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Targeting thyroid cancer microenvironment and epigenetic signalling: new frontiers in cancer endocrinology basic and clinical research

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192403 Year: Pages: 131 DOI: 10.3389/978-2-88919-240-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine --- Oncology
Added to DOAB on : 2015-11-16 15:44:59
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This Research Topic is devoted to the understanding of molecular mechanisms of Human Thyroid Cancers. Original research describing functional studies of genetic mutations that shed novel insights into the aetiology and pathogenesis of these cancers, as well as angiogenesis and tumor microenvironment, mouse models studies that describe mechanisms or novel potential therapeutic targets and biomarkers for these endocrine cancers are presented. Scopes: The scope of this Research Topic was to cover the entire field of thyroid cancers: the main focus of this topic is translational, with an emphasis on bench to bedside research. Experimental, pre-clinical and clinical research addressing the following aspects is included in this Research Topic: 1) Investigation of specific molecular patterns of thyroid tumorigenesis, which could allow the development of new directions in the field of pharmacotherapy research; 2) Emphasis on animal studies (preclinical models of human anaplastic thyroid cancers) for the validation of biomarkers with the potential to lead to clinical trials, and studies of targetable mechanisms of oncogenesis, progression of these malignancies, tumor microenvironment and extracellular matrix, and metastatic disease; 3) Assessment of biomarkers to predict the potential response or resistance to drug treatment (targeted cancer therapies) or to guide the follow-up of treated patients; 4) Investigation of new laboratory molecular tests (e.g. molecular techniques and applications of thyroid fine-needle aspiration biopsy) to translate in the clinical practice; In summary, specific areas of interest include: thyroid cancer genetics; genome-wide analysis; clinical and translational research; orthotopic mouse models of metastatic thyroid carcinoma; tumor microenvironment; epigenetic; biological insights of personalized medicine; novel applications of bioinformatics; large scale molecular characterization of tumors; diagnostic or prognostic biomarkers; endocrine pathology studies; thyroid fine-needle aspiration.

Thyroid hormone in brain and brain cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197026 Year: Pages: 106 DOI: 10.3389/978-2-88919-702-6 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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Thyroid hormone signaling has been known for a long time to be required for proper neurodevelopment and the maintenance of cognitive functions in the adult brain. As thyroid hormone excess or deficiency is usually well handled by clinicians, research dedicated to the neural function of thyroid hormone, have not been a priority within the field. This is changing mainly for two reasons. First, new genetic diseases have been discovered, altering thyroid hormone signaling in brain (THRA, MCT8, SBP2), with neurodevelopmental consequences which are currently incurable. Second, there is a growing concern that exposition of the general population to environmental chemicals able to interfere with thyroid hormone signaling compromises children neurodevelopment or induces central disorders in adults. Finally thyroid hormone is acting directly on gene transcription, by binding nuclear receptors, and therefore is an interesting entry point to identify genetic programs controlling brain development and function. Reaching a broad understanding of the multiple processes involving thyroid hormone in brain is a tremendous task which will necessitate a multidisciplinary approach: animal genetics, molecular biology, brain imaging, developmental biology, genomics, etc... This topic will be the occasion to combine recent contributions in the field and to identify priorities for future investigations. Due to devastating consequences of congenital hypothyroidism, the neurodevelopmental consequences of altered thyroid hormone signaling have been extensively studied over the years. The discovery of new genetic diseases, the concern about the possible neurotoxicity of environmental thyroid hormone disruptors, recently renewed the interest for an important research field. This Ebook gathers reviews and original data from experts in various disciplines. It provides a broad view of ongoing research and outlines key issues for future investigation.

Homeostasis and Allostasis of Thyroid Function

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455706 Year: Pages: 107 DOI: 10.3389/978-2-88945-570-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2019-01-23 14:53:43
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The discovery of the negative feedback of thyroid hormones on pituitary thyroid-stimulating hormone (TSH) secretion, a classical endocrine feedback control system, has shaped diagnosis and treatment of thyroid disease for the last decades. Based on this concept, a unique diagnostic category of subclinical thyroid disorders was introduced, being defined exclusively by an abnormal TSH response in the presence of thyroid hormone concentrations within the reference range. Although this approach was able to deliver a conceptually straightforward disease definition problems surfaced in clinical practice as neither the diagnostic reference range nor the appropriate threshold for initiating substitution treatment are universally agreed upon for subclinical thyroid disorders. The situation is further aggravated by the so-called syndrome T, which comprises a substantial but heterogeneous group of L-T4 treated patients with hypothyroidism with reduced quality of life despite “normal” TSH values.

A limited understanding of the physiological relationships between TSH and thyroid hormones may be a main reason for clinical difficulties in dealing with the causes of syndrome T and tailoring substitution therapy for hypothyroid patients with subclinical thyroid disorders.

Feedback regulation has recently been shown to be much more complex than previously assumed. The concept of homeostatic control has also been extended to include the lesser known but equally important allostatic thyroid regulation.The latter aims at adaptive homeostasis or stability through changing setpoints and modulating structural parameters of feedback control, as may be appropriate to adapt to a vast array of conditions spanning from fetal life, aging, pregnancy, exercise, starvation, obesity, psychiatric disorders to the severe non-thyroidal illness syndrome.

A better understanding of homeostatic and allostatic mechanisms, which govern the behaviour of pituitary-thyroid feedback control, is on the horizon. This promises to improve the diagnostic utility of laboratory methods, laying the foundation for personalised methods to optimise dosage and modality of substitution therapy. The emerging new world of thyroid physiology is reflected on the side of clinical medicine in a new, relational paradigm for diagnosis and treatment.

Considerable progress has been made in this respect in the following key areas:

• the significance of complementary information processing structures within the feedback loop, in particular ultrashort feedback of TSH on its own secretion and the action of a TSH-T3 shunt unburdening the thyroid from T4 synthesis in imminent thyroid failure,

• the unravelling of spatio-temporal dynamics of hormone concentrations ranging from ultradian to circannual rhythms and including hysteresis effects,

• the emergence of “non-canonical” mechanisms of thyroid hormone signalling beyond transcriptional control of gene expression,

• the physiological actions of thyronine metabolites, which have been previously regarded as biologically inactive, such as thyronamines and iodothyroacetates,

• the characterisation of distinct patterns in the adaptive processes to stress and strain and their conclusive explanation through reactions to type 1 and type 2 allostatic load.

This collective volume contains the contributions to the Research Topic “Homeostasis and Allostasis of Thyroid Function”, which was originally published by the journal Frontiers in Endocrinology. Authored by an international team of experts from three continents ,the book provides a comprehensive overview on thyroid control from recent research in basic, computational and clinical thyroidology. Many aspects addressed here can be expected to stimulate future research. A more comprehensive view and better integration of in-vitro, in-silico and in-vivo investigations will be invaluable in paving the way to this new world of thyroidology.

Type I Interferon in Human Autoimmunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193400 Year: Pages: 87 DOI: 10.3389/978-2-88919-340-0 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:32
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The type I interferon system plays a critical role in host defense in health, and a growing body of literature suggests that type I interferon is a critical mediator of human autoimmune disease. Type I interferons function as a bridge between the innate and adaptive immune systems, and as such play an important role in setting thresholds for response against self antigens. Many investigators have focused on the role type I interferons play in autoimmune disease. This fascinating and rapidly growing body of literature encompasses many different autoimmune diseases, including systemic lupus erythematosus, type I diabetes, multiple sclerosis, and others. In this Research Topic, we provide a comprehensive overview of the various roles type I interferons play in autoimmune diseases, with a focus on human immunology.

Development of the Hypothalamus

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196340 Year: Pages: 264 DOI: 10.3389/978-2-88919-634-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-08-16 10:34:25
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The hypothalamus is the region of the brain in charge of the maintenance of the internal milieu of the organism. It is also essential to orchestrate reproductive, parental, aggressive-defensive, and other social behaviors, and for the expression of emotions. Due to the structural complexity of the hypothalamus, however, many basic aspects of its ontogenesis are still mysterious. Nowadays we assist to a renewal of interest spurred in part by the growing realization that prenatal and early postnatal influences on the hypothalamus could entail pathological conditions later in life. Intriguing questions for the future include: do early specification phenomena reflect on adult hypothalamic function and possibly on some kinds of behavior? Can early events like specification, migration or formation of nuclei influence adult hypothalamic function? A change in morphological paradigm, from earlier columnar interpretations to neuromeric ones, is taking place. Concepts long taken for granted start to be challenged in view of advances in developmental and comparative neurobiology, and notably also in the molecular characterization of hypothalamic structures. How should we understand the position of the hypothalamus in relation to other brain regions? Should we bundle it together with the thalamus, a functionally, genetically and developmentally very different structure? Does the classic concept of “diencephalon” make sense, or should the hypothalamus be separated? Does the preoptic area belong to the hypothalamus or the telencephalon? The answer to these questions in the context of recent causal molecular analysis will help to understand hypothalamic evolution and morphogenesis as well as its adult function and connectivity. In this Research Topic we have reviewed the fundamentals of hypothalamic ontogenesis and evolution, summarizing present-day knowledge, taking stock of the latest advances, and anticipating future challenges.

Keywords

Cadherins --- circadian --- Mammillary --- MCH --- Nkx2.4 --- Notch --- Oxytocin --- prosomeric --- Shh --- thyroid

The Association of Other Autoimmune Diseases in Patients With Thyroid Autoimmunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456253 Year: Pages: 118 DOI: 10.3389/978-2-88945-625-3 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2019-01-23 14:53:43
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Autoimmune thyroid diseases (AITD) are T cell-mediated organ-specific autoimmune disorders resulting from an immune dysregulation leading to a thyroid immune attack (Antonelli and Benvenga). Graves’ disease and Hashimoto’s thyroiditis are the two main clinical presentations of AITD, and their clinical hallmarks are thyrotoxicosis and hypothyroidism, respectively. In many cases, AITD may be associated in the same patient with other organ-specific autoimmune attacks (such as in the case of type II autoimmune polyglandular syndrome, or type I diabetes, etc). Furthermore, AITD and thyroid function abnormalities have been frequently described in patients with systemic rheumatologic autoimmune diseases. Conversely, patients affected with the above mentioned autoimmune disorders are more frequently affected by AITD.In this Research Topic, constituted by nineteen papers, we review and discuss new evidence about the association of other autoimmune diseases in patients with AITD. Among other organ-specific autoimmune disorders, the associations of AITD with chronic autoimmune gastritis (Cellini et al.), vitiligo (Baldini E et al.), lichen (Guarneri et al.), psoriasis (Ruffilli et al.), myasthenia gravis (Lopomo and Berrih-Aknin) and glomerulopathies (Santoro et al.) have been treated. Also the associations of AITD, in systemic autoimmune diseases have been treated (as Sjögren’s syndrome, Baldini C et al.; systemic sclerosis, Fallahi et al.; systemic lupus erythematosus, Ferrari et al.; Antiphospholipid syndrome, Versini; sarcoidosis, Fazzi et al.; the autoimmune/inflammatory syndrome induced by adjuvants, Watad et al.; rheumatoid arthritis, Bliddal et al.; Hepatitis C Virus and mixed cryoglobulinemia, Ferri et al.; and, psoriathic arthritis, Ruffilli et al.). Furthermore peculiar aspects associated with post partum thyroiditis have been reviewed too (Di Bari et al., Le Donne et al.).The exact pathogenetic mechanisms underlying the above reported associations are not completely known. It has been hypothesized that the influence of genetic (Coppedè), and environmental factors (Antonelli and Benvenga), could lead to the onset of autoimmune phenomena in different organs in the same subject, characterized by predominance of a Th1 immune pattern at the beginning, and in the active phase of these disorders.In conclusion, an association of other autoimmune diseases in patients with thyroid autoimmunity has been shown, and this Research Topic provides an extensive update of the literature, and suggests interesting points for new investigations.

Hormonal and Neuroendocrine Regulation of Energy Balance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198856 Year: Pages: 117 DOI: 10.3389/978-2-88919-885-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2016-01-19 14:05:46
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Alteration in adequate energy balance maintenance results in serious disturbances such as obesity and its related metabolic disorders. In Mammals, energy balance is homeostatically controlled through hormonal and neuroendocrine systems which cooperation is based on cross-talk between central and peripheral signals. The hypothalamus as well as peripheral hormones among which adipokines from adipose tissue and thyroid hormones play a crucial role in energy homeostasis. Unraveling the physiological, cellular and molecular mechanisms through which hormonal and neuroendocrine systems regulate energy balance has been a long-standing challenge in biology and is now more necessary when considering the world-wide increasing prevalence of obesity. Indeed, recognizing and understanding the biochemical and nutrient signaling pathways contributing to the nervous and endocrine integration of physiological mechanisms involved in the normal and/or abnormal regulation of energy balance is fundamental also to the development of new, effective, and targeted treatments for obesity. Recent studies have highlighted the role of hypothalamic pro-opiomelanocortin-expressing neurons in the regulation of energy homeostasis by controlling energy expenditure and food intake. This is accomplished through a precise balance of production and degradation of a-melanocyte-stimulating hormone, an anorexigenic neuropeptide which is degraded to an inactive form unable to inhibit food intake by the key enzyme prolyl carboxypeptidase (PRCP), thus suggesting that pharmacologic approaches targeting PRCP may provide a novel and effective option for the management of obesity and its associated metabolic disorders. Indeed, efforts have been made to generate potent, brain-penetrant PRCP inhibitors. Weight loss due to negative energy balance is a goal for obese subjects not always reachable by dietary caloric restriction or increased physical activity. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. Recently, it has been reported that thyroid hormone (TH)- derivatives such as 3,5-diiodothyronine and 3-iodothyronamine possess interesting biological activities, opening new perspectives in thyroid physiology and TH derivatives therapeutic usage. Moreover, several studies, focusing on the interaction between thyroid hormone (TH), the autonomic nervous system and the liver, revealed an important role for the hypothalamus in the differential effects of TH on autonomic outflow to peripheral organs controlling energy balance. This Research Topic aims to give a comprehensive and integrate view of the factors involved in the endocrine and neuroendocrine signaling in energy balance regulation to highlight their involvement into physiological processes and regulatory systems as well as their perturbation during pathological processes.

Neurological and psychiatric disorders in endocrine diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195893 Year: Pages: 97 DOI: 10.3389/978-2-88919-589-3 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Neurological and psychiatric disorders can occur in endocrine diseases either in the setting of the clinical manifestations of the same (i.e., hyper- or hyposecretion of hormones or peptides from the endocrine glands) or as events secondary to the pathogenetic mechanisms of the endocrinopathy (i.e., autommunity affecting endocrine glands and the brain). Also the medical or surgical treatment of the endocrine disease can sometimes determine the occurrence of neurological or psychiatric abnormalities. Moreover some genetic alterations can lead to syndromes affecting both the endocrine and the nervous system with a variety of possible manifestations. In the last couple of decades a number of associations between dysfunctions of the endocrine system and neurological or psychiatric manifestations have appeared and only in the minority of the cases this link has been fully elucidated. Often the neurological or psychiatric alterations still represent a relevant challenge for clinicians with regard to the management of the patients. The complexity of the topic and the limited availability of laboratory research models for the study of the endocrine system-nervous system cross-interaction are making the scientific progresses intricate and, sometimes, slow. A dedicated focus to such broad and often still obscure topic might help and clarify the current state-of-the-art in the field and direct the goals of future research.

Current Knowledge in Thyroid Cancer — From Bench to Bedside

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ISBN: 9783038424765 9783038424772 Year: Pages: VIII, 212 DOI: 10.3390/books978-3-03842-477-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-08-11 11:32:17
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In recent years, studies in the field of thyroid cancer have been performed in order to identify and verify thyroid specific biomarkers, as well as cancer-specific changes in gene expression patterns and alterations of the protein content. Furthermore, new drugs, small molecules and antibodies were developed and tested in vitro and in vivo. Trials investigated the ratio between therapeutic and adverse effects. Tyrosine kinase inhibitors (TKI) have become a new therapeutic option of both differentiated thyroid cancer and medullary thyroid cancer. In the last few years, new substances for targeted systemic therapy have been approved after their efficacy was demonstrated in Phase III trials. Most of them show a moderate response. However, adverse effects are common. TKI are used in patients with advanced metastatic thyroid cancer that is radioiodine (RAI)-refractory.In this Special Issue, original studies on the pathophysiology, diagnosis, and therapy of thyroid cancer, including genetics, proteomics, metabolomics, molecular and cell biology, will be published. It will also cover reports on patients, providing novel mechanistic insights into the underlying pathogenesis or new aspects that may impact clinical therapy, and recent study results in order to review the current status of new therapy options in thyroid cancer.

Induction of Central Nervous System Disease by the Adaptive Immune Response

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453474 Year: Pages: 141 DOI: 10.3389/978-2-88945-347-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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Over the last years it has become evident that many neurological diseases of the central nervous system (CNS) are induced by a specific adaptive immune response directed against molecules expressed on CNS-resident cells. Well-recognized examples are anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis which is characterized by the presence of antibodies against neuron-expressed NMDAR, or neuromyelitis optica (NMO), induced by antibodies to astrocyte-expressed aquaporin-4. Many more examples exist, and antibodies, and T or/and B cells have increasingly been associated with CNS disease. Often the symptoms of these diseases have not been typically reported to have an immune aetiology. Beside classical neurological symptoms like ataxia, vision disturbance, and motor or sensory symptoms, these can include cognitive disturbances, behavioral abnormalities, or/and epileptic seizures. Although much has been learned regarding the pathophysiology of prototypic examples of these disorders, there are still major gaps in our understanding of their biology. This may be due to the fact that they are rare diseases, and their therapies are still very limited. This research topic includes contributions addressing the analysis of the adaptive immune response driving disease including target antigens, molecular epitope mapping, and factors involved in the disease pathogenesis such as complement activation cascades, genetic and genomic regulation, as well as environmental triggers. Diagnostic criteria and methods, and treatment are also discussed. The overall aim of the volume is to review progress in our pathophysiological understanding of immune-mediated CNS disorders in order to advance diagnostic and therapeutic approaches, and ultimately improve outcomes for patients.

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