Data documento
06/05/2024

Título
3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells

Autor(es)
Vital P.D.S. - Bonatelli M, - Dias M.P. - de Salis L.V.V. - Pinto M.T. - Baltazar F. - Maria-Engler S.S. - Pinheiro C.

Palavras chave
drug resistance - melanoma - metabolism - proto-oncogene protein B-raf - vemurafenib

Resumo
(1) BRAF mutations are associated with high mortality and are a substantial factor in therapeutic decisions. Therapies targeting BRAF-mutated tumors, such as vemurafenib (PLX), have significantly improved the overall survival of melanoma patients. However, patient relapse and low response rates remain challenging, even with contemporary therapeutic alternatives. Highly proliferative tumors often rely on glycolysis to sustain their aggressive phenotype. 3-bromopyruvate (3BP) is a promising glycolysis inhibitor reported to mitigate resistance in tumors. This study aimed to evaluate the potential of 3BP as an antineoplastic agent for PLX-resistant melanoma treatment. (2) The effect of 3BP alone or in combination with PLX on viability, proliferation, colony formation, cell death, migration, invasion, epithelial-mesenchymal marker and metabolic protein expression, extracellular glucose and lactate, and reactive species were evaluated in two PLX-resistant melanoma cell lines. (3) 3BP treatment, which was more effective as monotherapy than combined with PLX, disturbed the metabolic and epithelial-mesenchymal profile of PLX-resistant cells, impairing their proliferation, migration, and invasion and triggering cell death. (4) 3BP monotherapy is a potent metabolic-disrupting agent against PLX-resistant melanomas, supporting the suppression of the malignant phenotype in this type of neoplasia.

Citação
Vital PDS, Bonatelli M, Dias MP, de Salis LVV, Pinto MT, Baltazar F, Maria-Engler SS, Pinheiro C. 3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells. Int J Mol Sci. 2022 Dec 9;23(24):15650. doi: 10.3390/ijms232415650. PMID: 36555289; PMCID: PMC9779063.

Data documento
13/03/2025

Título
A Research Protocol for a Phase II Single-Arm Clinical Trial Assessing the Feasibility and Efficacy of Neoadjuvant Anastrozole in Patients With Luminal Breast Cancer and Low Proliferative Index: The ANNE Trial

Autor(es)
Carlos Eduardo Paiva - Alinne Tatiane Faria Silva - Izabella da Silva Oliveira - Vitor Souza Guimarães - Domício Carvalho Lacerda - Gustavo Ramos Teixeira - Anapaula Hidemi Uema Watanabe - Nilton Onari - Bianca Sakamoto Ribeiro Paiva - Idam de Oliveira-Junior - Marcia Maria Chiquitelli Marques - Yara Cristina de Paiva Maia.

Palavras chave
breast cancer - endocrine therapy - neoadjuvant - therapeutic response - anastrozole

Resumo
Introduction: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. Aims: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). Methods: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

Citação
Paiva CE, Silva ATF, Oliveira IDS, Guimarães VS, Lacerda DC, Teixeira GR, Watanabe AHU, Onari N, Paiva BSR, Oliveira-Junior I, Marques MMC, Maia YCP. Cancer Control. 2024 Jan-Dec;31:10732748241272463. doi: 10.1177/10732748241272463. PMID: 39140157

Data documento
06/05/2024

Título
Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients

Autor(es)
Teixeira S.A. - Burim R.V. - Viapiano M.S. - Bidinotto L.T. - Nagashi Marie S.K. - Fleury Malheiros S.M. - Oba-Shinjo S.M. - Andrade A.F. - Carlotti C.G.

Palavras chave
ITGA2 - brain microenvironment - extracellular matrix - invasion - low grade glioma - single nucleotide polymorphism - tumor progression

Resumo
Integrins are heterodimeric transmembrane glycoproteins resulting from the non-covalent association of an α and β chain. The major integrin receptor for collagen/laminin, α2β1 is expressed on a wide variety of cell types and plays an essential role in the adhesion of normal and tumor cells to the extracellular matrix. Integrin-triggered signaling pathways promote the invasion and survival of glioma cells by modifying the brain microenvironment. In this study, we investigated the association of a specific genetic polymorphism of integrin α2β1 with the incidence of diffusely infiltrating astrocytoma and the progression of these tumors. Single-nucleotide polymorphism in intron 7 of the integrin ITGA2 gene was examined in 158 patients and 162 controls using polymerase chain reaction and restriction enzyme analysis. The ITGA2 genotype +/+ (with a BglII restriction site in both alleles) exhibited higher frequency in grade II astrocytoma compared to control (P = 0.02) whereas the genotype -/- (lacking the BglII site) correlated with the poorest survival rate (P = 0.04). In addition, in silico analyses of ITGA2 expression from low-grade gliomas (LGG, n = 515) and glioblastomas (GBM, n = 159) indicated that the higher expression of ITGA2 in LGG was associated with poor overall survival (P < 0.0001). However, the distribution of integrin ITGA2 BglII genotypes (+/+, +/-, -/-) was not significantly different between astrocytoma subgroups III and IV (P = 0.65, 0.24 and 0.33; 0.29, 0.48, 0.25, respectively) compared to control. These results suggest a narrow association between the presence of this SNP and indicate that further studies with larger samples are warranted to analyze the relation between tumor grade and overall survival, highlighting the importance of determining these polymorphisms for prognosis of astrocytomas.

Citação
Teixeira SA, Burim RV, Viapiano MS, Bidinotto LT, Nagashi Marie SK, Fleury Malheiros SM, Oba-Shinjo SM, Andrade AF, Carlotti CG. Alpha2beta1 Integrin Polymorphism in Diffuse Astrocytoma Patients. Front Oncol. 2022 Jul 22;12:914156. doi: 10.3389/fonc.2022.914156. PMID: 35936750; PMCID: PMC9353741.

Data documento
06/05/2024

Título
ANÁLISE VACINAL DE ESTUDANTES EM UMA FACULDADE DE MEDICINA

Autor(es)
Modiano P,, Herrero A.L.O. - Silveira A.F. - Piai R.C. - Veríssimo V.H.M. - Moreira M.L.F.F. - Fabbro N. - Pileggi G.S.

Palavras chave
Estudantes de medicina - Conhecimento - Risco - Vacinação - Vacinas

Resumo
Objetivo: O estudo analisa a situação vacinal dos estudantes de medicina de uma faculdade do interior de São Paulo, além de verificar seu conhecimento em relação à imunização. Método: Foi realizada a análise na carteira vacinal de 277 estudantes de medicina e disponibilizado um questionário autoaplicável. A análise dos dados foi conduzida de maneira estatística descritiva para interpretação dos resultados. Resultados: Verificou-se que mais da metade dos estudantes apresentam carteiras vacinais desatualizadas e poucos conhecem quais vacinas são indicadas aos profissionais de saúde, embora mais da metade dos estudantes reconheça o risco de contágio e transmissão de doenças relacionadas ao esquema vacinal incompleto. Conclusão: Esses resultados demonstram a necessidade de conscientização dos acadêmicos de medicina quanto à atualização de seus cartões vacinais e do aprofundamento do conhecimento e domínio sobre o tema vacinação.

Citação
Modiano P, Herrero ALO, Silveira AF, Piai RC, Veríssimo VHM, Moreira MLFF, Fabbro N, Pileggi GS. Análise vacinal de estudantes em uma faculdade de medicina. Rev Enferm Atenção Saúde [Internet]. 2023 [acesso em:____]; 12(2):e202377. DOI: https://doi.org/ 10.18554/reas.v12i2.5681

Data documento
06/05/2024

Título
Aspectos psicológicos na recidiva do câncer colorretal: revisão integrativa

Autor(es)
Ramos, L. N. de S. - Ducatti, M.

Palavras chave
Neoplasia - Psico-oncologia - Recidiva

Resumo
Objetivo: Realizar uma revisão integrativa acerca dos aspectos psicológicos que envolvem a recidiva em pacientes após o tratamento de câncer colorretal e identificar as intervenções e instrumentos de maior validade dentro das estratégias propostas no campo da psicologia. Métodos: Trata-se de uma revisão integrativa, realizada nas bases de dados Pubmed, Cochrane Library e Biblioteca Virtual de Saúde (BVS). Utilizou-se os seguintes descritores para a realização da estratégia de busca: Recurrence, Psychological Aspects e Colorectal Neoplasm. Resultados: Após a inserção da estratégia de busca nas bases de dados, 19 artigos foram encontrados. Realizou a análise dos artigos com base nos critérios de inclusão e exclusão e 11 estudos foram selecionados para este trabalho. Considerações finais: Os resultados evidenciaram escassez de estudos sobre o tema. Identificou-se que a principal demanda psicológica identificada foi o medo; e que se faz o uso de diversos instrumentos para quantificar queixas e aspectos psicológicos sobre o tema citado.

Citação
RamosL. N. de S., & DucattiM. (2023). Aspectos psicológicos na recidiva do câncer colorretal: revisão integrativa. Revista Eletrônica Acervo Saúde, 23(3), e10662. https://doi.org/10.25248/reas.e10662.2023

Data documento
06/05/2024

Título
Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort

Autor(es)
Tostes F.T. - de Carvalho P.F.D.C. - Araújo R.L.C. - Ribeiro R.C. - Apodaca-Torrez F.R. - Lobo E.J. - Gomes D.B.D. - Callegaro-Filho D. - Schvartsman G. - Moura F. - Schraibman V. - Goldenberg A. - de Lima F.T. - Segatelli V. - Uson Junior P.L.S.

Palavras chave
Frantz tumor - Li-Fraumeni syndrome - pancreatic tumor - solid pseudopapillary pancreatic neoplasm

Resumo
Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.

Citação
Tostes FT, de Carvalho PFDC, Araújo RLC, Ribeiro RC, Apodaca-Torrez FR, Lobo EJ, Gomes DBD, Callegaro-Filho D, Schvartsman G, Moura F, Schraibman V, Goldenberg A, de Lima FT, Segatelli V, Uson Junior PLS. Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort. Genes (Basel). 2022 Oct 6;13(10):1809. doi: 10.3390/genes13101809. PMID: 36292694; PMCID: PMC9601385.

Data documento
06/05/2024

Título
Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines

Autor(es)
Gomes I.N.F. - da Silva-Oliveira R.J. - da Silva L.S. - Martinho O. - Evangelista A.F. - van Helvoort Lengert A. - Leal L.F. - Silva V.A.O. - Dos Santos S.P. - Nascimento F.C. - Lopes Carvalho A. - Reis R.M.

Palavras chave
EGFR - biomarkers - cetuximab - drug resistance - head and neck tumors - in vitro - pre-clinical

Resumo
Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eight months. The resistance and parental cells were evaluated for cell viability and functional assays. Protein expression was analyzed by Western blot and human cell surface panel by lyoplate. The mutational profile and copy number alterations (CNA) were analyzed using whole-exome sequencing (WES) and the NanoString platform. FaDu resistant clones exhibited at least two-fold higher IC50 compared to the parental cell line. WES showed relevant mutations in several cancer-related genes, and the comparative mRNA expression analysis showed 36 differentially expressed genes associated with EGFR tyrosine kinase inhibitors resistance, RAS, MAPK, and mTOR signaling. Importantly, we observed that overexpression of KRAS, RhoA, and CD44 was associated with cetuximab resistance. Protein analysis revealed EGFR phosphorylation inhibition and mTOR increase in resistant cells. Moreover, the resistant cell line demonstrated an aggressive phenotype with a significant increase in adhesion, the number of colonies, and migration rates. Overall, we identified several molecular alterations in the cetuximab resistant cell line that may constitute novel biomarkers of cetuximab response such as mTOR and RhoA overexpression. These findings indicate new strategies to overcome anti-EGFR resistance in HNSCC.

Citação
Gomes INF, da Silva-Oliveira RJ, da Silva LS, Martinho O, Evangelista AF, van Helvoort Lengert A, Leal LF, Silva VAO, Dos Santos SP, Nascimento FC, Lopes Carvalho A, Reis RM. Comprehensive Molecular Landscape of Cetuximab Resistance in Head and Neck Cancer Cell Lines. Cells. 2022 Jan 4;11(1):154. doi: 10.3390/cells11010154. PMID: 35011716; PMCID: PMC8750399.

Data documento
07/05/2024

Título
COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data

Autor(es)
Marques CDL, Ribeiro SLE, Albuquerque CP, de Sousa Studart SA, Ranzolin A, de Andrade NPB, Dantas AT, Mota GD, Resende GG, Marinho AO, Angelieri D, Andrade D, Ribeiro FM, Omura F, Silva NA, Rocha Junior L, Brito DE, Fernandino DC, Yazbek MA, Souza MPG, Ximenes AC, Martins ASS, Castro GRW, Oliveira LC, Freitas ABSB, Kakehasi AM, Gomides APM, Reis Neto ET, Pileggi GS, Ferreira GA, Mota LMH, Xavier RM, de Medeiros Pinheiro M.

Palavras chave
COVID-19 - Hospitalization - Psoriatic arthritis - SARS-CoV-2 - Spondyloarthritis

Resumo
Objectives: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). Methods: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. Results: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. Conclusions: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Citação
Marques CDL, Ribeiro SLE, Albuquerque CP, de Sousa Studart SA, Ranzolin A, de Andrade NPB, Dantas AT, Mota GD, Resende GG, Marinho AO, Angelieri D, Andrade D, Ribeiro FM, Omura F, Silva NA, Rocha Junior L, Brito DE, Fernandino DC, Yazbek MA, Souza MPG, Ximenes AC, Martins ASS, Castro GRW, Oliveira LC, Freitas ABSB, Kakehasi AM, Gomides APM, Reis Neto ET, Pileggi GS, Ferreira GA, Mota LMH, Xavier RM, de Medeiros Pinheiro M; ReumaCoV-Brasil Registry. COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data. Adv Rheumatol. 2022 Nov 22;62(1):45. doi: 10.1186/s42358-022-00268-x. PMID: 36419163; PMCID: PMC9685130.

Data documento
06/05/2024

Título
Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets

Autor(es)
Marques R.F. - Moreno D.A. - da Silva L. - Leal L.F. - de Paula F.E. - Santana I. - Teixeira G. - Saggioro F. - Neder L. - Junior C.A. - Mançano B. - Reis R.M.

Palavras chave
immune checkpoints - immune profile - immunotherapy - medulloblastoma - nCounter mRNA expression assay

Resumo
Introduction: Medulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy. However, many patients do not respond to therapy, and most suffer severe side effects. Cancer immunotherapy targeting immune checkpoints (IC) (PD-1, PD-L1, and CTLA4) has been getting disappointing outcomes in brain tumors. Nevertheless, other less explored immune checkpoints may be promising candidates for medulloblastoma therapy. Objectives: In the present study, we aimed to characterize the expression profile of 19 immune checkpoints in medulloblastoma. Methods: We analyzed 88 formalin-fixed paraffin-embedded medulloblastomas previously classified for each molecular subgroup and three non-tumoral brain tissue. mRNA levels of 19 immune checkpoint-related genes were quantified using the nCounter (PanCancer Immune Profiling Panel) assay. Further in silico analysis was performed in two larger public microarray datasets, one of which enabled comparisons between tumoral and non-tumoral tissues. Immunohistochemistry of PD-L1 was performed in a subset of cases. Microsatellite instability was also molecularly analyzed. Results: We observed an absence of expression of the canonic ICs, namely PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, as well as CD80, CD86, BTLA, IDO1, CD48, TNFSF14, CD160, CEACAM1, and CD244. PD-L1 protein expression was also practically absent. We found higher mRNA levels of CD24, CD47, CD276 (B7-H3), and PVR, and lower mRNA levels of HAVCR2, LAG3, and TIGIT genes, with significant differences across the four molecular subgroups. Compared to the non-tumor tissues, the expression levels of CD276 in all subgroups and CD24 in SHH, Group 3, and Group 4 subgroups are significantly higher. The in silico analysis confirmed the expression profile found in the Brazilian cohort, including the lower/absent expression of the canonic ICs. Moreover, it confirmed the overexpression of CD24 and CD276 in medulloblastomas compared with the non-tumor tissue. Additionally, CD276 and CD24 high levels were associated with worse survival. Conclusion: These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.

Citação
Marques RF, Moreno DA, da Silva L, Leal LF, de Paula FE, Santana I, Teixeira G, Saggioro F, Neder L, Junior CA, Mançano B, Reis RM. Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets. Front Immunol. 2023 Feb 7;14:1062856. doi: 10.3389/fimmu.2023.1062856. PMID: 36825029; PMCID: PMC9941636.

Data documento
03/05/2024

Título
EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome

Autor(es)
da Costa BHB, - Becker AP, - Neder L, - Gonçalves PG, - de Oliveira C, - Polverini AD, - Clara CA, - Teixeira GR, - Reis RM, - Bidinotto LT.

Palavras chave
EGFL7 - Glioblastoma IDH-wildtype - Notch pathway - PI3K-Akt pathway - Rap1 pathway

Resumo
Background: Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent to identity biomarkers of prognosis, treatment response, or development of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astrocytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches. Methods: Spearmans correlation analysis of The Cancer Genome Atlas RNA sequencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients samples, and was associated with clinicopathological data and overall survival. Results: In silico analysis found 78 genes strongly correlated to EGFL7 expression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase-Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expression in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041). Conclusions: This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology.

Citação
da Costa BHB, Becker AP, Neder L, Gonçalves PG, de Oliveira C, Polverini AD, Clara CA, Teixeira GR, Reis RM, Bidinotto LT. EGFL7 expression profile in IDH-wildtype glioblastomas is associated with poor patient outcome. J Pathol Transl Med. 2022 Jul;56(4):205-211. doi: 10.4132/jptm.2022.04.22. Epub 2022 Jun 15. PMID: 35698739; PMCID: PMC9288890.

Data documento
02/05/2024

Título
EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil

Autor(es)
Alves Pinto I, - de Oliveira Cavagna R, - Virginio da Silva AL, - Dias JM, - Santana IV, - Souza LC, - Ferreira da Silva FA, - Biazotto Fernandes MF, - Junqueira Pinto GD, - Negreiros IS, - Santiago Gonçalves MF, - de Paula FE, - Berardinelli GN, - Casagrande GMS, - Oliveira da Silva M, - Albino da Silva EC, - de Oliveira MA, - Jacinto AA, - Duval da Silva V, - Reis RM, - De Marchi P, - Leal LF.

Resumo
Background: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. Methods: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher’s test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. Results: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). Conclusion: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.

Citação
Alves Pinto I, de Oliveira Cavagna R, Virginio da Silva AL, Dias JM, Santana IV, Souza LC, Ferreira da Silva FA, Biazotto Fernandes MF, Junqueira Pinto GD, Negreiros IS, Santiago Gonçalves MF, de Paula FE, Berardinelli GN, Casagrande GMS, Oliveira da Silva M, Albino da Silva EC, de Oliveira MA, Jacinto AA, Duval da Silva V, Reis RM, De Marchi P, Leal LF. EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil. Oncologist. 2022 Nov 3;27(11):e899-e907. doi: 10.1093/oncolo/oyac167. PMID: 36099421; PMCID: PMC9632322.

Data documento
02/05/2024

Título
ERBB2 exon 20 insertions are rare in Brazilian non-small cell lung cancer

Autor(es)
Cavagna, R.O. - Zaniolo, B. G. - Paula, F.E. - Berardinelli, G.N. - Santana, I. - Silva, E.C.A. - Dias, J. M. - Jacinto, A.A. - Oliveira, R.E.N.N. - Marchi, P. - Leal, L.F. - Reis, R.M.

Palavras chave
Brazil - ERBB2 - exon 20 insertions - non-small cell lung cancer

Resumo
ERBB2 exon 20 insertions may impact the clinical management of lung cancer patients. However, the frequency of ERBB2 exon 20 insertions in lung cancer patients in Brazil is scarce. Here, we analyzed 722 Brazilian non-small cell lung cancer (NSCLC) patients from Barretos Cancer Hospital that were indicated to require routine lung cancer molecular testing. ERBB2 exon 20 insertions were evaluated by a targeted panel using next-generation sequencing (NGS). Clinicopathological and molecular data were collected from patient medical records. Among the 722 NSCLC patients, 85.2% had lung adenocarcinomas, 53.9% were male, 66.8% were quitter or current smokers, and 63.2% were diagnosed at an advanced stage of the disease. We identified 0.8% (6/722) of patients who harbored the insertion p. (Tyr772_Ala775dup) at exon 20 of the ERBB2 gene. All ERBB2 mutated patients were diagnosed with lung adenocarcinoma, were never smokers, and wild-type for EGFR, KRAS, and ALK hotspot alterations. Less than 1% of Brazilian NSCLC patients harbor ERBB2 exon 20 insertions, yet they could benefit in future from the new drugs in development.

Citação
de Oliveira Cavagna R, Zaniolo BG, de Paula FE, Berardinelli GN, Santana I, da Silva ECA, Dias JM, Jacinto AA, da Nóbrega Oliveira REN, de Marchi P, Leal LF, Reis RM. ERBB2 exon 20 insertions are rare in Brazilian non-small cell lung cancer. Thorac Cancer. 2022 Dec;13(23):3402-3407. doi: 10.1111/1759-7714.14605. Epub 2022 Oct 17. PMID: 36251951; PMCID: PMC9715798.

Data documento
02/05/2024

Título
Establishment and molecular characterization of HCB‑541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

Autor(es)
LAUS, Ana Carolina - GOMES, Izabela Natalia Faria - SILVA, Aline Larissa Virginio da - SILVA, Luciane Sussuchi da - MILAN, Mirella Baroni - TEIXEIRA, Silvia Aparecida - MARTINS, Ana Carolina Baptista Moreno - PEREIRA, Letícia do Nascimento Braga - CARVALHO, Carlos Eduardo Barbosa de - CROVADOR, Camila Souza - PAULA, Flávia Escremin de - NASCIMENTO, Flávia Caroline - FREITAS, Helder Teixeira de - VAZQUEZ, Vinicius de Lima - REIAS, Rui Manuel - OLIVEIRA, Renato José da Silva.

Palavras chave
Cutaneous squamous cell carcinoma - Molecular profile - Cell line establishment - In vivo model

Resumo
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line. Hum Cell. 2024 Apr 3. doi: 10.1007/s13577-024-01054-1. Epub ahead of print. PMID: 38565739.

Data documento
19/03/2025

Título
Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line.

Autor(es)
Laus AC - Gomes INF - da Silva ALV - da Silva LS - Milan MB - AparecidaTeixeira S - Martin ACBM - do Nascimento Braga Pereira L - de Carvalho CEB - Crovador CS - de Paula FE - Nascimento FC - de Freitas HT - de Lima Vazquez V - Reis RM - da Silva-Oliveira RJ

Palavras chave
Cell line establishment; Cutaneous squamous cell carcinoma; In vivo model; Molecular profile.

Resumo
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Citação
Laus AC, Gomes INF, da Silva ALV, da Silva LS, Milan MB, AparecidaTeixeira S, Martin ACBM, do Nascimento Braga Pereira L, de Carvalho CEB, Crovador CS, de Paula FE, Nascimento FC, de Freitas HT, de Lima Vazquez V, Reis RM, da Silva-Oliveira RJ. Hum Cell. 2024 Jul;37(4):1170-1183. doi: 10.1007/s13577-024-01054-1. Epub 2024 Apr 3. PMID: 38565739

Data documento
06/05/2024

Título
Factors associated with unsatisfactory cosmetic results in oncoplastic surgery

Autor(es)
de Oliveira-Junior I. - da Costa Vieira R.A. - Biller G. - Sarri A.J. - da Silva F.C.B. - Nahás E.A.P.

Palavras chave
breast cancer - conservative surgery - breast-conserving surgery - oncoplastic surgery - cosmesis

Resumo
Introduction Oncoplastic surgery (OS) has expanded the indications for breast-conserving surgery associated with an adequate aesthetic result. However, few studies have described the factors associated with unsatisfactory cosmetic outcomes from this surgical modality. Materials and methods This is a cross-sectional prospective study that included patients undergoing breast-conserving surgery (BCS) with or without OS. The patients self-evaluated the cosmetic results of the breasts posttreatment and had them photographed. The photos were analyzed by BCCT.core. Individual and treatment factors (local and systemic) for all patients were evaluated. These factors were dichotomized according to the use of OS and to the cosmetic result (satisfactory and unsatisfactory). Categorical variables were tested for association with surgical outcome using the chi-square test while numerical variables using the Mann−Whitney U test. Variables with p <0,2 were selected for multivariate analysis. Results Of the 300 patients evaluated, 72 (24,0%) underwent OS. According to the patient self-evaluations, an unsatisfactory cosmetic result from OS was significantly associated with younger age at diagnosis, higher body mass index (BMI) at the time of evaluation, larger tumor size and greater weight of the surgical specimen. According to the BCCT.core, only the laterality of the tumor (left) was significantly associated with an unsatisfactory cosmetic result. In logistic regression, considering OS as a control variable, the risk of an unsatisfactory outcome according to patient self-evaluation was related to the tumor ≥ T2 odds ratio (OR) 1,85 (1,027-3,34) and age at diagnosis < 40 [OR 5,0 (1,84-13,95)]. However, according to the software, the variables were associated with an increased risk of an unsatisfactory outcome were the time interval between surgery and evaluation [OR 1,27 (1,16-1,39)], the presence of lymphedema [OR 2,97 (1,36-6,46)], surgical wound infection [OR 3,6 (1,22-11,16)], tumor location on the left side [OR 3,06 (1,69-5,53)], overweight [OR 2,93 (1,48-5,8)] and obesity [OR 2,52 (1,2-5,31)]. Conclusion There is no standard methodology for breast cosmesis evaluation, which influences the factors associated with unsatisfactory results. Younger patients and those with increased BMI, left breast cancer and extensive resections tend to present with unsatisfactory cosmetic results when OS is performed.

Citação
de Oliveira-Junior I, da Costa Vieira RA, Biller G, Sarri AJ, da Silva FCB, Nahás EAP. Factors associated with unsatisfactory cosmetic results in oncoplastic surgery. Front Oncol. 2023 Jul 24;13:1071127. doi: 10.3389/fonc.2023.1071127. PMID: 37554162; PMCID: PMC10405917.

Data documento
18/10/2024

Título
Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC

Autor(es)
Pedro De Marchi - Leticia Ferro Leal - Luciane Sussuchi da Silva - Rodrigo de Oliveira Cavagna - Flavio Augusto Ferreira da Silva - Vinicius Duval da Silva - Eduardo Ca da Silva - Augusto O Saito - Vladmir C Cordeiro de Lima - Rui Manuel Reis.

Palavras chave
GEP; Gama interferon; Immunotherapy; Lung-tumor signature; NSCLC; Non-small cell lung cancer; PD-L1; TIS; anti-CTLA-4; anti-PD-(L)1; gene expression profile.

Resumo
Background: Immune checkpoint inhibitors (ICIs) revolutionized non-small-cell lung cancer (NSCLC) treatment. However, improving patients selection for this therapy is needed. Gene expression profile (GEP) is a promising biomarker tool. We assessed the predictive value of 48 onco-immune GEPs in an NSCLC real-world scenario. Methods: Retrospective cohort of Brazilian NSCLC patients treated with ICIs in any line. GEP was assessed in FFPE tumor tissue using the nCounter PanCancer IO360 panel, comprising 770 cancer immune genes. Results: The median age of the 135 patients was 61 years old, most male (57.8 %), history of smoking (83.6 %), ECOG-PS 0-1 (88.7 %), clinical stage IV (91.9 %) and adenocarcinoma (65.1 %). First-line ICI in 40 % of cases, alone or in combination with chemotherapy. The median follow-up was 28 months, overall survival after starting immunotherapy (post-immunotherapy survival - PIS) was 17.8 months, and real-world progression-free survival was 5.5 months. The GEP analysis was possible in 66 patients. We found that 14 different GEPs associated with PIS, namely IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM. TIS and IFN-γ were the most significant GEPs associated with favorable outcomes. The median PIS for patients with high TIS expression was 29.2 versus 15.5 months (HR 0.42; 95 %CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-γ. Conclusions: The TIS (tumor inflammation signature) and IFN-γ signatures constitute predictive biomarkers to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

Citação
Gene expression profiles (GEPs) of immuno-oncologic pathways as predictors of response to checkpoint inhibitors in advanced NSCLC. De Marchi P, Leal LF, da Silva LS, Cavagna RO, da Silva FAF, da Silva VD, da Silva EC, Saito AO, de Lima VCC, Reis RM.Transl Oncol. 2024 Jan;39:101818. doi: 10.1016/j.tranon.2023.101818. Epub 2023 Oct 31.PMID: 37918166

Data documento
06/05/2024

Título
Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing

Autor(es)
Garcia F.A.O. - Evangelista A.F. - Mançano B.M. - Moreno D.A. - Berardinelli G.N. - de Paula F.E. - Antoniazzi A.P. - Júnior C.A. - Lombardi I. - Santana I. - Teixeira G.R. - Costa C.E. - Reis R.M.

Palavras chave
neoplasm of the nervous system

Resumo
Choroid plexus tumors (CPTs) are rare intracranial neoplasms, representing <1% of all brain tumors, yet they represent 20% of first-year pediatric brain tumors. Although these tumors have been linked to TP53 germline mutations in the context of Li-Fraumeni syndrome, their somatic driver alterations remain poorly understood. In this study, we report two cases of lateral ventricle tumors: 3-yr-old male diagnosed with an atypical choroid plexus papilloma (aCPP), and a 6-mo-old female diagnosed with a choroid plexus carcinoma (CPC). We performed whole-exome sequencing of paired blood and tumor tissue in both patients, categorized somatic variants, and determined copy-number alterations. Our analysis revealed a tier II variant (Association for Molecular Pathology [AMP] criteria) in BRD1, a H3 and TP53 acetylation agent, in the aCPP. In addition, we detected copy-number gains on Chromosomes 12, 18, and 20 and copy-number losses on Chromosomes 13q and 22q (BRD1 locus) in this tumor. The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. The CPC patient presented loss of heterozygosity (LoH) of TP53 loci and hyperdiploid genome. Both tumors were microsatellite-stable. This is the first study performing whole-exome sequencing in Brazilian choroid plexus tumors, and in line with the literature, we corroborate the absence of recurrent somatic mutations in these tumors. Further studies with larger sample sizes are necessary to confirm our findings and better understand the underlying biology of these tumors.

Citação
Garcia FAO, Evangelista AF, Mançano BM, Moreno DA, Berardinelli GN, de Paula FE, Antoniazzi AP, Júnior CA, Lombardi I, Santana I, Teixeira GR, Costa CE, Reis RM. Genomic profile of two Brazilian choroid plexus tumors by whole-exome sequencing. Cold Spring Harb Mol Case Stud. 2023 Mar 24;9(1):a006245. doi: 10.1101/mcs.a006245. PMID: 36963804; PMCID: PMC10111795.

Data documento
02/05/2024

Título
High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population

Autor(es)
Moreno DA - Bonatelli M - Antoniazzi AP - de Paula FE - Leal LF - Garcia FAO - de Paula AE - Teixeira GR - Santana IVV - Saggioro F - Neder L - Valera ET - Scrideli CA - Stavale J - Malheiros SMF - Lima M - Hajj GNM - Garcia-Rivello H - Christiansen S - Nunes S - Gil-da-Costa MJ - Pinheiro J - Martins FD - Junior CA - Mançano BM - Reis RM.

Resumo
Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.

Citação
Moreno DA, Bonatelli M, Antoniazzi AP, de Paula FE, Leal LF, Garcia FAO, de Paula AE, Teixeira GR, Santana IVV, Saggioro F, Neder L, Valera ET, Scrideli CA, Stavale J, Malheiros SMF, Lima M, Hajj GNM, Garcia-Rivello H, Christiansen S, Nunes S, Gil-da-Costa MJ, Pinheiro J, Martins FD, Junior CA, Mançano BM, Reis RM. High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population. Front Oncol. 2023 Sep 4;13:1237170. doi: 10.3389/fonc.2023.1237170. PMID: 37746264; PMCID: PMC10513896.

Data documento
19/03/2025

Título
Immune-checkpoint gene expression and BCG response in non-muscle invasive bladder cancer

Autor(es)
Zucca LER, Laus AC - Sorroche BP - Paro E Sussuchi L - Marques RF - Teixeira GR - Berardinelli GN - Arantes LMRB - Reis RM - Cárcano FM.

Palavras chave
Urinary bladder neoplasms1 - BCG vaccine 2 - Gene expression profiling3 - Immunity active4

Resumo
Methods One-hundred-six patients diagnosed with non-muscle invasive bladder cancer and treated with intravesical BCG were included and divided into two groups, BCG-responsive (n = 47) and -unresponsive (n = 59). Immunohistochemistry was used to evaluate PD-L1 expression and MSI was assessed by a commercial multiplex PCR kit. The mRNA expression profile of 15 immune checkpoints was performed using the nCounter technology. For in silico validation, two distinct cohorts sourced from the Gene Expression Omnibus (GEO) database were used. Results Among the 106 patients, only one (<1 %) exhibited MSI instability. PD-L1 expression was present in 9.4 % of cases, and no association was found with BCG-responsive status. We found low gene expression of canonic actionable immune checkpoints PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, while high expression was observed for CD276 (B7-H3), CD47, TNFRSF14, IDO1 and PVR (CD155) genes. High IDO1 expression levels was associated with worst overall survival. The PDCD1, CTLA4 and TNFRSF14 expression levels were associated with BCG responsiveness, whereas TIGIT and CD276 were associated with unresponsiveness. Finally, CD276 was validated in silico cohorts. Conclusion In NMIBC, MSI is rare and PD-L1 expression is present in a small subset of cases. Expression levels of PDCD1, CTLA4, TNFRSF14, TIGIT and CD276 could constitute predictive biomarkers of BCG responsiveness.

Citação
Zucca LER, Laus AC, Sorroche BP, Paro E, Sussuchi L, Marques RF, Teixeira GR, Berardinelli GN, Arantes LMRB, Reis RM, Cárcano FM. Transl Oncol. 2024 Aug;46:102003. doi: 10.1016/j.tranon.2024.102003. Epub 2024 Jun 4. PMID: 38838438

Data documento
06/05/2024

Título
Immunophenotypic changes in juvenile myelomonocytic leukaemia after treatment with hypomethylating agent: Do they help to evaluate dept of response?

Autor(es)
Oliveira A.F. - Tansini A. - Toledo T. - Balceiro R. - Lee M.L.M. - Villela N. - Ikeuty P. - Metze K. - Lopes L.F. - Lorand-Metze I.

Palavras chave
azacytidine - immunophenotyping - juvenile myelomonocytic leukaemia - treatment

Resumo
5-Azacitidine has been used before stem cell transplantation in juvenile myelomonocytic leukaemia (JMML) patients. Recently, we have described immunophenotypic features in JMML at diagnosis. Here, our aim was to examine the changes in the immunophenotypic features during azacitidine treatment, correlating it with clinical response. Patients treated with 5-azacitidine were evaluated at diagnosis and after three and six cycles of medication. Among 32 patients entering the study, 28 patients were examined after three cycles and 25 patients after six. Patients showed a reduction in CD34/CD117+ cells: median 3.35% at diagnosis, 2.8% after three cycles and 1.63% after six. B-cell progenitors were decreased at diagnosis and decreased after treatment. Monocytes decreased: 11.91% to 6.4% and 4.18% respectively. Complete response was associated with increase in classical monocytes. T lymphocytes, reduced at diagnosis, increased in patients responding to 5-azacitidine. Immunophenotypic aberrancies including expression of CD7 in myeloid progenitors remained after treatment. This feature was associated with a worse response to treatment, as well as presence of NF1. Immunophenotyping was feasible in all patients. Clinical response was associated with a decrease of myeloid progenitors and monocytes and a rise in T lymphocytes although phenotypic aberrancies persisted. The largest effect was observed after three cycles.

Citação
Oliveira AF, Tansini A, Toledo T, Balceiro R, Lee MLM, Villela N, Ikeuty P, Metze K, Lopes LF, Lorand-Metze I. Immunophenotypic changes in juvenile myelomonocytic leukaemia after treatment with hypomethylating agent: Do they help to evaluate dept of response? Br J Haematol. 2022 May;197(3):339-348. Spanish. doi: 10.1111/bjh.18089. Epub 2022 Feb 21. PMID: 35187646.

Data documento
06/05/2024

Título
Impacto Psicossocial da Pandemia de COVID-19 em Trabalhadores de Instituição de Longa Permanência de Idosos

Autor(es)
MAIOLINO, Taís de Souza - REIS, Leticia Caldeira dos - COSTA, Ricardo Filipe Alves da - PETROUCIC, Roberta Thomé.

Palavras chave
Instituição de Longa Permanência para Idosos - Pessoal de saúde - Saúde mental - COVID-19

Resumo
Objetivos: Identificar o impacto psicossocial gerado pelo contexto pandêmico de COVID-19 nos cuidadores e profissionais da saúde de instituição de longa permanência de idosos e analisar as estratégias de enfretamento (coping) à pandemia. Métodos: Estudo observacional e transversal, aprovado por Comitê de Ética CAAE: 37255020.7.0000.5437. Realizado no período de outubro e novembro de 2020, com aplicação de questionários a cuidadores e profissionais da saúde da instituição “Casa Transitória André Luiz” de Barretos, estado de São Paulo. Foram aplicados os questionários: geral (sociodemográfico, laboral e testagem para COVID-19), o Self-Reporting Questionnaire (SRQ-20) para rastrear Distúrbios Psíquicos Menores (DPM) e o COPE-breve para elencar estratégias adotadas pelos trabalhadores no enfretamento à pandemia. Resultados: Foram incluídos no estudo 57 profissionais da saúde. Destes, 86,0% são do gênero feminino, 63,2% possuem escolaridade até o Ensino Médio/Técnico, 61,4% cumprem carga horária inferior a 40 horas semanais e 40,0% relataram já haver recebido testagem positiva para COVID-19. Considerado o escore maior ou igual a 7 no SRQ-20, foi rastreada a probabilidade de ocorrência de DPM em 35,1% dos trabalhadores, a qual não apresentou associação com as variáveis sociodemográficas, laborais e de testagem para COVID-19. As estratégias de enfrentamento mais utilizadas foram aquelas relacionadas à religião, aceitação, planejamento/coping ativo e reinterpretação positiva. Os profissionais de saúde com alta probabilidade de DPM apresentaram escores medianos mais elevados no suporte instrumental e na expressão de sentimentos, como estratégias de coping, do que os profissionais de saúde com baixa probabilidade de DPM. Conclusão: Foi identificada provável ocorrência de DPM entre profissionais da saúde da instituição. Esta se associou à busca por suporte instrumental e à expressão de sentimentos como estratégias de enfrentamento ao contexto de pandemia.

Citação
MAIOLINO, T. S.; REIS, L. C.; COSTA, R. F. A.; PETROUCIC, R. T.

Data documento
13/03/2025

Título
Implementation of the ProMisE classifier and validation of its prognostic impact in Brazilian endometrial carcinomas

Autor(es)
Andrade DAP, Bonatelli M, de Paula FE, Berardinelli GN, Teixeira GR, Dos Reis MT, Barbin FF, Andrade CEMDC, Aguiar VP, Hermoza AD, Hirai WY, Schmidt RL, Reis RM, Dos Reis R.

Palavras chave
Oncologia Ginecológica - Hospital do Amor Barretos SP

Resumo
Purpose Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients’ prognosis. Patient and methods A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted. Pathology diagnosis, staging, treatment, and follow-up data were collected. The traditional ProMisE methodology was carried out by POLE hotspot sequencing and immunohistochemistry (IHC) for p53 and mismatch repair (MMR) proteins. We further evaluate the MMR and TP53 status by molecular approach, namely microsatellite instability (MSI) by PCR-based and TP53 mutation analysis by next-generation sequencing (NGS). The results of the 4 molecular groups in both methodologies were compared regarding agreement accuracy and survival outcomes. Results Among the 114 cases, the traditional ProMisE groups were: POLEmut 15.8%, MMRd 28.1%, p53abn 27.2%, and no specific molecular profile (NSMP) 28.9%. Considering the molecular classification approach, we observed a POLEmut group of 15.8%, MSI group of 23.7%, TP53 mutation of 27.2%, and NSMP of 33.3%. The concordance rate of both approaches was 86.8% (99/114 cases) with an overall accuracy of 0.87. Importantly, both traditional and molecular ProMisE approaches were associated with significant distinct overall survival (OS) and progression-free survival (PFS) outcomes, with POLEmut patients exhibiting a better prognosis (93.8% OS, at 24 months), whereas the p53abn having a worse survival time (68.9% of OS, at 24 months). Conclusion We reported for the first time the Brazilian profile of the ProMisE classification of endometrial cancer and demonstrated the prognostic impact of the traditional and molecular ProMisE classification on patient outcomes.

Data documento
06/05/2024

Título
Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer

Autor(es)
Freitas A.J.A. - Causin R - L. - Varuzza M.B. - Calfa S. - Hidalgo Filho C.M.T. - Komoto T.T. - Souza C.P. - Marques M.M.C.

Palavras chave
breast cancer - liquid biopsy - precision medicine

Resumo
Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.

Citação
Freitas AJA, Causin RL, Varuzza MB, Calfa S, Hidalgo Filho CMT, Komoto TT, Souza CP, Marques MMC. Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer. Int J Mol Sci. 2022 Sep 1;23(17):9952. doi: 10.3390/ijms23179952. PMID: 36077348; PMCID: PMC9456236.

Data documento
03/05/2024

Título
Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs

Autor(es)
Casagrande GMS, - Silva MO, - Reis RM, - Leal LF.

Palavras chave
biomarkers - liquid biopsy - lung cancer - precision medicine

Resumo
Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy-techniques, molecules, and sample type-for lung cancer.

Citação
Casagrande GMS, Silva MO, Reis RM, Leal LF. Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. Int J Mol Sci. 2023 Jan 28;24(3):2505. doi: 10.3390/ijms24032505. PMID: 36768828; PMCID: PMC9917347.

Data documento
06/05/2024

Título
Management of Early-Stage Vulvar Cancer

Autor(es)
Pedrão P.G. - Guimarães Y.M. - Godoy L.R. - Possati-Resende J.C. - Bovo A.C. - Andrade C.E.M.C. - Longatto-Filho A. - Dos Reis R.

Palavras chave
vulvar cancer - vulvar neoplasms - diagnosis and staging - sentinel lymph node

Resumo
Vulvar cancer is a rare gynecological malignancy since it represents 4% of all cancers of the female genital tract. The most common histological type is squamous cell carcinoma (90%). This type can be classified into two clinicopathological subtypes according to the etiology. The first subtype is associated with persistent human papillomavirus infection and is usually diagnosed in younger women. The second subtype is associated with lichen sclerosus condition, and in most cases is diagnosed in postmenopausal women. Currently, an increase in first subtype cases has been observed, which raised the concern about associated mortality and treatment morbidity among young women. Vulvar cancer treatment depends on histopathology grade and staging, but surgery with or without radiotherapy as adjuvant treatment is considered the gold standard. In recent decades, sentinel lymph node biopsy has been incorporated as part of the treatment. Therefore, we sought to review and discuss the advances documented in the literature about vulvar cancer focusing on the treatment of early-stage disease. Relevant articles, such as the GROINS-V studies and the GOG protocols, are presented in this review. Additionally, we discuss key points such as the evolution of treatment from invasive surgery with high morbidity, to more conservative approaches without compromising oncologic safety; the role of sentinel lymph node mapping in the initial staging, since it reduces the complications caused by inguinofemoral lymphadenectomy; the recurrences rates, since local recurrence is common and curable, however, groin-associated, or distant recurrences have a poor prognosis; and, finally, the long-term follow-up that is essential for all patients.

Citação
Pedrão PG, Guimarães YM, Godoy LR, Possati-Resende JC, Bovo AC, Andrade CEMC, Longatto-Filho A, Dos Reis R. Management of Early-Stage Vulvar Cancer. Cancers (Basel). 2022 Aug 29;14(17):4184. doi: 10.3390/cancers14174184. PMID: 36077719; PMCID: PMC9454625.

Data documento
03/05/2024

Título
Maternal dietary zinc status alters offspring female mammary gland development and response to acute 7,12-dimethylbenzanthracene insult

Autor(es)
da Silva FRM, - Zapaterini JR, - Grassi TF, - Bidinotto LT, - Fernandes AAH, - Barbisan LF.

Palavras chave
Development - mammary gland - rats - zinc - dimethylbenzanthracene

Resumo
We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to 7,12-dimethylbenzanthracene (DMBA) in pubertal female rats. On gestational day 10 (GD 10), rat dams were allocated randomly into three experimental groups of 10: a Zn-adequate diet group (ZnA) fed 35 mg Zn/kg chow, a Zn-deficient diet group (ZnD) fed 3 mg ZN/kg chow and a Zn-supplemented diet group (ZnS) fed 180 mg Zn/kg chow. After weaning, female offspring were fed the same diet as their dams until postnatal day 53 (PND 53). All animals received a single 50 mg/kg dose of DMBA on PND 51 and were euthanized on PND 53. Female ZnD offspring exhibited significantly less weight gain compared to the ZnA group and reduced mammary gland development compared to the ZnD and ZnA groups. By PND 53, the Ki-67 labeling index in mammary gland epithelial cells was significantly greater for the ZnS group than for the ZnA and ZnD groups. Apoptosis and ER-α indices did not differ among groups. The ZnD group exhibited significantly increased lipid hydroperoxide (LOOH) levels and decreased catalase and glutathione peroxidase (GSH-Px) activity compared to the ZnA and ZnS groups. The ZnS group exhibited significantly reduced superoxide dismutase (SOD) activity compared to the ZnA and ZnS groups. We observed atypical ductal hyperplasia in the mammary gland of female ZnS group offspring compared to the ZnA and ZnD groups and decreased expression of the Api5 and Ercc1 genes related to apoptosis inhibition and DNA damage repair, respectively. Both the Zn-deficient and Zn-supplemented diet exerted adverse effects on offspring mammary gland morphology and acute response to DMBA.

Citação
da Silva FRM, Zapaterini JR, Grassi TF, Bidinotto LT, Fernandes AAH, Barbisan LF. Maternal dietary zinc status alters offspring female mammary gland development and response to acute 7,12-dimethylbenzanthracene insult. Biotech Histochem. 2023 Nov;98(5):360-371. doi: 10.1080/10520295.2023.2196092. Epub 2023 Apr 6. PMID: 37022146.

Data documento
06/05/2024

Título
Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood

Autor(es)
Zapaterini J.R. - Fonseca A.R.B. - Bidinotto L.T. - Colombelli K.T. - Rossi A.L.D. - Kass L. - Justulin L.A. - Barbisan L.F.

Palavras chave
DNA damage - DNA repair and replication - N-methyl-N-nitrosourea - female Sprague–Dawley - maternal low protein intake - perinatal programming - risk for mammary carcinogenesis

Resumo
Studies have shown that maternal malnutrition, especially a low-protein diet (LPD), plays a key role in the developmental mechanisms underlying mammary cancer programming in female offspring. However, the molecular pathways associated with this higher susceptibility are still poorly understood. Thus, this study investigated the adverse effects of gestational and lactational low protein intake on gene expression of key pathways involved in mammary tumor initiation after a single dose of N-methyl-N-nitrosourea (MNU) in female offspring rats. Pregnant Sprague-Dawley rats were fed a normal-protein diet (NPD) (17% protein) or LPD (6% protein) from gestational day 1 to postnatal day (PND) 21. After weaning (PND 21), female offspring (n = 5, each diet) were euthanized for histological analysis or received NPD (n = 56 each diet). At PND 28 or 35, female offspring received a single dose of MNU (25 mg/kg body weight) (n = 28 each diet/timepoint). After 24 h, some females (n = 10 each diet/timepoint) were euthanized for histological, immunohistochemical, and molecular analyses at PDN 29 or 36. The remaining animals (n = 18 each diet/timepoint) were euthanized when tumors reached ≥2 cm or at PND 250. Besides the mammary gland development delay observed in LPD 21 and 28 groups, the gene expression profile demonstrated that maternal LPD deregulated 21 genes related to DNA repair and DNA replication pathways in the mammary gland of LPD 35 group after MNU. We further confirmed an increased γ-H2AX (DNA damage biomarker) and in ER-α immunoreactivity in mammary epithelial cells in the LPD group at PND 36. Furthermore, these early postnatal events were followed by significantly higher mammary carcinogenesis susceptibility in offspring at adulthood. Thus, the results indicate that maternal LPD influenced the programming of chemically induced mammary carcinogenesis in female offspring through increase in DNA damage and deregulation of DNA repair and DNA replication pathways. Also, Cidea upregulation gene in the LPD 35 group may suggest that maternal LPD could deregulate genes possibly leading to increased risk of mammary cancer development and/or poor prognosis. These findings increase the body of evidence of early-transcriptional mammary gland changes influenced by maternal LPD, resulting in differential response to breast tumor initiation and susceptibility and may raise discussions about lifelong prevention of breast cancer risk.

Citação
Zapaterini JR, Fonseca ARB, Bidinotto LT, Colombelli KT, Rossi ALD, Kass L, Justulin LA, Barbisan LF. Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood. Front Cell Dev Biol. 2022 Feb 1;9:756616. doi: 10.3389/fcell.2021.756616. PMID: 35178394; PMCID: PMC8844450.

Data documento
02/05/2024

Título
Metodologias ativas de aprendizagem na capacitação de enfermeiros para a prevenção de lesão por pressão

Autor(es)
Assoni, M. A. S. - Oliveira, É. M. M. - Cardoso, D. M. - Lourenço, A. O. O. S. - Alvarenga, C. S.

Palavras chave
autocuidado - teoria da enfermaria - bibliometria - teses como temas

Resumo
Caracterizar a produção científica relacionada à Teoria do Autocuidado de OREM nas teses de enfermagem brasileiras disponíveis no banco de testes do portal CAPES. Método: Revisão bibliométrica de caráter descritivo, desenvolvida a partir da análise de teses disponíveis na CAPES. Pesquisa descritiva com Análise de Conteúdo, desenvolvida pela categorização dos conteúdos das teses conforme a utilização da teoria do autocuidado. Resultados: Foram incluídas 10 teses que apresentaram diferentes formas de aplicabilidade da teoria de Orem validação de protocolo e escala, adaptação, desenvolvimento da consulta de enfermagem e elaboração de instrumento norteador da consulta de enfermagem. As estruturas semânticas relacionadas às categorizações principais de utilização da teoria do autocuidado envolveram ação, instrumento, condições básicas e suplementares do ser humano e lócus do cuidado. Conclusão: A Teoria de Orem foi utilizada em contextos diversificados, fomentando caminhos para reflexões sobre a construção e aplicação do conhecimento próprio da enfermagem.

Citação
Assoni, M. A. S.; Oliveira, É. M. M.; Cardoso, D. M.; Lourenço, A. O. O. S.; Alvarenga, C. S. Metodologias ativas de aprendizagem na capacitação de enfermeiros para a prevenção de lesão por pressão, Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1372463

Data documento
13/03/2025

Título
Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies

Autor(es)
Rodrigo de Oliveira Cavagna - Flávia Escremim de Paula - Gustavo Noriz Berardinelli - Murilo Bonatelli - Iara Santana - Eduardo Caetano Albino da Silva - Gustavo Ramos Teixeira - Beatriz Garbe Zaniolo - Flávio Augusto Ferreira da Silva - Carlos Eduardo Baston Silva - Josiane Mourão Dias - Marcela Gondim Borges Guimarães - Camila Pinto Barone - Alexandre Arthur Jacinto - Rachid Eduardo Noleto da Nóbrega Oliveira - José Elias Miziara - Pedro De Marchi - Miguel A. Molina-Vila - Letícia Ferro Leal - Rui Manuel Reis

Palavras chave
lung adenocarcinoma; molecular profile; driver mutations; never smoker; Latin America.

Resumo
Introduction: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS. Methods: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients’ genetic ancestry. Results: The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations. Conclusion: Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.

Citação
Cavagna RO, Escremim de Paula F, Berardinelli GN, Bonatelli M, Santana I, Albino da Silva EC, Teixeira GR, Zaniolo BG, Mourão Dias J, Ferreira da Silva FA, Baston Silva CE, Guimarães MGB, Barone CP, Jacinto AA, Noleto da Nóbrega Oliveira RE, Miziara JE, De Marchi P, Molina-Vila MA, Leal LF, Reis RM. Oncologist. 2024 Oct 3;29(10):e1419-e1424. doi: 10.1093/oncolo/oyae129. PMID: 38944844

Data documento
06/05/2024

Título
Paracoccidioidomycosis with sarcoid-like cutaneous lesion: A clinicopathological challenge

Autor(es)
Cárcano C.B.M. - Tanaka V.D. - Alessi C. - Reis M.T. - Ferreira M.S.

Palavras chave
Paracoccidioidomycosis - Mycoses - Histology - Dermatology - Diagnosis - Sarcoidosis

Resumo
We describe a case of sarcoid-like cutaneous paracoccidioidomycosis in a 26-year-old male, with a 10-year evolution, wrongly diagnosed as granulomatous rosacea. The correct diagnosis was only possible after the appearance of a new skin lesion with a more typical characteristic of the dermatosis, correlated with anatomopathological, laboratory and imaging exams. The clinical presentation of paracoccidioidomycosis is diverse, and the sarcoid-like form can mimic several chronic granulomatous diseases, such as sarcoidosis, tuberculoid leprosy, leishmaniasis, or tuberculosis. This presentation of cutaneous paracoccidioidomycosis is rare, and its diagnosis depends on the clinicopathological correlation, which can be a challenge for the dermatologist.

Citação
Cárcano CBM, Tanaka VD, Alessi C, Reis MT, Ferreira MS. Paracoccidioidomycosis with sarcoid-like cutaneous lesion: A clinicopathological challenge. IDCases. 2022 Jul 18;29:e01574. doi: 10.1016/j.idcr.2022.e01574. PMID: 35923859; PMCID: PMC9340507.

Data documento
26/04/2024

Título
PD L1 expression and microsatellite instability (MSI) in cancer of unknown primary site

Autor(es)
JÚNIOR, João Neif Antonio - PRETO, Daniel D.’Almeida - LAZARINI, Maria Eduarda Zanatta Neder - LIMA, Marcos Alves de - BONATELLI, Murilo - BERARDINELLI, Gustavo Noriz - SILVA, Vinicius Duval da - PINHEIRO, Céline - REIS, Rui Manuel, CÁRCANO, Flavio Mavignier -

Palavras chave
Neoplasms - Unknown primary - Microsatellite instability - Immune checkpoint proteins - Immunotherapy

Resumo
Background Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features. Methods The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. Results Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). Conclusion PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Citação
Junior JNA, Preto DD, Lazarini MEZN, de Lima MA, Bonatelli M, Berardinelli GN, da Silva VD, Pinheiro C, Reis RM, Cárcano FM. PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site. Int J Clin Oncol. 2024 Mar 25. doi: 10.1007/s10147-024-02494-3. Epub ahead of print. PMID: 38528294.

Data documento
19/03/2025

Título
PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site

Autor(es)
João Neif Antonio Junior - Daniel D Almeida Preto - Maria Eduarda Zanatta Neder Lazarini - Marcos Alves de Lima - Murilo Bonatelli - Gustavo Noriz Berardinelli - Vinicius Duval da Silva - Céline Pinheiro - Rui Manuel Reis - Flavio Mavignier Cárcano.

Palavras chave
Immune checkpoint proteins; Immunotherapy; Microsatellite instability; Neoplasms; Unknown primary.

Resumo
Background: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. Methods: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. Results: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). Conclusion: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Citação
unior JNA, Preto DD, Lazarini MEZN, de Lima MA, Bonatelli M, Berardinelli GN, da Silva VD, Pinheiro C, Reis RM, Cárcano FM.Int J Clin Oncol. 2024 Jun;29(6):726-734. doi: 10.1007/s10147-024-02494-3.Epub 2024 Mar 25. PMID: 38528294

Data documento
02/05/2024

Título
Role of EGFL7 in human cancers: A review

Autor(es)
de Oliveira C, - Gonçalves PG, - Bidinotto LT.

Palavras chave
angiogenesis - cancer - EGFL7 - pathways

Resumo
EGFL7 is a proangiogenic factor. It has been widely described with having a vital role in tubulogenesis and regulation of angiogenesis, mainly during embryogenesis and organogenesis. It has been mainly associated with NOTCH pathway, but there are reports showing association with MAPK and integrin pathways. Given its association with angiogenesis and these other pathways, there are several studies associating EGFL7 with carcinogenesis. In fact, most of the studies have pointed to EGFL7 as an oncogene, and some of them suggest EGFL7 expression as a possible biomarker of prognosis or use for a patients follow‐up. Here, we review the molecular pathways which EGFL7 is associated and highlight several studies describing the role of EGFL7 in tumorigenesis, separated by tumor type. Besides its role on angiogenesis, EGFL7 may act in other pathways as oncogene, which makes it a possible biomarker and a candidate to targeted therapy.

Citação
de Oliveira C, Gonçalves PG, Bidinotto LT. Role of EGFL7 in human cancers: A review. J Cell Physiol. 2023 Aug;238(8):1756-1767. doi: 10.1002/jcp.31084. Epub 2023 Jul 25. PMID: 37490307.

Data documento
02/05/2024

Título
Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes

Autor(es)
de Oliveira WE Jr, - Murra MS, - Tufi LMB, - Cavalcante CEB, - de Oliveira MA, - da Costa RFA, - Rosa BR, - da Silva RZM, - Ribeiro RC, - Ladas EJ, - Barr RD.

Palavras chave
sarcopenia - psoas muscle area - Wilms tumor

Resumo
The therapeutic approach to Wilms tumor (WT) is multidisciplinary and leads to significant patient impairment, increasing the risk of nutritional compromise and malnutrition. Children with cancer are vulnerable to sarcopenia which has been recognized as a negative impact of anticancer therapy. Recent studies have highlighted the reduction in the total psoas muscle area (TPMA) to be associated with a poor prognosis inmany pediatric diseases, including cancer. This study aims to evaluate changes in the TPMA compartment during the treatment of children with WT. An observational, longitudinal, and retrospective study was undertaken in a single institution evaluating children (1 to 14 y, n=38) with WT between 2014 and 2020. TPMA was assessed by the analysis of previously collected, electronically stored computed tomography images of the abdomen obtained at 3 time points: diagnosis, preoperatively, and 1 year after surgery. For all patients, TPMA/age were calculated with a specific online calculator. Our data show a high incidence of sarcopenia (55.3%) at diagnosis which increased after 4 to 6 weeks of neoadjuvant chemotherapy (73.7%) and remained high (78.9%) 1 year after the surgical procedure. Using TPMA/age Z-score curves we have found significant and rapid muscle loss in children with WT, with little or no recovery in the study period.

Citação
de Oliveira WE Jr, Murra MS, Tufi LMB, Cavalcante CEB, de Oliveira MA, da Costa RFA, Rosa BR, da Silva RZM, Ribeiro RC, Ladas EJ, Barr RD. Sarcopenia in Children With Wilms Tumor: A Marker of Undernutrition Which May Impact Adversely on Clinical Outcomes. J Pediatr Hematol Oncol. 2023 Oct 1;45(7):e817-e822. doi: 10.1097/MPH.0000000000002732. Epub 2023 Jul 31. PMID: 37526408.

Data documento
18/12/2023

Título
SERS sensing for cancer biomarker: Approaches and directions

Autor(es)
Lorena Vázquez-Iglesias - Giovanna Maria Stanfoca Casagrande - Daniel García-Lojo - Letícia Ferro Leal - Tien Anh Ngo - Jorge Pérez-Juste - Rui Manue

Palavras chave
Cancer biomarkers; Invasive and non-invasive biomarkers; Microfluidic devices; Point of care detection; Surface-enhanced Raman scattering (SERS).

Resumo
These days, cancer is thought to be more than just one illness, with several complex subtypes that require different screening approaches. These subtypes can be distinguished by the distinct markings left by metabolites, proteins, miRNA, and DNA. Personalized illness management may be possible if cancer is categorized according to its biomarkers. In order to stop cancer from spreading and posing a significant risk to patient survival, early detection and prompt treatment are essential. Traditional cancer screening techniques are tedious, time-consuming, and require expert personnel for analysis. This has led scientists to reevaluate screening methodologies and make use of emerging technologies to achieve better results. Using time and money saving techniques, these methodologies integrate the procedures from sample preparation to detection in small devices with high accuracy and sensitivity. With its proven potential for biomedical use, surface-enhanced Raman scattering (SERS) has been widely used in biosensing applications, particularly in biomarker identification. Consideration was given especially to the potential of SERS as a portable clinical diagnostic tool. The approaches to SERS-based sensing technologies for both invasive and non-invasive samples are reviewed in this article, along with sample preparation techniques and obstacles. Aside from these significant constraints in the detection approach and techniques, the review also takes into account the complexity of biological fluids, the availability of biomarkers, and their sensitivity and selectivity, which are generally lowered. Massive ways to maintain sensing capabilities in clinical samples are being developed recently to get over this restriction. SERS is known to be a reliable diagnostic method for treatment judgments. Nonetheless, there is still room for advancement in terms of portability, creation of diagnostic apps, and interdisciplinary AI-based applications. Therefore, we will outline the current state of technological maturity for SERS-based cancer biomarker detection in this article. The review will meet the demand for reviewing various sample types (invasive and non-invasive) of cancer biomarkers and their detection using SERS. It will also shed light on the growing body of research on portable methods for clinical application and quick cancer detection.

Citação
SERS sensing for cancer biomarker: Approaches and directions. Vázquez-Iglesias L, Stanfoca Casagrande GM, García-Lojo D, Ferro Leal L, Ngo TA, Pérez-Juste J, Reis RM, Kant K, Pastoriza-Santos I. Bioact Mater. 2023 Dec 31;34:248-268. doi: 10.1016/j.bioactmat.2023.12.018. eCollection 2024 Apr. PMID: 38260819

Data documento
07/05/2024

Título
Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis

Autor(es)
Gonçalves PG, Reis RM, Bidinotto LT.

Palavras chave
locus - In silico analysis - TCGA - gene expression - prognostic value

Resumo
Background/aim: Deletions in chr9p22.1-21.3 locus have been related to the development of several types of cancer, mainly due to the presence of CDKN2A and CDKN2B genes. However, there are several other genes in the region with potential importance in tumorigenesis. We, therefore, aimed to analyze in silico the potential prognostic significance of alterations in copy number and expression of genes present in the chr9p22.1-21.3 locus in 33 TCGA datasets (approximately 10,000 patients). Materials and methods: We analyzed which of the 27 genes are expressed in the datasets. Additionally, we associated the deletion of the locus with survival (log rank analysis) and hazard ratio (HR) (univariate cox regression). Finally, we performed univariate, multivariate, and overall survival analyses in 13 datasets considering the expression of 10 genes present in the locus. Results: We identified 10 genes of the chr9p22.1-21.3 locus expressed in the datasets (MLLT3, FOCAD, PTPLAD2, KLHL9, IFNE, MTAP, CDKN2A, CDKN2B, DMRTA1 and ELAVL2). Moreover, we found that deletion in at least 1 of these genes was associated with poor survival and increased HR in 13 datasets: adrenocortical carcinoma (ACC), glioblastoma (GBM), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), low-grade glioma (LGG), lung adenocarcinoma (LUAD), mesothelioma (MESO), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), sarcoma (SARC) and uterine corpus endometrial carcinoma (UCEC). Finally, we found an association of survival/HR and altered expression of MLLT3 in the MESO dataset, of FOCAD in the READ dataset, of PTPLAD2 in the KIRP dataset, of KLHL9 in the LGG and UCEC datasets, of IFNE in ACC, GBM, KIRC and LUAD datasets, of MTAP in LGG, LUAD and MESO datasets, of CDKN2A in the HNSC, KIRC and MESO datasets, of CDKN2B in the LGG and READ datasets, of DMRTA1 in SARC datasets and of ELAVL2 in the LGG dataset (p<0.01 for all associations). Conclusion: Besides CDKN2A and CDKN2B, numerous other genes are possibly related to cancer development, requiring further investigation.

Citação
Gonçalves PG, Reis RM, Bidinotto LT. Significance of Chr9p22.1-p21.3 Deletion in Cancer Development: A Pan-cancer In Silico Analysis. Anticancer Res. 2022 Nov;42(11):5291-5304. doi: 10.21873/anticanres.16036. PMID: 36288884.

Data documento
03/05/2024

Título
Somatic mutation detection and KRAS amplification in testicular germ cell tumors

Autor(es)
Cabral ERM, - Pacanhella MF, - Lengert AVH, - Dos Reis MB, - Leal LF, - de Lima MA, - da Silva ALV, - Pinto IA, - Reis RM, - Pinto MT, - Cárcano FM.

Palavras chave
K-ras Gene - TP53 Gene - mutation - next-generation sequencing - testicular germ cell tumor - testicular neoplasms

Resumo
Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Citação
Cabral ERM, Pacanhella MF, Lengert AVH, Dos Reis MB, Leal LF, de Lima MA, da Silva ALV, Pinto IA, Reis RM, Pinto MT, Cárcano FM. Somatic mutation detection and KRAS amplification in testicular germ cell tumors. Front Oncol. 2023 Mar 16;13:1133363. doi: 10.3389/fonc.2023.1133363. PMID: 37007070; PMCID: PMC10060882.

Data documento
02/05/2024

Título
The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models

Autor(es)
Teixeira, S.A. - Luzzi, M.d.C. - Martin, A.C.B.M. - Duarte, T.T. - Leal, M.d.O. - Teixeira, G.R. - Reis, M.T. - Junior, C.R.A. - Santos, K. - Melendez, M.E. - et al.

Palavras chave
PTCH1-knockout - ApcMin - xenografts - PDX - genetically engineered mouse models - personalized therapy - tumor biology

Resumo
The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy

Citação
Teixeira, S.A.; Luzzi, M.d.C.; Martin, A.C.B.M.; Duarte, T.T.; Leal, M.d.O.; Teixeira, G.R.; Reis, M.T.; Junior, C.R.A.; Santos, K.; Melendez, M.E.; et al. The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models. Vet. Sci. 2022, 9, 636. https://doi.org/10.3390/vetsci9110636

Data documento
02/05/2024

Título
The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high‐grade cervical lesion detection in liquid‐based cytology

Autor(es)
Causin RL, - Sussuchi da Silva L, - Leal LF, - Possati-Resende JC, - Evangelista AF, - Matsushita GM, - Scapulatempo-Neto C, - Tavares Guerreiro Fregnani JH, - Antônio de Oliveira M, - Musselwhite LW, - Chiquitelli Marques MM, - Reis RM.

Palavras chave
biomarkers - cervical cancer - cervical intraepithelial neoplasia - gene expression - liquid‐based cytology

Resumo
Background: Some studies reported that differential gene expression could be used as a biomarker for high‐grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid‐based cytology (LBC) samples. Methods: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer‐related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from

Descrição

Citação
Causin RL, Sussuchi da Silva L, Leal LF, Possati-Resende JC, Evangelista AF, Matsushita GM, Scapulatempo-Neto C, Tavares Guerreiro Fregnani JH, Antônio de Oliveira M, Musselwhite LW, Chiquitelli Marques MM, Reis RM. The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high-grade cervical lesion detection in liquid-based cytology. Cancer Cytopathol. 2023 Jul;131(7):454-464. doi: 10.1002/cncy.22704. Epub 2023 Apr 17. PMID: 37069588.

Data documento
13/01/2024

Título
The Magee 3 Equation Predicts Favorable Pathologic Response to Neoadjuvant Endocrine Therapy in Breast Cancer Patients

Autor(es)
Carlos Eduardo Paiva - Maria Paola Montesso Zonta - Rafaela Carvalho Granero - Vitor Souza Guimarães - Layla Melo Pimenta - Gustavo Ramos Teixeira - Bianca Sakamoto Ribeiro Paiva.

Palavras chave
Magee equation; breast cancer; luminal; neoadjuvant endocrine therapy; pathologic response.

Resumo
Background: Breast cancer (BC) remains a significant health care challenge, and treatment approaches continue to evolve. Among these, neoadjuvant endocrine therapy (NET) has gained prominence, particularly for postmenopausal, hormone-receptor positive, HER2-negative (HR+/HER2-) BC patients. Despite this, a significant gap exists in identifying patients who stand to benefit from NET. The objective of this study was to assess whether Magee equations (MEs) could serve as predictors of response to NET. Methods: This retrospective study included adult patients with invasive BC who underwent NET followed by curative surgery. Assessment of sociodemographic, clinical, and tumor-related variables was conducted. The ME1, ME2, ME3, and ME mean were analyzed to explore their predictive role for NET response. Receiver operating characteristic (ROC) curves were employed, along with the determination of optimal cutoff points. Logistic regression models were utilized to identify the most significant predictors of pathological response. Results: Among the 75 female participants, the mean age was 69.4 years, with the majority being postmenopausal (n = 72, 96%) and having an ECOG-PS of 0/1 (n = 63, 84%). Most patients were classified as luminal A (n = 41, 54.7%). ME3 emerged as a promising predictor, boasting an AUC of 0.734, with sensitivity of 90.62% and specificity of 57.50% when the threshold was ≤ 19.97. In univariate analysis, clinical staging (p = 0.002), molecular subtype (p = 0.001), and ME3 (continuous = 0.001, original 3-tier: p = 0.013, new 2-tier: <0.001) categories exhibited significant associations with pathological response. In the multivariate model, clinical staging and new 2-tier ME3 (<20 vs. ≥20) were included as significant variables. Conclusions: Patients with ME3 < 20 have a higher likelihood of presenting a pathological response, offering a cost-effective alternative tool to Oncotype DX. Larger future studies with a prospective design are awaited to confirm our findings.

Citação
The Magee 3 Equation Predicts Favorable Pathologic Response to Neoadjuvant Endocrine Therapy in Breast Cancer Patients.Paiva CE, Zonta MPM, Granero RC, Guimarães VS, Pimenta LM, Teixeira GR, Paiva BSR.Cancers (Basel). 2024 Jan 13;16(2):339. doi: 10.3390/cancers16020339. PMID: 38254828

Data documento
18/02/2024

Título
The Role of Pelvic Exenteration in Cervical Cancer: A Review of the Literature.

Autor(es)
AnaCarla Franco Ubinha - Priscila Grecca Pedrão - Aline Cássia Tadini - Ronaldo Luis Schmidt - Marcelo Henrique dos Santos - Carlos Eduardo Mattos da Cunha Andrade - Adhemar Longatto Filho - Ricardo dos Reis.

Palavras chave
cervical cancer; pelvic exenteration; recurrent cervical cancer; extended pelvic resection

Resumo
Pelvic exenteration represents a radical procedure aimed at achieving complete tumor resection with negative margins. Although it is the only therapeutic option for some cases of advanced tumors, it is associated with several perioperative complications. We believe that careful patient selection is related to better oncologic outcomes and lower complication rates. The objectives of this review are to identify the most current indications for this intervention, suggest criteria for case selection, evaluate recommendations for perioperative care, and review oncologic outcomes and potential associated complications. To this end, an analysis of English language articles in PubMed was performed, searching for topics such as the indication for pelvic exenteration for recurrent gynecologic neoplasms selection of oncologic cases, the impact of tumor size and extent on oncologic outcomes, preoperative and postoperative surgical management, surgical complications, and outcomes of overall survival and recurrence-free survival.

Citação
The Role of Pelvic Exenteration in Cervical Cancer: A Review of the Literature. Ubinha ACF, Pedrão PG, Tadini AC, Schmidt RL, Santos MHD, Andrade CEMDC, Longatto Filho A, Reis RD.Cancers (Basel). 2024 Feb 18;16(4):817. doi: 10.3390/cancers16040817. PMID: 38398208

Data documento
10/02/2020

Título
Vasopressors and nutrition therapy: safe dose for the outset of enteral nutrition?

Autor(es)
Luı - s Henrique Simõ - es Covello - Marcella Giovana Gava-Brandolis - Melina Gouveia Castro - Martins Fidelis Dos Santos Netos - William Manzanares - Diogo Oliveira Toledo

Palavras chave
Nutrição - Terapia nutricional - Nutrição enteral - Vasopressores

Resumo
Background and aims: Patients with hemodynamic instability need to receive intensive treatment as fluid replacement and vasoactive drugs. In the meantime, it is supposed to initiate nutritional therapy within 24 to 48 hours after admission to the intensive care unit (ICU), as an essential part of patients intensive care and better outcomes. However, there are many controversies tangential to the prescription of enteral nutrition (EN) concomitant to the use of vasopressor and its doses. In this way, the present study aimed to identify what the literature presents of evidence to guide the clinical practice concerning the safe dose of vasopressors for the initiation of nutritional therapy in critically ill patients. Methods: This review was carried out in PubMed, ProQuest, Web of Science, and Medline databases. The descriptors were used to perform the search strategy: Critical Care, Intensive Care Units, Vasoconstrictor Agents, and Enteral Nutrition. Inclusion criteria were patients of both genders, over 18 years of age, using vasoactive drugs, with the possibility of receiving EN therapy, and articles written in English, Portuguese, and Spanish. In addition, exclusion criteria were case reports, non-papers, and repeated papers. Results: 10 articles met our inclusion criteria. Conclusion: It was observed that there are many controversies about the supply of EN in critically ill patients using vasopressor, especially about the safe dose, and it was not possible to identify a cutoff value for the beginning therapy. Despite the drug doses, clinical signs are still the most important parameters in the evaluation of EN tolerance.

Citação
Simoes Covello LH, Gava-Brandolis MG, Castro MG, Dos Santos Netos MF, Manzanares W, Toledo DO. Vasopressors and nutrition therapy: safe dose for the outset of enteral nutrition? Crit Care Res Pract. 2020;2020:1095693. doi: 10.1155/2020/1095693.

Data documento
06/05/2024

Título
VENTILAÇÃO NÃO INVASIVA EM ONCOPEDIATRIA NA UNIDADE DE TERAPIA INTENSIVA

Autor(es)
SENTENO, M. B. - MELO, É. S. - DA SILVA, J. J.

Palavras chave
Oncologia - Pediatria - Ventilação não invasiva - Fisioterapia - Cuidados críticos

Resumo
RESUMO- O câncer é uma doença que afeta não somente o paciente como também os familiares, sendo a segunda maior causa de óbito em crianças entre 1 a 14 anos no Brasil. O indivíduo com câncer apresenta algumas complicações que dentre elas se destaca a dispneia, onde normalmente necessita do suporte da UTI, sendo a Ventilação não Invasiva (VNI) o recurso mais utilizado para minimizar este sintoma. Tem como objetivo analisar a importância e os benefícios quanto ao uso da ventilação não invasiva em pacientes oncopediátricos. O presente estudo trata-se de uma revisão sistemática de acordo com a declaração do PRISMA, com base em artigos pesquisados através dos bancos de dados do Pubmed, Scielo, Cochrane, BVS e OVID. As buscas foram realizadas nas línguas inglesa, espanhola e portuguesa e sem filtro de data inicial e até o ano de 2020. Foram identificados 98 estudos nas bases de dados selecionadas, dos quais três estudos foram incluídos por corresponderem aos critérios de elegibilidade. A amostra total foi de 145 internações de pacientes oncopediátricos com idade média de 9,6 anos. A VNI é de suma importância no tratamento de pacientes oncopediátricos, principalmente os que necessitam do suporte oferecido pela UTI, refletindo consideravelmente no conforto, redução do tempo no âmbito hospitalar e melhora da qualidade de vida.

Citação
SENTENO, M. B.; MELO, É. S.; DA SILVA, J. J. VENTILAÇÃO NÃO INVASIVA EM ONCOPEDIATRIA NA UNIDADE DE TERAPIA INTENSIVA. v. 1 n. 1 (2021). Revista Eletrônica Ciência & Tecnologia Futura.