Isabel Gonçalves Silva

Instituto de Medicina Integral Professor Fernando Figueira

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Bernhard F. Gibbs

Canterbury Christ Church University

Vadim V. Sumbayev

Medway School of Pharmacy

Inna M. Yasinska

Medway School of Pharmacy

Elizaveta Fasler‐Kan

University Children’s Hospital Bern

Steffen Berger

University Hospital of Bern

Marco Bardelli

Università della Svizzera italiana

Svetlana Sakhnevych

Queen's University Belfast

Luca Varani

Università della Svizzera italiana

Jennifer M. A. Tullet

University of Kent

Rohanah Hussain

Diamond Light Source

Cooperative Institutions

Neurological Surgery

The University of Tokyo

University of Kent

University College London

Johns Hopkins University

University of California, Los Angeles

Inserm

New York University

University of Toronto

Universidad de Salamanca

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Fernando Martorell (1906-1984): Centenary of a Pioneer in Angiology

Angiology (2008)

Francisco S. Lozano Xabier Cabot Isabel Gonçalves Silva E. Roche J.M. Callejas

Angiology

10.1177/0003319707304535

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Citations (2)

Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells

Oncotarget (2015)

Isabel Gonçalves Silva Bernhard F. Gibbs Marco Bardelli Luca Varani Vadim V. Sumbayev

The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated receptor which is involved in a variety of biological responses in human immune cells. It is highly expressed in most acute myeloid leukaemia (AML) cells and therefore may serve as a possible target for AML therapy. However, its biochemical activities in primary human AML cells remain unclear. We therefore analysed the total expression and surface presence of the Tim-3 receptor in primary human AML blasts and healthy primary human leukocytes isolated from human blood. We found that Tim-3 expression was significantly higher in primary AML cells compared to primary healthy leukocytes. Tim-3 receptor molecules were distributed largely on the surface of primary AML cells, whereas in healthy leukocytes Tim-3 protein was mainly expressed intracellularly. In primary human AML blasts, both Tim-3 agonistic antibody and galectin-9 (a Tim-3 natural ligand) significantly upregulated mTOR pathway activity. This was in line with increased accumulation of hypoxia-inducible factor 1 alpha (HIF-1α) and secretion of VEGF and TNF-α. Similar results were obtained in primary human healthy leukocytes. Importantly, in both types of primary cells, Tim-3-mediated effects were compared with those induced by lipopolysaccharide (LPS) and stem cell factor (SCF). Tim-3 induced comparatively moderate responses in both AML cells and healthy leukocytes. However, Tim-3, like LPS, mediated the release of both TNF-α and VEGF, while SCF induced mostly VEGF secretion and did not upregulate TNF-α release.

10.18632/oncotarget.5257

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Citations (50)

Biochemical mechanisms implemented by human acute myeloid leukemia cells to suppress host immune surveillance

Cellular and Molecular Immunology (2018)

Inna M. Yasinska Isabel Gonçalves Silva Svetlana Sakhnevych Bernhard F. Gibbs Ulrike Raap

Immune surveillance

10.1038/s41423-018-0047-6

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Citations (17)

Neuronal SKN-1B Modulates Nutritional Signalling Pathways and Mitochondrial Networks to Control Satiety

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Nikolaos Tataridas-Pallas Maximillian Thompson Alexander Howard Ian R. Brown Marina Ezcurra

Abstract The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans , chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism and respiration, because can mediate the increased lifespan incurred by dietary restriction. We show that actually SKN-1B is not essential for dietary restriction longevity and instead, controls a variety of food-related behaviours. It acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.

Energy homeostasis

Signalling

10.1101/2020.07.21.213504

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Gold nanoparticle-based fluorescence immunoassay for malaria antigen detection

Analytical and Bioanalytical Chemistry (2011)

Bassem S. Guirgis Cláudia Sá e Cunha Inês Gomes Miguel Cavadas Isabel Gonçalves Silva

10.1007/s00216-011-5489-y

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Citations (84)

Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety

PLoS Genetics (2021)

Nikolaos Tataridas-Pallas Maximillian A. Thompson Alexander Howard Ian R. Brown Marina Ezcurra

The feeling of hunger or satiety results from integration of the sensory nervous system with other physiological and metabolic cues. This regulates food intake, maintains homeostasis and prevents disease. In C. elegans, chemosensory neurons sense food and relay information to the rest of the animal via hormones to control food-related behaviour and physiology. Here we identify a new component of this system, SKN-1B which acts as a central food-responsive node, ultimately controlling satiety and metabolic homeostasis. SKN-1B, an ortholog of mammalian NF-E2 related transcription factors (Nrfs), has previously been implicated with metabolism, respiration and the increased lifespan incurred by dietary restriction. Here we show that SKN-1B acts in two hypothalamus-like ASI neurons to sense food, communicate nutritional status to the organism, and control satiety and exploratory behaviours. This is achieved by SKN-1B modulating endocrine signalling pathways (IIS and TGF-β), and by promoting a robust mitochondrial network. Our data suggest a food-sensing and satiety role for mammalian Nrf proteins.

Signalling

Signalling pathways

10.1371/journal.pgen.1009358

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Citations (21)

A Radioterapia no tratamento dos sarcomas

Revista Portuguesa de Cirurgia (2011)

Isabel Gonçalves Silva

Source

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Citations (0)

Abstracts

Stereotactic and Functional Neurosurgery (1990)

J.R. Smith Herman F. Flanigin D.W. King Jorge Aceves David Hung‐Chi Pan

10.1159/000100254

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Timing of TORC1 inhibition dictates Pol III involvement inCaenorhabditis eleganslongevity

Life Science Alliance (2024)

Yasir Malik Isabel Gonçalves Silva Rene Rivera Diazgranados Colin Selman Nazif Alic

Organismal growth and lifespan are inextricably linked. Target of Rapamycin (TOR) signalling regulates protein production for growth and development, but if reduced, extends lifespan across species. Reduction in the enzyme RNA polymerase III, which transcribes tRNAs and 5S rRNA, also extends longevity. Here, we identify a temporal genetic relationship between TOR and Pol III in Caenorhabditis elegans , showing that they collaborate to regulate progeny production and lifespan. Interestingly, the lifespan interaction between Pol III and TOR is only revealed when TOR signaling is reduced, specifically in adulthood, demonstrating the importance of timing to control TOR regulated developmental versus adult programs. In addition, we show that Pol III acts in C. elegans muscle to promote both longevity and healthspan and that reducing Pol III even in late adulthood is sufficient to extend lifespan. This demonstrates the importance of Pol III for lifespan and age-related health in adult C. elegans .

10.26508/lsa.202402735

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Citations (1)

Doença de Hodgkin: Experiência de 20 anos num Centro de Referência

Portuguese Journal of Pediatrics (2004)

Vitor Pereira Costa Tereza Oliva Isabel Gonçalves Silva Mariana Bento B.P. Sodré Borges

Objectivos: O objectivo deste estudo foi o de avaliar a sobrevivencia, frequencia de recidivas e sequelas em criancas com Doenca de Hodgkin tratadas neste servico nos ultimos vinte anos. Material e Metodos: Foi efectuado um estudo de coorte retrospectivo. Foram analisados os seguintes parâmetros: idade, sexo, data do diagnostico, tiemoglobina (Hb) (g/dl): 10,5, velocidade de sedimentacao (VS): > 40 mm/h e <40 mm/h, tipo histologico, estadio da doenca, tipo de tratamento, resposta inicial a quimioterapia (QT), toxicidade aguda, complicacoes tardias» recidivas e estado actual. Sobrevivencia livre de doenca (SLD) e sobrevivencia global (SG) foram determinadas desde a data do diagnostico ate a recidiva ou morte por qualquer causa, respectivamente. Para avaliar a importância das variaveis clinicas foi utilizado o teste de Log-Rank (resultado significativo p<0,05). Resultados: No Servico de Pediatria entre Abril de 1983 e Abril de 2002 foram tratadas cinquenta e sete criancas (33 do sexo masculino e 24 do sexo feminino) com idades compreendidas entre 2 e 14 anos (mediana 12 anos), portadoras de Doenca de Hodgkin(DH). De acordo com a classificacao de Ann Arbor, 15 doentes apresentavam DH estadio 1 (26%), 23 estadio 11 (40%), 14 estadio Hl(25%) e 5 doentes apresentavam DH estadio IV (9%). Os sintomas B estavam presentes em 15 doentes (26%). De acordo com a classificacao de RYE 36 criancas tinham esclerose nodular (64%), 11 celularidade mista (20%) e 9 predominio linfocitico (16%). De 1983 a 1998 foram tratadas 25 criancas de acordo com o protocolo ChlVPP/RT e desde 1999 18 criancas de acordo com o protocolo da SFOP MDH 90. Catorze criancas foram tratadas com outros protocolos. Radioterapia foi aplicada em 52 criancas (91%). Verificou-se remissao completa em 91% dos casos. Verificaram-se 2 obitos (12 meses e 3 anos apos o diagnostico, por DH e leucemia mieloblastica aguda respectivamente). Quatro doentes apresentaram neoplasias secundarias, 4 tiveram hipotiroidismo e 3 rapazes infertilidade. A primeira recaida verificou-se 40 meses apos o inicio da terapeutica com ChlVPP e 42 meses no grupo da SFOP MDH 90. Conclusao: No nosso grupo de 57 doentes, com um tempo mediano de seguimento de 67 meses (11 - 239 meses), a sobrevivencia livre de doenca foi de 89% e a sobrevivencia global foi de 97% aos 5 anos. A maioria das criancas com DH foi curada sem importantes efeitos adversos. Palavras-Chave: Doenca de Hodgkin, crianca, sobrevivencia

10.25754/pjp.2004.4938

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