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Thyroid resistance

Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
Anastasios Anyfantakis, Dimitrios Anyfantakis, Irene Vourliotaki
Resistance to thyroid hormone (RTH) is an extremely rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormone (TH). Most patients with RTH have mutations in the gene that encodes the β isoform of the receptor of thyroid hormone (THR-β gene). Mutant receptors are unable to activate or repress target genes. The majority of them are asymptomatic or rarely have hypo- or hyperthyroidism. RTH is suspected by the finding of persistent elevation of serum levels of free T3 (FT3) and free T4 (FT4) and nonsuppressed TSH...
2016: Case Reports in Endocrinology
Nghi C Nguyen, Muhammad Shah, Leonard J Appleman, Rahul Parikh, James M Mountz
Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC...
2016: International Journal of Molecular Imaging
Esra Özdil Demiryürek, Atilla Tekin, Engin Çakmak, Osman Temizkan, Oğuz Karamustafalıoğlu, Sibel Gökova, Enes Demiryürek
OBJECTIVE: The aim of this study was to investigate the relationship between anger, impulsiveness, and biochemical parameters (testosterone, insulin, insulin resistance) in women with polycystic ovary syndrome. STUDY DESIGN: We recruited 84 women diagnosed with polycystic ovary syndrome according to the Rotterdam diagnostic criteria. Psychiatric interviews were performed using the Structured Clinical Interview for DSM-IV Axis I Disorders. The Barratt Impulsiveness Scale and the State Trait Anger Expression Inventory were also administered to each participant...
October 6, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Chutintorn Sriphrapradang, Panudda Srichomkwun, Samuel Refetoff, Sunee Mamanasiri
We report a patient with resistance to thyroid hormone beta caused by a novel <i>THRB</i> gene mutation and coexisting pituitary microadenoma. A 41-year-old Thai woman presented with elevated serum thyroid hormone levels and non-suppressed TSH. MRI showed a 4x2-mm pituitary adenoma. Five of her relatives had similar thyroid tests abnormalities, but a sister had Graves' disease. TPO and TG antibodies were positive in all affected family members except for a 4.5 year-old. Lack of thyrotoxic symptoms and TSH suppression by T3, indicated incidentaloma rather than a TSH-secreting pituitary adenoma...
October 19, 2016: Thyroid: Official Journal of the American Thyroid Association
Marina Parra-Robert, Aida Orois, Josep Maria Augé, Irene Halperin, Xavier Filella, Rafael Molina
BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor caused by a malignant transformation in the parafollicular C-cells of the thyroid, where calcitonin (CT) is released. Nowadays the main tumor markers (TM) used in the diagnosis and follow-up of MTC patients are CT and carcinoembryonic antigen (CEA). Nonetheless, progastrin releasing peptide (proGRP) has been recently proposed as a TM useful in the MTC. Our aims were to investigate the release of proGRP in thyroid tumors, its role in the assessment of advanced MTC and its utility in the differential diagnosis between MTC and non-MTC thyroid tumors...
October 18, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Weibin Wang, Helen Kang, Yinu Zhao, Irene Min, Brian Wyrwas, Maureen Moore, Lisong Teng, Rasa Zarnegar, Xuejun Jiang, Thomas J Fahey
CONTEXT: The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anti-cancer therapy induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. OBJECTIVE: In this study, we investigate if autophagy is activated in vemurafenib treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
Alina Gavrila, Per-Olof Hasselgren, Allison Glasgow, Ashley N Doyle, Alice Lee, Peter Fox, Gautam Shiva, James V Hennessey, Gerald M Kolodny, Aaron M Cypess
BACKGROUND: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insight regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase...
October 17, 2016: Thyroid: Official Journal of the American Thyroid Association
Ana Kober Nogueira Leite, Marco Aurélio Vamondes Kulcsar, Beatriz de Godoi Cavalheiro, Evandro Sobroza de Mello, Venâncio Avancini F Alves, Claudio Roberto Cernea, Leandro Luongo Matos
OBJECTIVE: The purpose of the present study was to investigate the predictive factors for worse disease-specific survival in patients with pulmonary disease secondary to differentiated thyroid cancer. METHODS: This was a retrospective cohort study conducted over a 5-year period that included 54 patients with pulmonary disease secondary to DTC during the follow-up. Among these patients, 13 (24.1%) died from the disease. Dedifferentiation characteristics were identified at pathological examination of the metastatic disease (lymph node or distant metastases), and was defined as the abrupt transformation of a well-differentiated tumor into high grade morphology that lacks the original distinct histologic characteristics...
October 17, 2016: Endocrine Practice
Kento Kurata, Naoyoshi Onoda, Satoru Noda, Shinichiro Kashiwagi, Yuka Asano, Kosei Hirakawa, Masaichi Ohira
Anaplastic thyroid cancer (ATC) is a rare malignancy that progresses extremely aggressively and often results in dismal prognosis. We investigated the efficacy of inhibiting the activated RAS/RAF/MEK pathway in ATC cells aiming to clarify the mechanism of effect and resistance. Four human ATC cell lines (ACT-1, OCUT-2, OCUT-4 and OCUT-6) were used. OCUT-4 had a BRAF mutation. OCUT-2 had both BRAF and PI3KCA mutations. ACT-1 and OCUT-6 had wild-type BRAF and NRAS mutations. The effects of dabrafenib, a selective inhibitor of the BRAFV600E kinase, and trametinib, a reversible inhibitor of MEK activity, were investigated...
October 7, 2016: International Journal of Oncology
Tatiana Moro, Grant Tinsley, Antonino Bianco, Giuseppe Marcolin, Quirico Francesco Pacelli, Giuseppe Battaglia, Antonio Palma, Paulo Gentil, Marco Neri, Antonio Paoli
BACKGROUND: Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males...
October 13, 2016: Journal of Translational Medicine
Man-Li Guo, Xiao Zheng, Liu-Xue Yang, Ya-Li Qiu, Liang Cheng, Shao-Gang Ma
Resistance to thyroid hormone (RTH) coexisting with ectopic thyroid is rare. Here we report a case of RTH with ectopic thyroid. A ten-year-old girl had been misdiagnosed as congenital hypothyroidism and treated with levothyroxine since she was born. Ten-year follow-up showed that the elevated thyrotropin was never suppressed by levothyroxine and no signs indicating hyperthyroidism or hypothyroidism despite elevated FT3 and FT4 levels. Therefore the girl developed no defects in physical and cognitive development...
October 10, 2016: Archives of Endocrinology and Metabolism
Jana Ježková, Josef Marek
Adenomas which secrete thyrotropic hormone (thyrotropinomas) are rare and constitute less than 3 % of pituitary adenomas. In laboratory studies there is a typical elevation of thyroid hormones with nonsupressible TSH. In differential diagnostics it is necessary to distinguish above all the syndrome of resistance to thyroid hormones. Clinical symptoms are usually mild and correspond to symptoms of hyperthyroidism. Goiter is a common finding. In 80 % of cases thyrotropinomas are diagnosed in a stage of invasively growing macroadenoma...
2016: Vnitr̆ní Lékar̆ství
Vojtěch Hainer, Hana Zamrazilová, Irena Aldhoon Hainerová
Associations of both hypothyroidism and subclinical hypothyroidism with metabolic syndrome are well established. Nowadays, more attention has been paid to the role of thyroid hormones and thyrotropin (TSH) within the euthyroid range on the development of cardiometabolic health risks. The paper summarizes current knowledge related to the associations of lower free thyroxine (fT4) level and higher levels of both free triiodothyronine (fT3) and TSH with body adiposity, metabolic syndrome and insulin resistance in euthyroid subjects...
2016: Vnitr̆ní Lékar̆ství
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
Cinthia García-Luna, Paulina Soberanes-Chavez, Patricia de Gortari
Feeding patterns are important factors in obesity evolvement. Time-restricted feeding schedules (tRF) during resting phase change energy homeostasis regulation, disrupting the circadian release of metabolism-regulating hormones, such as leptin, insulin and corticosterone and promoting body weight gain. Thyroid (HPT) and adrenal (HPA) axes exhibit a circadian regulation and are involved in energy expenditure, thus studying their parameters in tRF paradigms will elucidate their role in energy homeostasis impairments under such conditions...
October 11, 2016: Journal of Endocrinology
Altaf Ali Naushad, Rajeev Philip, Viswanathan
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Alessandro D Genazzani
Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols...
September 16, 2016: Reproductive Biomedicine Online
Shu Meng, Hongyan Wu, Jing Wang, Qiyuan Qiu
The proto-oncogene protein RET is a receptor tyrosine kinase that plays an important role in the development and progress of various human cancers. Currently, targeting RET with small-molecule tyrosine kinase inhibitors (TKIs) has been established as promising therapeutic strategy for thyroid carcinoma (TC). However, two gatekeeper mutations V804M and V804L in RET kinase domain have been frequently observed to cause drug resistance during the targeted therapy, largely limiting the application of reversible TKIs in TC...
October 2016: Molecular Informatics
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