Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.024.205
Filtrar
1.
Rev Paul Pediatr ; 39: e2020217, 2021.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-32876096

RESUMEN

OBJECTIVE: To analyze the current scientific literature to document, in an integrative review, the main findings that correlate Kawasaki disease (KD) to COVID-19. DATA SOURCES: The search was carried out in June 2020 in the following databases: Biblioteca Virtual em Saúde (BVS), periódico da CAPES and U.S National Library of Medicine (PubMed). The combination of descriptors used was [(COVID-19 OR SARS-CoV-2) AND (Kawasaki disease)], and the inclusion criteria stipulated were studies published from January 2019 to June 2020, without restriction of language or location, and available online in full. News, editorials, comments, and letters, as well as duplicates and articles that did not answer the guiding question were excluded. DATA SYNTHESIS: A total of 97 articles were identified, of which seven comprised this review. The association of KD to the new coronavirus appears to trigger a severe clinical condition of vasculitis. Different from the usual, in this inflammatory syndrome, patients are older, and prevalence is higher in children from African or Caribbean ancestry; clinical and laboratory manifestations are also atypical, with a predominance of abdominal complaints and exaggerated elevation of inflammatory markers. In addition, there was a greater report of rare complications and greater resistance to the recommended treatment for KD. CONCLUSIONS: Pediatric COVID-19 and its potential association to severe KD, still unfamiliar to health professionals, reinforces the importance of testing patients with vasculitis for the new coronavirus and the need to wage high surveillance and preparation of the health system during the current pandemic.


Asunto(s)
Infecciones por Coronavirus , Síndrome Mucocutáneo Linfonodular , Pandemias , Neumonía Viral , Síndrome de Respuesta Inflamatoria Sistémica/virología , Betacoronavirus/aislamiento & purificación , Niño , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Manejo de la Enfermedad , Humanos , Síndrome Mucocutáneo Linfonodular/epidemiología , Síndrome Mucocutáneo Linfonodular/terapia , Síndrome Mucocutáneo Linfonodular/virología , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/fisiopatología
3.
Ann Lab Med ; 41(2): 129-138, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063674

RESUMEN

Since its first report in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged as a pandemic affecting nearly all countries worldwide. As the COVID-19 pandemic progresses, the need to identify genetic risk factors for susceptibility to this serious illness has emerged. Host genetic factors, along with other risk factors may help determine susceptibility to respiratory tract infections. It is hypothesized that the ACE2 gene, encoding angiotensin-converting enzyme 2 (ACE2), is a genetic risk factor for SARS-CoV-2 infection and is required by the virus to enter cells. Together with ACE2, transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-4 (DPP4) also play an important role in disease severity. Evaluating the role of genetic variants in determining the direction of respiratory infections will help identify potential drug target candidates for further study in COVID-19 patients. We have summarized the latest reports demonstrating that ACE2 variants, their expression, and epigenetic factors may influence an individual's susceptibility to SARS-CoV-2 infection and disease outcome.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/patología , Variación Genética , Neumonía Viral/patología , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/genética , Dipeptidil Peptidasa 4/metabolismo , Susceptibilidad a Enfermedades , Expresión Génica , Humanos , Pandemias , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/virología , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad
4.
Ann Lab Med ; 41(2): 225-229, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33063685

RESUMEN

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, an online laboratory surveillance system was established to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacities and results. SARS-CoV-2 rRT-PCR testing data were collected from 97 clinical laboratories, including 84 medical institutions and 13 independent clinical laboratories in Korea. We assessed the testing capacities to utilize SARS-CoV-2 rRT-PCR based on surveillance data obtained from February 7th to June 4th, 2020 and evaluated positive result characteristics according to the reagents used and sample types. A total of 1,890,319 SARS-CoV-2 rRT-PCR testing were performed, 2.3% of which were positive. Strong correlations were observed between the envelope (E) gene and RNA-dependent RNA polymerase (RdRp)/nucleocapsid (N) genes threshold cycle (Ct) values for each reagent. No statistically significant differences in gene Ct values were observed between the paired upper and lower respiratory tract samples, except in the N gene for nasopharyngeal swab and sputum samples. Our study showed that clinical laboratories in Korea have rapidly expanded their testing capacities in response to the COVID-19 outbreak, with a peak daily capacity of 34,193 tests. Rapid expansion in testing capacity is a critical component of the national response to the ongoing pandemic.


Asunto(s)
Betacoronavirus/genética , Servicios de Laboratorio Clínico/estadística & datos numéricos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Humanos , Laboratorios de Hospital , Pandemias , Neumonía Viral/virología , ARN Replicasa/genética , ARN Viral/genética , ARN Viral/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea , Proteínas del Envoltorio Viral/genética , Proteínas Virales/genética
5.
Artículo en Inglés | MEDLINE | ID: mdl-32730915

RESUMEN

In December 2019, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) infection was reported. In only few weeks it has caused a global pandemic, with mortality reaching 3.4%, mostly due to a severe pneumonia. However, the impact of SARS-CoV-2 virus on the central nervous system (CNS) and mental health outcomes remains unclear. Previous studies have demonstrated the presence of other types of coronaviruses in the brain, especially in the brainstem. There is evidence that the novel coronavirus can penetrate CNS through the olfactory or circulatory route as well as it can have an indirect impact on the brain by causing cytokine storm. There are also first reports of neurological signs in patients infected by the SARS-Cov-2. They show that COVID-19 patients have neurologic manifestations like acute cerebrovascular disease, conscious disturbance, taste and olfactory disturbances. In addition, there are studies showing that certain psychopathological symptoms might appear in infected patients, including those related to mood and psychotic disorders as well as post-traumatic stress disorder. Accumulating evidence also indicates that the pandemic might have a great impact on mental health from the global perspective, with medical workers being particularly vulnerable. In this article, we provide a review of studies investigating the impact of the SARS-CoV-2 on the CNS and mental health outcomes. We describe neurobiology of the virus, highlighting the relevance to mental disorders. Furthermore, this article summarizes the impact of the SARS-CoV-2 from the public health perspective. Finally, we present a critical appraisal of evidence and indicate future directions for studies in this field.


Asunto(s)
Infecciones por Coronavirus/psicología , Trastornos Mentales/psicología , Salud Mental , Neumonía Viral/psicología , Betacoronavirus , Encéfalo/virología , Infecciones por Coronavirus/complicaciones , Humanos , Trastornos Mentales/complicaciones , Trastornos Mentales/etiología , Enfermedades del Sistema Nervioso/etiología , Pandemias , Neumonía Viral/complicaciones , Resultado del Tratamiento
6.
Artículo en Inglés | MEDLINE | ID: mdl-32771337

RESUMEN

BACKGROUND: Psychological suffering by health professionals may be associated with the uncertainty of a safe workplace. Front-line professionals exposed and involved in the diagnosis and treatment of COVID-19 patients are more susceptible. METHOD: This review was conducted based on papers that were published at MEDLINE, BMJ, PsycINFO, and LILACS, the according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). RESULTS: Health professionals had a higher level of anxiety (13.0 vs. 8.5%, p < 0.01, OR = 1.6152; 95%CI 1.3283 to 1.9641; p < 0.0001) and depression 12.2 vs. 9.5%; p = 0.04; OR = 1.3246; 95%CI 1.0930 to 1.6053; p = 0.0042), besides somatizations and insomnia compared to professionals from other areas. CONCLUSION: Health professionals, regardless of their age, showed significant levels of mental disorders. We observed a prevalence of anxiety and depression. Insomnia was a risk factor for both.


Asunto(s)
Infecciones por Coronavirus , Personal de Salud/psicología , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Enfermedades Profesionales/etiología , Enfermedades Profesionales/psicología , Pandemias , Neumonía Viral , Humanos , Trastornos Mentales/epidemiología , Enfermedades Profesionales/epidemiología , Prevalencia , Estrés Psicológico
7.
Artículo en Inglés | MEDLINE | ID: mdl-32777327

RESUMEN

BACKGROUND: Health professionals are key personnel to containing infectious diseases like COVID-19. In the face of long work shifts (that reach 16 h per day on average), the risk of getting infected by a high-infectious disease and the lack of enough biological protection measures, mental suffering among health professionals suddenly became evident. METHOD: We carried out an updated meta-analysis to investigate the psychiatric impacts on health professionals in the face of the physical and psychological conditions to which they are subjected due to the high demands of the COVID-19 pandemic. Papers were researched in four databases from December 2019 to April 2020. In total, eight papers were included in the study. RESULTS: Health professionals working to fight COVID-19 are being more severely affected by psychiatric disorders associated with depression, anxiety, distress and insomnia, stress, and indirect traumatization than other occupational groups. No significant differences were observed in the publication bias. CONCLUSION: There is a strong association between health professionals and COVID-19 in terms of psychiatric repercussions. Our meta-analysis showed that health professionals have a higher level of indirect traumatization, in which the level of damage exceeds psychological and emotional tolerance and indirectly results in psychological abnormalities. The incidence of obsessive-compulsive traces and somatizations was higher in situations involving front-line professionals.


Asunto(s)
Infecciones por Coronavirus , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Enfermedades Profesionales/etiología , Enfermedades Profesionales/psicología , Pandemias , Neumonía Viral , Ansiedad/etiología , Ansiedad/psicología , Depresión/etiología , Depresión/psicología , Personal de Salud , Humanos , Distrés Psicológico , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Estrés Psicológico/epidemiología
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118825, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-32866803

RESUMEN

Novel antiviral active molecule 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl)acetamide has been synthesised and characterized by FT-IR and FT-Raman spectra. The equilibrium geometry, natural bond orbital calculations and vibrational assignments have been carried out using density functional B3LYP method with the 6-311G++(d,p) basis set. The complete vibrational assignments for all the vibrational modes have been supported by normal coordinate analysis, force constants and potential energy distributions. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces. Drug likeness has been carried out based on Lipinski's rule and the absorption, distribution, metabolism, excretion and toxicity of the title molecule has been calculated. Antiviral potency of 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro-phenyl) acetamide has been investigated by docking against SARS-CoV-2 protein. The optimized geometry shows near-planarity between the phenyl ring and the pyrimidine ring. Differences in the geometries due to the substitution of the most electronegative fluorine atom and intermolecular contacts due to amino pyrimidine were analyzed. NBO analysis reveals the formation of two strong stable hydrogen bonded N-H···N intermolecular interactions and weak intramolecular interactions C-H···O and N-H···O. The Hirshfeld surfaces and consequently the 2D-fingerprint confirm the nature of intermolecular interactions and their quantitative contributions towards the crystal packing. The red shift in N-H stretching frequency exposed from IR substantiate the formation of N-H···N intermolecular hydrogen bond. Drug likeness and absorption, distribution, metabolism, excretion and toxicity properties analysis gives an idea about the pharmacokinetic properties of the title molecule. The binding energy -8.7 kcal/mol of the nonbonding interaction present a clear view that 2- [(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(4-fluoro- phenyl) acetamide can irreversibly interact with SARS-CoV-2 protease.


Asunto(s)
Antivirales/química , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Pandemias , Neumonía Viral/tratamiento farmacológico , Inhibidores de Proteasas/química , Proteínas no Estructurales Virales/antagonistas & inhibidores , Antivirales/farmacocinética , Betacoronavirus/enzimología , Cristalografía por Rayos X , Cisteína Endopeptidasas , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Dinámicas no Lineales , Inhibidores de Proteasas/farmacocinética , Conformación Proteica , Teoría Cuántica , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Termodinámica , Vibración
9.
Adv Exp Med Biol ; 1287: 1-7, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034022

RESUMEN

The evolutionary conserved Notch pathway that first developed in metazoans and that was first discovered in fruit flies (Drosophila melanogaster) governs fundamental cell fate decisions and many other cellular key processes not only in embryonic development but also during initiation, promotion, and progression of cancer. On a first look, the Notch pathway appears remarkably simple, with its key feature representing a direct connection between an extracellular signal and transcriptional output without the need of a long chain of protein intermediaries as known from many other signaling pathways. However, on a second, closer look, this obvious simplicity exerts surprising complexity. There is no doubt that the enormous scientific progress in unraveling the functional mechanisms that underlie this complexity has recently greatly increased our knowledge about the role of Notch signaling for pathogenesis and progression of many types of cancer. Moreover, these new scientific findings have shown promise in opening new avenues for cancer prevention and therapy, although this goal is still challenging. Vol. III of the second edition of the book Notch Signaling in Embryology and Cancer, entitled Notch Signaling in Cancer, summarizes important recent developments in this fast-moving and fascinating field. Here, we give an introduction to this book and a short summary of the individual chapters that are written by leading scientists, covering the latest developments in this intriguing research area.


Asunto(s)
Neoplasias/prevención & control , Neoplasias/terapia , Receptores Notch/metabolismo , Transducción de Señal , Animales , Diferenciación Celular , Humanos , Neoplasias/patología
10.
Adv Exp Med Biol ; 1287: 9-30, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034023

RESUMEN

The Notch signal transduction cascade requires cell-to-cell contact and results in the proteolytic processing of the Notch receptor and subsequent assembly of a transcriptional coactivator complex containing the Notch intracellular domain (NICD) and transcription factor RBPJ. In the absence of a Notch signal, RBPJ remains at Notch target genes and dampens transcriptional output. Like in other signaling pathways, RBPJ is able to switch from activation to repression by associating with corepressor complexes containing several chromatin-modifying enzymes. Here, we focus on the recent advances concerning RBPJ-corepressor functions, especially in regard to chromatin regulation. We put this into the context of one of the best-studied model systems for Notch, blood cell development. Alterations in the RBPJ-corepressor functions can contribute to the development of leukemia, especially in the case of acute myeloid leukemia (AML). The versatile role of transcription factor RBPJ in regulating pivotal target genes like c-MYC and HES1 may contribute to the better understanding of the development of leukemia.


Asunto(s)
Regulación de la Expresión Génica , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Receptores Notch/metabolismo , Cromatina/genética , Cromatina/metabolismo , Humanos , Transducción de Señal
11.
Adv Exp Med Biol ; 1287: 31-46, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034024

RESUMEN

The endosomal pathway plays a pivotal role upon signal transduction in the Notch pathway. Recent work on lethal (2) giant discs (lgd) points to an additional critical role in avoiding uncontrolled ligand-independent signalling during trafficking of the Notch receptor through the endosomal pathway to the lysosome for degradation. In this chapter, we will outline the journey of Notch through the endosomal system and present an overview of the current knowledge about Lgd and its mammalian orthologs Lgd1/CC2D1b and Lgd2/CC2D1a. We will then discuss how Notch is activated in the absence of lgd function in Drosophila and ask whether there is evidence that a similar ligand-independent activation of the Notch pathway can also happen in mammals if the orthologs are inactivated.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Neoplasias/metabolismo , Receptores Notch/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal , Proteínas Supresoras de Tumor/metabolismo , Animales , Endosomas/metabolismo , Humanos
12.
Adv Exp Med Biol ; 1287: 47-57, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034025

RESUMEN

The human endometrium is a unique, highly dynamic tissue that undergoes cyclic changes of cell proliferation, differentiation, and death. Endometrial cancer is the most common malignancy among women in developed countries. Importantly, the incidence of endometrial cancer is rising in high-income countries. Currently histological classification is used for subtyping of endometrial cancer, while ongoing research is evaluating markers for more accurate molecular classification. Evolutionary conserved Notch signaling pathway regulates diverse cellular processes such as proliferation, differentiation, and cell invasion. Accumulating evidence links aberrant Notch signaling with diseases such as hyperplasia and endometrial cancer. This chapter summarizes the current state of Notch signaling investigations in the endometrium, endometriosis, and endometrial cancer.


Asunto(s)
Neoplasias Endometriales , Endometriosis , Receptores Notch/metabolismo , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/metabolismo , Endometrio/patología , Femenino , Humanos , Transducción de Señal
13.
Adv Exp Med Biol ; 1287: 59-68, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034026

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research on its mechanisms, prevention, and therapy. Recent studies have shown that NOTCH mutations are commonly seen in human ESCC. This chapter summarizes our current understanding of the NOTCH pathway in normal esophagus and in ESCC. In normal esophagus, NOTCH pathway regulates the development of esophageal squamous epithelium, in particular, squamous differentiation. Exposure to extrinsic and intrinsic factors, such as gastroesophageal reflux, alcohol drinking, and inflammation, downregulates the NOTCH pathway and thus inhibits squamous differentiation of esophageal squamous epithelial cells. In ESCC, NOTCH plays a dual role as both a tumor suppressor pathway and an oncogenic pathway. In summary, further studies are warranted to develop NOTCH activators for the prevention of ESCC and NOTCH inhibitors for targeted therapy of a subset of ESCC with activated NOTCH pathway.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Receptores Notch/metabolismo , Carcinogénesis , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Transducción de Señal
14.
Adv Exp Med Biol ; 1287: 69-80, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034027

RESUMEN

Interactions between liver cells are closely regulated by Notch signaling. Notch signaling has been reported clinically related to bile duct hypogenesis in Alagille syndrome, which is caused by mutations in the Jagged1 gene. Notch activation and hepatocarcinogenesis are closely associated since cancer signaling is affected by the development of liver cells and cancer stem cells. Gene expression and genomic analysis using a microarray revealed that abnormalities in Notch-related genes were associated with the aggressiveness of liver cancer. This pattern was also accompanied with α-fetoprotein- and EpCAM-expressing phenotypes in vitro, in vivo, and in clinical tissues. Hepatitis B or C virus chronic infection or alcohol- or steatosis-related liver fibrosis induces liver cancer. Previous reports demonstrated that HBx, a hepatitis B virus protein, was associated with Jagged1 expression. We found that the Jagged1 and Notch1 signaling pathways were closely associated with the transcription of covalently closed circular hepatitis B virus DNA, which regulated cAMP response element-binding protein, thereby affecting Notch1 regulation by the E3 ubiquitin ligase ITCH. This viral pathogenesis in hepatocytes induces liver cancer. In conclusion, Notch signaling exerts various actions and is a clinical signature associated with hepatocarcinogenesis and liver context-related developmental function.


Asunto(s)
Neoplasias Hepáticas , Receptores Notch/metabolismo , Transducción de Señal , Hepatitis/metabolismo , Hepatitis/virología , Virus de la Hepatitis B/patogenicidad , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virología , Proteínas Represoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
15.
Adv Exp Med Biol ; 1287: 81-103, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034028

RESUMEN

Head and neck cancer is a group of neoplastic diseases affecting the facial, oral, and neck region. It is one of the most common cancers worldwide with an aggressive, invasive evolution. Due to the heterogeneity of the tissues affected, it is particularly challenging to study the molecular mechanisms at the basis of these tumors, and to date we are still lacking accurate targets for prevention and therapy. The Notch signaling is involved in a variety of tumorigenic mechanisms, such as regulation of the tumor microenvironment, aberrant intercellular communication, and altered metabolism. Here, we provide an up-to-date review of the role of Notch in head and neck cancer and draw parallels with other types of solid tumors where the Notch pathway plays a crucial role in emergence, maintenance, and progression of the disease. We therefore give a perspective view on the importance of the pathway in neoplastic development in order to define future lines of research and novel therapeutic approaches.


Asunto(s)
Neoplasias de Cabeza y Cuello , Receptores Notch , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/terapia , Humanos , Transducción de Señal , Microambiente Tumoral
16.
Adv Exp Med Biol ; 1287: 105-122, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034029

RESUMEN

The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)-associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.


Asunto(s)
Carcinogénesis , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/virología , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Humanos , Infecciones por Papillomavirus/virología
17.
Adv Exp Med Biol ; 1287: 123-154, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034030

RESUMEN

Since many decades, nonmelanoma skin cancer (NMSCs) is the most common malignancy worldwide. Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the major types of NMSCs, representing approximately 70% and 25% of these neoplasias, respectively. Because of their continuously rising incidence rates, NMSCs represent a constantly increasing global challenge for healthcare, although they are in most cases nonlethal and curable (e.g., by surgery). While at present, carcinogenesis of NMSC is still not fully understood, the relevance of genetic and molecular alterations in several pathways, including evolutionary highly conserved Notch signaling, has now been shown convincingly. The Notch pathway, which was first developed during evolution in metazoans and that was first discovered in fruit flies (Drosophila melanogaster), governs cell fate decisions and many other fundamental processes that are of high relevance not only for embryonic development, but also for initiation, promotion, and progression of cancer. Choosing NMSC as a model, we give in this review a brief overview on the interaction of Notch signaling with important oncogenic and tumor suppressor pathways and on its role for several hallmarks of carcinogenesis and cancer progression, including the regulation of cancer stem cells, tumor angiogenesis, and senescence.


Asunto(s)
Carcinogénesis , Células Madre Neoplásicas/patología , Neovascularización Patológica , Receptores Notch/metabolismo , Transducción de Señal , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Animales , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Humanos , Neoplasias Cutáneas/irrigación sanguínea
18.
Adv Exp Med Biol ; 1287: 155-168, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034031

RESUMEN

Thyroid cancer is the most common malignancy of the endocrine system with a steadily rising incidence. The term "thyroid cancer" encompasses a spectrum of subtypes, namely papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer. Each subtype differs histopathologically and in degrees of cellular differentiation, which may be in part due to signaling of the Notch pathway. The Notch pathway is an evolutionarily conserved signal transduction mechanism that regulates cell proliferation, differentiation, survival, stem cell maintenance, embryonic and adult development, epithelial-mesenchymal transition, and angiogenesis. Its role in cancer biology is controversial, as it has been shown to play both an oncogenic and tumor-suppressive role in many different types of cancers. This discordance holds true for each subtype of thyroid cancer, indicating that Notch signaling is likely cell type and context dependent. Whether oncogenic or not, Notch signaling has proven to be significantly involved in the tumorigenesis of thyroid cancer and has thus earned interest as a therapeutic target. Advancement in the understanding of Notch signaling in thyroid cancer holds great promise for the development of novel treatment strategies to benefit patients.


Asunto(s)
Receptores Notch/metabolismo , Transducción de Señal , Neoplasias de la Tiroides/metabolismo , Humanos , Oncogenes , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología
19.
Adv Exp Med Biol ; 1287: 169-181, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034032

RESUMEN

The Notch signaling pathway controls normal embryonic development and tissue homeostasis of many cell types. It regulates cell proliferation, fate, differentiation, and cell death by short-range signaling between nearby cells that come in contact. The Notch pathway has also been critically involved in the pathobiology of a variety of malignancies, regulating cancer initiation and development, as well as early stages of cancer progression, by adjusting conserved cellular programs. Fibroblasts, an essential for tumor growth component of stroma, have also been affected by Notch regulation. Sequencing Notch gene mutations have been identified in a number of human tumors, revealing information on the progression of specific cancer types, such as ovarian cancer and melanoma, immune-associated tumors such as myeloid neoplasms, but especially in lymphocytic leukemia. Activation of the Notch can be either oncogenic or it may contain growth-suppressive functions, acting as a tumor suppressor in other hematopoietic cells, hepatocytes, skin, and pancreatic epithelium.


Asunto(s)
Progresión de la Enfermedad , Neoplasias/patología , Receptores Notch , Transducción de Señal , Genes Supresores de Tumor , Humanos , Neoplasias/genética , Oncogenes , Receptores Notch/metabolismo
20.
Adv Exp Med Biol ; 1287: 183-200, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33034033

RESUMEN

Notch promotes breast cancer progression through tumor initiating cell maintenance, tumor cell fate specification, proliferation, survival, and motility. In addition, Notch is recognized as a decisive mechanism in regulating various juxtacrine and paracrine communications in the tumor microenvironment (TME). In this chapter, we review recent studies on stress-mediated Notch activation within the TME and sequelae such as angiogenesis, extracellular matrix remodeling, changes in the innate and adaptive immunophenotype, and therapeutic perspectives.


Asunto(s)
Neoplasias de la Mama , Receptores Notch/metabolismo , Transducción de Señal , Microambiente Tumoral , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Humanos , Neovascularización Patológica , Comunicación Paracrina
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA