Anti-EGFR therapy: strategies in head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that activates downstream signaling pathways, including the Ras-MEK-Erk and PI3K-AKT pathways, leading to cell proliferation, resistance to apoptosis, angiogenesis and the ability to metastasize. EGFR overexpression is a significant finding in cancer, particularly in head and neck cancer, where it is also associated with a poor prognosis. In recent years, several molecules have been designed to inhibit EGFR activation. Among the many available anti-EGFR drugs, only cetuximab was approved for the treatment of head and neck cancers. However, no predictive biomarkers of cetuximab response are currently known. In the present review, we provide an updated assessment of EGFR biology and its clinical impact in head and neck cancers. A special emphasis is placed on novel patents of EGFR-inhibitors that are anticipated to diversify the anti-EGFR therapies available to treat head and neck cancers. In particular, we outline a new class of irreversible multi-target inhibitors (e.g. afatinib, icotinib, CUDC-101), which may significantly contribute to new head and neck cancer therapies.The authors would like to acknowledge Dr. Laura Mussel white for critical revision of the manuscript. André L. Carvalho and Rui M. Reis have a National Counsel of Technological and Scientific Development (CNPq) scholarship. A.C.C, has a FAPESP (2013/13834-7) scholarship.info:eu-repo/semantics/publishedVersio

AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

Epidemiological screening of pathogenicity factors associated with multidrug-resistant bacteria isolated in uroculture of hospitalized neonates in the lakes region from Rio de Janeiro.

The discovery of antimicrobials revolutionized the treatment of infectious diseases caused by bacteria, as they are drugs that contribute to reducing morbidity and mortality rates associated with infectious diseases (JANEBRO, et al., 2008). However, the irrational use of antimicrobial drugs represents one of the main concerns worldwide, since the misuse of these drugs accelerates the natural process of bacteria resistance to antibiotics (ZIMERMAN, 2010). In view of all these problems, the objective of this study was to evaluate the profile of resistance of bacteria identified in the urine culture of neonates who are hospitalized, based on the records of the Laboratory of Clinical Analysis of a hospital in the lakes region from Rio de Janeiro. To do so, we used the following methodologies: (i) literature review for contextualization of the problem and basis for discussion; (ii) and monitoring of a descriptive observational study that had as instrument the reports of records containing results of urine culture and antibiogram of neonatal patients, referring to the period from January 2020 to September 2021. The results showed a higher incidence of Escherichia coli (44% - 2020; 56% - 2021) among the microorganisms isolated in the analyzed urine cultures, followed by Klebsiella pneumoniae (14% - 2020; 28% - 2021). Antimicrobials from the β-lactam group caused high bacterial resistance, among the strains of different microorganisms analyzed, increasingly indicating the need for the replacement of these drugs in the clinic, in order to choose a better therapy for the patient. As in any infectious pathology, to establish appropriate prevention and treatment of community-acquired urinary tract infections, effective and continuous research is needed, with the goal of defining in detail the etiology and profile of bacterial resistance in regional, national, and international standards. It is hoped that these new data profiling the level of resistance in which microorganisms isolated from neonatal patients admitted under hospital regimen are found will be of great value to the academic community and to health professionals, providing users with increasingly accurate and quality treatment.The discovery of antimicrobials revolutionized the treatment of infectious diseases caused by bacteria, as they are drugs that contribute to reducing morbidity and mortality rates associated with infectious diseases (JANEBRO, et al., 2008). However, the irrational use of antimicrobial drugs represents one of the main concerns worldwide, since the misuse of these drugs accelerates the natural process of bacteria resistance to antibiotics (ZIMERMAN, 2010). In view of all these problems, the objective of this study was to evaluate the profile of resistance of bacteria identified in the urine culture of neonates who are hospitalized, based on the records of the Laboratory of Clinical Analysis of a hospital in the lakes region from Rio de Janeiro. To do so, we used the following methodologies: (i) literature review for contextualization of the problem and basis for discussion; (ii) and monitoring of a descriptive observational study that had as instrument the reports of records containing results of urine culture and antibiogram of neonatal patients, referring to the period from January 2020 to September 2021. The results showed a higher incidence of Escherichia coli (44% - 2020; 56% - 2021) among the microorganisms isolated in the analyzed urine cultures, followed by Klebsiella pneumoniae (14% - 2020; 28% - 2021). Antimicrobials from the β-lactam group caused high bacterial resistance, among the strains of different microorganisms analyzed, increasingly indicating the need for the replacement of these drugs in the clinic, in order to choose a better therapy for the patient. As in any infectious pathology, to establish appropriate prevention and treatment of community-acquired urinary tract infections, effective and continuous research is needed, with the goal of defining in detail the etiology and profile of bacterial resistance in regional, national, and international standards. It is hoped that these new data profiling the level of resistance in which microorganisms isolated from neonatal patients admitted under hospital regimen are found will be of great value to the academic community and to health professionals, providing users with increasingly accurate and quality treatment

Socio-environmental impact with inadequate destination of chemical residues pharmaceuticals: project with alternative of receiving and processing of residues generated by the city of Araruama in the Region of Lakes of Rio de Janeiro: Impacto socioambiental com destino inadequado dos resíduos químicos farmacêuticos: projeto com alternativa de recebimento e processamento dos resíduos gerados pela cidade de Araruama na Região dos Lagos do Rio de Janeiro

Many pharmaceutical chemical residues (PCR) have shown great potential to pollute the environment, especially in marine habitats. The conjecture stems from direct participation of human beings. Toxicological studies carried with drugs showed the possibility of appearance of physiological sexual alterations already observed in certain species of fish and other marine animals, in addition to the increase of resistant bacteria. In this way, evidence drives the reduction or interruption of exposure to CRP in the environment. The objective of this work is to propose a project to receive expired medicines and other therapeutic products, without use or leftovers from inappropriate uses by several individuals. To achieve these objectives, we will carry out the following methodologies: (i) Conduct a literature review on the subject, to consolidate the problem; (ii) present an advertising plan using social communication vehicles, such as radio, television and social networks, for information and awareness of society about the PCR disposal campaign correctly, using the motto "save the world so you don't lose anyone you love” (iii) To officially request the support of the Municipal Environment Department of Araruama city and the CRF-RJ to standardize and delimit the processing of PCR collected, as a result, several studies were found that indicate and reinforce the socio-environmental impact associated with disposal of PCRs, as well as the evolutionary trend of aggravation of this socio-environmental issue. The introduction of different programs to encourage the proper and rational management and treatment of PCRs with the direct mobilization of different social ties such as the media and especially the different levels of government of the direct and/or indirect administration presents itself as an important tool to achieve of measures that can reduce the social impacts caused by PCRs

Spatial and temporal variability of grain yield under no-tillage cropping system

O objetivo deste trabalho foi avaliar a variabilidade espacial e temporal da produtividade de soja, milho e trigo, em uma lavoura comercial de 57 ha, não irrigada, manejada há mais de dez anos sob sistema plantio direto, em um Latossolo Vermelho distrófico típico, em Palmeira das Missões, RS. A coleta de dados de produtividade de seis cultivos, entre 2000 e 2005, foi realizada por colhedora equipada com monitor de produtividade. Análises estatísticas e geoestatísticas foram realizadas a fim de avaliar a variabilidade espacial e a presença de dependência espacial ao longo dos anos. A produtividade da soja, do milho e do trigo alcançada apresenta variabilidade com continuidade espacial, correlacionando-se entre si, ao longo dos anos. Em anos de deficit hídrico, verifica-se aumento da variabilidade espacial da produtividade. A cultura do milho é mais eficiente do que a da soja em detectar a variabilidade espacial da produtividade existente na lavoura.The objective of this work was to analyze the spatial and temporal yield variability of soybean, corn and wheat in a 57 ha cropland, without irrigation, under no-till for more than ten years in a Typic Hapludox, located in Palmeira das Missões, RS. Yield data of crops from 2000 to 2005 were collected using a combine equipped with yield monitor. Statistical and geostatistical analysis were performed to monitor the range of the spatial variability and its spatial dependence, as well as its behavior over the years. Soybean, corn and wheat yield present spatial variability, which is maintained over time. In dry years, yield variance coefficient increases compared to wet years. Corn was more efficient than soybean to identify spatial yield variability in the cropland

Anemia como fator preditivo negativo de resposta ao tratamento do câncer de colo uterino / Anemia as a negative predictive factor for response to treatment of cervical cancer

Introdução: No Brasil, o câncer cervical (CC) é o terceiro tumor maligno mais frequente nas mulheres e a quarta causa de morte por câncer entre a população feminina, de acordo com o Instituto Nacional do Câncer (INCA). O agrupamento TNM, o tipo e grau histológico, a invasão linfovascular e/ou perineural são fatores prognósticos independentes, assim como a anemia. Objetivos: O presente estudo analisou o risco de óbito no primeiro ano de seguimento oncológico após término da radioterapia, conforme nível de hemoglobina (HB) pré tratamento (<10g/dl vs ≥10g/dl). Método: Estudo tipo coorte retrospectiva que incluiu pacientes com diagnóstico de CC, admitidas e tratadas em centro especializado de oncologia de Ipatinga - MG, Brasil no período de 2014 a 2017. Resultados: Pacientes com HB ≥ 10g/dl no pós tratamento apresentaram menor chance de evoluir para o óbito com relação às pacientes com HB < 10g/dl. 66,1% dos pacientes com HB ≥ 10g/dl no baseline foram classificados como livre da doença após término da radioterapia. O valor da HB após término da radioterapia também foi preditivo de resposta à radioterapia. Conclusão: A presença de HB < 10g/dl após término do tratamento correlacionou-se negativamente com tipo de resposta e risco de óbito

Os impactos da resistência bacteriana por uso de antibióticos durante o período da pandemia da Covid-19

Objetivo: Analisar na literatura o aumento da resistência bacteriana durante o período da pandemia por COVID-19 e colher dados que evidencie que houve um aumento da resistência bacteriana pelo uso incorreto de antibióticos e fazer um alerta sobre esse problema de saúde pública. Método: Trata-se de um estudo bibliográfico de abordagem qualitativa  do tipo de revisão integrativa de literatura(RIL).Para  construção do estudo, foram feitas coletas nas bases de dados  Biblioteca Virtual em Saúde (BVS) e Brasil Scientific Electronic Library Online(SCIELO) nos períodos de 2021 a 2023.Diante disso, foram escolhidos estudos que possuíam compatibilidade e competência com o tema proposto. Resultados: Os resultados encontrados nas bases literárias foram organizados em periódicos seguindo em autor/ano, título, objetivos, resultados e organizados em ordem alfabética. Conclusão: Com isto, que possamos ter mais estudos futuros sobre esse problema que pode gerar um colapso o sistema de saúde caso na haja um controle adequado no uso dessa classe medicamentos

AVALIAÇÃO DA RIQUEZA DE ESPÉCIES ARBÓREAS ATRAVÉS DOS MÉTODOS BOOTSTRAP E REGRESSAO QUADRÁTICA DE PLATÔ

As florestas tropicais no Brasil apresentam elevada diversidade de espécies arbóreas e, vêm sofrendo grande pressão devido a expansão agrícola, pecuária e outras atividades econômicas antrópicas. Diante desses fatores torna-se cada vez mais importante estudos fitossociológicos que envolvam riqueza de espécies, com intuito de conhecer o potencial biológico existente, bem como justificar a conservação dos remanescentes florestais nativos. Sendo assim, o objetivo deste trabalho foi verificar a suficiência amostral necessária para a quantificação da riqueza arbórea da Bacia Hidrográfica do Rio Grande (BHRG), no sul de Minas Gerais, avaliando em nível de fragmentos (parcelas por fragmento) e para toda a área da bacia (fragmentos na área total), essa análise foi estendida para a análise pontual da fitofisionomia Floresta Estacional Semidecidual, que é a principal fisionomia de ocorrência na bacia hidrográfica, verificando também a utilização da modelagem para a estimativa total de espécies arbóreas. O método utilizado foi a regressão de platô, para isso utilizou-se a reamostragem bootstrap sem reposição para a retirada da subjetividade na entrada dos dados no ajuste do modelo. A regressão de platô indicou o ponto onde seria encontrada a suficiência amostral. Concluiu-se, pelo modelo quadrático de resposta em platô, que a amostragem realizada para a bacia como um todo atingiu a suficiência amostral com 26 fragmentos. Já a nível de fragmentos, a suficiência amostral foi atingida em 55% dos fragmentos amostrados. Os resultados aqui apresentados podem ser utilizados para fins de indicação de espécies destinadas à recuperação de ecossistemas degradados, dentre outras aplicações de conservação florestal