Perspectives on label-free microscopy of heterogeneous and dynamic biological systems.

Significance: Advancements in label-free microscopy could provide real-time, non-invasive imaging with unique sources of contrast and automated standardized analysis to characterize heterogeneous and dynamic biological processes. These tools would overcome challenges with widely used methods that are destructive (e.g., histology, flow cytometry) or lack cellular resolution (e.g., plate-based assays, whole animal bioluminescence imaging). Aim: This perspective aims to (1) justify the need for label-free microscopy to track heterogeneous cellular functions over time and space within unperturbed systems and (2) recommend improvements regarding instrumentation, image analysis, and image interpretation to address these needs. Approach: Three key research areas (cancer research, autoimmune disease, and tissue and cell engineering) are considered to support the need for label-free microscopy to characterize heterogeneity and dynamics within biological systems. Based on the strengths (e.g., multiple sources of molecular contrast, non-invasive monitoring) and weaknesses (e.g., imaging depth, image interpretation) of several label-free microscopy modalities, improvements for future imaging systems are recommended. Conclusion: Improvements in instrumentation including strategies that increase resolution and imaging speed, standardization and centralization of image analysis tools, and robust data validation and interpretation will expand the applications of label-free microscopy to study heterogeneous and dynamic biological systems.

Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Efectividad del entrenamiento muscular pélvico temprano en la fuerza de suelo pélvico, síntomas de incontinencia urinaria, función sexual y calidad de vida en pacientes posprostatectomía radical: revisión sistemática de ensayos clínicos aleatorizados / Effectiveness of early pelvic muscle training on pelvic floor strength, urinary incontinence symptoms, sexual function, and quality of life in post-radical prostatectomy patients: Systematic review of randomized clinical trials

Este estudio tuvo como objetivo evaluar la efectividad del entrenamiento muscular pélvico temprano para reducir los síntomas de incontinencia urinaria, mejorar la calidad de vida, función sexual y aumentar la fuerza de suelo pélvico en pacientes posprostatectomía radical. Se realizó una búsqueda en 8 bases de datos hasta el 26 de octubre de 2022, se evaluó la calidad metodológica y el riesgo de sesgo de 14 estudios incluidos (n=1236), se calculó la evidencia y el metaanálisis. El entrenamiento redujo significativamente los síntomas de incontinencia urinaria en comparación con un grupo control (DME=−2,80; IC 95%=−5,21 a −0,39; p=0,02), con heterogeneidad significativa (I2=83%; p=<0,0001) y evidencia moderada. Además, presentó evidencia moderada para mejorar la calidad de vida, y muy baja para mejorar la función sexual y fuerza de suelo pélvico. Estos resultados deben ser observados con precaución debido a la heterogeneidad significativa de los estudios analizados. (AU)

This study aimed to evaluate the effectiveness of early pelvic muscle training in reducing urinary incontinence symptoms, improving quality of life, sexual function, and increasing pelvic floor strength in post-radical prostatectomy patients. A search was carried out in 8 databases until October 26, 2022, the methodological quality and the risk of bias of 14 included studies (n=1236) were evaluated, moreover, the evidence and the meta-analysis were calculated. The intervention significantly reduced urinary incontinence symptoms compared to a control group (SMD=−2.80, 95% CI=−5.21 to −0.39, P=.02), with significant heterogeneity (I2=83%; P=<.0001) and moderate evidence. In addition, it presented moderate evidence to improve quality of life, and very low evidence to improve sexual function and pelvic floor strength. These results should be viewed with caution due to the significant heterogeneity of the studies analysed. (AU)

Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico / Hypertensive Emergency as the Debut of Paraneoplastic Cushing Syndrome

Presentamos el caso de un paciente con antecedentes de hipertensión arterial vasculorrenal tratada un año antes, que acude a urgencias por emergencia hipertensiva (HTA) y disnea. Descartada primera sospecha de reestenosis de arteria renal con angiografía por tomografía computarizada (angioTC), se completa el estudio confirmándose diagnóstico de cáncer de pulmón mediante prueba de imagen y anatomía patológica. En el estudio de hipertensión se detecta elevación de hormona adrenocorticótropa (ACTH), hipercortisolismo y datos analíticos de hiperaldosteronismo. Con el diagnóstico final de síndrome de Cushing secundario a producción ectópica de ACTH se inicia tratamiento médico, sin llegar a recibir nada más por fallecimiento del paciente a los pocos días.(AU)

We present the case of a patient with a history of renal-vascular hypertension treated with stent one year previously, who attended the emergency room due to hypertensive emergency and dyspnea. Once the first suspicion of renal artery restenosis was ruled out with CT angiography, the study was completed, confirming the diagnosis of lung cancer through imaging and pathological anatomy. In the hormonal study, elevation of ACTH, hypercortisolism and analytical data of hyperaldosteronism were detected. With the final diagnosis of Cushing's syndrome secondary to ectopic production of ACTH, medical treatment was started, without being able to receive anything else due to the death of the patient after a few days.(AU)

Primary hepatic pleomorphic liposarcoma: Case report and literature review / Liposarcoma pleomorfo hepático primario: presentación de un caso y revisión bibliográfica

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)

El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)

Tumor fibroso calcificante intestinal: reporte de caso / Intestinal calcifying fibrous tumor: case report

El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)

Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)

Extraskeletal myxoid chondrosarcoma metastasis to a Meckel's diverticulum adenocarcinoma / Metástasis de condrosarcoma mixoide extraesquelético a un adenocarcinoma de divertículo de Meckel

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature. (AU)

El condrosarcoma mixoide extraesquelético es un tumor de tejidos blandos poco frecuente, con una elevada tasa de recurrencia y metástasis a distancia y una respuesta limitada a la quimioterapia. El divertículo de Meckel es la anomalía congénita más frecuente y se asocia a un riesgo considerable de transformación maligna. En este caso clínico describimos a una paciente de 50 años con antecedentes de condrosarcoma mixoide extraesquelético de miembro inferior y metástasis en el antebrazo que acudió al servicio de urgencias por dolor abdominal. La exploración reveló un vólvulo cecal. Se descubrió incidentalmente una lesión en el tercio medio del íleon, que se extirpó durante la intervención quirúrgica. El examen patológico reveló un adenocarcinoma de divertículo de Meckel, afectado por metástasis de condrosarcoma mixoide extraesquelético. La resección fue completa; sin embargo, la paciente presentaba enfermedad pulmonar metastásica difusa y falleció ocho meses después debido a la progresión de la enfermedad. Este mecanismo de metástasis entre tumores está descrito en otras localizaciones, pero en lo que respecta al divertículo de Meckel, se trata de una situación única en la literatura. (AU)

Tumor espermatocítico variante anaplásica sincrónico bilateral: reporte de una neoplasia infrecuente / Bilateral synchronous anaplastic variant spermatocytic tumor: Report of a rare neoplasm

El tumor espermatocítico es una neoplasia testicular de células germinales, muy infrecuente, que representa menos del 1% de los cánceres testiculares. Afecta generalmente a hombres mayores con una edad media de 53,6 años (rango 19-92 años). El tumor espermatocítico se clasifica dentro del grupo de tumores germinales no relacionados con la neoplasia de células germinales in situ. Muestra características clinicopatológicas diferentes del seminoma clásico y no se considera una variante de este último. Debido a una superposición morfológica con el seminoma clásico, en el pasado se denominó «seminoma espermatocítico». La variante anaplásica del tumor espermatocítico es excepcional, se han descrito pocos casos en la literatura, presenta un inicio más temprano en comparación con el tumor espermatocítico y un buen comportamiento a pesar de mostrar patrones histológicos similares al seminoma clásico. Presentamos el segundo caso de tumor espermatocítico anaplásico sincrónico bilateral, en un paciente joven tratado con orquiectomía y quimioterapia. (AU)

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called “sperm cell seminoma” in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy. (AU)

Evaluation of Cytotoxic effect of Moringa peregrina seeds on Oral Cancer, CAL 27, Cell Line and Red Blood Cells Hemolysis / Evaluación del efecto citotóxico de las semillas de Moringa peregrina en el cáncer oral, CAL 27, líneas celulares y hemólisis de glóbulos rojos

Background: Moringa peregrina Forssk is a well-known plant in ethnomedicine due to its widespread uses in various diseases like cough, wound healing, rhinitis, fever, and detoxification. The plant seeds contain compounds that are cytotoxic to many cancer cells. During the therapeutic use of plants via the oral route, some compounds present in the plants may be cytotoxic to normal cell lines and red blood cells. Objective: This study was the first report of investigation of the cytotoxic profile on oral cancer, CAL 27, cell line, and hemolytic activities on human erythrocytes of Moringa peregrina seeds ethanolic extract (MPSE). Methods: MPSE was screened for its cytotoxic effect against oral cancer, CAL 27, cell line using 3-(4, 5-dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT) assay. The toxicity of MPSE on human erythrocytes was determined by in vitro hemolytic assay. Results: MPSE showed significant anti-proliferative activity against oral cancer, CAL 27 cell line at lower concentrations with half maximal inhibitory concentration (IC50) value of 21.03 µg/mL. At 1,000 µg/ml of MPSE, the maximum hemolysis was found to be 14.3% which is within safer limit. Conclusions: This study revealed a potential anti-oral cancer of MPSE and provided a baseline for its potential use in oral cancer treatment with minimum hemolytic effect on human RBCs.

La Moringa peregrina Forssk es una planta muy conocida en etnomedicina debido a sus usos generalizados en diversas enfermedades como la tos, la cicatrización de heridas, la rinitis, la fiebre y la desintoxicación. Las semillas de la planta contienen compuestos citotóxicos para muchas células cancerosas. Durante el uso terapéutico de las plantas por vía oral, algunos compuestos presentes en ellas pueden ser citotóxicos para las líneas celulares normales y los glóbulos rojos. Objetivo: Este estudio fue el primer informe de investigación del perfil citotóxico sobre el cáncer oral, CAL 27, línea celular, y las actividades hemolíticas en eritrocitos humanos del extracto etanólico de semillas de Moringa peregrina (MPSE). Métodos: Se examinó el efecto citotóxico del MPSE contra la línea celular de cáncer oral CAL 27 mediante el ensayo con bromuro de 3-(4, 5-dimetiltiazol-2-il)-2, 5,-difeniltetrazolio (MTT). La toxicidad del MPSE sobre los eritrocitos humanos se determinó mediante un ensayo hemolítico in vitro. Resultados: MPSE mostró una actividad antiproliferativa significativa contra el cáncer oral, línea celular CAL 27 a concentraciones más bajas con un valor de concentración inhibitoria media máxima (IC50) de 21,03 µg/mL. A 1.000 µg/ml de MPSE, la hemólisis máxima fue del 14,3%, lo que está dentro del límite de seguridad. Conclusiones: Este estudio reveló un potencial anticancerígeno oral de MPSE y proporcionó una base para su uso potencial en el tratamiento del cáncer oral con un efecto hemolítico mínimo en los glóbulos rojos humanos.

Enzyme Inhibitory and Anti-cancer Properties of Moringa peregrina / Propiedades inhibidoras Enzimáticas y Anticancerígenas de la Moringa peregrina

Background: Moringa peregrina is widely used in the traditional medicine of the Arabian Peninsula to treat various ailments, because it has many pharmacologically active components with several therapeutic effects. Objective: This study aimed to investigate the inhibitory effect of Moringaperegrina seed ethanolic extract (MPSE) against key enzymes involved in human pathologies, such as angiogenesis (thymidine phosphorylase), diabetes (α-glucosidase), and idiopathic intracranial hypertension (carbonic anhydrase). In addition, the anticancer properties were tested against the SH-SY5Y (human neuroblastoma). Results: MPSE extract significantly inhibited α-glucosidase, thymidine phosphorylase, and carbonic anhydrase with half-maximal inhibitory concentrations (IC50) values of 303.1 ± 1.3, 471.30 ± 0.3, and 271.30 ± 5.1 µg/mL, respectively. Furthermore, the antiproliferative effect of the MPSE was observed on the SH-SY5Y cancer cell line with IC50 values of 55.1 µg/mL. Conclusions: MPSE has interesting inhibitory capacities against key enzymes and human neuroblastoma cancer cell line.

Antecedentes: La Moringa peregrina se utiliza ampliamente en la medicina tradicional de la Península Arábiga para tratar diversas dolencias, ya que posee numerosos componentes farmacológicamente activos con varios efectos terapéuticos. Objetivo: Este estudio tenía como objetivo investigar el efecto inhibidor del extracto etanólico de semillas de Moringaperegrina (MPSE) frente a enzimas clave implicadas en patologías humanas, como la angiogénesis (timidina fosforilasa), la diabetes (α-glucosidasa) y la hipertensión intracraneal idiopática (anhidrasa carbónica). Además, se comprobaron las propiedades anticancerígenas frente al SH-SY5Y (neuroblastoma humano). Resultados: El extracto de MPSE inhibió significativamente la α-glucosidasa, la timidina fosforilasa y la anhidrasa carbónica con concentraciones inhibitorias semimáximas (IC50) de 303,1 ± 1,3, 471,30 ± 0,3 y 271,30 ± 5,1 µg/mL, respectivamente. Además, se observó el efecto antiproliferativo del MPSE en la línea celular del cáncer SH-SY5Y con valores de IC50 de 55,1 µg/mL. Conclusiones: MPSE posee interesantes capacidades inhibitorias frente a enzimas clave y línea celular de neuroblastoma canceroso humano.

Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma / El valor de ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico del glioma

Background: Glioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. Methods: The miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan–Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. Results: HAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis.Conclusions: Normal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients.(AU)

Introducción: Los gliomas presentan una alta incidencia y un mal pronóstico, por lo que es necesario un tratamiento más efectivo. Algunos estudios han confirmado que los ARN no codificantes de cadena larga (ARNncl) regulan diferentes enfermedades, entre las que se incluyen los gliomas. Se ha postulado que HAS2-AS1 actúa como un ARNncl, con un efecto oncogénico en diferentes tipos de cáncer. Este estudio tiene como objetivo analizar el valor del ARNncl HAS2-AS1 como marcador diagnóstico y pronóstico de glioma. Métodos: Descargamos los datos clínicos y de expresión de micro-ARN de la base de datos del Atlas del Genoma del Cáncer (TCGA) para realizar el análisis diferencial y de supervivencia. También analizamos la expresión de HAS2-AS1 en muestras patológicas y muestras de tejido adyacente normal de 80 pacientes con glioma. Para analizar la capacidad diagnóstica y el valor pronóstico de HAS2-AS1 en el glioma, recurrimos a la curva ROC. También utilizamos curvas de Kaplan-Meier para evaluar la supervivencia de los pacientes con glioma con diferentes niveles de expresión de HAS2-AS1. Resultados: La expresión de HAS2-AS1 era significativamente mayor en las muestras patológicas que en el tejido normal. Las curvas de supervivencia demostraron que la sobreexpresión de HAS2-AS1 estaba relacionada con una menor supervivencia general y supervivencia libre de progresión. Algunos factores clínico-patológicos de los pacientes con glioma, como el tamaño del tumor y su grado, según la clasificación de la OMS, mostraron una correlación significativa con la expresión de HAS2-AS1 en los tejidos afectados. La curva ROC mostró un área bajo la curva de 0,863, lo que indica que la expresión de HAS2-AS1 posee un importante valor diagnóstico. El área bajo la curva de la supervivencia general estimada fue de 0,906; para la supervivencia libre de progresión estimada, de 0,88. Ambos valores muestran que la sobreexpresión de HAS2-AS1 se asocia con un mal pronóstico...(AU)

Addressing childhood cancer: actions taken in the Dominican Republic / Abordaje del cáncer infantil: medidas adoptadas en República Dominicana / Enfrentamento do câncer infantil: medidas tomadas na República Dominicana

[ABSTRACT]. This report provides a summary of childhood cancer and the efforts made in the Dominican Republic to address child and adolescent cancer in line with the World Health Organization’s Global Initiative for Childhood Cancer. Information was obtained by review of recent local and international literature on pediatric oncology. As a result of the Global Initiative, a meeting was held by the Council of Ministers of Health of Central America to support the development of national pediatric cancer plans for each country. The objectives of these plans are to improve overall survival and quality of care for children with cancer through early detection, diagnosis, and treatment. In the Dominican Republic, several steps have been taken in the past 5 years to enhance diagnosis and care of children with cancer. For example, the National Committee of Childhood Cancer, headed by the Ministry of Public Health and including relevant stakeholders, was established to develop the national childhood cancer plan. In addition, a campaign was launched to raise awareness of childhood cancer, and the first early detection manual and public policy on child and adolescent cancer were published. A government initiative has been working to improve the hospital infrastructure and expand the pediatric cancer center, and a national course on early detection of pediatric cancers has been held. In 2023, the National Strategic Childhood Cancer Plan 2023–2030 was launched in the Dominican Republic. The plan will help policy-makers, implementers, researchers, and advocates enhance diagnosis and care of children with cancer.

[RESUMEN]. En este informe se presenta un resumen del cáncer infantil y las medidas adoptadas por República Dominicana para abordar el cáncer en la población infantil y adolescente en consonancia con la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. La información se obtuvo mediante el análisis de las publicaciones nacionales e internacionales recientes sobre oncología pediátrica. Como resultado de la Iniciativa Mundial, el Consejo de Ministros de Salud de Centroamérica celebró una reunión para brindar apoyo a la elaboración de planes nacionales sobre el cáncer infantil para cada país. Los objetivos de estos planes son mejorar la supervivencia general y la calidad de la atención que se presta a la población infantil con cáncer mediante la detección temprana, el diagnóstico y el tratamiento. En los últimos cinco años, República Dominicana ha adoptado varias medidas para mejorar el diagnóstico y la atención prestada a la población infantil con cáncer. Así, por ejemplo, se creó el Comité Nacional de Cáncer Infantil, encabezado por el Ministerio de Salud e integrado por las partes interesadas pertinentes, para elaborar el plan nacional sobre el cáncer infantil. Además, se puso en marcha una campaña de sensibilización sobre el cáncer infantil y se publicaron el primer manual de detección precoz y la primera política pública sobre el cáncer en la población infantil y adolescente. Mediante una iniciativa gubernamental se ha buscado mejorar la infraestructura hospitalaria y ampliar el centro de atención a pacientes oncológicos pediátricos, al tiempo que se ha impartido un curso nacional sobre detección precoz del cáncer infantil. En el 2023, República Dominicana puso en marcha el Plan Estratégico Nacional sobre Cáncer Infantil 2023-2030. Este plan será útil a los responsables de la formulación de políticas, las personas encargadas de su ejecución, los investigadores y los promotores para mejorar el diagnóstico y la atención prestada a la población infantil con cáncer.

[RESUMO]. Este relatório fornece um resumo sobre o câncer infantil e os esforços da República Dominicana para enfrentar a doença em crianças e adolescentes, em consonância com a Iniciativa Global para o Câncer Infantil da Organização Mundial da Saúde. As informações foram obtidas por meio de uma revisão da literatura local e internacional recente sobre oncologia pediátrica. Em consequência da Iniciativa Global, o Conselho de Ministros da Saúde da América Central se reuniu para apoiar a elaboração de planos nacionais de câncer pediátrico para cada país. Os objetivos desses planos são melhorar a sobrevida global e a qualidade da atenção a crianças com câncer por meio de detecção, diagnóstico e tratamento precoces. Na República Dominicana, várias medidas foram tomadas nos últimos cinco anos para melhorar o diagnóstico e a atenção a crianças com câncer. Por exemplo, o Comitê Nacional de Câncer Infantil, que é chefiado pelo Ministério da Saúde e inclui as partes interessadas pertinentes, foi criado para elaborar o plano nacional de câncer infantil. Foi lançada uma campanha de conscientização sobre o câncer infantil no país. Além disso, foram publica- dos o primeiro manual de detecção precoce e a política pública de câncer infantojuvenil. Uma iniciativa do governo vem trabalhando para melhorar a infraestrutura hospitalar e ampliar o centro de câncer pediátrico e ministrou um curso nacional sobre a detecção precoce de cânceres pediátricos. Em 2023, foi lançado o Plano Estratégico Nacional de Câncer Infantil 2023–2030 na República Dominicana. O plano ajudará formuladores de políticas, implementadores, pesquisadores e defensores da causa a aprimorar o diagnóstico e a atenção a crianças com câncer.

Entenda como o papilomavírus humano (HPV) pode se manifestar

Principal causa do câncer de colo de útero, também relacionado a mais outros cinco tipos de cânceres, a infecção pelo papilomavírus humano (HPV) não apresenta sinais ou sintomas na maioria das pessoas. Assim, o vírus acaba por ser transmitido de forma silenciosa, pelo fato de a pessoa desconhecer que contraiu a infecção. Em alguns casos, o HPV pode ficar latente de meses a anos, sem manifestar sinais visíveis ou apresentar manifestações subclínicas, isto é, detectáveis por exames.

Alimentação saudável: dicas práticas para variedade e sabor: Alimentos ricos em fibras

As fibras ajudam a promover a saúde intestinal, na digestão adequada e no controle do peso, fatores importantes na prevenção do câncer

Alimentação saudável: dicas práticas para variedade e sabor: Experimente novas receitas

Procure receitas saudáveis e saborosas. Manter um peso corporal saudável é essencial na prevenção da obesidade e do câncer

Alimentação saudável: dicas práticas para variedade e sabor: Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Reduzir o consumo de carnes vermelhas e evitar carnes processadas é uma das formas de se proteger do câncer de cólon e reto

Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors.

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in the open configuration. Remarkably, Polθi binding to the Polθ-pol:DNA/DNA closed complex traps the polymerase on DNA for more than forty minutes which elucidates the inhibitory mechanism of action. These data reveal a unique small-molecule DNA polymerase:DNA trapping mechanism that induces synthetic lethality in HR-deficient cells and potentiates the activity of PARPi.

Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.

DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease.

Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer.

Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location. Among 200 patients, 28% and 6% exhibited expression scores of 2+ and 3+, respectively. HER2 3+ scores were observed in 23%, 11%, 9%, and 5% of mucinous, endometrioid, clear cell, and high-grade serous tumors, respectively, and were exclusively identified in BRCA-wildtype, mismatch repair-proficient, or PD-L1-low-expressing tumors. The TP53 mutation rate was low, whereas ARID1A, KRAS, and PIK3CA mutations were relatively more prevalent with HER2 scores of 2+ or 3+ than with 0 or 1+. Four of the five tumors with an HER2 3+ score exhibited ERBB2 amplification. Among 19 patients who underwent multiple time-lagged biopsies, 11 showed increased HER2 expression in subsequent biopsies. Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

Identification of fibronectin type III domain containing 3B as a potential prognostic and therapeutic target for pancreatic cancer: a preliminary analysis.

BACKGROUND: Fibronectin type III domain containing 3B (FNDC3B), a member of the fibronectin type III domain-containing protein family, has been indicated in various malignancies. However, the precise role of FNDC3B in the progression of pancreatic cancer (PC) still remains to be elucidated. METHODS: In this study, we integrated data from the National Center for Biotechnology Information, the Cancer Genome Atlas, Genotype-Tissue Expression database, and Gene Expression Omnibus datasets to analyze FNDC3B expression and its association with various clinicopathological parameters. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, along with Gene Set Enrichment Analysis (GSEA), single sample Gene Set Enrichment Analysis (ssGSEA) and estimate analysis were recruited to delve into the biological function and immune infiltration based on FNDC3B expression. Additionally, the prognostic estimation was conducted using Cox analysis and Kaplan-Meier analysis. Subsequently, a nomogram was constructed according to the result of Cox analysis to enhance the prognostic ability of FNDC3B. Finally, the preliminary biological function of FNDC3B in PC cells was explored. RESULTS: The study demonstrated a significantly higher expression of FNDC3B in tumor tissues compared to normal pancreatic tissues, and this expression was significantly associated with various clinicopathological parameters. GSEA revealed the involvement of FNDC3B in biological processes and signaling pathways related to integrin signaling pathway and cell adhesion. Additionally, ssGSEA analysis indicated a positive correlation between FNDC3B expression and infiltration of Th2 cells and neutrophils, while showing a negative correlation with plasmacytoid dendritic cells and Th17 cells infiltration. Kaplan-Meier analysis further supported that high FNDC3B expression in PC patients was linked to shorter overall survival, disease-specific survival, and progression-free interval. However, although univariate analysis demonstrated a significant correlation between FNDC3B expression and prognosis in PC patients, this association did not hold true in multivariate analysis. Finally, our findings highlight the crucial role of FNDC3B expression in regulating proliferation, migration, and invasion abilities of PC cells. CONCLUSION: Despite limitations, the findings of this study underscored the potential of FNDC3B as a prognostic biomarker and its pivotal role in driving the progression of PC, particularly in orchestrating immune responses.