatic and ovarian metastases but no recurrence at the original site. She was started on SUN for disseminated disease, after ...
Persistent RET activation is a frequent event in papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). In these cancers, RET activates the ERK/MAPK, the PI3K/AKT/mTOR and the JAK/STAT3 pathways. Here, we tested the efficacy of a JAK1/2- inhibitor, AZD1480, in the in vitro and in vivo growth of thyroid cancer cell lines expressing oncogenic RET. Thyroid cancer cell lines harboring RET/PTC1 (TPC-1), RET M918T (MZ-CRC1) and RET C634W (TT) alterations, as well as TPC-1 xenografts, were treated with JAK inhibitor, AZD1480. This inhibitor led to growth inhibition and/or apoptosis of the thyroid cancer cell lines in vitro, as well as to tumor regression of TPC-1 xenografts, where it efficiently blocked STAT3 activation in tumor and stromal cells. This inhibition was associated with decreased proliferation, decreased blood vessel density, coupled with increased necrosis. However, AZD1480 repressed the growth of STAT3- deficient TPC-1 cells in vitro and in vivo, demonstrating that its effects
OBJECTIVE: The role of routine central lymph node dissection (CLND) for clinically central lymph node negative (CN0) papillary thyroid microcarcinoma (PTMC) remains uncertain. We aim to determine the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma. PATIENTS AND METHODS: A total of 273 patients diagnosed with clinically central lymph node negative PTMC from 2014 to 2016 were included. The predictive risk factors for CLNM were analyzed with respect to age, sex, tumor size, tumor multifocal, lymphadenectasis of lateral neck, capsular invasion, extra capsular spread (ECS), coexistence of chronic lymphocytic thyroiditis (Hashimoto thyroiditis, HT) and nodular goiter (NG), BRAFV600E mutation and subtype of papillary thyroid carcinoma (PTC ...
Studies on genetic susceptibility for thyroid cancer could have important relevance to understand the etiology of this pathology. Thus, association studies aimed to identify genes for thyroid cancer risk have been recently published (9-12), although no specific genes for thyroid cancer susceptibility have yet been described. Our previous study, using the BAT-40 marker in a case-control study, indicated that the chromosome 1p12-13 is related to thyroid cancer susceptibility (13). Therefore, in the present study, we aimed to map the susceptibility loci on this region. In this context, we have scanned a region of ∼2.4 Mb surrounding the BAT-40 marker by genotyping six single-nucleotide polymorphisms in a Spanish population. This study has allowed us to identify in our population two independent genetic susceptibility loci on chromosome 1p12.. Association analysis using a case-control design showed a strong association between the rs2145418 marker and thyroid cancer incidence, and similar results ...
TY - JOUR. T1 - PD-1 Blockade in Anaplastic Thyroid Carcinoma. AU - Capdevila, Jaume. AU - Wirth, Lori J.. AU - Ernst, Thomas. AU - Ponce Aix, Santiago. AU - Lin, Chia Chi. AU - Ramlau, Rodryg. AU - Butler, Marcus O.. AU - Delord, Jean Pierre. AU - Gelderblom, Hans. AU - Ascierto, Paolo A.. AU - Fasolo, Angelica. AU - Führer, Dagmar. AU - Hütter-Krönke, Marie Luise. AU - Forde, Patrick M.. AU - Wrona, Anna. AU - Santoro, Armando. AU - Sadow, Peter M.. AU - Szpakowski, Sebastian. AU - Wu, Hongqian. AU - Bostel, Geraldine. AU - Faris, Jason. AU - Cameron, Scott. AU - Varga, Andreea. AU - Taylor, Matthew. PY - 2020/8/10. Y1 - 2020/8/10. N2 - PURPOSE: Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with BRAF-wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized ...
The incidence of thyroid cancer, the most common endocrine malignancy, continues to increase steadily during the past few decades worldwide [1, 2]. The majority of thyroid cancer types are classified as: follicular epithelial cell-derived papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC), and para-follicular C-cell derived medullary thyroid cancer (MTC) [3]. The prognosis of patients with thyroid cancer is closely correlated with local invasion outside the thyroid capsule and the development of distant metastases [4]. Therefore, dissecting the molecular mechanisms underlying thyroid cancer invasion and metastasis is still imperative and may put new insight into the clinical treatment of thyroid cancer.. Human tumor-associated calcium signal transducer 2 (TACSTD2), also known as trophoblast cell-surface antigen 2 (Trop2), is a type I transmembrane glycoprotein originally identified in human placental trophoblastic tissue [5]. As a cell surface ...
The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1α,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1α,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1α,25(OH)2D3. The anti-metastatic effect of 1α,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease
A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: Confirmation of linkage to TCO1. About 5% of nonmedullary thyroid cancer is familial. These familial nonmedullary thyroid cancer cases are characterized by an earlier age of onset, more aggressive phenotype, and in some families a high propensity to benign thyroid disease. Little is known about the genes conferring predisposition to nonmedullary thyroid cancer. Three loci have been identified through genetic linkage: MNG1 on 14q32, TCO1 on 19p13.2, and fPTC on 1p21. In addition to these putative genes, a number of loci represent candidate familial nonmedullary thyroid cancer predisposition genes by virtue of their involvement in sporadic disease (TRKA), their role in benign disease (TSHR), and because they underlie syndromes with a risk of nonmedullary thyroid cancer (PTEN). To evaluate the roles of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer, we have ...
TY - JOUR. T1 - Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status. AU - Means, Casey. AU - Clayburgh, Daniel. AU - Maloney, Lauren. AU - Sauer, David. AU - Taylor, Matthew H.. AU - Shindo, Maisie. AU - Coussens, Lisa. AU - Tsujikawa, Takahiro. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. Results: mIHC ...
Sorafenib (Nexavar), is a multikinase inhibitor, which has demonstrated both antiproliferative and antiangiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumoral cells (c-RAF [proto-oncogene serine/threonine-protein kinase], BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3) and in tumor vessels (c-RAF, vascular endothelial growth factor receptor [VEGFR]-2, VEGFR-3, and platelet-derived growth factor receptor β). Sorafenib was initially approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. Experimental studies have demonstrated that sorafenib has both antiproliferative and antiangiogenic properties in vitro and in vivo, against thyroid cancer cells. Furthermore, several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary, follicular and medullary aggressive thyroid cancer. The results of the different studies showed good clinical ...
Inclusion Criteria: - Histologically confirmed locally advanced or metastatic thyroid cancer - Measurable disease - Normal blood pressure (if history of hypertension, blood pressure must be controlled with medication) - Evidence of disease progression within 6 months before starting study (for differentiated thyroid cancer subjects) - Evidence of disease progression within 6 months before starting study OR symptomatic disease (for medullary thyroid cancer subjects) - Not a candidate for surgical resection, external beam radiotherapy, radioiodine therapy, or other local therapy - At least 18 years of age Exclusion Criteria: - Undifferentiated/anaplastic thyroid cancer - Untreated or symptomatic brain metastases - Prior malignancy, unless cured with treatment and no evidence of disease for greater than or equal to 3 years before starting study (history of thyroid cancer, in situ cervical cancer, or basal cell cancer of skin are exceptions) - Myocardial infarction or any unstable cardiac condition ...
Objective: To assess predictors of well-differentiated thyroid cancer (WDTC) persistence/recurrence. Design: This was a retrospective chart review of thyroid carcinoma patients seen 1979-2007 in a Boston, Massachusetts-area multispecialty group. Of 1,025 patients, 431 met eligibility criteria. Cox proportional hazards models were used to assess predictors (gender, age, ethnicity, tumor size, surgical histology) of WDTC persistence/recurrence (elevated thyroglobulin levels with negative thyroglobulin-antibodies; or positive imaging). Local extension of disease and lymph node involvement could not be assessed. Results: Mean age at initial surgery (n = 431, 74% women, 79% Caucasian) was 45.8 \(\pm\) 13.5(SD) years. Mean tumor (papillary, 91%; follicular, 5%; Hurthle cell, 2%; \(\ge\)1 type, 2%) size was 2.5 \(\pm\) 1.6(SD) cm. Most tumors were unifocal (57%) and \(\ge\)1 cm (89%). Over 2,600 person-years of follow-up, persistence/recurrence occurred in 52 patients (12%) 4.3 years (median; range ...
Thyroid cancer, the commonest of endocrine malignancies, continues increasing in incidence being the 5th more prevalent cancer among women in the United States in 2012. Familial thyroid cancer has become a well-recognized, unique, clinical entity in patients with thyroid cancer originating from follicular cells, that is, nonmedullary thyroid carcinoma. Hereditary nonmedullary thyroid cancer may occur as a minor component of familial cancer syndromes (familial adenomatous polyposis, Gardners...
This study aims to determine the functional roles of microRNA-34b-5p (miR-34b) in the suppression of anaplastic thyroid carcinoma. We used hydration-of-freeze-dried-matrix (HFDM) formulated liposomes (liposome-loaded miR-34b) for effective delivery of miR-34b to anaplastic thyroid carcinoma in vitro and in vivo. Real time polymerase chain was used to determine the level of miR-34b. Immunocytochemistry, Western blot and ELISA were carried out to determine the effect of this manipulation on VEGF-A expression. In addition, an in vivo xenotransplantation mouse model was used to investigate the functional roles of overexpression of miR-34b in the carcinoma. In anaplastic thyroid carcinoma cells, miR-34b expression was low and significant overexpression (p , 0.05) was noted following transfection with liposome-loaded miR-34b. The miR-34b overexpressed thyroid carcinoma cell lines showed reduction in VEGF-A protein expression, decreased cell proliferation, decreased wound healing, reduced cell cycle ...
Though most types of thyroid cancer are cured by surgery and adjuvant radio- iodine therapy and TSH suppression, patients with radio-iodine refractory thyroid carcinoma as well as with medullary thyroid carcinoma, a neuroendocrine malignancy that does not express iodine transporter, are difficult to treat because of the lack of effective systemic treatment. Therefore, there is an urgent need of novel therapeutic measures for these patients. Thyroid cancer is frequently associated to the oncogenic conversion of protein kinases such as RET (medullary thyroid cancer) and BRAF (papillary and undifferentiated thyroid cancer). Therefore, protein kinase small molecule inhibitors (PKI) have been considered as promising novel agents for the treatment of thyroid carcinoma. Compounds that revealed good RET and BRAF activity both in clinical (vandetanib for RET) and in pre-clinical (vemurafenib for BRAF) settings have been identified. Recently, vandetanib was approved for patients with medullary thyroid ...
Objective: Describe a case of a patient diagnosed with papillary thyroid carcinoma by a retropharyngeal tumor.. Methods: A 46-year-old male was referred from the otorhinolaryngology consult to our department with the post-operative diagnosis of papillary thyroid carcinoma, with 6 months history of upper airway dyspnea and dysphagia to solids. Physical examination: right side adenopathies, not painful on palpation. No goitre. Laryngoscopy: hypertrophy of right posterior pharyngeal wall, epiglottis with rotation. Glotis was permeable. Mobile vocal cords. Pyriform sinus free. Cervical and thoracic TC: right retropharyngeal and internal jugular adenopathic conglomerates. Subcentimetrical mediastinal lymph nodes. Nasopharyngeal MRI: right retropharyngeal paracentral mass rejecting adjacent structures. FNA of cervical lymph node: lymph node with metastases of papillary thyroid carcinoma.. Results: Surgical treatment is decided. Transcervical excision was performed in right parapharyngeal tumor, ...
Anaplastic thyroid cancer arises from cells of the thyroid, which are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Anaplastic thyroid tumor is always considered as stage IV. Genes involved in the pathogenesis of follicular thyroid cancer include P53 and BRAF. ...
Through a transcriptome microarray analysis, we have isolated Anterior gradient protein 2 (AGR2) as a gene up-regulated in papillary thyroid carcinoma (PTC). AGR2 is a disulfide isomerase over-expressed in several human carcinomas and recently linked to endoplasmic reticulum (ER) stress. Here, we analyzed the expression of AGR2 in PTC and its functional role. Expression of AGR2 was studied by immunohistochemistry and real time PCR in normal thyroids and in PTC samples. The function of AGR2 was studied by knockdown in PTC cells and by ectopic expression in non-transformed thyroid cells. The role of AGR2 in the ER stress was analyzed upon treatment of cells, expressing or not AGR2, with Bortezomib and analyzing by Western blot the expression levels of GADD153. PTC over-expressed AGR2 at mRNA and protein levels. Knockdown of AGR2 in PTC cells induced apoptosis and decreased migration and invasion. Ectopic expression of AGR2 in non-transformed human thyroid cells increased migration and invasion and
TY - JOUR. T1 - Foxo3a drives proliferation in anaplastic thyroid carcinoma through transcriptional regulation of cyclin A1. T2 - A paradigm shift that impacts current therapeutic strategies. AU - Marlow, Laura A.. AU - von Roemeling, Christina A.. AU - Cooper, Simon J.. AU - Zhang, Yilin. AU - Rohl, Stephen D.. AU - Arora, Shilpi. AU - Gonzales, Irma M.. AU - Azorsa, David O.. AU - Reddi, Honey V.. AU - Tun, Han W. AU - Dö ppler, Heike R.. AU - Storz, Peter. AU - Smallridge, Robert Christian. AU - Copland, John A III. PY - 2012. Y1 - 2012. N2 - The Forkhead transcription factor, FoxO3a, is a known suppressor of primary tumor growth through transcriptional regulation of key genes regulating cell cycle arrest and apoptosis. In many types of cancer, in response to growth factor signaling, FoxO3a is phosphorylated by Akt, resulting in its exclusion from the nucleus. Here we show that FoxO3a remains nuclear in anaplastic thyroid carcinoma (ATC). This correlates with lack of Akt phosphorylation at ...
Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid 2011;21(2):125-34. https://doi.org/10.1089/thy.2010.0021. Lang BH, Yih PCL, Shek TWH, Wan KY, Wong KP, Lo CY. Factors affecting the adequacy of lymph node yield in prophylactic unilateral central neck dissection for papillary thyroid carcinoma. J Surg Oncol 2012;106(8):966-71. https://doi.org/10.1002/jso.23201. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016 [cited 2016 November 10]. Available from: https://old.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Cooper D, Doherty G, Haugen B, Kloos R, Lee S, Mandel S, et al. American Thyroid Association (ATA) guidelines task force on thyroid nodules and differentiated thyroid cancer. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid ...
TY - JOUR. T1 - Obatoclax overcomes resistance to cell death in aggressive thyroid carcinomas by countering Bcl2a1 and Mcl1 overexpression. AU - Champa, Devora. AU - Russo, Marika A.. AU - Liao, Xiao Hui. AU - Refetoff, Samuel. AU - Ghossein, Ronald A.. AU - Di Cristofano, Antonio. PY - 2014/10/1. Y1 - 2014/10/1. N2 - Poorly differentiated tumors of the thyroid gland (PDTC) are generally characterized by a poor prognosis due to their resistance to available therapeutic approaches. The relative rarity of these tumors is a major obstacle to our understanding of the molecular mechanisms leading to tumor aggressiveness and drug resistance, and consequently to the development of novel therapies. By simultaneously activating Kras and deleting p53 (Trp53) in thyroid follicular cells, we have generated a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC. In several cases, tumors further progress to anaplastic carcinomas. The poorly differentiated tumors are ...
Tumor invasiveness is directly related to the ability of tumor cells to migrate and invade surrounding tissues, usually degrading extracellular matrix. Despite significant progress in the knowledge about migration and invasion, there is much more to elucidate about their regulatory mechanisms, especially in cancer cells. MicroRNAs (miRs) were recently described as important regulators of migration. Differential expression of miRs in cancer is frequently associated with progression, invasion and metastasis. In papillary thyroid carcinoma (PTC), miR-146b-5p is highly expressed and positively correlated to the degree of malignancy. This study aimed to investigate the role of miR-146b-5p on the migratory and invasive behaviors of thyroid cells, using a non tumor rat thyroid follicular cell line (PCCl3) transfected with the miR-146b-5p genomic region, and two PTC cell lines (TPC-1 and BCPAP, bearing distinct oncogenic backgrounds), which express high levels of miR-146b-5p, after miR-146b inhibition by
Although conventional histology and FNA are considered as gold standards, the pathologists are confronted with difficulties in reaching an accurate differential diagnosis between benign and malignant thyroid nodules. To improve disease identification, immunohistochemical markers, such as cytokeratin-19 (CK19) and galectin-3, have been proposed and their efficiencies for thyroid cancer diagnosis have been evaluated. CK19 is the smallest member of cytokeratin family and belongs to the intermediate filaments. Several studies reported that CK19 expression is strong and diffuse in papillary carcinoma and absent or low in benign thyroid lesions (8,9,15-17). Galectin-3, a structurally unique member of galectin family with an N-terminal tail composed of nine collagen-like repeats and a peptide with sites for Ser phosphorylation (39), is anti-apoptotic, associated with the pathogenesis of well-differentiated thyroid carcinoma (7,10-14). However, these markers have shown some limitations because ...
1.A study by Kim et al evaluated the efficacy and safety of radiofrequency ablation for localized small recurrent thyroid cancers less than 2 cm by comparing them with those at repeat surgery.. 2. 73 patients with recurrent thyroid cancer who had been treated with (RFA) or repeat surgery.. 3. Recurrence-free survival rates and post-treatment complication rates were compared between RFA and reoperation groups.. 4.The 1- and 3-year recurrence-free survival rates and post-treatment hoarseness rates were comparable for RFA and reoperation groups.. 5. Post-treatment hypocalcemia occurred exclusively in the reoperation group.. 6 RFA may be an effective and safe alternative to repeat surgery in patients with locally recurrent small thyroid cancers.. Kim JH et al. Radiology. 2015;276(3):909-918.. RFA can also be used in combination with External beam to shrink thyroid cancer and relieve airway obstruction as seen in this case from Dr.JH Bek for Seoul Korea.. ...
Second of a new series of Mini-Editorials in Thyroid News. While accounting for only 1% of solid malignancies, thyroid carcinoma is the most common malignancy of the endocrine system. The majority are patients with well-differentiated thyroid carcinoma of follicular cell origin who are cured with adequate surgical management and radioiodine therapy. However, some thyroid malignancies, such as medullary thyroid carcinoma (MTC) or poorly differentiated thyroid carcinoma, frequently metastasize, precluding patients from a curative resection.. The molecular bases of differentiated thyroid carcinoma, MTC, and anaplastic thyroid cancer are well characterized and the critical genetic pathways involved in the development of specific tumor histological types have been elucidated. Of primary importance has been the recognition of key oncogenic mutations such as BRAF, RET and RAS in papillary (PTC) and RET in medullary (MTC) carcinomas. These genes code for kinases that activate signalling through the ...
Six patients experienced voice change immediately after RFA. Voice change was recovered in 5 patients. One patient without recovery was treated with vocal cord medialization. All 6 patients with voice change had tumors in the level VI. There were no other significant complications, and most of the patients tolerated the RFA procedure well. Although some patients reported a burning sensation, pain, or both, the symptoms were relieved by reducing the RF power or stopping the ablation for several seconds.. In conclusion, RFA can be effective in treating loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk.. ...
Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting
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BACKGROUND. Thyroid carcinomas are relatively common dogs, particularly in breeds such as Beagles, Boxers, Golden Retrievers, and Siberian Huskies. The majority of thyroid carcinomas in dogs are non-functional, with , 25% of dogs presenting with either hypothyroidism or hyperthryoidism. Thyroid carcinomas can either be unilateral (67%-75%) or bilateral (25%-33%), and they can either be non-invasive or invasive. Thyroid carcinomas can also reported in ectopic locations in 7.5% of dogs with thyroid carcinoma. The hyoid apparatus and cranial mediastinum are the two most common locations for ectopic thyroid carcinoma, but they can occur anywhere from the tongue to the heart.. Thyroid carcinomas are rare in cats (2% of all thyroid diseases), whereas functional benign thyroid adenomas and hyperplasia are common and cause hyperthyroidism. DIAGNOSIS. Thyroid carcinomas are generally diagnosed by palpation of a mass in the ventral or ventrolateral cervical region. An important step in determining ...
HATFIELD, England, October 15, 2015 /PRNewswire/ -- - INVITATION FOR EUROPEAN AND ASIAN
Medullary Thyroid Cancer (MTC) accounts for 1%- 2% of thyroid cancers in the United States. MTC is different from other types of thyroid cancers (which are derived from thyroid follicular cells - the cells that make thyroid hormone), because it originates from the parafollicular C cells (also called "C cells") of the thyroid gland. These cells do not make thyroid hormone and instead make a different hormone called calcitonin.. MTC can, and frequently does, spread to lymph nodes and can also spread to other organs. MTC is likely to run in families (inherited forms) in up to 25% of diagnoses, and inherited forms can be associated with other endocrine tumors, in syndromes called Multiple Endocrine Neoplasia (MEN) 2A and MEN 2B. In addition to MTC, patients with MEN2A may have tumors of the adrenal glands called pheochromocytomas or in the parathyroid glands (parathyroid adenomas). Patients with MEN2B, have MTC, pheochromocytomas and neuromas (typically a benign growth or tumor of nerve tissue) in ...
Clinical evidence indicates that high periostin expression correlates with aggressive phenotype in thyroid carcinoma. However, the biological roles of periostin in thyroid carcinoma development and progression are still unclear. In this study, we explored the effects of periostin silencing on thyroid carcinoma cell growth, invasion, and tumorigenesis. We also studied the impact of periostin on the activation of phosphoinositide 3-kinase (PI3-K)/Akt signaling, which is involved in the pathogenesis of thyroid carcinoma. It was found that downregulation of periostin significantly inhibited the proliferation, colony formation, and invasion in both FTC-133 and BCPAP thyroid carcinoma cells. In vivo tumorigenic studies confirmed that periostin depletion retarded the growth of subcutaneous FTC-133 xenograft tumors, which was coupled with a significant decline in the percentage of Ki-67-positive proliferating cells. Western blot analysis demonstrated that periostin downregulation caused a marked inhibition of
Among adolescents and young adults, those who develop thyroid cancer as a secondary malignant neoplasm have decreased overall survival than those with primary thyroid cancer
Background: Inactivation of p16 by methylation of CpG islands is a frequent early event in human cancers, including papillary thyroid carcinoma (PTC). This study was to observe the methylation status of the p16 gene in papillary thyroid carcinoma (PTC) and its correlation with clinical parameters.. Methods: Methylation-specific PCR (MSP) was used to analyze the methylation status of the p16 gene in 74 PTCs and 21 adjacent normal thyroid tissues.. Results: Hypermethylation of p16 gene was observed in 27.0% (20/74) of PTC. None of the normal thyroid tissues was methylated, when compared to the PTCs (p < 0.05). There was no marked relationship between the methylation of p16 gene and the patients′ age, gender, size of cancer, histological subtypes and occurrence of recurrent disease (p > 0.05). The methylation of p16 gene was positively associated with metastasis, a high AMES (age, metastasis to distant sites, extrathyroidal invasion, size) risk group (p < 0.05) and advanced pathological tumor ...
The thyroid gland is small in comparison to other organs of the body, but it is still very important. It is responsible for helping to regulate the body s metabolism and heart rate. Yet, for whatever reason, sometimes the thyroid will develop nodules, which are benign tumors containing a lot of fluid. For many people these nodules will not cause any harm. However, for others the growths may become malignant, resulting in a condition known as thyroid cancer. When thyroid cancer develops, the unhealthy cells attack the thyroid and, (in the case of extreme metastasizing), possibly even other parts of the body.. There are several types of thyroid cancer that exist. The most common type of thyroid cancer is known as papillary. With this type of thyroid cancer, tumors develop in the follicle cells of the thyroid gland. These are the cells that are responsible for producing hormones that regulate various metabolic functions of the body. Anyway, the general progression of papillary thyroid cancer is ...
Hemonc Today | The American Thyroid Association has released the first set of comprehensive guidelines for the management of anaplastic thyroid cancer, a rare but lethal form of thyroid cancer. Members of the American Thyroid Association (ATA) task force compiled a list of 65 recommendations based on relevant literature.
Whereas adenomas and goiters belong to highly prevalent lesions of the thyroid not only in iodine-deficient regions malignant thyroid tumors are rare. Both papillary and follicular carcinomas of the thyroid are supposed to originate from the thyroid epithelium. At least for the follicular carcinomas a possible continuum from thyroid adenomas to follicular carcinomas has been proposed [21]. This idea is at least supported by a particular subtype of follicular tumors i.e. those characterized by a PAX8-PPARγ fusion due to a chromosomal rearrangement between chromosomal bands 2q13 and 3p25. As witnessed by the results of several studies, this abnormality can be found in follicular adenomas as well as in carcinomas [22-24]. However, the question arises whether or not other genetic subtypes of thyroid adenomas may predispose to malignant transformation. Recently, we have been able to demonstrate that translocations of chromosomal band 19q13.4, a frequent genetic alteration in thyroid adenomas, ...
Summary Global Markets Directs, Papillary Thyroid Cancer - Pipeline Review, H1 2016, provides an overview of the Papillary Thyroid Cancer pipeline landscape. The report provides comprehensive information on the therapeutics under development for Papillary Thyroid Cancer, complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA
Yim JH , Kim WB , Kim EY , Kim WG , Kim TY , Ryu JS , Gong G , Hong SJ , Shong YK. J Clin Endocrinol Metab April, 2011. The primary treatment of locoregionally recurrent/persistent papillary thyroid cancer (PTC) is surgical removal by reoperation. This study evaluated the efficacy of the first reoperation for loco-regionally recurrent/persistent papillary thyroid carcinoma and the usefulness of stimulated TG for evaluating efficacy of reoperation. A retrospective observational cohort study was done in a tertiary referral hospital. A total of 83 patients, who underwent initial total thyroidectomy and nodal dissection with radioactive iodine remnant ablation, received reoperation for loco-regionally recurrent/persistent PTC and were included in this study. Stimulated TG levels were assessed before and after reoperation. We assessed biochemical remission (stimulated TG,1 ng/ml) after reoperation and evaluated second clinical recurrence-free survival rate according to stimulated TG value. There was ...