Produção Nacional
Revisado por pares
Bruna Alves Fenerich, João Agostinho Machado‐Neto, Ana Paula Nunes Rodrigues Alves, Paula de Melo Campos, Jaqueline Cristina Fernandes, Juan Luiz Coelho‐Silva, Renata Scopim Ribeiro, Fernanda B da Silva, Priscila Santos Scheucher, Lorena Lôbo Figueiredo-Pontes, Eduardo Magalhães Rego, Fabı́ola Traina,
Abstract Introduction: The recurrent V617F mutation in JAK2 plays an important role in the pathogenesis of BCR-ABL1 negative myeloproliferative neoplasms (MPN). Absence of complete clinical response to ruxolitinib, a JAK1/2 inhibitor, highlights the need to target other signaling pathways that contribute to JAK2. Recent evidence indicates that the IGF1R/IRS pathway is a potential target in MPN: (i) insulin receptor substrate 2 (IRS2) cooperates with malignant transformation induced by JAK2V617F, and ( ...
Tópico(s): Cytokine Signaling Pathways and Interactions
2017 - Elsevier BV | Blood
Produção Nacional
Revisado por pares
João Agostinho Machado‐Neto, Bruna Alves Fenerich, Ana Paula Nunes Rodrigues Alves, Jaqueline Cristina Fernandes, Renata Scopim‐Ribeiro, Juan Luiz Coelho‐Silva, Fabı́ola Traina,
The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation.The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways).However, novel signaling axes involving IRS proteins (noncanonical ...
Tópico(s): Acute Myeloid Leukemia Research
2018 - Elsevier BV | Clinics
Produção Nacional
Revisado por pares
João Agostinho Machado‐Neto, Bruna Alves Fenerich, Renata Scopim‐Ribeiro, Christopher A. Eide, Juan Luiz Coelho‐Silva, Carlos Roberto Porto Dechandt, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Priscila Santos Scheucher, Belinda Pinto Simões, Luciane C. Alberici, Lorena Lôbo Figueiredo-Pontes, Cristina E. Tognon, Brian J. Druker, Eduardo Magalhães Rego, Fabı́ola Traina,
Abstract The recurrent gain-of-function JAK2 V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we ...
Tópico(s): Kruppel-like factors research
2018 - Springer Nature | Cell Death and Disease
Produção Nacional
Revisado por pares
Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, João Agostinho Machado‐Neto, Renata Scopim‐Ribeiro, Bruna Alves Fenerich, Fernanda Borges da Silva, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabı́ola Traina,
Insulin-like growth factor 1 (IGF1) and its receptor IGF1R regulate normal cell growth and contribute to cell transformation through activation of downstream signaling pathways. In fibroblast cells, insulin receptor substrate 1 (IRS1), through IGF1 signaling, was found to be the key protein for nuclear translocation of β-catenin and MYC transcription activation. We herein investigated the IRS1/β-catenin axis in acute lymphoblastic leukemia (ALL) cells. Samples were obtained from 45 patients with ALL ...
Tópico(s): Childhood Cancer Survivors' Quality of Life
2016 - Wiley | Journal of Cellular Biochemistry
Produção Nacional
Revisado por pares
Ana Paula Nunes Rodrigues Alves, Jaqueline Cristina Fernandes, Bruna Alves Fenerich, Juan Luiz Coelho‐Silva, Priscila Santos Scheucher, Belinda Pinto Simões, Eduardo Magalhães Rego, Anne J. Ridley, João Agostinho Machado‐Neto, Fabı́ola Traina,
The IGF1R/IRS1 signaling is activated in acute lymphoblastic leukemia (ALL) and can be targeted by the pharmacological inhibitors NT157 (IGF1R-IRS1/2 inhibitor) and OSI-906 (IGF1R/IR inhibitor). Here we investigate the cellular and molecular effects of NT157 and OSI-906 in ALL cells. NT157 and OSI-906 treatment reduced viability, proliferation and cell cycle progression in ALL cell lines. Similarly, in primary samples of patients with ALL, both OSI-906 and NT157 reduced viability, but only NT157 induced ...
Tópico(s): Growth Hormone and Insulin-like Growth Factors
2019 - Elsevier BV | Cancer Letters
Produção Nacional
Revisado por pares
Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Juan Luiz Coelho‐Silva, Renata Scopim‐Ribeiro, Priscila Santos Scheucher, Christopher A. Eide, Cristina E. Tognon, Brian J. Druker, Eduardo Magalhães Rego, João Agostinho Machado‐Neto, Fabı́ola Traina,
Abstract Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms (MPN); in this pathway, IRS2 is involved in the malignant transformation induced by JAK2 V617F , and upregulation of IGF1R signaling induces the MPN phenotype. NT157, a synthetic compound designed as an IGF1R-IRS1/2 inhibitor, has been shown to induce antineoplastic effects in solid tumors. Herein, we aimed to characterize the molecular and cellular effects of NT157 ...
Tópico(s): Acute Myeloid Leukemia Research
2020 - Springer Nature | Signal Transduction and Targeted Therapy
Produção Nacional
Revisado por pares
Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Juan Luiz Coelho‐Silva, Renata Scopim‐Ribeiro, Bruna Alves Fenerich, Belinda Pinto Simões, Eduardo Magalhães Rego, João Agostinho Machado‐Neto, Fabı́ola Traina,
Cyclin D1 is a protein essential for transition from G1 to S phase during cell cycle progression, which has an oncogenic potential and is highly expressed in several human malignancies. However, in view of the heterogeneity of the findings in the literature, the prognostic value of cyclin D1 expression still needs to be validated in different cohorts of adult acute lymphoblastic leukemia (ALL) patients. Bone marrow samples from 13 healthy donors and 45 adult patients with acute lymphoblastic leukemia ...
Tópico(s): Cancer-related Molecular Pathways
2018 - Springer Science+Business Media | Applied cancer research/Applied Cancer Research
Produção Nacional
Revisado por pares
Renata Scopim‐Ribeiro, João Agostinho Machado‐Neto, Christopher A. Eide, Juan Luiz Coelho‐Silva, Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Priscila Santos Scheucher, Samantha L. Savage, Paula de Melo Campos, Sara Teresinha Olalla Saad, Leonardo de Carvalho Palma, Lorena Lôbo Figueiredo-Pontes, Belinda Pinto Simões, Eduardo Magalhães Rego, Cristina E. Tognon, Brian J. Druker, Fabı́ola Traina,
Tópico(s): Acute Myeloid Leukemia Research
2021 - Springer Science+Business Media | Investigational New Drugs
Produção Nacional
Revisado por pares
João Agostinho Machado‐Neto, Ana Paula Nunes Rodrigues Alves, Jaqueline Cristina Fernandes, Juan Luiz Coelho‐Silva, Renata Scopim‐Ribeiro, Bruna Alves Fenerich, Fernanda Borges da Silva, Priscila Santos Scheucher, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabı́ola Traina,
Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by abnormal proliferation and accumulation of lymphoblasts in the hematopoietic system. Stathmin 1 is a proliferation marker for normal lymphocytes, which has been described as highly expressed in ALL patients and functionally important for leukemia phenotype. In the present study, we expand our previous observations and aim to investigate Stathmin 1 expression and its impact on laboratory features and clinical outcomes ...
Tópico(s): Epigenetics and DNA Methylation
2017 - Elsevier BV | Heliyon
Produção Nacional
Revisado por pares
MA Melo, NP Fonseca, ABA Silva, BA Fenerich, BGS Macedo, João Agostinho Machado‐Neto, F Traina,
Mutações no gene FLT3 atingem cerca de 30% dos pacientes com leucemia mieloide aguda (LMA), sendo a FLT3-ITD a mais frequente e relacionada a pior prognóstico. O desenvolvimento de inibidores de FLT3 representou um avanço no tratamento da LMA, pois reduzem a proliferação celular e melhoram a sobrevida dos pacientes. Contudo, a limitação clínica no tratamento com essas drogas representa uma oportunidade de investigar combinações de fármacos que resultem em melhores resultados terapêuticos. O presente ...
Tópico(s): Acute Myeloid Leukemia Research
2022 - Elsevier BV | Hematology Transfusion and Cell Therapy
Produção Nacional
João Batista Pamplona, João Lúcio de Azevedo Fenerich,
<p>O objetivo deste artigo é apresentar a evolução do debate em torno da ideia de centralidade ou não da indústria no desenvolvimento econômico brasileiro. O debate clássico no Brasil acerca da função exclusiva da indústria de transformação no desenvolvimento econômico está longe de ser resolvido. Continuam existindo dois grupos dominantes de autores com posições claramente delimitadas entre si. Um grupo heterodoxo continua defendendo a centralidade da indústria no desenvolvimento brasileiro. ...
Tópico(s): Economic Theory and Policy
2016 - UNIV. REGIONAL DO NOROESTE DO ESTADO DO RIO GRANDE DO SUL | Desenvolvimento em Questão
Produção Nacional
Revisado por pares
Natasha Peixoto Fonseca, Bruna Alves Fenerich, Diego A. Pereira‐Martins, Pedro Manoel Marques Garibaldi, Juan Luiz Coelho‐Silva, Antonio Bruno Alves Silva, Jaqueline Cristina Fernandes, Cleide Lucia Silva, Eduardo Magalhães Rego, João Agostinho Machado‐Neto, Fabı́ola Traina,
Introduction: In the light of the discovery of the CSF3R mutation in chronic neutrophilic leukemia (CNL) patients, the T618I mutation demonstrated to be a molecular marker and a possible target for new therapies due to the JAK/STAT signaling pathway activation [N Engl J Med (2013) 368(19):1781-90]. Since no curative treatment options are available for patients diagnosed with CNL, it is of interest the study new therapeutical approaches for these patients. In this regard, the treatment of JAK2V617F ...
Tópico(s): Chronic Lymphocytic Leukemia Research
2022 - Elsevier BV | Blood
Produção Nacional
Revisado por pares
João Cândido Fernandes, Bruna Alves Fenerich, Juan Luiz Coelho‐Silva, A.B. Alves da Silva, Priscila Santos Scheucher, Fernando Chahud, Eduardo Magalhães Rego, Lorena Lôbo Figueiredo-Pontes, JA Machado-Neto, Fabı́ola Traina,
Background: The recurrent V617F mutation in JAK2 confers growth factor‐independent proliferation for hematopoietic cells and plays an important role in the pathogenesis of myeloproliferative neoplasms (MPN). Absence of complete clinical remission in most MPN patients treated with the JAK1/2 inhibitor ruxolitinib highlights the need of new therapeutic strategies. Recent evidence indicates that IGF1R/IRS pathway is a potential target in MPN. In mice, AIRAPL down‐regulation induces MPN transformation ...
Tópico(s): Cytokine Signaling Pathways and Interactions
2019 - Wolters Kluwer | HemaSphere
Produção Nacional
Revisado por pares
Jaqueline Cristina Fernandes, Bruna Alves Fenerich, Antônio Bruno Alves-Silva, Natasha Peixoto Fonseca, Juan Luiz Coelho‐Silva, Priscila Santos Scheucher, Eduardo Magalhães Rego, Lorena Lôbo Figueiredo-Pontes, João Agostinho Machado‐Neto, Fabı́ola Traina,
Myeloproliferative neoplasms (MPN) belong to a group of clonal diseases of hematopoietic stem cells characterized by aberrant proliferation of mature myeloid lineages. The constitutive activation of the JAK2/STAT signaling pathway is now well established to play a central role in MPN pathogenesis; however, accumulating evidence now indicates that the IGF1R-mediated signaling pathway contributes to the maintenance of the malignant phenotype. Studies using inhibitors of IGF1-mediated signaling have ...
Tópico(s): Eosinophilic Disorders and Syndromes
2022 - Elsevier BV | Toxicology in Vitro
Produção Nacional
Revisado por pares
João Agostinho Machado‐Neto, Bruna Alves Fenerich, Renata Scopim‐Ribeiro, Carlos Roberto Porto Dechandt, Ana Paula Nunes Rodrigues Alves, Jaqueline Cristina Fernandes, Priscila Santos Scheucher, Belinda Pinto Simões, Luciane C. Alberici, Lorena Lôbo Figueiredo-Pontes, Eduardo Magalhães Rego, Fabı́ola Traina,
Abstract Background: The recurrent JAK2V617F gain-of-function mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that inhibits the mitochondrial complex I and metformin antineoplastic activity has been ...
Tópico(s): Chronic Myeloid Leukemia Treatments
2016 - Elsevier BV | Blood
Ana Paula Nunes Rodrigues Alves, João Agostinho Machado Neto, Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabı́ola Traina,
Tópico(s): Acute Lymphoblastic Leukemia research
2017 - Elsevier BV | Revista Brasileira de Hematologia e Hemoterapia
Produção Nacional
Revisado por pares
BA Fenerich, AB Alves-Silva, NP Fonseca, JC Fernandes, JL Coelho-Silva, CLA Silva, PS Scheucher, João Agostinho Machado‐Neto, F Traina,
O substrato do receptor de insulina 2 (IRS2) interage com receptores envolvidos no processo hematopoético e sua expressão é reduzida em pacientes com síndrome mielodisplásica. Em trabalho anterior, nosso grupo descreveu os resultados da avaliação da reconstituição da hematopoese a curto prazo após transplante de medula óssea (TMO) de camundongos nocaute para Irs2 (Irs2 KO) em receptores C57BL/6. A análise, 4 e 8 semanas após o transplante, evidenciou uma redução nos níveis de hemácias, hematócrito ...
Tópico(s): Hematopoietic Stem Cell Transplantation
2021 - Elsevier BV | Hematology Transfusion and Cell Therapy
Produção Nacional
Revisado por pares
Ana Paula Nunes Rodrigues Alves, João Agostinho Machado‐Neto, Jaqueline Cristina Fernandes, Bruna Alves Fenerich, Fernanda Borges da Silva, Priscila Santos Scheucher, Belinda Pinto Simões, Eduardo Magalhães Rego, Fabı́ola Traina,
Abstract Background: Acute lymphoblastic leukemia (ALL) is an aggressive cancer of immature progenitors that shows aberrant activation of signaling pathways. The IGF1/IGF1R signaling pathway is initiated through binding of the ligand (IGF1) to its transmembrane receptor (IGF1R), and subsequent activation of IRS1 and IRS2 proteins activating PI3K/Akt/mTOR and MAPK pathways, which are important signaling pathways reported to contributes to pathogenesis of ALL. However, the therapeutic potential of IGF1R/ ...
Tópico(s): Lung Cancer Treatments and Mutations
2016 - Elsevier BV | Blood
Produção Nacional
Revisado por pares
Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Cleide Lúcia Araújo Silva, Juan Luiz Coelho‐Silva, Antonio Bruno Alves Silva, Natasha Peixoto Fonseca, João Agostinho Machado‐Neto, Fabı́ola Traina,
Introduction: Pharmacological inhibition of insulin receptor substrate 1 (IRS1) protein has been demonstrated to promote antineoplastic effects in hematological disorders, including myeloproliferative neoplasms, chronic myeloid leukemia and acute lymphoblastic leukemia. However, the role of IRS1 in normal hematopoiesis has not yet been elucidated. In this scenario, using a murine Irs1 knockout model represents an interesting tool to evaluate the role of this gene in normal hematopoiesis. B6.129S2- ...
Tópico(s): Acute Myeloid Leukemia Research
2020 - Elsevier BV | Blood
Produção Nacional
Revisado por pares
Antônio Bruno Alves-Silva, Bruna Alves Fenerich, Natasha Peixoto Fonseca, Jaqueline Cristina Fernandes, Juan Luiz Coelho‐Silva, Diego A. Pereira‐Martins, Thiago Mantello Bianco, Priscila Santos Scheucher, Eduardo Magalhães Rego, Fernando Chahud, João Agostinho Machado‐Neto, Lorena Lôbo Figueiredo-Pontes, Fabı́ola Traina,
Background. Myeloproliferative neoplasms (MPN) are disorders characterized by an alteration at the hematopoietic stem cell (HSC) level, where the JAK2 mutation is the most common genetic alteration found in classic MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis). We and others previously demonstrated that metformin reduced splenomegaly and platelets counts in peripheral blood in JAK2V617F pre-clinical MPN models, which highlighted the antineoplastic potential of biguanides ...
Tópico(s): Acute Myeloid Leukemia Research
2022 - Springer Science+Business Media | Investigational New Drugs
Produção Nacional
Revisado por pares
BA Fenerich, A.B. Alves-Silva, Natasha Peixoto Fonseca, Julio Fernandes, Juan Luiz Coelho‐Silva, TM Bianco, C.L.A. Silva, Priscila Santos Scheucher, Lorena Lôbo Figueiredo-Pontes, Eduardo Magalhães Rego, João Agostinho Machado‐Neto, Fabı́ola Traina,
2020 - Elsevier BV | Hematology Transfusion and Cell Therapy
Produção Nacional
Revisado por pares
João Agostinho Machado‐Neto, Renata Scopim Ribeiro, Juan Luiz Coelho‐Silva, Christopher A. Eide, Bruna Alves Fenerich, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Priscila Santos Scheucher, Cristina E. Tognon, Lorena Lôbo Figueiredo-Pontes, Brian J. Druker, Eduardo Magalhães Rego, Fabı́ola Traina,
Abstract Introduction : The recurrent gain-of-function JAK2V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). Metformin (1,1-dimethylbiguanide) is a biguanide widely prescribed for the treatment of type II diabetes and metabolic syndromes. In recent years, studies using cancer cell lines and murine models have provided evidence for potential anticancer activity of metformin. Previous ...
Tópico(s): Kruppel-like factors research
2017 - Elsevier BV | Blood