scholarly journals Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junguee Lee ◽  
Ki Cheol Park ◽  
Hae Joung Sul ◽  
Hyun Jung Hong ◽  
Kun-Ho Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Primary Cilia ◽  
Apoptotic Cell ◽  
Follicular Carcinoma ◽  
Loss Of Function ◽  
Apoptosis Pathway ◽  
Thyroid Cancers ◽  
Oncocytic Variant ◽  
Differentiated Thyroid Cancers ◽  
Thyroid Cancer Cell Lines

AbstractThe primary cilium is well-preserved in human differentiated thyroid cancers such as papillary and follicular carcinoma. Specific thyroid cancers such as Hürthle cell carcinoma, oncocytic variant of papillary thyroid carcinoma (PTC), and PTC with Hashimoto’s thyroiditis show reduced biogenesis of primary cilia; these cancers are often associated the abnormalities in mitochondrial function. Here, we examined the association between primary cilia and the mitochondria-dependent apoptosis pathway. Tg-Cre;Ift88flox/flox mice (in which thyroid follicles lacked primary cilia) showed irregularly dilated follicles and increased apoptosis of thyrocytes. Defective ciliogenesis caused by deleting the IFT88 and KIF3A genes from thyroid cancer cell lines increased VDAC1 oligomerization following VDAC1 overexpression, thereby facilitating upregulation of mitochondria-dependent apoptosis. Furthermore, VDAC1 localized with the basal bodies of primary cilia in thyroid cancer cells. These results demonstrate that loss-of-function of primary cilia results in apoptogenic stimuli, which are responsible for mitochondrial-dependent apoptotic cell death in differentiated thyroid cancers. Therefore, regulating primary ciliogenesis might be a therapeutic approach to targeting differentiated thyroid cancers.

scholarly journals Highly prevalent TERT promoter mutations in aggressive thyroid cancers

2013 ◽  
Vol 20 (4) ◽  
pp. 603-610 ◽  
Author(s):  
Xiaoli Liu ◽  
Justin Bishop ◽  
Yuan Shan ◽  
Sara Pai ◽  
Dingxie Liu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancers ◽  
Tall Cell ◽  
Differentiated Thyroid Cancers ◽  
Thyroid Cancer Cell Lines ◽  
Promoter Mutations

Mutations 1 295 228 C>T and 1 295 250 C>T (termed C228T and C250T respectively), corresponding to −124 C>T and −146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene, have recently been reported in human cancers, but not in thyroid cancers yet. We explored these mutations in thyroid cancers by genomic sequencing of a large number of primary tumor samples. We found the C228T mutation in 0 of 85 (0.0%) benign thyroid tumors, 30 of 257 (11.7%) papillary thyroid cancers (PTC), 9 of 79 (11.4%) follicular thyroid cancers (FTC), 3 of 8 (37.5%) poorly differentiated thyroid cancers (PDTC), 23 of 54 (42.6%) anaplastic thyroid cancers (ATC), and 8 of 12 (66.7%) thyroid cancer cell lines. The C250T mutation was uncommon, but mutually exclusive with the C228T mutation, and the two mutations were collectively found in 11 of 79 (13.9%) FTC, 25 of 54 (46.3%) ATC, and 11 of 12 (91.7%) thyroid cancer cell lines. Among PTC variants, the C228T mutation was found in 4 of 13 (30.8%) tall-cell PTC (TCPTC), 23 of 187 (12.3%) conventional PTC, and 2 of 56 (3.6%) follicular variant PTC samples. No TERT mutation was found in 16 medullary thyroid cancer samples. The C228T mutation was associated with the BRAF V600E mutation in PTC, being present in 19 of 104 (18.3%) BRAF mutation-positive PTC vs 11 of 153 (7.2%) the BRAF mutation-negative PTC samples (P=0.0094). Conversely, BRAF mutation was found in 19 of 30 (63.3%) C228T mutation-positive PTC vs 85 of 227 (37.4%) C228T mutation-negative PTC samples (P=0.0094). We thus for the first time, to our knowledge, demonstrate TERT promoter mutations in thyroid cancers, that are particularly prevalent in the aggressive thyroid cancers TCPTC, PDTC, ATC and BRAF mutation-positive PTC, revealing a novel genetic background for thyroid cancers.

scholarly journals Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities

2021 ◽  
Vol 22 (6) ◽  
pp. 3117
Author(s):  
Loredana Lorusso ◽  
Virginia Cappagli ◽  
Laura Valerio ◽  
Carlotta Giani ◽  
David Viola ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Thyroid Cancers ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Approved Drugs ◽  
New Generation ◽  
Systemic Therapies

Differentiated thyroid cancers (DTC) are commonly and successfully treated with total thyroidectomy plus/minus radioiodine therapy (RAI). Medullary thyroid cancer (MTC) is only treated with surgery but only intrathyroidal tumors are cured. The worst prognosis is for anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC). Whenever a local or metastatic advanced disease is present, other treatments are required, varying from local to systemic therapies. In the last decade, the efficacy of the targeted therapies and, in particular, tyrosine kinase inhibitors (TKIs) has been demonstrated. They can prolong the disease progression-free survival and represent the most important therapeutic option for the treatment of advanced and progressive thyroid cancer. Currently, lenvatinib and sorafenib are the approved drugs for the treatment of RAI-refractory DTC and PDTC while advanced MTC can be treated with either cabozantinib or vandetanib. Dabrafenib plus trametinib is the only approved treatment by FDA for BRAFV600E mutated ATC. A new generation of TKIs, specifically for single altered oncogenes, is under evaluation in phase 2 and 3 clinical trials. The aim of this review was to provide an overview of the current and future treatments of thyroid cancer with regards to the advanced and progressive cases that require systemic therapies that are becoming more and more targeted on the molecular identity of the tumor.

scholarly journals Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

2017 ◽  
Vol 24 (12) ◽  
pp. T311-T329 ◽  
Author(s):  
Robert C Mould ◽  
Jacob P van Vloten ◽  
Amanda W K AuYeung ◽  
Khalil Karimi ◽  
Byram W Bridle
Keyword(s):  
Thyroid Cancer ◽  
Immune System ◽  
Treatment Options ◽  
Survival Rates ◽  
Standard Of Care ◽  
Cancer Microenvironment ◽  
Current Standard ◽  
Thyroid Cancers ◽  
Hormonal Modulation ◽  
Differentiated Thyroid Cancers

The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient’s immune system to kill their tumor. The thyroid cancer microenvironment is rich in immunological cells, making it a reasonable candidate for immunotherapy. This review maps out the immunological features of thyroid cancers and how these can be modulated. There are surprising immunological consequences of conventional therapies that demand attention. Also, hormonal modulation of the immune system is highlighted as a unique and confounding feature of thyroid cancers. A variety of cutting-edge immune-based therapies are discussed, with an emphasis placed on how these can be integrated with the current standard of care. Several high priority areas in need of research are also highlighted.

scholarly journals What's New in Molecular Targeted Therapies for Thyroid Cancer?

2021 ◽  
Vol 37 (2) ◽  
pp. 1-9
Author(s):  
Seonyoung Min ◽  
Hyunseok Kang
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Radioactive Iodine ◽  
Checkpoint Inhibitors ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Thyroid Cancers ◽  
Ret Mutation ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

scholarly journals Unusual Presentation of Differentiated Thyroid Cancer Metastasis

2017 ◽  
Vol 22 (02) ◽  
pp. 167-170 ◽  
Author(s):  
Haissan Iftikhar ◽  
Mubasher Ikram ◽  
Adnan Muhammad ◽  
Karim Nathani
Keyword(s):  
Thyroid Cancer ◽  
Distant Metastasis ◽  
Differentiated Thyroid Cancer ◽  
Cancer Metastasis ◽  
Treatment Protocol ◽  
Neck Of Femur ◽  
Thyroid Cancers ◽  
Well Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Histopathology Exam

Introduction The rates of thyroid cancers are on a rise, especially well-differentiated thyroid cancers. This could be partly due to newer diagnostic modalities, like high-resolution ultrasound, that can pick up smaller lesions. Differentiated thyroid cancers with distant metastases are not common, and even rarer is the initial presentation with complaints not related to the neck. Objectives The objective of this series was to study and report the unusual cases of patients with differentiated thyroid cancer with distant metastasis. There is a lack of data in the literature on these cases, and due to the rarity of such metastases, no definite treatment protocol has been defined. Methods A retrospective chart review of 1,200 cases of thyroid surgeries was performed. A total of 10 cases of well-differentiated thyroid cancer on the final histopathology exam that had initially presented with usual complaints to departments other than the Otolaryngology Department were identified. Results A total of 6 patients had papillary carcinoma, whereas 4 patients had follicular carcinoma on final the histopathology exam. Two patients presented with iliac crest lesions, 2 with vertebral lesions one each with parapharyngeal mass, supraclavicular mass, labia majora swelling and bleeding, lung, rib and neck of femur lesion. Conclusion There are still no specific guidelines on how to address these patients with differentiated thyroid cancer with distant metastasis (except for the cases of bone and lung lesions) and on which treatment should be offered in case of recurrence. More studies on the subject are required.

scholarly journals Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Naifa Lamki Busaidy ◽  
Maria E. Cabanillas
Keyword(s):  
Thyroid Cancer ◽  
Radioactive Iodine ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Cancers ◽  
Cancer Management ◽  
Oncogenic Mutations ◽  
Differentiated Thyroid Cancers ◽  
Disease Free ◽  
Metastatic Thyroid Cancer

Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine.

scholarly journals Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2775
Author(s):  
Assunta Melaccio ◽  
Lucia Ilaria Sgaramella ◽  
Alessandro Pasculli ◽  
Giovanna Di Meo ◽  
Angela Gurrado ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Cell Cycle Control ◽  
Current Status ◽  
Thyroid Cancers ◽  
Angiogenic Switch ◽  
Poorly Differentiated ◽  
Differentiated Thyroid Cancers ◽  
Disease Understanding

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.

scholarly journals Nelfinavir inhibits proliferation and induces DNA damage in thyroid cancer cells

2017 ◽  
Vol 24 (3) ◽  
pp. 147-156 ◽  
Author(s):  
Kirk Jensen ◽  
Athanasios Bikas ◽  
Aneeta Patel ◽  
Yevgeniya Kushchayeva ◽  
John Costello ◽  
...  
Keyword(s):  
Dna Damage ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Real Time ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Thyroid Cancers ◽  
Mesenchymal Transition ◽  
Thyroid Cancer Cells

The HIV protease inhibitor Nelfinavir (NFV) inhibits PI3K/AKT and MAPK/ERK signaling pathways, emerging targets in thyroid cancers. We examined the effects of NFV on cancer cells that derived from follicular (FTC), papillary (PTC) and anaplastic (ATC) thyroid cancers. NFV (1–20 µM) was tested in FTC133, BCPAP and SW1736 cell lines. The effects of NFV on cell proliferation were determined in vitro using real-time microscopy and by flow cytometry. DNA damage, apoptotic cell death and expression of molecular markers of epithelial–mesenchymal transition (EMT) were determined by Western blot and real-time PCR. Real-time imaging demonstrated that NFV (10 µM) increased the time required for the cell passage through the phases of cell cycle and induced DNA fragmentation. Growth inhibitory effects of NFV were associated with the accumulation of cells in G0/G1 phase, downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). NFV also induced the expression of γH2AX and p53BP1 indicating DNA damage. Treatment with NFV (20 µM) resulted in caspase-3 cleavage in all examined cells. NFV (20 µM) decreased the levels of total and p-AKT in PTEN-deficient FTC133 cells. NFV had no significant effects on total ERK and p-ERK in BRAF-positive BCPAP and SW1736 cells. NFV had no effects on the expression of EMT markers (Twist, Vimentin, E- and N-Cadherin), but inhibited the migration and decreased the abilities of thyroid cancer cells to survive in non-adherent conditions. We conclude that NFV inhibits proliferation and induces DNA damage in thyroid cancer cell lines. Our in vitro data suggest that NFV has a potential to become a new thyroid cancer therapeutic agent.

scholarly journals Management of papillary and follicular (differentiated) thyroid carcinoma - an update

1970 ◽  
Vol 16 (2) ◽  
pp. 126-130
Author(s):  
Md Abdul Mobin Choudhury ◽  
Md Abdul Alim Shaikh
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Differentiated Thyroid Cancer ◽  
Radioiodine Therapy ◽  
Endemic Goiter ◽  
Follicular Carcinoma ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroid Cancers ◽  
Surgical Options ◽  
Definitive Management

Thyroid cancers are quite rare, accounting for only 1.5% of all cancers in adults and 3% of all cancers in children. Differentiated thyroid cancer comprises 95% of all thyroid cancers. Of all thyroid cancers 74-80% of cases are papillary cancers. Incidences of follicular carcinoma are higher in regions where incidence of endemic goiter is high. Surgery is the definitive management of thyroid cancer. There is agreement that patients with large, locally aggressive or metastatic differentiated thyroid cancer require total thyroidectomy but there is continuing disagreement on the most appropriate operation for 'low risk' differentiated thyroid cancer. Adjuvant treatments are thyroid hormone suppression and radioiodine therapy rather than chemotherapy and radiotherapy. Prognosis is generally excellent and is influenced by factors related to the patient, the disease and the therapy. This article reviews the basis of surgical treatment of differentiated thyroid cancer and assesses the evidences supporting the surgical options. Key words: Papillary Carcinoma; Follicular Carcinoma; Hemithyroidectomy; Total Thyroidectomy DOI: 10.3329/bjo.v16i2.6848Bangladesh J Otorhinolaryngol 2010; 16(2): 126-130

Sign in / Sign up

Export Citation Format

Share Document