Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats. Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model. Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses. Stool samples were collected and processed for analysis of the short-chain fatty acid. Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation. Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Introducción. Los antiinflamatorios, inmunosupresores e inmunobiológicos se utilizan comúnmente para tratar la enfermedad intestinal inflamatoria. Sin embargo, algunos pacientes no presentan una respuesta adecuada o pierden respuesta efectiva durante el tratamiento. En un estudio reciente, se encontró un potencial efecto antiinflamatorio del extracto hidroalcohólico de Mimosa caesalpiniifolia en la colitis inducida por el ácido trinitrobenceno sulfónico utilizando ratas Wistar. Objetivo. Evaluar los efectos de la preformulación de M. caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico. Materiales y métodos. Los extractos de hojas se prepararon con una solución que contenía 70 % de etanol y se secaron con un secador por aspersión Mini B19 de Buchi usando una solución con 20 % de Aerosil®. Treinta y dos ratas Wistar macho se aleatorizaron en cuatro grupos: control basal, colitis sin tratar, control con preformulación (125 mg/kg/ día) y colitis tratada con preformulación (125 mg/kg/día). El índice de actividad clínica se registró diariamente y todas las ratas se sacrificaron el noveno día. Los fragmentos de colon se fijaron y se procesaron para análisis histológicos y ultraestructurales. Se recolectaron muestras de heces y se procesaron para el análisis de ácidos grasos de cadena corta. Resultados. El tratamiento con la preformulación disminuyó la actividad clínica (diarrea sanguinolenta), el infiltrado inflamatorio y las úlceras. La preformulación no reparó la barrera epitelial y no hubo diferencias significativas en el índice de células caliciformes. Se obtuvo una diferencia significativa en los niveles de butirato en las ratas tratadas con la preformulación. Conclusiones: La preformulación minimizó los síntomas clínicos de colitis e inflamación intestinal pero no minimizó el daño a la barrera intestinal.

Immunoexpressão das proteínas DEK e Fosfo-P38 no câncer retal antes da quimiorradioterapia / Immunoexpression of dek and phospho-p38 proteins in rectal cancer before chemoradiation therapy

ABSTRACT Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. Results: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). Conclusion: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.

RESUMO Contexto: O câncer colorretal é mundialmente, a terceira causa de câncer e um quarto destes estão localizados no reto. O oncogene DEK está envolvido em vários processos nucleares e pode acelerar a tumorigênese. Objetivo: Este estudo tem como objetivo avaliar a imunoexpressão das proteínas DEK e Fosfo-P38 antes da terapia neoadjuvante em pacientes com adenocarcinoma de reto e correlacioná-la com resposta clínica e sobrevida. Métodos: Foram incluídos pacientes com adenocarcinoma de reto médio e baixo submetidos à quimio e radioterapia seguida de ressecção cirúrgica do tumor. A expressão e quantificação foram estudadas por imuno-histoquímica nos tecidos de biópsia tumoral utilizando um sistema HScore. Escores ≥4 foram considerados positivos e aqueles com <4 negativos. Resultados: Foram incluídos 22 pacientes com média de idade de 63,55 anos (DP: ±13,49). O estágio clínico antes do tratamento era T3 em 72,7%, T4 em 18,2%, 31,8% eram N1, 50% N0 e todos M0. Após a quimio e radioterapia, 54,6% eram T3; 22,7% eram T2; 9,1% eram T1 e 13,6% T0. Entre os tumores, 22,7% foram positivos para DEK e 63,6% positivos para Phospho-P38. Houve uma correlação positiva para a imunoexpressão da proteína DEK e o estágio pTNM (P=0,011). A proteína fosfo-P38 não apresentou correlação com esses parâmetros. Pacientes com HScore negativo para DEK tiveram sobrevida média de 141,33 meses (IC95%: 112,41-170,25) e aqueles com HScore positivo tiveram sobrevida média de 25,10 meses (IC95%: 17,36-32,84) (P<0,001). Conclusão: Observou-se maior expressão de DEK em estágios avançados. Os pacientes que apresentaram expressão de DEK <4 tiveram maior sobrevida, sendo um fator de pior prognóstico.

Câncer gástrico com expressão positiva do receptor de estrogênio alfa: uma série de casos de um único centro ocidental / Gastric cancer with positive expression of estrogen receptor alpha: a case series from a single western center

RESUMO - RACIONAL: Apesar do avanço nas terapias, o prognóstico de pacientes com câncer gástrico (CG) avançado permanece ruim. Vários estudos demonstraram a expressão do receptor de estrogênio alfa (REa), porém seu significado no CG permanece controverso. OBJETIVO: relatar uma série de casos de CG com expressão de REa-positivo, e descrever suas características clínicopatológicas e prognóstico. MÉTODOS: Avaliamos retrospectivamente os pacientes com CG submetidos à gastrectomia com intenção curativa entre 2009 e 2019. A expressão do REa foi avaliada por imuno-histoquímica por meio da construção de microarranjos de tecido (TMA). Pacientes com adenocarcinoma gástrico ERa-negativos serviram como grupo comparação. RESULTADOS: No período selecionado, foram identificados 6 (1,8%) CG REa-positivos entre os 345 CG analisados. Todos os ERa-positivos eram homens, com idades entre 34-78 anos, tinham CG do tipo difuso de Lauren e pN+. Comparado aos REa-negativos, os CG REa-positivos associaram-se a maior diâmetro (p=0,031), gastrectomia total (p=0,012), tipo de Lauren difuso/misto (p=0,012), presença de invasão perineural (p=0,030) e metástase linfonodal (p=0,215). O estágio final foi o IIA em um caso; IIIA em três e IIIB em dois casos. Entre os 6 pacientes REa -positivos, 3 tiveram recorrência da doença (peritoneal) e morreram. Não houve diferença significativa na sobrevida entre os grupos REa-positivo e negativo. CONCLUSÃO: A expressão do REa é menos comum no CG, estando associada à histologia difusa e presença de metástases linfonodal, podendo servir como um marcador relacionado à progressão tumoral e pior prognóstico. Além disso, uma alta taxa de recorrência peritoneal foi observada em pacientes ERa-positivos.

ABSTRACT - BACKGROUND: Despite advances in therapies, the prognosis of patients with advanced gastric cancer (GC) remains poor. Several studies have demonstrated the expression of estrogen receptor alpha (ERa); however, its significance in GC remains controversial. AIM: The present study aims to report a case series of GC with ERa-positive expression and describe their clinicopathological characteristics and prognosis. METHODS: We retrospectively evaluated patients with GC who underwent gastrectomy with curative intent between 2009 and 2019. ERa expression was assessed by immunohistochemistry through tissue microarray construction. Patients with ERa-negative gastric adenocarcinoma served as a comparison group. RESULTS: During the selected period, 6 (1.8%) ERa-positive GC were identified among the 345 GC patients analyzed. All ERa-positive patients were men, aged 34-78 years, and had Lauren diffuse GC and pN+ status. Compared with ERa-negative patients, ERa-positive patients had larger tumor size (p=0.031), total gastrectomy (p=0.012), diffuse/mixed Lauren type (p=0.012), presence of perineural invasion (p=0.030), and lymph node metastasis (p=0.215). The final stage was IIA in one case, IIIA in three cases, and IIIB in two cases. Among the six ERa-positive patients, three had disease recurrence (peritoneal) and died. There was no significant difference in survival between ERa-positive and ERa-negative groups. CONCLUSIONS: ERa expression is less common in GC, is associated with diffuse histology and presence of lymph node metastasis, and may be a marker related to tumor progression and worse prognosis. Also, a high rate of peritoneal recurrence was observed in ERa-positive patients.

BRAFV600E and KIT immunoexpression in early-stage melanoma

Abstract: Melanoma is widely known as the most lethal skin cancer. Specific tumor-related mortality can be significantly reduced if diagnosis and treatment are properly performed during initial phases of the disease. The current search for biomarkers in early-stage melanomas is a high-priority challenge for physicians and researchers. We aimed to assess the immunoexpression of BRAFV600E and KIT in a case series consisting of 44 early-stage melanomas. Formalin-fixed paraffin-embedded samples were systematically evaluated using a semi-quantitative method based on scores of percentage and intensity for immunostained tumor cells. We observed significant concordance between BRAFV600E and KIT immunoexpression in thin invasive melanomas. Our findings corroborate previous evidence showing abnormal expression of proteins associated with MAPK intracellular signaling pathway in early-stage melanomas.

Acquired cystic kidney disease in allograft with long-standing poor function / Doença renal cística adquirida em um enxerto cronicamente disfuncional

Abstract Acquired Cystic Kidney Disease (ACKD) is regarded as a common late condition of end stage renal damage and expresses its most important features when associated with long term hemodialysis. ACKD is also widely known as a premalignant lesion. Its occurrence in chronically rejected renal allografts is rare and its frequency and behavior in this setting are not well known. Herein we report a case of ACKD in a long standing nonfunctional allograft (215 months) which is not associated with malignancy and briefly review the related literature.

Resumo A doença renal cística adquirida (ACKD) é considerada uma condição tardia relacionada à doença renal crônica terminal e manifesta-se de modo mais evidente no contexto de hemodiálise de longo prazo. ACKD é amplamente reconhecida como lesão pré-maligna. Sua ocorrência em enxertos renais cronicamente rejeitados é rara, de modo que a frequência e o comportamento da entidade nesse cenário não estão bem documentados. Relatamos a ocorrência de ACKD em um aloenxerto renal não funcionante sem malignidade após 215 meses de transplante e brevemente revisamos a literatura relacionada.