scholarly journals Pathological processes and therapeutic advances in radioiodide refractory thyroid cancer

2017 ◽  
Vol 59 (4) ◽  
pp. R141-R154 ◽  
Author(s):  
Marika H Tesselaar ◽  
Johannes W Smit ◽  
James Nagarajah ◽  
Romana T Netea-Maier ◽  
Theo S Plantinga
Keyword(s):  
Thyroid Cancer ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Medullary Thyroid Cancer ◽  
Disease Remission ◽  
Intracellular Signaling Pathways ◽  
Oncogenic Mutations ◽  
Diagnostics And Therapy ◽  
Disease Present

While in most patients with non-medullary thyroid cancer (TC), disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations inBRAF,TERTpromoter andTP53are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated. Also immune, metabolic, stemness and microRNA pathways have emerged as important determinants of TC dedifferentiation and RAI resistance. These signaling pathways have major clinical implications since their targeting could inhibit TC progression and could enable redifferentiation to restore RAI sensitivity. In this review, we discuss the current insights into the pathological processes conferring dedifferentiation and RAI resistance in TC and elaborate on novel advances in diagnostics and therapy to improve the clinical outcome of RAI-refractory TC patients.

scholarly journals Update on the Pathophysiological Role of Intracellular Signaling Pathways in Atherosclerotic Plaques and Ischemic Myocardium

2012 ◽  
Vol 7 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Fabrizio Montecucco ◽  
Vincent Braunersreuther ◽  
Giorgio Luciano Viviani ◽  
Sébastien Lenglet ◽  
François Mach
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Ischemic Myocardium ◽  
Atherosclerotic Plaques ◽  
Intracellular Signaling Pathways ◽  
Pathophysiological Role

scholarly journals Fine-tuned regulation of the PGC-1α gene transcription by different intracellular signaling pathways

2011 ◽  
Vol 300 (3) ◽  
pp. E500-E507 ◽  
Author(s):  
Tao Hong ◽  
Jie Ning ◽  
Xuefeng Yang ◽  
Hui-Yu Liu ◽  
Jianmin Han ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Insulin Response ◽  
P38 Map Kinase ◽  
Mapk Phosphorylation ◽  
Response Elements ◽  
Intracellular Signaling Pathways

It has previously been known that transcription of the PGC-1α gene can be either inhibited or stimulated by p38 MAP kinase (p38 MAPK). To determine whether p38 MAPK plays an inhibitory or stimulatory role in PGC-1α gene transcription, we further investigated the role of p38 MAPK in this study. Our results showed that the basal level of p38 MAPK phosphorylation was increased in gastrocnemius of mice under HFD and that p38 MAPK stimulated PGC-1α gene transcription in C2C12 myotubes. Our results also provided new mechanisms in myotubes that the p38 MAPK-induced PGC-1α gene transcription was mediated by CREB. In exploring the role of the Akt-dependent insulin signaling on PGC-1α gene transcription, we found that the basal Akt-dependent signaling was increased in gastrocnemius of mice under HFD. The p38 MAPK-induced PGC-1α gene transcription was prevented by insulin. Insulin suppression of PGC-1α gene transcription was neutralized by overexpression of the constitutively nuclear form of FoxO1. Finally, we located three insulin response elements (IREs) in the PGC-1α promoter, and mutations of these IREs abolish or blunt activity of the PGC-1α promoter. Together, our results show that transcription of the PGC-1α gene is balanced by different intracellular signaling pathways.

scholarly journals Role of α7 nicotinic receptor in the immune system and intracellular signaling pathways

2015 ◽  
Vol 3 ◽  
pp. 373-379 ◽  
Author(s):  
Robert Zdanowski ◽  
Małgorzata Krzyżowska ◽  
Dominika Ujazdowska ◽  
Aneta Lewicka ◽  
Sławomir Lewicki
Keyword(s):  
Immune System ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Nicotinic Receptor ◽  
Intracellular Signaling Pathways

Intracellular Signaling Pathways in Human Eosinophil Activation: Role of a β2 Integrin, αMβ2

1999 ◽  
Vol 120 (1) ◽  
pp. 51-53 ◽  
Author(s):  
Masahiko Kato ◽  
Hirokazu Kimura ◽  
Atsushi Tachibana ◽  
Youichi Motegi ◽  
Kenichi Tokuyama ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Human Eosinophil ◽  
Intracellular Signaling Pathways ◽  
Eosinophil Activation

scholarly journals How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Hugo Prazeres ◽  
Joana Torres ◽  
Fernando Rodrigues ◽  
Joana P. Couto ◽  
João Vinagre ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Age Of Onset ◽  
Point Mutations ◽  
Tyrosine Kinase Receptor ◽  
Intracellular Signaling Pathways ◽  
Activating Mutation

The significance ofRETin thyroid cancer comes from solid evidence that, when inherited, anRETactivating mutation primes C-cells to transform into medullary carcinomas. Moreover, environmental exposure to radiation also induces rearranged transforming RET “isoforms” that are found in papillary thyroid cancer. TheRETgene codes for a tyrosine kinase receptor that targets a diverse set of intracellular signaling pathways. The nature ofRETpoint mutations predicts differences in the mechanisms by which the receptor becomes activated and correlates with different forms of clinical presentation, age of onset, and biological aggressiveness. A number of RET-targeting Tyrosine Kinase Inhibitors (TKIs) are currently undergoing clinical trials to evaluate their effectiveness in the treatment of thyroid cancer, and it is conceivable that the RET genotype may also influence response to these compounds. The question that now emerges is whether, in the future, the rational for treatment of refractory thyroid cancer will be based on the management of an abnormal RET signal. In this paper we address the RET-targeting TKIs and review studies about the signaling properties of distinct RET mutants as a means to predict response and design combinatorial therapies for the soon to be available TKIs.

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