scholarly journals Molecular Markers and Targets in Melanoma

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2320
Author(s):  
Cristina Teixido ◽  
Paola Castillo ◽  
Clara Martinez-Vila ◽  
Ana Arance ◽  
Llucia Alos
Keyword(s):  
Kinase Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
World Health ◽  
Molecular Signaling ◽  
Superficial Spreading ◽  
Molecular Alterations ◽  
Mutation Burden ◽  
Health Organization

Melanoma develops as a result of several genetic alterations, with UV radiation often acting as a mutagenic risk factor. Deep knowledge of the molecular signaling pathways of different types of melanoma allows better characterization and provides tools for the development of therapies based on the intervention of signals promoted by these cascades. The latest World Health Organization classification acknowledged the specific genetic drivers leading to melanoma and classifies melanocytic lesions into nine distinct categories according to the associate cumulative sun damage (CSD), which correlates with the molecular alterations of tumors. The largest groups are melanomas associated with low-CSD or superficial spreading melanomas, characterized by frequent presentation of the BRAFV600 mutation. High-CSD melanomas include lentigo maligna type and desmoplastic melanomas, which often have a high mutation burden and can harbor NRAS, BRAFnon-V600E, or NF1 mutations. Non-CSD-associated melanomas encompass acral and mucosal melanomas that usually do not show BRAF, NRAS, or NF1 mutations (triple wild-type), but in a subset may have KIT or SF3B1 mutations. To improve survival, these driver alterations can be treated with targeted therapy achieving significant antitumor activity. In recent years, relevant improvement in the prognosis and survival of patients with melanoma has been achieved, since the introduction of BRAF/MEK tyrosine kinase inhibitors and immune checkpoint inhibitors. In this review, we describe the current knowledge of molecular pathways and discuss current and potential therapeutic targets in melanoma, focusing on their clinical relevance of development.

scholarly journals Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel

2020 ◽  
Vol 15 (5) ◽  
pp. 540-554 ◽  
Author(s):  
Adnan I Qureshi ◽  
Foad Abd-Allah ◽  
Fahmi Al-Senani ◽  
Emrah Aytac ◽  
Afshin Borhani-Haghighi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Current Knowledge ◽  
Intravenous Thrombolysis ◽  
Adult Patients ◽  
World Health ◽  
Stroke Patients ◽  
International Panel ◽  
Health Organization ◽  
Tract Infections

Background and purpose On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. Methods The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. Results This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. Conclusions These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

scholarly journals 405 - Music Therapy in the management of dementia

2020 ◽  
Vol 32 (S1) ◽  
pp. 121-121
Author(s):  
Catarina Pedro ◽  
Beatriz Jorge ◽  
Mariana Duarte
Keyword(s):  
Cognitive Function ◽  
Music Therapy ◽  
Behavioral Problems ◽  
Positive Impact ◽  
Current Knowledge ◽  
Neuropsychiatric Symptoms ◽  
World Health ◽  
Psychotic Symptoms ◽  
The World ◽  
Health Organization

Introduction:Dementia has become a worldwide concern. According to the World Health Organization, there are 50 million individuals suffering from dementia across the world and approximately 20 million new cases are diagnosed each year. The efficacy of medications in controlling agitation and psychotic symptoms is modest and may cause serious adverse effects, outlining the urge for new treatment methods for patients with dementia. Music therapy (MT) is a nonpharmacologic strategy that is used in patients with early-to-late stages of dementia with promising results.Objectives:The aim of this presentation is to evaluate the benefits of music therapy in cognitive functioning and neuropsychiatric symptoms in patients diagnosed with dementia. We also summarize the current knowledge about this topic.Methods:A non-systematic review of the literature was performed on PubMed, PsycINFO and Web of science using selected keywords.Results:MT sustains its benefit because musical memory regions in the brain are relatively spared compared to cognitive function. “Musical memories” can, thus, be stored longer than non-musical memories, allowing to recall associated life events and emotions. Systematic reviews suggest that MT seem to have a positive effect on symptoms such as depression, anxiety and behavioral problems while the findings concerning agitation/aggression are inconsistent. No large differences were found between studies using live or recorded music although the latter reported more of a consistently positive impact on behavioral and psychological outcomes. The studies using live music, however, reported specific benefits to relationships and interactions.Conclusions:The majority of the studies have methodological limitations, making it difficult to offer firm conclusions. Despite this, there were positive results on aspects of quality of life, cognitive function, behavioral, psychological, physiological and communication outcomes.

scholarly journals The Wnt Signalling Pathway: A Tailored Target in Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7697 ◽  
Author(s):  
Malvina Koni ◽  
Veronica Pinnarò ◽  
Maria Felice Brizzi
Keyword(s):  
Animal Species ◽  
Current Knowledge ◽  
Integration Site ◽  
World Health ◽  
Cancer Driver ◽  
Common Cancer ◽  
Public Health Challenges ◽  
Health Organization ◽  
Canonical Wnt ◽  
The Impact

Cancer is one of the greatest public health challenges. According to the World Health Organization (WHO), 9.6 million cancer deaths have been reported in 2018. The most common cancers include lung, breast, colorectal, prostate, skin (non-melanoma) and stomach cancer. The unbalance of physiological signalling pathways due to the acquisition of mutations in tumour cells is considered the most common cancer driver. The Wingless-related integration site (Wnt)/β-catenin pathway is crucial for tissue development and homeostasis in all animal species and its dysregulation is one of the most relevant events linked to cancer development and dissemination. The canonical and the non-canonical Wnt/β-catenin pathways are known to control both physiological and pathological processes, including cancer. Herein, the impact of the Wnt/β-catenin cascade in driving cancers from different origin has been examined. Finally, based on the impact of Extracellular Vesicles (EVs) on tumour growth, invasion and chemoresistance, and their role as tumour diagnostic and prognostic tools, an overview of the current knowledge linking EVs to the Wnt/β-catenin pathway is also discussed.

scholarly journals Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Brain Tumors ◽  
Clonal Evolution ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
World Health ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Genetic Profiling ◽  
Health Organization

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.

scholarly journals Targeting Oncogenic BRAF: Past, Present, and Future

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1197 ◽  
Author(s):  
Zaman ◽  
Wu ◽  
Bivona
Keyword(s):  
Kinase Inhibitors ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Wild Type ◽  
Braf Mutations ◽  
Molecular Alterations ◽  
Mutant Braf

Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies.

Management for Different Glioma Subtypes: Are All Low-Grade Gliomas Created Equal?

2019 ◽  
pp. 133-145 ◽  
Author(s):  
Martin C. Tom ◽  
Daniel P. Cahill ◽  
Jan C. Buckner ◽  
Jörg Dietrich ◽  
Michael W. Parsons ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
World Health ◽  
Low Grade ◽  
Lower Grade ◽  
Future Directions ◽  
Molecular Alterations ◽  
Lower Grade Glioma ◽  
Grade 3 ◽  
Health Organization

Following the identification of key molecular alterations that provided superior prognostication and led to the updated 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumor Classification, the understanding of glioma behavior has rapidly evolved. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 are present in the majority of adult grade 2 and 3 gliomas, and when used in conjunction with 1p/19q codeletion for classification, the prognostic distinction between grade 2 versus grade 3 is diminished. As such, the previously often used term of “low-grade glioma,” which referred to grade 2 gliomas, has now been replaced by the phrase “lower-grade glioma” to encompass both grade 2 and 3 tumors. Additional molecular characterization is ongoing to even further classify this heterogeneous group of tumors. With such a colossal shift in the understanding of lower-grade gliomas, management of disease is being redefined in the setting of emerging molecular-genetic biomarkers. In this article, we review recent progress and future directions regarding the surgical, radiotherapeutic, chemotherapeutic, and long-term management of adult lower-grade gliomas.

Can luteolin be a therapeutic molecule for both colon cancer and diabetes?

2018 ◽  
Vol 18 (4) ◽  
pp. 230-239 ◽  
Author(s):  
Rashmi K Ambasta ◽  
Rohan Gupta ◽  
Dhiraj Kumar ◽  
Saurabh Bhattacharya ◽  
Aditi Sarkar ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
World Health ◽  
Molecular Signaling ◽  
Immunofluorescence Analysis ◽  
Number Of Patients ◽  
Patients With Diabetes ◽  
Health Organization ◽  
Multiple Signaling

Abstract Diabetes and colon cancer are the leading cause of mortality worldwide. According to World Health Organization, the number of patients with diabetes and cancer is going to be elevated by 50% in 2020. However, several flavonoids have been known to be useful in reducing the chance of cancer/diabetes but the hunt of a single biomolecule that can act as therapeutic and preventive molecules for future epidemic continues. In this review, we aim to perform an illustration of all researches done that target molecular signaling using luteolin in cancer/diabetes and predicted target protein using PharmMapper. The search confirms that luteolin can be a remedial molecule for both cancer and diabetes via acting on variety of signaling pathway. Furthermore, we also intend to illustrate/compare the predicted and verified molecular modes of action of luteolin. Fluorescence in situ hybridization analysis confirms the expression of CCND1 in colon cancer while immunofluorescence analysis confirms the CDK4 in diabetes. Finally, an effort has been made to map docking of marker protein-luteolin at a particular site using docking software. This review gives a holistic overview about luteolin as a therapeutic molecule for cancer/diabetes via acting on multiple signaling cascade such as p53, Wnt, eNOS, iNOS, SOD and MMP9, with especial emphasis on the cyclin-CDK pathway. Altogether, the review concludes that luteolin can be a molecule for the therapy of both cancer and diabetes by acting on broad signaling pathway.

scholarly journals Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches

2019 ◽  
Vol 20 (12) ◽  
pp. 2976 ◽  
Author(s):  
Peter Valent ◽  
Cem Akin ◽  
Karoline V. Gleixner ◽  
Wolfgang R. Sperr ◽  
Andreas Reiter ◽  
...  
Keyword(s):  
Mast Cell ◽  
Personalized Medicine ◽  
Current Knowledge ◽  
Systemic Mastocytosis ◽  
Daily Practice ◽  
World Health ◽  
Survival Times ◽  
Tryptase Level ◽  
Organ Systems ◽  
Health Organization

Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into cutaneous forms, systemic variants, and localized mast cell tumors. In >80% of patients with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is found. Whereas patients with indolent forms of the disease have a normal or near-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM and mast cell leukemia, have a poor prognosis with short survival times. In a majority of these patients, multiple somatic mutations and/or an associated hematologic neoplasm, such as a myeloid leukemia, may be detected. Independent of the category of mastocytosis and the serum tryptase level, patients may suffer from mediator-related symptoms and/or osteopathy. Depending on the presence of co-morbidities, the symptomatology in such patients may be mild, severe or even life-threatening. Most relevant co-morbidities in such patients are IgE-dependent allergies, psychiatric, psychological or mental problems, and vitamin D deficiency. The diagnosis and management of mastocytosis is an emerging challenge in clinical practice and requires vast knowledge, a multidisciplinary approach, and personalized medicine procedures. In this article, the current knowledge about mastocytosis is reviewed with special emphasis on the multidisciplinary aspects of the disease and related challenges in daily practice.

scholarly journals BCR-ABL1–like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review

2019 ◽  
Vol 144 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Sarika Jain ◽  
Anu Abraham
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
World Health Organization ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Comprehensive Review ◽  
The World ◽  
Health Organization ◽  
Stimulating Factor

Context.— In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, BCR-ABL1–like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the BCR-ABL1 translocation but shows a pattern of gene expression very similar to that seen in B-ALL with BCR-ABL1. Objective.— To review the kinase-activating alterations and the diagnostic approach for BCR-ABL1–like B-ALL. Data Sources.— We provide a comprehensive review of BCR-ABL1–like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms. Conclusions.— Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1–like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1–like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of BCR-ABL1–like B-ALL.

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