Dataset Information

Update on Fundamental Mechanisms of Thyroid Cancer.

ABSTRACT: The incidence of thyroid cancer (TC) has increased worldwide over the past four decades. TC is divided into three main histological types: differentiated (papillary and follicular TC), undifferentiated (poorly differentiated and anaplastic TC), and medullary TC, arising from TC cells. This review discusses the molecular mechanisms associated to the pathogenesis of different types of TC and their clinical relevance. In the last years, progresses in the genetic characterization of TC have provided molecular markers for diagnosis, risk stratification, and treatment targets. Recently, papillary TC, the most frequent form of TC, has been reclassified into two molecular subtypes, named BRAF-like and RAS-like, associated to a different range of cancer risks. Similarly, the genetic characterization of follicular TC has been proposed to complement the new histopathological classification in order to estimate the prognosis. New analyses characterized a comprehensive molecular profile of medullary TC, raising the role of RET mutations. More recent evidences suggested that immune microenvironment associated to TC may play a critical role in tumor invasion, with potential immunotherapeutic implications in advanced and metastatic TC. Several types of ancillary approaches have been developed to improve the diagnostic value of fine needle aspiration biopsies in indeterminate thyroid nodules. Finally, liquid biopsy, as a non-invasive diagnostic tool for body fluid genotyping, brings a new prospective of disease and therapy monitoring. Despite all these novelties, much work remains to be done to fully understand the pathogenesis and biological behaviors of the different types of TC and to transfer this knowledge in clinical practice.

SUBMITTER: Prete A

PROVIDER: S-EPMC7082927 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Update on Fundamental Mechanisms of Thyroid Cancer.

Prete Alessandro A Borges de Souza Patricia P Censi Simona S Muzza Marina M Nucci Nicole N Sponziello Marialuisa M

Frontiers in endocrinology 20200313

The incidence of thyroid cancer (TC) has increased worldwide over the past four decades. TC is divided into three main histological types: differentiated (papillary and follicular TC), undifferentiated (poorly differentiated and anaplastic TC), and medullary TC, arising from TC cells. This review discusses the molecular mechanisms associated to the pathogenesis of different types of TC and their clinical relevance. In the last years, progresses in the genetic characterization of TC have provided ...[more]

PMID: 32231639

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Project description:The development of thyroid hormone (TH) analogues was prompted by the attempt to exploit the effects of TH on lipid metabolism, avoiding cardiac thyrotoxicosis. Analysis of the relative distribution of the α and β subtypes of nuclear TH receptors (TRα and TRβ) showed that TRα and TRβ are responsible for cardiac and metabolic responses, respectively. Therefore, analogues with TRβ selectivity were developed, and four different compounds have been used in clinical trials: GC-1 (sobetirome), KB-2115 (eprotirome), MB07344/VK2809, and MGL-3196 (resmetirom). Each of these compounds was able to reduce low-density lipoprotein cholesterol, but a phase 3 trial with eprotirome was interrupted because of a significant increase in liver enzymes and the contemporary report of cartilage side effects in animals. As a consequence, the other projects were terminated as well. However, in recent years, TRβ agonists have raised new interest for the treatment of nonalcoholic fatty liver disease (NAFLD). After obtaining excellent results in experimental models, clinical trials have been started with MGL-3196 and VK2809, and the initial reports are encouraging. Sobetirome turned out to be effective also in experimental models of demyelinating disease. Aside TRβ agonists, TH analogues include some TH metabolites that are biologically active on their own, and their synthetic analogues. 3,5,3'-triiodothyroacetic acid has already found clinical use in the treatment of some cases of TH resistance due to TRβ mutations, and interesting results have recently been reported in patients with the Allan-Herndon-Dudley syndrome, a rare disease caused by mutations in the TH transporter MCT8. 3,5-diiodothyronine (T2) has been used with success in rat models of dyslipidemia and NAFLD, but the outcome of a clinical trial with a synthetic T2 analogue was disappointing. 3-iodothyronamine (T1AM) is the last entry in the group of active TH metabolites. Promising results have been obtained in animal models of neurological injury induced by β-amyloid or by convulsive agents, but no clinical data are available so far.

Project description:Many governments have instructed the population to wear simple mouse-and-nose covers or surgical face masks to protect themselves from droplet infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public. However, the basic protection mechanisms and benefits of these masks remain controversial. Therefore, the aim of this work is to show from a fluid physics point of view under which circumstances these masks can protect against droplet infection. First of all, we show that the masks protect people in the surrounding area quite well, since the flow resistance of the face masks effectively prevents the spread of exhaled air, e.g. when breathing, speaking, singing, coughing and sneezing. Secondly, we provide visual evidence that typical household materials used by the population to make masks do not provide highly efficient protection against respirable particles and droplets with a diameter of 0.3-2 ?m as they pass through the materials largely unfiltered. According to our tests, only vacuum cleaner bags with fine dust filters show a comparable or even better filtering effect than commercial particle filtering FFP2/N95/KN95 half masks. Thirdly, we show that even simple mouse-and-nose covers made of good filter material cannot reliably protect against droplet infection in contaminated ambient air, since most of the air flows through gaps at the edge of the masks. Only a close-fitting, particle-filtering respirator offers good self-protection against droplet infection. Nevertheless, wearing simple homemade or surgical face masks in public is highly recommended if no particle filtrating respiratory mask is available. Firstly, because they protect against habitual contact of the face with the hands and thus serve as self-protection against contact infection. Secondly, because the flow resistance of the masks ensures that the air remains close to the head when breathing, speaking, singing, coughing and sneezing, thus protecting other people if they have sufficient distance from each other. However, if the distance rules cannot be observed and the risk of inhalation-based infection becomes high because many people in the vicinity are infectious and the air exchange rate is small, improved filtration efficiency masks are needed, to take full advantage of the three fundamental protective mechanisms these masks provide.

Dataset Information

Update on Fundamental Mechanisms of Thyroid Cancer.

Publications

Update on Fundamental Mechanisms of Thyroid Cancer.

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