Are both distinct epithelial and stromal cells molecular analysis from phyllodes tumors versus fibroadenoma components affected in breast fibroepithelial progression?

PURPOSE: To determine molecular events involved in the tumorigenesis of phyllodes tumors (PT) and the role of each stromal (SC) and epithelial (EC) cell. METHODS: Frozen breast samples enriched with epithelial and stromal cells from three fibroadenomas and 14 PT were retrieved and laser microdissected. Sanger and polymerase chain reaction-based sequencing of exon 2 MED12 and TERT promoter hotspot mutations were performed; 44K microarray platform was used to analyze gene expression. RESULTS: All three fibroadenomas (FAs) presented mutations in MED12, but not in TERT, whose mutation was observed in five of the 14 PTs. EC and SC of each affected tumor displayed identical alterations. Of the total differentially expressed genes (DEG) (EC = 1,543 and SC = 850), 984 were EC-eDEGs and 291 were SC-eDEGs. We found a high similarity of diseases and functions enriched by both cell types, but dissimilarity in the number of enriched canonical pathways. Three signaling canonical pathways overlapping with EC and SC were predicted to be activated in one cell type and inactivated in the other, while no overlap in eDEGs was assigned to them. We also identified 13 EC-eDEGs and five SC-eDEGs enriched networks, in which the SC-eDEGs were able to segregate FA from PT samples. CONCLUSIONS: Identical TERT mutations from both SC and ES origins might affect the PTs tumorigenesis. Gene expression differences suggest coordinated molecular processes between these components with determinant differences acquired by SC, able to fully distinguish PTs from FAs lesions.

Are both distinct epithelial and stromal cells molecular analysis from phyllodes tumors versus fibroadenoma components affected in breast fibroepithelial progression?

Purpose: To determine molecular events involved in the tumorigenesis of phyllodes tumors (PT) and the role of each stromal (SC) and epithelial (EC) cell. Methods: Frozen breast samples enriched with epithelial and stromal cells from three fibroadenomas and 14 PT were retrieved and laser microdissected. Sanger and polymerase chain reaction-based sequencing of exon 2 MED12 and TERT promoter hotspot mutations were performed; 44K microarray platform was used to analyze gene expression. Results: All three fibroadenomas (FAs) presented mutations in MED12, but not in TERT, whose mutation was observed in five of the 14 PTs. EC and SC of each affected tumor displayed identical alterations. Of the total differentially expressed genes (DEG) (EC = 1,543 and SC = 850), 984 were EC-eDEGs and 291 were SC-eDEGs. We found a high similarity of diseases and functions enriched by both cell types, but dissimilarity in the number of enriched canonical pathways. Three signaling canonical pathways overlapping with EC and SC were predicted to be activated in one cell type and inactivated in the other, while no overlap in eDEGs was assigned to them. We also identified 13 EC-eDEGs and five SC-eDEGs enriched networks, in which the SC-eDEGs were able to segregate FA from PT samples. Conclusions: Identical TERT mutations from both SC and ES origins might affect the PTs tumorigenesis. Gene expression differences suggest coordinated molecular processes between these components with determinant differences acquired by SC, able to fully distinguish PTs from FAs lesions.

The use of micronucleus assay in oral mucosa cells as a suitable biomarker in children exposed to environmental mutagens: theoretical concepts, guidelines and future directions.

In the last decades, the micronucleus assay has been recognized as a suitable biomarker for monitoring populations exposed to many different occupational factors, lifestyle, environmental conditions, radiation exposure, and deleterious effects of pesticides. The objective of this work is to direct the design of future field studies in the assessment of the risk of children exposed to environmental mutagens, radiation, and pesticides. This review sought available information on the analysis of micronuclei in oral cells in children. A literature search for papers investigating DNA damage, genetic damage, oral cells, buccal cells, genotoxicity, mutagenicity and micronucleus was begun in 2000 and is scheduled to be concluded in May, 2022. Briefly, a search of PubMed, MEDLINE, and Google Scholar for a variety of articles was performed. The results showed that there are still few studies that addressed micronuclei of oral cells in children exposed to the most diverse environmental conditions. Only environmental pollution was associated with damage to the genome of oral cells in children. Therefore, researchers need to be calibrated in cell analysis, standardization of field study protocols and the development of new research in the evaluation of children using the micronucleus test as a tool in child biomonitoring.

Complementary tool in diagnosis of hydatidiform mole: Review.

Hydatidiform mole is an abnormal pregnancy in which two copies of paternal genetic material are present. Molar gestation is divided into complete and partial hydatidiform moles. Clinical, morphological, and cytogenetic characteristics are usually sufficient to distinguish them, but and the rare cases that are necessary to know the paternal origin to establish the diagnosis and segment? Mutations in the Gene for Factor V Leiden and G20210A prothrombin polymorphism in women with recurrent spontaneous abortion: a retrospective study in a Brazilian population.

Functions of astrocytes in multiple sclerosis: A review.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), which usually affects young adults between 20 and 40 years old. In chronic neurodegenerative diseases such as multiple sclerosis, CNS cells take on several adaptations during neuroinflammation. The main cells involved in this inflammatory process are the glial cells, in which the astrocytes stand out. These cells play a complex role, and several studies report that reactive astrocytes lose their supporting role and gain toxic function in the progression of these diseases. RESULTS: The beneficial and injurious effects of this group of cells in MS are addressed in this work, as well as some drugs that are already used in the treatment of patients with multiple sclerosis, aiming to regulate astrocytic activities. CONCLUSIONS: The knowledge about the functions of astrocytes is essential for the expansion of scientific research in this area, since these cells are so important and involved in different mechanisms of action, especially in neurodegenerative and autoimmune diseases.

Compartilhando conhecimento sobre o novo coronavírus: relato de experiência / Sharing knowledge about the new coronavirus: experience report / Compartir conocimientos sobre el nuevo coronavirus: informe de experiencia

Introdução: Em março de 2020 a Organização Mundial da Saúde decretou pandemia pelo novo coronavírus (SARS-CoV-2), causador da doença COVID-19. Objetivo: relatar a experiência sobre a disseminação de informações acerca do coronavírus. Método: Trata-se de um relato de experiência de graduandos do curso de enfermagem e pós-graduandos em patologia da Universidade Federal de São Paulo, na campanha Pílulas do conhecimento sobre a pandemia do novo coronavírus, realizada em março de 2020. Foi elaborado um boletim informativo e um vídeo educativo, baseado na literatura, com informações sobre o coronavírus (o que é, sintomas, transmissão, grupos de risco, prevenção, ação, uso de máscara e vacina) e o material foi disponibilizado virtualmente. Resultado: O boletim informativo e o vídeo educativo foram elaborados baseados na literatura. O vídeo obteve 151 visualizações no canal do Clube do Saber no YouTube e 490 pessoas no Facebook. Conclusão: A disseminação de informações sobre o novo coronavírus obteve grande alcance da população.

Introduction: In March 2020, World Health Organization declared a pandemic due tothenew coronavirus (SARS-CoV-2), which causes COVID-19. Objective: to promote health education, bringing relevant, clear and objective information about diseases. Methods: Thisisan experience report of undergraduate nursing students and graduate students in pathology, Universidade Federal de São Paulo, in the Pills of Knowledge campaign on the new coronavirus pandemic, held in March 2020. A newsletter and an educational video, withinformation about the coronavirus (what is, symptoms, transmission, risk groups, prevention, action, use of mask and vaccine) and, the material was made available virtually. Result: Thevideo obtained 151 views on the Clube do Saber channel on YouTube and 490 peoplebyFacebook. Conclusion: The dissemination of information about the coronavirus has reachedawide reach of the population

Introducción: en marzo de 2020, la Organización Mundial de la Salud declaró una pandemia debido al nuevo coronavirus (SARS-CoV-2), que causa COVID-19. Objetivo: realizar uninforme de experiencia acerca de la difusión de la información sobre el coronavirus. Métodos: Este es un informe de experiencia de estudiantes de la carrera de enfermería y estudiantes de posgrado en patología de la Universidad Federal de San Pablo, en la campaña Píldoras del conocimiento sobre la pandemia del nuevo coronavirus, realizada en marzo de 2020. Se elaboró un boletín informativo y un video educativo, con información sobre el coronavirus (qué es, síntomas, transmisión, grupos de riesgo, prevención, acción, uso de mascarilla y vacuna) y el material se puso a disposición de forma virtual. Resultado: la elaboración del boletín informativo y del video educativo se realizó en base a la literatura. El videoobtuvo151 visitas en el canal Clube do Saber en YouTube y llegó a 490 personas en Facebook. Conclusión: La difusión de información sobre el coronavirus tuvo un gran alcance en la población.

Dimethoate induces genotoxicity as a result of oxidative stress: in vivo and in vitro studies.

Dimethoate ([O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithioate]) is an organophosphate insecticide and acaricide widely used for agricultural purposes. Genotoxicity refers to the ability of a chemical agent interact directly to DNA or act indirectly leading to DNA damage by affecting spindle apparatus or enzymes involved in DNA replication, thereby causing mutations. Taking into consideration the importance of genotoxicity induced by dimethoate, the purpose of this manuscript was to provide a mini review regarding genotoxicity induced by dimethoate as a result of oxidative stress. The present study was conducted on studies available in MEDLINE, PUBMED, EMBASE, and Google scholar for all kind of articles (all publications published until May, 2020) using the following key words: dimethoate, omethoate, DNA damage, genetic damage, oxidative stress, genotoxicity, mutation, and mutagenicity. The results showed that many studies were published in the scientific literature; the approach was clearly demonstrated in multiple tissues and organs, but few papers were designed in humans. In summary, new studies within the field are important for better understanding the pathobiological events of genotoxicity on human cells, particularly to explain what cells and/or tissues are more sensitive to genotoxic insult induced by dimethoate.

Entendendo o câncer de mama: educação em saúde / Understanding breast cancer: health education

Objetivo: Demonstrar os benefícios da educação em saúde sobre o câncer de mama para a população. Métodos: Trata-se de um relato de experiência sobre educação em saúde, utilizando boletins informativos e banners elaborados pelos discentes, monitorado pelos alunos de pós-graduação em patologia e supervisionados pelos colaboradores e coordenadores do projeto, divulgados presencialmente para a comunidade. Resultados: Essa experiência trouxe como resultado maior aproveitamento das atividades didáticas e dinâmicas do ambulatório, com uma metodologia ativa, assim como o empoderamento dos usuários para a autonomia, capacidade de identificar determinantes para sua saúde e cuidar de si e dos outros a sua volta. Conclusão: Conclui-se então que esta atividade de educação foi enriquecedora tanto para os discentes que a organizaram quanto para clientes do ambulatório, expondo uma relação entre a prevenção e a promoção da saúde dos usuários e com um projeto de extensão que visa compartilhar o conhecimento adquirido na academia, transcendendo seus muros para todos. (AU)

Objective: To demonstrate the benefits of health education on breast cancer for the population. Methods: Descriptive-exploratory study with a qualitative approach, using newsletters and banners prepared by students, monitored by graduate students in pathology and supervised by project collaborators and coordinators and disseminated to the community. Results: This experience resulted in greater use of the didactic and dynamic activities of the clinic, with an active methodology, as well as the empowerment of users for autonomy, the ability to identify determinants for their health and to take care of themselves and others around them. Conclusion: We conclude then that the campaign was enriching both for the students who organized it and for clients of the outpatient clinic, exposing a relationship between prevention and health promotion of users and with an extension project that aims to share the knowledge acquired in the academy, transcending their walls for everyone. (AU)

Objetivo: Demostrar los beneficios de la educación para la salud sobre el cáncer para la población. Métodos: Estudio descriptivo-exploratorio con un enfoque cualitativo, utilizando boletines y pancartas preparados por estudiantes, monitoreados por estudiantes graduados en patología y supervisados por colaboradores y coordinadores del proyecto y entregado a la comunidad. Resultados: Esta experiencia resultó en un mayor uso de las actividades didácticas y dinámicas de la clínica, con una metodología activa, así como el empoderamiento de los usuarios para la autonomía, la capacidad de identificar determinantes para su salud y para cuidarse a sí mismos y a los demás a su alrededor. Conclusión: Concluimos entonces que la campaña fue enriquecedora tanto para los estudiantes que la organizaron como para los clientes de la clínica ambulatoria, exponiendo una relación entre prevención y promoción de la salud de los usuarios y con un proyecto de extensión que tiene como objetivo compartir el conocimiento adquirido en la academia, trascendiendo sus muros para todos. (AU)

Pilocytic Astrocytoma: A Review of General, Clinical, and Molecular Characteristics.

Pilocytic astrocytomas are the primary tumors most frequently found in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all gliomas. They are mostly found in infratentorial structures such as the cerebellum and in midline cerebral structures such as the optic nerve, hypothalamus, and brain stem. The present study aimed to list the main characteristics about this tumor, to better understand the diagnosis and treatment of these patients, and was conducted on search of the published studies available in NCBI, PubMed, MEDLINE, Scielo, and Google Scholar. It was possible to define the main histologic findings observed in these cases, such as mitoses, necrosis, and Rosenthal fibers. We described the locations usually most affected by tumor development, and this was associated with the most frequent clinical features. The comparison between the molecular diagnostic methods showed great use of fluorescent in situ hybridization, polymerase chain reaction (PCR), and reverse transcriptase-PCR, important techniques for the detection of BRAF V600E mutation and BRAF-KIAA1549 fusion, characteristic molecular alterations in pilocytic astrocytomas.

THE CANONICAL WNT PATHWAY IN GASTRIC CARCINOMA.

BACKGROUND: It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. AIM: To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. METHOD: The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3ß, axin, CK1, ubiquitin, cyclin D1 and c-myc. RESULTS: There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. CONCLUSION: The canonical WNT pathway is involved in gastric carcinoma.

The canonical wnt pathway in gastric carcinoma / Via canônica do wnt no carcinoma gástrico

ABSTRACT Background : It is believed that the Wnt pathway is one of the most important signaling involved in gastric carcinogenesis. Aim : To analyze the protein expression of canonical and non-canonical Wnt pathways in gastric carcinoma. Method : The immunohistochemistry was performed in 72 specimens of gastric carcinomas for evaluating the expression of Wnt-5a, FZD5, GSK3β, axin, CK1, ubiquitin, cyclin D1 and c-myc. Results : There were significant differences for cytoplasm and nucleus ubiquitin for moderately and well differentiated tumors (p=0.03) and for those of the intestinal type of the Lauren classification (p=0.03). The absence of c-myc was related to Lauren's intestinal tumors (p=0.03). Expression of CK1 in the cytoplasm was related to compromised margin (p=0.03). Expression of cyclin D1 protein was more intense in male patients (p=0.03) There was no relation of the positive or negative expression of the Wnt-5a, FZD5, GSK3 and Axin with any clinicopathological variables. Conclusion: The canonical WNT pathway is involved in gastric carcinoma.

RESUMO Racional : Acredita-se que a via Wnt é uma das mais importantes da sinalização envolvidas na carcinogênese gástrica. Objetivos : Analisar a expressão das proteínas das vias Wnt canônicas e não-canônicas no carcinoma gástrico e relacionar sua expressão com as variáveisclinicopatológicas. Método : Foram coletadas 72 amostras de carcinoma gástrico, e áreas representativas do tumor foram selecionadas para o Tissue Microarray. Imunoistoquímica foi realizada para avaliar a expressão de Wnt-5a, FZD5, GSK3β, axina, CK1, ubiquitina, ciclina D1 e c-myc. Resultados : Houve diferenças significativas para a expressão de ubiquitina no citoplasma e núcleo para tumores moderadamente e bem diferenciados (p=0,03) e para aqueles do tipo intestinal da classificação de Lauren (p=0,03). A expressão negativa da proteína c-myc no citoplasma foi relacionada aos tumores intestinais de Lauren (p=0,028). A expressão positiva de CK1 no citoplasma das células neoplásicas foi relacionada a tumores com margens cirúrgicas livre de envolvimento neoplásico (p=0,03). A expressão positiva da proteína ciclina D1 foi maior nos tumores dos homens (p=0,03). Não houve relação da expressão positiva ou negativa das proteínas Wnt-5a e FZD5 no citoplasma ou núcleo com quaisquer variáveis clinicopatológicas. O mesmo foi observado para GSK3β e Axin. Conclusões : A relação da expressão das proteínas da via canônica com as variáveis epidemiológicas e tumorais sugere sua participação na carcinogênese gástrica. Por outro lado, a ausência da relação das expressões das proteínas da via não-canônica sugere sua não participação na carcinogênese gástrica.