scholarly journals Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy

2020 ◽  
Vol 21 (14) ◽  
pp. 4951
Author(s):  
María San Román Gil ◽  
Javier Pozas ◽  
Javier Molina-Cerrillo ◽  
Joaquín Gómez ◽  
Héctor Pian ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Genetic Alterations ◽  
Point Of View ◽  
Adequate Treatment ◽  
Comprehensive Review ◽  
Tumor Characterization ◽  
Therapeutic Algorithm ◽  
Clinical Point

Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets. Within this promising and rapid changing scenario, current efforts are directed to improve tumor characterization for an accurate guidance in the therapeutic management. In this sense, it is strongly recommended to perform tissue genotyping to patients that are going to be considered for systemic therapy in order to select the adequate treatment, according to recent clinical trials data. Overall, the aim of this article is to provide a comprehensive review on the molecular biology of thyroid cancer focusing on the key role of tyrosine kinases. Additionally, from a clinical point of view, we provide a thorough perspective, current and future, in the treatment landscape of this tumor.

Molecular defects in thyroid carcinomas: Role of the RET oncogene in thyroid neoplastic transformation

1995 ◽  
Vol 133 (5) ◽  
pp. 513-522 ◽  
Author(s):  
Massimo Santoro ◽  
Michele Grieco ◽  
Rosa Marina Melillo ◽  
Alfredo Fusco ◽  
Giancarlo Vecchio
Keyword(s):  
Tyrosine Kinases ◽  
Point Mutations ◽  
Neoplastic Transformation ◽  
Thyroid Neoplasms ◽  
Genetic Alterations ◽  
Thyroid Carcinomas ◽  
Molecular Defects ◽  
Genetic And Environmental Factors ◽  
Definition Of

Santoro M, Grieco M, Melillo RM, Fusco A, Vecchio G. Molecular defects in thyroid carcinomas. Role of the RET oncogene in thyroid neoplastic transformation. Eur J Endocrinol 1995;133:513–22. ISSN 0804–4643 Tumors are believed to arise as a result of an accumulation of mutations in critical genes involved in the control of cell proliferation. Thyroid neoplasms represent a good model for studying the role of these mutations in epithelial cell multistep carcinogenesis because they comprise a broad spectrum of lesions with different degrees of malignancy. Recent reports have described the involvement of specific genetic alterations in different types of thyroid neoplasms. Papillary carcinomas are characterized by the activation of the receptor tyrosine kinases RET and TRK-A proto-oncogenes. Ras point mutations are frequently observed in tumors with follicular histology and a high prevalence of p53 point mutations have been found in anaplastic carcinomas. A definition of molecular defects characterizing thyroid tumors will be helpful in establishing sensitive and specific detection strategies and, in addition, to define genetic and environmental factors important for their pathogenesis. Giancarlo Vecchio, Dipartimento di Biologia e Patologia Cellulare e Molecolare "L, Califano", Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli "Federico II", via S Pansini 5, 80131 Napoli, Italy

scholarly journals Recent Advances in Molecular Diagnosis of Thyroid Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Ioannis Legakis ◽  
Konstantinos Syrigos
Keyword(s):  
Thyroid Cancer ◽  
Tumor Development ◽  
Disease Process ◽  
Genetic Alterations ◽  
Aberrant Methylation ◽  
Novel Treatments ◽  
Molecular Alterations ◽  
Molecular Events ◽  
Diagnosis Of Thyroid Cancer

Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. In particular, remarkable advances have occurred in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process.

scholarly journals Highly Prevalent Genetic Alterations in Receptor Tyrosine Kinases and Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase Pathways in Anaplastic and Follicular Thyroid Cancers

2008 ◽  
Vol 93 (8) ◽  
pp. 3106-3116 ◽  
Author(s):  
Zhi Liu ◽  
Peng Hou ◽  
Meiju Ji ◽  
Haixia Guan ◽  
Kimberly Studeman ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Genetic Basis ◽  
Receptor Tyrosine Kinases ◽  
Genetic Alterations ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Thyroid Cancers ◽  
Mapk Pathways ◽  
Phosphatidylinositol 3

Abstract Context: Genetic alterations in receptor tyrosine kinases (RTKs) and phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK pathways have not been fully defined in anaplastic and follicular thyroid cancers [anaplastic thyroid cancer (ATC), follicular thyroid cancer (FTC)]. Objective: The objective of the study was to explore a wide-range genetic basis for the involvement of these pathways in ATC. Design: We examined mutations and copy number gains of a large panel of genes in these pathways and corresponding phosphorylation of ERK (p-ERK) and Akt. Results: We found frequent copy gains of RTK genes, including EGFR, PDGFRα and -β, VEGFR1 and 2, KIT, and MET and in PIK3Ca, PIK3Cb, and PDK1 genes in the PI3K/Akt pathway. Mutations of Ras, PIK3Ca, PTEN, and BRAF genes and RET/PTC rearrangements were common, whereas mutations in PDK1, Akt1, Akt2, and RTK genes were uncommon in ATC. Overall, 46 of 48 ATC (95.8%) harbored at least one genetic alteration, and coexistence of two or more was seen in 37 of 48 ATC (77.1%). These genetic alterations were somewhat less common in FTC. Genetic alterations that could activate both the PI3K/Akt and MAPK pathways were found in 39 of 48 ATC (81.3%). RTK gene copy gains were preferentially associated with p-Akt, suggesting their dominant role in activating the PI3K/Akt pathway. The phosphorylation of Akt was far more common than p-ERK in FTC, and both were relatively common and often coexisted in ATC. Conclusions: Genetic alterations in the RTKs and PI3K/Akt and MAPK pathways are extremely prevalent in ATC and FTC, providing a strong genetic basis for an extensive role of these signaling pathways and the development of therapies targeting these pathways for ATC and FTC, particularly the former.

scholarly journals Bulgarian vocative within HPSG framework

2003 ◽  
Author(s):  
Petya N. Osenova ◽  
Kiril Iv. Simov
Keyword(s):  
Point Of View ◽  
Dialogue Systems ◽  
Adequate Treatment ◽  
Semantic Properties ◽  
Linguistic Phenomenon

Crosslinguistically vocatives are an underexplored linguistic phenomenon and in different languages they can be highly idiosyncratic and complex (Levinson, 1987, p.71). Therefore, the problem, which is discussed in this paper, is not a language-specific one, in spite of the fact that most of the languages have their own repositories for marking the role of the addressee in the communicative utterances. In our opinion this linguistic phenomenon needs its adequate treatment in HPSG because of three main reasons:  The vocative is supposed to be present on two levels: syntax and pragmatics. Therefore it needs more elaborate interpretation on the interface side, which, in HPSG, is more developed for morphology/syntax and syntax/semantics than syntax/pragmatics. Note that a challenge for the theory is the semantic weight of the vocatives with respect to the head sentence.  It will be useful for HPSG-oriented implementations, especially treebanks and dialogue systems.  On prosodic grounds the vocatives are often viewed as being 'side or extended parts' of the sentence and therefore - very close to the parenthetical constructions. From our point of view, both phenomena are pragmatic and hence, the treatment of vocative, presented here, could be generalized to cover other phenomena of pragmatic nature.  In our work the vocatives are viewed through the possibility of the integration/separation of their pragmatic, syntactic and semantic properties.

scholarly journals The Role of the NIS (SLC5A5) Gene in Papillary Thyroid Cancer: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Rafael Martins de Morais ◽  
Alaor Barra Sobrinho ◽  
Calliandra Maria de Souza Silva ◽  
Jamila Reis de Oliveira ◽  
Izabel Cristina Rodrigues da Silva ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Decisive Role ◽  
Genetic Alterations ◽  
Epigenetic Alterations ◽  
Papillary Thyroid ◽  
Transmembrane Glycoprotein ◽  
Cancer Pathogenesis ◽  
Nis Gene

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic and epigenetic alterations play a decisive role in the onset of several human neoplasms. Mutations and polymorphisms are two frequent genetic alterations. Located on chromosome 19 (19p13.11), the NIS SLC5A5 (solute carrier family 5 member 5) gene encodes a highly specialized and efficient 80–90 kDa transmembrane glycoprotein that mediates active transport of iodide from the bloodstream into the follicular cells. Given the highly significant role of NIS in the physiology and the cancer pathogenesis process, this paper’s objective is to provide a comprehensive assessment of the associations between NIS gene and protein with papillary thyroid cancer.

scholarly journals Prospects for using agonists and antagonists of P2 receptors in clinical ophthalmology

2012 ◽  
Vol 93 (3) ◽  
pp. 508-512 ◽  
Author(s):  
A P Ziganshina ◽  
B A Ziganshin ◽  
A N Samoilov ◽  
A U Ziganshin
Keyword(s):  
P2 Receptors ◽  
Point Of View ◽  
Physiological Processes ◽  
Age Related ◽  
Corneal Wound ◽  
Clinical Point ◽  
Fluid Production ◽  
Neuronal Transmission ◽  
Stimulation Of

This literature review focuses on the role of purinergic P2-receptors in the physiology and pathophysiology of the eye, as well as on the possibilities of pharmacologic stimulation of these receptors. The most important studies from the clinical point of view on the involvement of purinergic neuronal transmission in the physiological processes have been analyzed, ranging from normal embryogenesis to cell apoptosis in age-related degenerative diseases of the eye. Data on the effect of agonists and antagonists of P2 receptors on corneal wound healing, lacrimal fluid production, regulation of intraocular pressure, neurotransmission, proliferation of glial tissue in the retina has been presented along with data on the possibilities of modulating these processes by using potential drugs acting via P2 receptors.

scholarly journals Heart failure and senile asthenia syndrome

2018 ◽  
pp. 72-79
Author(s):  
Yu. V. Kotovskaya ◽  
A. V. Rozanov ◽  
D. H. Kurashev ◽  
O. N. Tkacheva
Keyword(s):  
Heart Failure ◽  
Treatment Adherence ◽  
Point Of View ◽  
Geriatric Syndromes ◽  
Patients With Heart Failure ◽  
Clinical Point ◽  
Physiological Reserve ◽  
Reduced Mobility ◽  
Emergency Hospitalization

The role of specific approaches to the management of patients with heart failure (HF) increases steeply with increasing age, as the patients of this age need attention to geriatric problems: reduced mobility, multiple diseases and cognitive impairment. Senile asthenia is a syndrome that reflects a decline in physiological reserve and increased vulnerability to various stressors. Senile asthenia is detected in 15–74% of patients with heart failure, the prevalence depends on the method of diagnosis and the studied population. This review discusses the effects of senile asthenia, comorbidity and geriatric syndromes on diagnosis, treatment, and outcomes in elderly patients with heart failure. The detection of senile asthenia in patients with HF is important from a clinical point of view, since this condition has an adverse effect on the course of heart failure and is associated with a higher incidence of emergency hospitalization and mortality. Bodily exercises can improve mobility, and the introduction of nursing observation can enhance treatment adherence among patients.

scholarly journals When and how ruling out cystic fibrosis in adult patients with bronchiectasis

2019 ◽  
Author(s):  
Andrea Gramegna ◽  
Stefano Aliberti ◽  
Manuela Seia ◽  
Luigi Porcaro ◽  
Vera Bianchi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Human Lung ◽  
Adult Population ◽  
Point Of View ◽  
Main Step ◽  
Main Body ◽  
Careful Evaluation ◽  
Clinical Point ◽  
Cftr Mutations

Background: Bronchiectasis is the final result of different processes and most of the guidelines advocate for a careful evaluation of those etiologies which might be treated or might change patients’ management, including cystic fibrosis (CF). Main body: CFTR mutations have been reported with higher frequency in bronchiectasis population. Although ruling out CF is considered as a main step for etiological screening in bronchiectasis, CF testing lacks of a standardized approach both from a research and clinical point of view. In this review a list of most widely used tests in CF is provided. Conclusions: Exclusion of CF is imperative for patients with bronchiectasis and CFTR testing should be implemented in usual screening for investigating bronchiectasis etiology. Physicians taking care of bronchiectasis patients should be aware of CFTR testing and its limitations in the adult population. Further studies on CFTR expression in human lung and translational research might elucidate the possible role of CFTR in the pathogenesis of bronchiectasis.

Genetic Alterations in Thyroid Cancer: The Role of Mouse Models

2007 ◽  
Vol 44 (1) ◽  
pp. 1-14 ◽  
Author(s):  
K. A. B. Knostman ◽  
S. M. Jhiang ◽  
C. C. Capen
Keyword(s):  
Thyroid Cancer ◽  
Mouse Models ◽  
Genetic Alterations

scholarly journals Adjuvant Treatment in Pancreatic Cancer: Shaping the Future of the Curative Setting

2021 ◽  
Vol 11 ◽  
Author(s):  
Annalisa Pappalardo ◽  
Emilio Francesco Giunta ◽  
Giuseppe Tirino ◽  
Luca Pompella ◽  
Piera Federico ◽  
...  
Keyword(s):  
Early Stage ◽  
Current Treatment ◽  
Point Of View ◽  
Ductal Adenocarcinoma ◽  
Adjuvant Setting ◽  
Therapeutic Approaches ◽  
Treatment Scenario ◽  
Clinical Point ◽  
Localized Disease

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease even in the early stages, despite progresses in surgical and pharmacological treatment in recent years. High potential for metastases is the main cause of therapeutic failure in localized disease, highlighting the current limited knowledge of underlying pathological processes. However, nowadays research is focusing on the search for personalized approaches also in the adjuvant setting for PDAC, by implementing the use of biomarkers and investigating new therapeutic targets. In this context, the aim of this narrative review is to summarize the current treatment scenario and new potential therapeutic approaches in early stage PDAC, from both a preclinical and clinical point of view. Additionally, the review examines the role of target therapies in localized PDAC and the influence of neoadjuvant treatments on survival outcomes.

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