Endocrinology and Metabolism

Review Articles

Thyroid
Tumor Cells and Cancer-Associated Fibroblasts: A Synergistic Crosstalk to Promote Thyroid Cancer: Laura Fozzatti, Sheue-yann Cheng; Endocrinol Metab. 2020;35(4):673-680. Published online November 9, 2020; DOI: https://doi.org/10.3803/EnM.2020.401

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Thyroid cancer is the most common endocrine malignancy. Although most thyroid cancer patients are successfully treated and have an excellent prognosis, a percentage of these patients will develop aggressive disease and, eventually, progress to anaplastic thyroid cancer. Since most patients with this type of aggressive thyroid carcinoma will die from the disease, new treatment strategies are urgently needed. Tumor cells live in a complex and dynamic tumor microenvironment composed of different types of stromal cells. Cancer-associated fibroblasts (CAFs) are one of the most important cell components in the tumor microenvironment of most solid tumors, including thyroid cancer. CAFs originate mainly from mesenchymal cells and resident fibroblasts that are activated and reprogrammed in response to paracrine factors and cytokines produced and released by tumor cells. Upon reprogramming, which is distinguished by the expression of different marker proteins, CAFs synthesize and secret soluble factors. The secretome of CAFs directly impacts different functions of tumor cells. This bi-directional interplay between CAFs and tumor cells within the tumor microenvironment ends up fostering tumor cancer progression. CAFs are therefore key regulators of tumor progression and represent an under-explored therapeutic target in thyroid cancer.

Citations

Citations to this article as recorded by

FAPi-Based Agents in Thyroid Cancer: A New Step towards Diagnosis and Therapy? A Systematic Review of the Literature
Priscilla Guglielmo, Pierpaolo Alongi, Lucia Baratto, Miriam Conte, Elisabetta Maria Abenavoli, Ambra Buschiazzo, Greta Celesti, Francesco Dondi, Rossella Filice, Joana Gorica, Lorenzo Jonghi-Lavarini, Riccardo Laudicella, Maria Librando, Flavia Linguanti
Cancers.2024; 16(4): 839. CrossRef
Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer
Ece Ozmen, Tevriz Dilan Demir, Gulnihal Ozcan
Frontiers in Molecular Biosciences.2024;[Epub] CrossRef
Co-cultivation of human granulosa cells with ovarian cancer cells leads to a significant increase in progesterone production
Detlef Pietrowski, Martina Grgic, Isabella Haslinger, Julian Marschalek, Christian Schneeberger
Archives of Gynecology and Obstetrics.2023; 307(5): 1593. CrossRef
Secretome of Stromal Cancer-Associated Fibroblasts (CAFs): Relevance in Cancer
Deepshikha Mishra, Debabrata Banerjee
Cells.2023; 12(4): 628. CrossRef
Head-to-Head Comparison of [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer
Sanjana Ballal, Madhav Prasad Yadav, Frank Roesch, Shobhana Raju, Swayamjeet Satapathy, Parvind Sheokand, Euy Sung Moon, Marcel Martin, Shipra Awarwal, Madhavi Tripathi, Chandrasekhar Bal
Thyroid®.2023; 33(8): 974. CrossRef
Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers
Sanjana Ballal, Madhav P. Yadav, Frank Roesch, Swayamjeet Satapathy, Euy Sung Moon, Marcel Martin, Nicky Wakade, Parvind Sheokand, Madhavi Tripathi, Kunal R. Chandekar, Shipra Agarwal, Ranjit Kumar Sahoo, Sameer Rastogi, Chandrasekhar Bal
European Journal of Nuclear Medicine and Molecular Imaging.2023; 51(1): 233. CrossRef
Identifying the cancer-associated fibroblast signature to predict the prognosis and immunotherapy response in patients with lung squamous cell carcinoma
Yinhui Zhu, Yingqun Zhu, Sirui Chen, Qian Cai
Computer Methods in Biomechanics and Biomedical Engineering.2023; : 1. CrossRef
Roles and new Insights of Macrophages in the Tumor Microenvironment of Thyroid Cancer
Qi Liu, Wei Sun, Hao Zhang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Rab22a Promotes Epithelial-Mesenchymal Transition in Papillary Thyroid Carcinoma by Activating PI3K/AKT/mTOR Signaling Pathway
Xue Luo, Jinping Wang, Jinxi Lu, Xi Wang, Yuan Miao, Qingchang Li, Xiaoman Li, Liang Wang, Yong Xin Ma
BioMed Research International.2022; 2022: 1. CrossRef
Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling
Rocío del Carmen Bravo-Miana, María Florencia Soler, Danilo Guillermo Ceschin, Félix Royo, Dana María Negretti-Borga, Mikel Azkargorta, Félix Elortza, María del Mar Montesinos, Claudia Gabriela Pellizas, Juan Manuel Falcón-Pérez, Ana Carolina Donadio
European Journal of Cell Biology.2022; 101(3): 151254. CrossRef
The clinical significance of thyroid hormone-responsive in thyroid carcinoma and its potential regulatory pathway
Zhen-xing Yu, Cheng Xiang, Sheng-gui Xu, Yang-ping Zhang
Medicine.2022; 101(31): e29972. CrossRef
Thyroid Cancer and Fibroblasts
Angelica Avagliano, Giuseppe Fiume, Claudio Bellevicine, Giancarlo Troncone, Alessandro Venuta, Vittoria Acampora, Sabrina De Lella, Maria Rosaria Ruocco, Stefania Masone, Nunzio Velotti, Pietro Carotenuto, Massimo Mallardo, Carmen Caiazza, Stefania Monta
Cancers.2022; 14(17): 4172. CrossRef
TIM3 Expression in Anaplastic-Thyroid-Cancer-Infiltrating Macrophages: An Emerging Immunotherapeutic Target
Luz Maria Palacios, Victoria Peyret, María Estefania Viano, Romina Celeste Geysels, Yair Aron Chocobar, Ximena Volpini, Claudia Gabriela Pellizas, Juan Pablo Nicola, Claudia Cristina Motran, María Cecilia Rodriguez-Galan, Laura Fozzatti
Biology.2022; 11(11): 1609. CrossRef
Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma
Zhao-Shan Niu, Wen-Hong Wang, Xiao-Jun Niu
World Journal of Gastroenterology.2022; 28(46): 6433. CrossRef
Recent advances in regenerative medicine strategies for cancer treatment
Vahid Mansouri, Nima Beheshtizadeh, Maliheh Gharibshahian, Leila Sabouri, Mohammad Varzandeh, Nima Rezaei
Biomedicine & Pharmacotherapy.2021; 141: 111875. CrossRef
Secreted Factors by Anaplastic Thyroid Cancer Cells Induce Tumor-Promoting M2-like Macrophage Polarization through a TIM3-Dependent Mechanism
Cinthia Carolina Stempin, Romina Celeste Geysels, Sunmi Park, Luz Maria Palacios, Ximena Volpini, Claudia Cristina Motran, Eva Virginia Acosta Rodríguez, Juan Pablo Nicola, Sheue-yann Cheng, Claudia Gabriela Pellizas, Laura Fozzatti
Cancers.2021; 13(19): 4821. CrossRef
Novel Fibroblast Activation Protein Inhibitor-Based Targeted Theranostics for Radioiodine-Refractory Differentiated Thyroid Cancer Patients: A Pilot Study
Sanjana Ballal, Madhav Prasad Yadav, Euy Sung Moon, Frank Roesch, Samta Kumari, Shipra Agarwal, Madhavi Tripathi, Ranjit Kumar Sahoo, Bharadwaj Srinivas Mangu, Avinash Tupalli, Chandrasekhar Bal
Thyroid.2021;[Epub] CrossRef
Emerging Biomarkers in Thyroid Practice and Research
Shipra Agarwal, Andrey Bychkov, Chan-Kwon Jung
Cancers.2021; 14(1): 204. CrossRef

Thyroid
Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers: Seong-Keun Yoo, Young Shin Song, Young Joo Park, Jeong-Sun Seo; Endocrinol Metab. 2020;35(1):44-54. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.44

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Abstract PDF PubReader ePub

Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

Citations

Citations to this article as recorded by

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma
Peter Y.F. Zeng, Stephenie D. Prokopec, Stephen Y. Lai, Nicole Pinto, Michelle A. Chan-Seng-Yue, Roderick Clifton-Bligh, Michelle D. Williams, Christopher J. Howlett, Paul Plantinga, Matthew J. Cecchini, Alfred K. Lam, Iram Siddiqui, Jianxin Wang, Ren X.
Cell Reports.2024; 43(3): 113826. CrossRef
Comparative study between poorly differentiated thyroid cancer and anaplastic thyroid cancer: real-world pathological distribution, death attribution, and prognostic factor estimation
Kun Zhang, Xinyi Wang, Tao Wei, Zhihui Li, Jingqiang Zhu, Ya-Wen Chen
Frontiers in Endocrinology.2024;[Epub] CrossRef
Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer – Real-World Outcomes From UK Centres
C. Lorimer, L. Cheng, R. Chandler, K. Garcez, V. Gill, K. Graham, W. Grant, S. Sardo Infirri, J. Wadsley, L. Wall, N. Webber, K.H. Wong, K. Newbold
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MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions
E. Macerola, A. M. Poma, P. Vignali, A. Proietti, L. Torregrossa, C. Ugolini, A. Basolo, A. Matrone, R. Elisei, F. Santini, F. Basolo
Journal of Endocrinological Investigation.2023; 46(8): 1651. CrossRef
RBX1 regulates PKM alternative splicing to facilitate anaplastic thyroid carcinoma metastasis and aerobic glycolysis by destroying the SMAR1/HDAC6 complex
Debin Xu, Jichun Yu, Yuting Yang, Yunyan Du, Hongcheng Lu, Shouhua Zhang, Qian Feng, Yi Yu, Liang Hao, Jun Shao, Leifeng Chen
Cell & Bioscience.2023;[Epub] CrossRef
Multi-Omics and Management of Follicular Carcinoma of the Thyroid
Thifhelimbilu Emmanuel Luvhengo, Ifongo Bombil, Arian Mokhtari, Maeyane Stephens Moeng, Demetra Demetriou, Claire Sanders, Zodwa Dlamini
Biomedicines.2023; 11(4): 1217. CrossRef
Genomic landscape of anaplastic thyroid cancer and implications on therapy
Leslie Cheng, Kate Newbold
Current Opinion in Endocrine and Metabolic Research.2023; 30: 100458. CrossRef
Modeling the tumor microenvironment of anaplastic thyroid cancer: an orthotopic tumor model in C57BL/6 mice
Zhen Xu, Hyo Shik Shin, Yoo Hyung Kim, Seong Yun Ha, Jae-Kyung Won, Su-jin Kim, Young Joo Park, Sareh Parangi, Sun Wook Cho, Kyu Eun Lee
Frontiers in Immunology.2023;[Epub] CrossRef
Characterization of the genomic alterations in poorly differentiated thyroid cancer
Yeeun Lee, SeongRyeol Moon, Jae Yeon Seok, Joon-Hyop Lee, Seungyoon Nam, Yoo Seung Chung
Scientific Reports.2023;[Epub] CrossRef
Genetica del carcinoma anaplastico della tiroide
Teresa Ramone, Chiara Mulè, Cristina Romei, Raffaele Ciampi, Eleonora Molinaro, Rossella Elisei
L'Endocrinologo.2022; 23(2): 208. CrossRef
Tissue and circulating PD-L2: moving from health and immune-mediated diseases to head and neck oncology
Elena Muraro, Rebecca Romanò, Giuseppe Fanetti, Emanuela Vaccher, Irene Turturici, Valentina Lupato, Fabio Biagio La Torre, Jerry Polesel, Elisabetta Fratta, Vittorio Giacomarra, Giovanni Franchin, Agostino Steffan, Michele Spina, Salvatore Alfieri
Critical Reviews in Oncology/Hematology.2022; 175: 103707. CrossRef
Recent Improvements in the Treatment of High-Risk Thyroid Cancer
Eun Kyung Lee
Korean Society for Head and Neck Oncology.2022; 38(1): 1. CrossRef
Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Cytotoxicity in Anaplastic Thyroid Cancer in Female Mice
Cole D Davidson, Jennifer A Tomczak, Eyal Amiel, Frances E Carr
Endocrinology.2022;[Epub] CrossRef
Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis
Hao Zhao, Chun-Hao Liu, Yue Cao, Li-Yang Zhang, Ya Zhao, Yue-Wu Liu, Hong-Feng Liu, Yan-Song Lin, Xiao-Yi Li
Frontiers in Oncology.2022;[Epub] CrossRef
2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer
Keith C. Bible, Electron Kebebew, James Brierley, Juan P. Brito, Maria E. Cabanillas, Thomas J. Clark, Antonio Di Cristofano, Robert Foote, Thomas Giordano, Jan Kasperbauer, Kate Newbold, Yuri E. Nikiforov, Gregory Randolph, M. Sara Rosenthal, Anna M. Saw
Thyroid.2021; 31(3): 337. CrossRef
Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine
Antonio Ieni, Roberto Vita, Cristina Pizzimenti, Salvatore Benvenga, Giovanni Tuccari
Journal of Personalized Medicine.2021; 11(5): 333. CrossRef
The Role of Altered Mitochondrial Metabolism in Thyroid Cancer Development and Mitochondria-Targeted Thyroid Cancer Treatment
Siarhei A. Dabravolski, Nikita G. Nikiforov, Alexander D. Zhuravlev, Nikolay A. Orekhov, Liudmila M. Mikhaleva, Alexander N. Orekhov
International Journal of Molecular Sciences.2021; 23(1): 460. CrossRef
Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E
Young Shin Song, Young Joo Park
Endocrinology and Metabolism.2020; 35(3): 515. CrossRef

Case Report

A Case of Primary Parathyroid Carcinoma with full-brown Symptom.: Chang Soo Ryu, Deok Ki Kim, Kee Hyun Park, Shi Gyeong Seong, Dong Ho Kim, Sang Min Woo, In Sung Cho; J Korean Endocr Soc. 1996;11(2):221-226. Published online November 7, 2019

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Abstract PDF: Primary hyperparathyroicism is a state of hypersecretion of PTH by the parathyroid. The etiology has not been established. The three possible etiologies of piimary hyperparathyroidism and incidences are adencena(83%), hyperplasia(15%), and carcinoma(1~2%). Parathyroid carcinoma usually presents in the fourth decades. The hallmark preoperative signs are hypercalcemia(serum calcium 15mg/dl). Palpable neck mass and bane and renal disease. Patients may present with multiple signs and syrnptoms, including recurrent nephrolithiasis, peptic ulcers, mental change, less frequently, extensive bone resorption. However, with greater awareness of the disease and wider use of screening tests, including blood calcium determinations, the diagnosis is frequently made in patients who have no symptoms and minimal, if any, signs of the disease ather than hypercalcemia and elevated levels of parathyroid Hormone. An 38-years-old woman was admitted to the hospital due to pain on the left knee joint. We experienced full-brown symptom pertaining to hyperpara- thyroidism. Thus we report a case herein and also discuss clinical anifestation, histologic features and treatment.

Original Article

Clinical Significance of Routine Measurement of Serum Calcitonin in Korean Patients with Thyroid Nodules as a Screening test of Sporadic Thyroid Medullary Carcinoma.: Young Kee Shong, Cheol Soo Choi, Hye Young Park, Bo Youn Cho; J Korean Endocr Soc. 1996;11(1):11-17. Published online November 7, 2019

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Abstract PDF: Background
: It is not easy to diagnose sporadic medullary thyroid carcinoma(MTC) before surgery and this might lead the patient reoperation and/or lowered chance of definite cure. Methods : The prevalence of sporadic MTC in Korean was studied in patients with thyroid nodules. A prospective study of 1048 consecutive patients with thyroid nodules was performed. In all patients, measurements of basal serum calcitonin, thyroid hormones, TSH, anti-thyroglobulin antibody and anti-thyroperoxidase antibody were undertaken along with technetium-99m thyroid scintigraphy and fine needle aspiration cytology. In patients with elevated basal calcitonin levels, calcium stimulated calcitonin level was determined. Results: Two patient had markedly elevated calcitonin levels(over 3,200 pg/mL and 1,763 pg/ mL) and another one slightly elevated calcitoni#n(71.9 pg/mL). Fine needle aspiration cytology was suggestive of MTC in one and nodular hyperplasia in the other two. They underwent surgery and histological examination revealed MTC in those two with markedly elevated calcitonin levels. The patient with slightly elevated calcitonin, who was on the maintenance hemodialysis due to chronic renal failure, had nodular hyperplasia. Conclusion: MTC was found in 0.19% of patients with thyroid nodules, which was not different with the previously reported prevalence in Europe. Routine measurements of serum calcitonin might be of value to detect sporadic MTC; however, the cost-effectiveness of routine measurement of serum calcitonin is not clear, considering the relatively low prevalence of MTC in Koreans.

Case Report

A Case of Polyglandular Autoimmune Syndrome.: In Pyo Jun, Suck Hwan Lim, Won Hyep Bae, Seung Jun Kim, Youn Ho Lee, Sun Ho Kim, Jung Kyu Lim, Jin Duk Hur; J Korean Endocr Soc. 1994;10(2):142-147. Published online November 6, 2019

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Abstract PDF: Polyglandular autoimmune(PGA) syndrome designates the dysfunction of endocrine and nonendocrine system involving two or more glands on the basis of autoimmunity. There are three types of PGA syndrome and their pathogenesis is still not completely understood. A 27-year-old woman developed polyglandular autoimmune syndrome manifesting insulin-dependent diabetes mellitus, myasthenia gravis and Graves' disease associated papillary thyroid carcinoma. The thyroid antimicrosomal antibody and antiacetylcholine receptor antibody were positive. Her HLA serotype was A2, A11, A62, B60, CW3, CW4, DR4, DR9.We report here a case of polyglandular autoimmune syndrome, type III manifesting insulin-dependent diabetes mellitus, myasthenia gravis and Graves' disease associated with papillary thyroid carcinoma.

Original Articles

Thyroid
^99mTc-Pertechnetate Scintigraphy Predicts Successful Postoperative Ablation in Differentiated Thyroid Carcinoma Patients Treated with Low Radioiodine Activities: Luca Giovanella, Gaetano Paone, Teresa Ruberto, Luca Ceriani, Pierpaolo Trimboli; Endocrinol Metab. 2019;34(1):63-69. Published online February 15, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.63

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Background

Postoperative routine radioiodine (RAI) treatment is currently debated for patients with low-risk differentiated thyroid carcinoma (DTC) patients. If performed, a low ¹³¹I activity (i.e., 1 to 2 GBq) is recommended with the aim to ablate thyroid remnant and facilitate subsequent follow-up by thyroglobulin measurement. The purpose of this study was to evaluate the relationship between postsurgical technetium-99m (^99mTc)-pertechnetate scintigraphy and the rate of successful remnant ablation after low activity radioiodine ablation in patients with DTC.

Methods

Enrolled were 193 patients with low risk DTC who underwent total thyroidectomy and RAI ablation with a fixed 1.1 GBq activity of ¹³¹I. ^99mTc-pertechnetate scans were done and thyrotropin stimulated thyroglobulin (sTg) levels measured just before ablation. Ablation effectiveness was assessed 6 to 12 months later by sTg measurement, neck ultrasound and diagnostic whole body scan.

Results

A negative ^99mTc-perthecnetate scans was the best predictor of successful ablation (P<0.001) followed by preablative sTg levels <0.8 ng/mL (P=0.008) and ^99mTc-pertechnetate uptake rate values <0.9% (P=0.065). Neither sex nor age of the patient at the time of ablation or tumor histology and size showed a significant association with the rate of successful ablation.

Conclusion

The ^99mTc-pertechnetate scintigraphy is a simple and feasible tool to predict effectiveness of low activity ¹³¹I thyroid to ablate thyroid remnants in patients with DTC.

Citations

Citations to this article as recorded by

Combined clinical variable and radiomics of post-treatment total body scan for prediction of successful I-131 ablation in low-risk papillary thyroid carcinoma patients
Maythinee Chantadisai, Jirarot Wongwijitsook, Napat Ritlumlert, Yothin Rakvongthai
Scientific Reports.2024;[Epub] CrossRef
The prognostic value of post thyroidectomy Tc-99m pertechnetate thyroid scan in patients with differentiated thyroid cancer
L.M. Eloteify, Samy M. Algizawy, Aya K.M. Abdelnaim, Nesreen Mekkawy
Nuclear Medicine Communications.2023; 44(1): 38. CrossRef
Correlation analysis of I-131 SPECT/CT uptake parameters with the success ablation treatment of thyroid remnant in patients with low-intermediate-risk differentiated thyroid cancer
Qian Zhang, Weina Xu
Nuclear Medicine Communications.2022; 43(10): 1051. CrossRef
Clinical significance of extra-thyroid 99mTc-pertechnetate uptake before initial radioiodine therapy for differentiated thyroid carcinoma
Bin Long, Li-Fang Yao, Shou-Cong Chen, Jin Shui, Xue-Mei Ye, He-Qing Yi, Cen Lou
Journal of International Medical Research.2021; 49(5): 030006052110126. CrossRef
Thyroglobulin Changes are Highly Dependent on TSH in Low-risk DTC Patients not Treated with Radioiodine
Antonio Matrone, Alessio Faranda, Francesco Latrofa, Carla Gambale, Delio Stefani Donati, Eleonora Molinaro, Laura Agate, David Viola, Paolo Piaggi, Liborio Torregrossa, Fulvio Basolo, Rossella Elisei
The Journal of Clinical Endocrinology & Metabolism.2020; 105(8): e2845. CrossRef

Thyroid
Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways: Chan Ho Park, Se Eun Han, Il Seong Nam-Goong, Young Il Kim, Eun Sook Kim; Endocrinol Metab. 2018;33(1):121-132. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.121

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Background

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells.

Methods

The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis.

Results

The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt.

Conclusion

The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

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Endocrine Research
Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer: Dae In Kim, Eunyoung Kim, Young A Kim, Sun Wook Cho, Jung Ah Lim, Young Joo Park; Endocrinol Metab. 2016;31(3):469-475. Published online August 2, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.469

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Background

Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment.

Methods

Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups.

Results

The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013).

Conclusion

Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.

Citations

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IL2RA+VSIG4+ tumor-associated macrophage is a key subpopulation of the immunosuppressive microenvironment in anaplastic thyroid cancer
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Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2023; 1869(1): 166591. CrossRef
Crosstalk between Thyroid Carcinoma and Tumor-Correlated Immune Cells in the Tumor Microenvironment
Mingyuan Song, Qi Liu, Wei Sun, Hao Zhang
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Modeling the tumor microenvironment of anaplastic thyroid cancer: an orthotopic tumor model in C57BL/6 mice
Zhen Xu, Hyo Shik Shin, Yoo Hyung Kim, Seong Yun Ha, Jae-Kyung Won, Su-jin Kim, Young Joo Park, Sareh Parangi, Sun Wook Cho, Kyu Eun Lee
Frontiers in Immunology.2023;[Epub] CrossRef
Tumor-associated macrophages as a potential therapeutic target in thyroid cancers
Liya Zhu, Xiu Juan Li, Prakash Gangadaran, Xiuli Jing, Byeong-Cheol Ahn
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Functional Phenotypes of Peritoneal Macrophages Upon AMD3100 Treatment During Colitis-Associated Tumorigenesis
Shuai Wu, Weiwei Luo, Xing Wu, Zhaohua Shen, Xiaoyan Wang
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Integrated analysis of novel macrophage related signature in anaplastic thyroid cancer
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Secreted Factors by Anaplastic Thyroid Cancer Cells Induce Tumor-Promoting M2-like Macrophage Polarization through a TIM3-Dependent Mechanism
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Nobiletin Alone or in Combination with Cisplatin Decreases the Viability of Anaplastic Thyroid Cancer Cell Lines
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Low Lymphocyte-to-Monocyte Ratios Are Associated with Poor Overall Survival in Anaplastic Thyroid Carcinoma Patients
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Maria E. Cabanillas, Mark Zafereo, Michelle D. Williams, Renata Ferrarotto, Ramona Dadu, Neil Gross, G. Brandon Gunn, Heath Skinner, Gilbert Cote, Horiana B. Grosu, Priyanka Iyer, Naifa L. Busaidy
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Endocrine Research
Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo: Dmytro Starenki, Jong-In Park; Endocrinol Metab. 2015;30(4):593-603. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.593

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Background

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET) proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077), a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.

Methods

The effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53), and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.

Results

MKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.

Conclusion

MKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.

Citations

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Namgok Lecture 2014

Thyroid
A Closer Look at Papillary Thyroid Carcinoma: Won Bae Kim; Endocrinol Metab. 2015;30(1):1-6. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.1

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Recent surge of thyroid cancer, especially papillary thyroid carcinoma (PTC), ignited a debate on over-diagnosis of cancer. Such increase in incidence is a worldwide phenomenon, but it has been the most prominent in Korea. Although increased detection might have played a major role, some evidences suggest that true increase in incidence have also contributed to such phenomenon. PTC is a very common disease being the most common cancer in human. As the mortality due to PTC is relatively low, understanding pathophysiology of the disease and risk prediction in individual patient have particular importance for optimal management, but little has been known. I suggest a reason for such a commonality of PTC, and would like to describe my view on some aspects of PTC including unresolved issue on management based on our recent observations.

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Case Report

Thyroid
Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome: Hong Seok Choi, Min Joo Kim, Chae Ho Moon, Jong Ho Yoon, Ha Ra Ku, Geon Wook Kang, Im Il Na, Seung-Sook Lee, Byung-Chul Lee, Young Joo Park, Hong Il Kim, Yun Hyi Ku; Endocrinol Metab. 2014;29(1):96-100. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.96

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Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Citations

Citations to this article as recorded by

Medullary Thyroid Cancer with Ectopic Cushing's Syndrome: A Case Report and Systematic Review of Detailed Cases from the Literature
Andrea Corsello, Vittoria Ramunno, Pietro Locantore, Giovanni Pacini, Esther Diana Rossi, Francesco Torino, Alfredo Pontecorvi, Carmela De Crea, Rosa Maria Paragliola, Marco Raffaelli, Salvatore Maria Corsello
Thyroid.2022; 32(11): 1281. CrossRef
Mucosal Neuroma Cues for Endocrine Emergency Treatment
Gyu Gang Choi, Hwan Jin Lee, Hyo Jin Han, Young Beom Jeong, Heung Bum Lee, Ji Hyun Park
Endocrinology and Metabolism.2021; 36(6): 1312. CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef
Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome
Fabián Pitoia, Fernanda Bueno, Angélica Schmidt, Sabrina Lucas, Graciela Cross
Archives of Endocrinology and Metabolism.2015; 59(4): 343. CrossRef

Original Article

Predictive Factors for Incidental Contralateral Carcinoma in Patients with Unilateral Micropapillary Thyroid Carcinoma.: Jung Eun Huh, Sang Soo Kim, Ji Hyun Kang, Bo Gwang Choi, Byung Joo Lee, Jin Choon Lee, Yun Kyung Jeon, Bo Hyun Kim, Soo Geun Wang, Yong Ki Kim, In Joo Kim; Endocrinol Metab. 2012;27(3):194-199. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.194

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BACKGROUND
Whether thyroid lobectomy alone is a sufficient treatment for papillary thyroid microcarcinoma (PTMC) remains controversial. The aim of this study is to evaluate the predictive factors for incidental contralateral carcinoma in patients confirmed of unilateral PTMC preoperatively. METHODS: Between January 2007 and December 2009, 393 patients underwent thyroid surgery for unifocal and unilateral PTMC preoperatively at Pusan National University Hospital. A total thyroidectomy with central neck dissection was routinely performed for these patients during this study period. RESULTS: Among the 393 cases in the cohort, 77 patients (19.6%) had incidental PTMC in the contralateral lobe. In patients with incidental contralateral carcinoma, there was higher prevalence in extrathyroid extension, occult ipsilateral carcinoma, pathologic Hashimoto's thyroiditis, and central lymph node metastasis compared to those without contralateral carcinoma. The mean tumor size also increased in patients with contralateral carcinoma. Multivariate logistic regression showed that extrathyroid extension (P = 0.049), occult ipsilateral carcinoma (P < 0.001), pathologic Hashimoto's thyroiditis (P = 0.038), and central lymph node metastasis (P = 0.002) were predictive factors for incidental contralateral carcinoma. CONCLUSION: In conclusion, multifocality in the ipsilateral lobe, central lymph node metastasis, extrathyroid extension, and Hashimoto's thyroiditis is associated with the presence of contralateral carcinoma. Thus, if these factors are found by preoperative and/or postoperative evaluation, total thyroidectomy or completion thyroidectomy is necessary for the treatment of PTMC.

Citations

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Extent of surgery did not affect recurrence during 7‐years follow‐up in papillary thyroid cancer sized 1‐4 cm: Preliminary results
Min Joo Kim, Myung‐Chul Lee, Guk Haeng Lee, Hoon Sung Choi, Sun Wook Cho, Su‐jin Kim, Kyu Eun Lee, Young Joo Park, Do Joon Park
Clinical Endocrinology.2017; 87(1): 80. CrossRef

Case Reports

Four Cases of Malignant Pleural Effusion in Patients with Papillary Thyroid Carcinoma.: Min Ji Jeon, Ji Hye Yim, Eui Young Kim, Won Gu Kim, Tae Yong Kim, Won Bae Kim, Young Kee Shong; Endocrinol Metab. 2011;26(4):330-334. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.330

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Papillary thyroid carcinoma could be a rare cause of malignant pleural effusion. The development of malignant pleural effusion in patients with papillary thyroid cancer is an extremely adverse prognostic indicator. Here, we report four cases that showed development of malignant pleural effusion during the clinical course of the papillary thyroid carcinoma and consider the prognosis. In four patients, the median survival time after the development of malignant pleural effusion was only 17 months.

Citations

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Pleural fluid due to papillary thyroid cancer
Tomohiro Tamura, Toshihiro Shiozawa, Hiroaki Satoh, Koichi Kurishima, Katsunori Kagohashi, Norio Takayashiki, Nobuyuki Hizawa
Oncology Letters.2019;[Epub] CrossRef
Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma
Chisato Tomoda, Yuna Ogimi, Fumi Saito, Chie Masaki, Junko Akaishi, Kenichi Matsuzu, Akifumi Suzuki, Takashi Uruno, Keiko Ohkuwa, Hiroshi Shibuya, Wataru Kitagawa, Mitsuji Nagahama, Kiminori Sugino, Koichi Ito
Endocrine Journal.2016; 63(3): 257. CrossRef
A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report
Andrew Rosenstengel, Ee Mun Lim, Michael Millward, YC Gary Lee
Journal of Medical Case Reports.2013;[Epub] CrossRef

A Case of Subacute Thyroiditis Associated with Papillary Thyroid Carcinoma and Takayasu's Arteritis.: Dongwon Yi, Seung Hoon Baek, Seok Man Son, Yang Ho Kang; Endocrinol Metab. 2011;26(4):324-329. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.324

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Abstract PDF: Subacute thyroiditis is a self-limiting inflammation of the thyroid, presenting with painful thyroid swelling, thyrotoxicosis and low radioactive iodine uptake. The characteristic US findings for this disease are focal ill-defined hypoechoic areas in one lobe or diffuse hypoechoic areas in both lobes. Thyroid carcinomas should be included in the differential diagnosis for a lesion with focal hypoechoic areas and have been rarely reported to coexist with subacute thyroiditis. Takayasu's arteritis is an autoimmune disease that affects the aorta and its branches as well as pulmonary arteries. Subacute thyroiditis associated with Takayasu's arteritis is extremely rare, with only three cases being reported. We report here on the first case with the simultaneous diagnosis of subacute thyroiditis, papillary thyroid carcinoma and Takayasu's arteritis.

Original Article

Association between Serum Thyroid Stimulating Hormone Level and Papillary Thyroid Microcarcinoma in Korean Euthyroid Patients.: Hyun Sook Kim, Seung Joon Lee, Jung Kyu Park, Chang Ho Jo, Ho Sang Shon, Eui Dal Jung; Endocrinol Metab. 2011;26(4):297-302. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.297

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BACKGROUND
Thyroid cancer is a common disease and its prevalence is increasing. Recent reports have shown that an elevated thyrotropin (thyroid stimulating hormone, TSH) level is associated with thyroid cancer risk. However, the association between TSH level and thyroid cancer risk is not yet known for euthyroid patients diagnosed with papillary thyroid microcarcinoma (PTMC). METHODS: Our study included 425 patients who underwent thyroid surgery and were diagnosed with PTMC between 2008 and 2009. Control group patients were diagnosed with benign nodules < or = 1 cm in size by US-guided fine needle aspiration. Nodules with one or more suspected malignant-ultrasonographic feature(s) were excluded from this study. Patients who were not euthyroid or who took thyroid medication were also excluded. RESULTS: The mean age of all patients was 48.5 +/- 11.0 years and 88.8% were women. The mean age of those with PTMC was significantly lower than that of the control group. The mean TSH level was 1.78 +/- 0.93 mIU/L, and the mean free T4 level was 15.96 +/- 2.32 pmol/L. There was no difference in TSH level between the PTMC and control groups (1.77 +/- 0.93 mIU/L vs. 1.79 +/- 0.91 mIU/L, P = 0.829). After adjusting for age, TSH level was not correlated with tumor size (r = 0.02, P = 0.678) in the PTMC group. Moreover, the TSH level did not differ between patients with stage I and stage III-IV carcinoma (stage I, 1.77 +/- 0.95 mIU/L; stage III-IV, 1.79 +/- 0.87 mIU/L; P = 0.856). CONCLUSION: TSH levels are not elevated in euthyroid PTMC patients. Thus, further evaluation is needed before serum TSH can be used as a tumor marker for small nodules < or = 1 cm in size in euthyroid patients.

Citations

Citations to this article as recorded by

Evaluation of serum thyroid‐stimulating hormone as indicator for fine‐needle aspiration in patients with thyroid nodules
Ji Soo Choi, Chung Mo Nam, Eun‐Kyung Kim, Hee Jung Moon, Kyung Hwa Han, Jin Young Kwak
Head & Neck.2015; 37(4): 498. CrossRef

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