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https://www.readbyqxmd.com/read/29142004/advances-in-the-management-of-men2
#1
Samuel Wells
Medullary thyroid carcinoma (MTC), a tumor derived from the neural crest, occurs either sporadically or as the dominant component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A and MEN2B. The discovery that mutations in the RET protooncogene cause hereditary MTC was of great importance, since it led to the development of novel methods of diagnosis and treatment. For example, the detection of a mutated RET allele in family members at risk for inheriting MEN2A or MEN2B signaled that they would develop MTC, and possibly other components of the syndromes...
November 15, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29141453/relationship-between-metabolic-syndrome-and-nodular-thyroid-diseases
#2
Seher Kir, Yusuf Aydin, Hulya Coskun
Nodular thyroid diseases are common in Turkey. Insulin resistance (IR) is considered as the most important component of metabolic syndrome (MetS), and it is thought to directly affect thyroid diseases, together with other components of MetS. The aim of this study was to evaluate potential factors associated with thyroid nodularity. This study was part of the prospective MELEN study. In total, randomly selected 2233 subjects were evaluated. A euthyroid subgroup of participants (n = 1432) was selected and 421 of them had MetS...
November 16, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29136407/phospholipase-d-inhibitors-reduce-human-prostate-cancer-cell-proliferation-and-colony-formation
#3
Amanda R Noble, Norman J Maitland, Daniel M Berney, Martin G Rumsby
BACKGROUND: Phospholipases D1 and D2 (PLD1/2) hydrolyse cell membrane glycerophospholipids to generate phosphatidic acid, a signalling lipid, which regulates cell growth and cancer progression through effects on mTOR and PKB/Akt. PLD expression and/or activity is raised in breast, colorectal, gastric, kidney and thyroid carcinomas but its role in prostate cancer (PCa), the major cancer of men in the western world, is unclear. METHODS: PLD1 protein expression in cultured PNT2C2, PNT1A, P4E6, LNCaP, PC3, PC3M, VCaP, 22RV1 cell lines and patient-derived PCa cells was analysed by western blotting...
November 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29133048/structural-optimization-and-structure-activity-relationship-studies-of-n-phenyl-7-8-dihydro-6h-pyrimido-5-4-b-1-4-oxazin-4-amine-derivatives-as-a-new-class-of-inhibitors-of-ret-and-its-drug-resistance-mutants
#4
Jiao Yang, Kai Chen, Guo Zhang, Qiu-Yuan Yang, Yue-Shan Li, Shen-Zhen Huang, Yan-Lin Wang, Wei Yang, Xiao-Juan Jiang, Heng-Xiu Yan, Jing-Qiang Zhu, Rong Xiang, You-Fu Luo, Wei-Min Li, Yu-Quan Wei, Lin-Li Li, Sheng-Yong Yang
The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants...
September 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29132997/thyroid-hormone-improves-insulin-signaling-and-reduces-the-activation-of-neurodegenerative-pathway-in-the-hippocampus-of-diabetic-adult-male-rats
#5
Fernanda Prieto-Almeida, Ana Carolina Panveloski-Costa, Fernanda Crunfli, Silvania da Silva Teixeira, Maria Tereza Nunes, Andréa da Silva Torrão
AIMS: Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system...
November 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/29113311/the-anti-apoptotic-bag3-protein-is-involved-in-braf-inhibitor-resistance-in-melanoma-cells
#6
Luana Guerriero, Giuseppe Palmieri, Margot De Marco, Antonio Cossu, Paolo Remondelli, Mario Capunzo, Maria Caterina Turco, Alessandra Rosati
BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29105496/a-helicobacter-pylori-associated-insulin-resistance-in-asymptomatic-sedentary-young-men-does-not-correlate-with-inflammatory-markers-and-urine-levels-of-8-iso-pgf2-%C3%AE-or-1-4-dihydroxynonane-mercapturic-acid
#7
Andriy Cherkas, Sergii Golota, Françoise Guéraud, Orest Abrahamovych, Christoph Pichler, Armen Nersesyan, Volodymyr Krupak, Vira Bugiichyk, Ostap Yatskevych, Mykhaylo Pliatsko, Peter Eckl, Siegfried Knasmüller
A potential contribution of H. pylori contamination to low-grade inflammation, oxidative stress (OS) and insulin resistance as well as correlations between these parameters in asymptomatic sedentary males was analysed. We enrolled 30 apparently healthy asymptomatic young subjects (18 H. pylori negative and 12 positive) and measured whole blood glucose, glycated haemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, TNF-alpha and comet assay...
November 6, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29101248/increased-circulating-interleukin-8-in-patients-with-resistance-to-thyroid-hormone-receptor-%C3%AE
#8
Anne H van der Spek, Olga V Surovtseva, Saskia Aan, Anton T J Tool, Annemarie van de Geer, Korcan Demir, Anja L M van Gucht, A S Paul van Trotsenburg, Timo K van den Berg, Eric Fliers, Anita Boelen
Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the predominant TR in these cells, has not been studied to date. Studies in TRα(0/0) mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα) and compared these results to healthy controls...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29094913/secondary-hypertension-discovering-the-underlying-cause
#9
Lesley Charles, Jean Triscott, Bonnie Dobbs
Most patients with hypertension have no clear etiology and are classified as having primary hypertension. However, 5% to 10% of these patients may have secondary hypertension, which indicates an underlying and potentially reversible cause. The prevalence and potential etiologies of secondary hypertension vary by age. The most common causes in children are renal parenchymal disease and coarctation of the aorta. In adults 65 years and older, atherosclerotic renal artery stenosis, renal failure, and hypothyroidism are common causes...
October 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/29083246/reduced-insulin-sensitivity-in-differentiated-thyroid-cancer-patients-with-suppressed-tsh
#10
Thaís Gomes De Melo, Aglecio Luiz Souza, Elizabeth Ficher, Arlete Maria Fernandes, Ligia Vera Montali Da Assumpção, Sarah Monte Alegre, Denise Engelbrecht Zantut-Wittmann
OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic...
October 30, 2017: Endocrine Research
https://www.readbyqxmd.com/read/29073114/pathogenesis-of-hypothyroidism-induced-nafld-is-driven-by-intra-and-extrahepatic-mechanisms
#11
Giuseppe Ferrandino, Rachel R Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J Perry, Rebecca Cardone, Richard G Kibbey, Gerald I Shulman, Vishwa Deep Dixit, Nancy Carrasco
Hypothyroidism, a metabolic disease characterized by low thyroid hormone (TH) and high thyroid-stimulating hormone (TSH) levels in the serum, is strongly associated with nonalcoholic fatty liver disease (NAFLD). Hypothyroidism-induced NAFLD has generally been attributed to reduced TH signaling in the liver with a consequent decrease in lipid utilization. Here, we found that mildly hypothyroid mice develop NAFLD without down-regulation of hepatic TH signaling or decreased hepatic lipid utilization. NAFLD was induced by impaired suppression of adipose tissue lipolysis due to decreased insulin secretion and to a reduced response of adipose tissue itself to insulin...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29062583/the-end-diastolic-velocity-of-thyroid-arteries-is-strongly-correlated-with-the-peak-systolic-velocity-and-gland-volume-in-patients-with-autoimmune-thyroiditis
#12
Danilo Bianchini Höfling, Suemi Marui, Carlos Alberto Buchpiguel, Giovanni Guido Cerri, Maria Cristina Chammas
BACKGROUND: The end-diastolic velocity (EDV) of thyroid arteries reflects peripheral blood flow resistance. OBJECTIVE: The aim was to evaluate EDV correlations with other Doppler sonography parameters and with clinical and biochemical variables in a sample of patients with hypothyroidism caused by chronic autoimmune thyroiditis (CAT). METHODS: A sample of 48 CAT hypothyroid patients receiving treatment with stable doses of levothyroxine was selected...
2017: Journal of Thyroid Research
https://www.readbyqxmd.com/read/29061379/comparative-effects-of-transforming-growth-factor-beta-isoforms-on-redox-metabolism-in-thyroid-cells
#13
Romina Oglio, Lisa Thomasz, Leonardo Salvarredi, Guillermo Juvenal, Mario Pisarev
INTRODUCTION: Transforming growth factor beta (TGF-β) regulates thyroid function and growth. However, tumoral thyroid cells became resistant to this factor as they undifferentiated. Little is known about the effects of TGF-β isoforms. We compared the role of redox metabolism in the response to TGF-β isoforms between non tumoral and tumoral thyroid cells. METHODOLOGY AND RESULTS: Differentiated rat thyroid cells (FRTL-5) and human thyroid follicular carcinoma cells (WRO) were treated with the three isoforms of TGF-β...
October 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29044514/ccdc6-the-identity-of-a-protein-known-to-be-partner-in-fusion
#14
REVIEW
Aniello Cerrato, Francesco Merolla, Francesco Morra, Angela Celetti
Coiled Coil Domain Containing 6 gene, CCDC6, was initially isolated as part of a tumorigenic DNA originated by the fusion of CCDC6 with the tyrosine kinase of RET receptor, following a paracentric inversion of chromosome 10. For a long time CCDC6 has been considered as an accidental partner of the RET protooncogene, providing the promoter and the first 101 aa necessary for the constitutive activation of the oncogenic Tyrosine Kinase (TK) RET in thyroid cells. With the advent of more refined diagnostic tools and bioinformatic algorithms, an exponential growth in fusion genes discoveries has allowed the identification of CCDC6 as partner of genes other than RET in different tumor types...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29042997/cd19-cd24-hi-cd38-hi-regulatory-b-cells-are-associated-with-insulin-resistance-in-type-i-hashimoto-s-thyroiditis-in-chinese-females
#15
Min Yang, Changji Du, Yinping Wang, Jun Liu
Hashimoto's thyroiditis (HT) is typically associated with insulin resistance. The aim of the present study was to investigate the role of regulatory B cells (Bregs) in insulin resistance in patients with HT. A total of 52 female patients with type I HT and 35 matched healthy volunteers were enrolled. Demographic and laboratorial data were collected. A 75 g oral glucose tolerance test was performed on each subject. Flow cytometry was performed to evaluate the levels of CD19(+)CD24(hi)CD38(hi) Bregs in peripheral blood...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29037214/thyroid-function-and-metabolic-syndrome-in-the-population-based-lifelines-cohort-study
#16
Bruce H R Wolffenbuttel, Hanneke J C M Wouters, Sandra N Slagter, Robert P van Waateringe, Anneke C Muller Kobold, Jana V van Vliet-Ostaptchouk, Thera P Links, Melanie M van der Klauw
BACKGROUND: The metabolic syndrome (MetS) is a combination of unfavourable health factors which includes abdominal obesity, dyslipidaemia, elevated blood pressure and impaired fasting glucose. Earlier studies have reported a relationship between thyroid function and some MetS components or suggested that serum free thyroxine (FT4) or free triiodothyronine (FT3) levels within the normal range were independently associated with insulin resistance. We assessed how thyroid function relates to MetS prevalence in a large population-based study...
October 16, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29033690/dual-egfr-and-braf-blockade-overcomes-resistance-to-vemurafenib-in-braf-mutated-thyroid-carcinoma-cells
#17
Tiziana Notarangelo, Lorenza Sisinni, Valentina Condelli, Matteo Landriscina
BACKGROUND: BRAF inhibitors are effective anticancer agents in BRAF-mutated melanomas. By contrast, evidences about sensitivity of thyroid carcinomas to BRAF inhibition are conflicting and it has been proposed that BRAF V600E thyroid carcinoma cells are less sensitive to BRAF inhibitors due to activation of parallel signaling pathways. This study evaluated the hypothesis that feedback activation of EGFR signaling counteracts the cytostatic activity of vemurafenib (PLX4032) in BRAF V600E thyroid carcinoma cells...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28990511/sunitinib-in-the-treatment-of-thyroid-cancer
#18
Ferrari Silvia Martinaa, Centanni Marco, Virili Camilla, Miccoli Mario, Ferrari Paola, Ruffilli Ilaria, Ragusa Francesca, Antonelli Alessandro, Fallahi Poupak
BACKGROUND: Sunitinib (SU11248) is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor (TKI), that inhibits receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), c-KIT, fms-related tyrosine kinase 3 (FLT3) and RET. The concurrent inhibition of these pathways reduces tumor vascularization and causes cancer cell apoptosis, inducing a tumor shrinkage. Sunitinib is approved for the treatment of imatinib-resistant gastrointestinal stromal tumor (GIST), renal carcinoma, and pancreatic neuroendocrine tumors...
October 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28988510/tyrosine-kinase-inhibitors-rechallenge-in-solid-tumors-a-review-of-literature-and-a-case-description-with-lenvatinib-in-thyroid-cancer
#19
Francesco Felicetti, Alice Nervo, Alessandro Piovesan, Rita Berardelli, Filippo Marchisio, Marco Gallo, Emanuela Arvat
In the last decade tyrosine kinase inhibitors (TKIs) have been employed for a wide range of hematological and solid tumors and today they represent a valid therapeutic option for different neoplasms. Among them, both sorafenib and lenvatinib were approved for the treatment of radioactive iodine (RAI) refractory differentiated thyroid carcinoma (DTC). Unfortunately, in some cases the efficacy of TKIs is limited by the onset of drug resistance after the initial response. Areas Covered: We report the case of a patient with a RAI refractory advanced DTC, treated with lenvatinib after surgery, multiple RAI administrations, traditional chemotherapy, and sorafenib...
October 9, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28984291/new-perspectives-for-targeting-raf-kinase-in-human-cancer
#20
REVIEW
Zoi Karoulia, Evripidis Gavathiotis, Poulikos I Poulikakos
The discovery that a subset of human tumours is dependent on mutationally deregulated BRAF kinase intensified the development of RAF inhibitors to be used as potential therapeutics. The US Food and Drug Administration (FDA)-approved second-generation RAF inhibitors vemurafenib and dabrafenib have elicited remarkable responses and improved survival of patients with BRAF-V600E/K melanoma, but their effectiveness is limited by resistance. Beyond melanoma, current clinical RAF inhibitors show modest efficacy when used for colorectal and thyroid BRAF-V600E tumours or for tumours harbouring BRAF alterations other than the V600 mutation...
November 2017: Nature Reviews. Cancer
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