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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

Introdução: Em março de 2020 a OMS decretou pandemia pelo novo coronavírus (SARS-CoV-2), causador da COVID-19. Objetivo: relatar a experiência sobre a disseminação de informações sobre o coronavíus. Método: Trata-se de um relato de experiência de graduandos do curso de enfermagem e pós-graduandos em patologia, UNIFESP, 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 e validado por especialistas, com informações sobre o coronavírus e o material foi disponibilizado virtualmente. Resultado: O boletim informativo e o vídeo educativo foram elaborados baseados na literatura e validados por três profissionais da área da saúde. 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 coronavírus obteve grande alcance da população.

No cenário da pandemia, a enfermagem desempenha um papel fundamental na prática da educação em saúde com vistas à promoção da saúde e prevenção de doenças, sobretudo o câncer, cuja incidência está prevista para aumentar nos próximos anos. O objetivo foi relatar a experiência de uma extensão universitária acerca das campanhas de prevenção ao câncer durante a pandemia da COVID-19. Trata-se do relato de experiência sobre a utilização de estratégias educacionais adotadas para as campanhas de prevenção ao câncer no contexto da pandemia da COVID-19 (2020-2021). Realizaram-se quatro campanhas educativas de prevenção ao câncer, pautando-se no compartilhamento dos materiais desenvolvidos nas redes sociais do projeto. O projeto buscou estratégias para desenvolver suas campanhas educativas e compartilhar informações assertivas acerca da prevenção ao câncer por meio da divulgação nas redes sociais, cumprindo o papel social da universidade. Descritores: Educação em Saúde, Enfermagem, Oncologia, Infecções por Coronavírus. Nursing in cancer prevention: experience report in the pandemic Abstract: In the pandemic scenario, nursing plays a fundamental role in the practice of health education with a view to promoting health and preventing diseases, especially cancer, whose incidence is expected to increase in the coming years. The purpose was to report the experience of a university extension about cancer prevention campaigns during the COVID-19 pandemic. This is an experience report on the use of educational strategies adopted for cancer prevention campaigns in the context of the COVID-19 pandemic (2020-2021). Four educational campaigns for cancer prevention were carried out, based on the sharing of materials developed on the project's social networks. The project sought strategies to develop its educational campaigns and share assertive information about cancer prevention through dissemination on social networks, fulfilling the university's social role. Descriptors: Health Education, Nursing, Oncology, Coronavirus Infections. Enfermería en la prevención del cáncer: relato de experiencia en la pandemia Resumen: En el escenario pandémico, la enfermería juega un papel fundamental en la práctica de la educación para la salud con miras a promover la salud y prevenir enfermedades, especialmente el cáncer, cuya incidencia se espera aumente en los próximos años. El objetivo fue reportar la experiencia de una extensión universitaria sobre campañas de prevención del cáncer durante la pandemia COVID-19. Se trata de un informe de experiencia sobre el uso de estrategias educativas adoptadas para campañas de prevención del cáncer en el contexto de la pandemia COVID-19 (2020-2021). Se llevaron a cabo cuatro campañas educativas de prevención del cáncer, basadas en el intercambio de materiales desarrollados en las redes sociales del proyecto. El proyecto buscó estrategias para desarrollar sus campañas educativas y compartir información asertiva sobre la prevención del cáncer a través de la difusión en las redes sociales, cumpliendo con el rol social de la universidad. Descriptores: Educación para la Salud, Enfermería, Oncología, Infecciones por Coronavirus.

To measure the villous height, the crypt depth, and the number of intraepithelial lymphocytes/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and to classify these findings according to Q- Marsh and Q-histology scales.Retrospective study of a database from the Department of Pathology of biopsies from the second portion of the duodenum of pediatric patients. According to the histological report, three groups were established: celiac disease at diagnosis (n = 50), controls (n = 26), giardiasis (n = 10). In each biopsy, software (cellSens and Image J) evaluated 5 villous heights, 5 crypt depth and the number of intraepithelial lymphocytes/100 enterocytes.The celiac group had the lowest mean villous height (197.83 μm) of all three groups (control = 477.70 μm; giardiasis = 397.04 μm. The celiac group's villous:crypt ratio (0.78) was significantly lower than the control group (1.89). The number of intraepithelial lymphocytes ≥25 was exclusive to the celiac group, with a sensitivity and specificity of 100 %. Only celiac patients were included in types 2 and 3 of the Q-histology classification.Celiac disease patients showed shorter villous height than other groups, and the number of intraepithelial lymphocytes ≥25 was the best parameter to differentiate celiac from controls and giardiasis groups. Intraepithelial lymphocytes ≥25/100 enterocytes associated with any degree of villous atrophy, the classic Marsh 3 type, set the histological parameters of celiac disease. Quantitative histology is a valuable tool for diagnosing celiac disease, enabling histological changes in a short time, and the Q-histology scale appears to be more suitable than the Q-Marsh scale.

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient’s life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Objetivo: Demonstrar os beneficios da educacao em saude sobre o câncer de mama para a populacao. Metodos: Trata-se de um relato de experiencia sobre educacao em saude, utilizando boletins informativos e banners elaborados pelos discentes, monitorado pelos alunos de pos-graduacao em patologia e supervisionados pelos colaboradores e coordenadores do projeto, divulgados presencialmente para a comunidade. Resultados: Essa experiencia trouxe como resultado maior aproveitamento das atividades didaticas e dinâmicas do ambulatorio, com uma metodologia ativa, assim como o empoderamento dos usuarios para a autonomia, capacidade de identificar determinantes para sua saude e cuidar de si e dos outros a sua volta. Conclusao: Conclui-se entao que esta atividade de educacao foi enriquecedora tanto para os discentes que a organizaram quanto para clientes do ambulatorio, expondo uma relacao entre a prevencao e a promocao da saude dos usuarios e com um projeto de extensao que visa compartilhar o conhecimento adquirido na academia, transcendendo seus muros para todos. Descritores: Educacao em saude; Educacao em enfermagem; Neoplasias da mama; Promocao da saude. UNDERSTANDING BREAST CANCER: HEALTH EDUCATION 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. Descriptors: Health education; Education, nursing; Breast neoplasms; Health promotion. COMPRENDER EL CANCER DE MAMA: EDUCACION EN SALUD Objetivo: Demostrar los beneficios de la educacion para la salud sobre el cancer para la poblacion. Metodos: Estudio descriptivo-exploratorio con un enfoque cualitativo, utilizando boletines y pancartas preparados por estudiantes, monitoreados por estudiantes graduados en patologia y supervisados por colaboradores y coordinadores del proyecto y entregado a la comunidad. Resultados: Esta experiencia resulto en un mayor uso de las actividades didacticas y dinamicas de la clinica, con una metodologia activa, asi como el empoderamiento de los usuarios para la autonomia, la capacidad de identificar determinantes para su salud y para cuidarse a si mismos y a los demas a su alrededor. Conclusion: Concluimos entonces que la campana fue enriquecedora tanto para los estudiantes que la organizaron como para los clientes de la clinica ambulatoria, exponiendo una relacion entre prevencion y promocion de la salud de los usuarios y con un proyecto de extension que tiene como objetivo compartir el conocimiento adquirido en la academia, trascendiendo sus muros para todos. Descriptores: Educacion em salud; Educacion em enfermaria; Neoplasias de la mama; Promocion de la salud.

Purpose To compare tissue inflammatory response, foreign body reaction, fibroplasia, and proportion of type I/III collagen between closure of abdominal wall aponeurosis using polyglactin suture and intraperitoneal implant of polypropylene, polypropylene/polyglecaprone, and polyester/porcine collagen meshes to repair defects in the abdominal wall of rats. Methods Forty Wistar rats were placed in four groups, ten animals each, for the intraperitoneal implant of polypropylene, polypropylene/polyglecaprone, and polyester/porcine collagen meshes or suture with polyglactin (sham) after creation of defect in the abdominal wall. Twenty-one days later, histological analysis was performed after staining with hematoxylin-eosin and picrosirius red. Results The groups with meshes had a higher inflammation score (p < 0.05) and higher number of gigantocytes (p < 0.05) than the sham group, which had a better fibroplasia with a higher proportion of type I/III collagen than the tissue separating meshes (p < 0.05). There were no statistically significant differences between the three groups with meshes. Conclusions The intraperitoneal implant of polypropylene/polyglecaprone and polyester/porcine collagen meshes determined a more intense tissue inflammatory response with exuberant foreign body reaction, immature fibroplasia and low tissue proportion of type I/III collagen compared to suture with polyglactin of abdominal aponeurosis. However, there were no significant differences in relation to the polypropylene mesh group.

O tumor estromal gastrointestinal e uma neoplasia rara que afeta as celulas intersticiais cajais devido a disfuncao nos genes KIT ou PDGFRA. E considerado um tumor mesenquimal raro, mas comum no trato digestivo. O objetivo foi analisar um tratamento, epidemiologia e imunolocalizacao da proteina KIT e a atuacao do enfermeiro em relacao aos pacientes com GIST. Os criterios de inclusao foram laudos anatomopatologicos expedidos pelo servico de Anatomia Patologica da UNIFESP / EPM, a partir de 2010, com diagnostico de GIST. Vinte e uma escolhidos foram selecionados para analise imunohistoquimica do KIT. Entre as mulheres, 54,6% tinham mais de 60 anos e entre os homens 90%. A localizacao mais comum entre as mulheres foi o estomago com 63,7%, enquanto nos homens, o estomago teve a mesma porcentagem do intestino (40%). A imunohistoquimica mostrou positividade para C-KIT em 81,8% das mulheres e 90% dos homens. O tamanho medio da lesao foi de 5,58 cm e 3,8 cm nas mulheres e nos homens, respectivamente. A presenca de necrose foi verificada em 27,3% das mulheres e 30% dos homens. A morfologia mais prevalente foi uma celula fusiforme com aproximadamente 70% em mulheres e homens. Dos 21 casos, tres pacientes morreram, dois tiveram recidiva e, em cinco casos, foi realizado tratamento adjuvante com mesilato de imatinibe. Para a atuacao da enfermeira na frente do paciente com GIST, foi necessario confirmar a expressao da proteina KIT, o que permite um diagnostico diferencial. A analise da incidencia e da epidemiologia dessa populacao agregada aos enfermeiros agregar mais conhecimentos sobre esse tumor.

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

Purpose: To compare four types of mesh regarding visceral adhesions, inflammatory response and incorporation. Methods: Sixty Wistar rats were divided into four groups, with different meshes implanted intraperitoneally: polytetrafluoroethylene (ePTFE group); polypropylene with polydioxanone and oxidized cellulose (PCD); polypropylene (PM) and polypropylene with silicone (PMS). The variables analyzed were: area covered by adhesions, incorporation of the mesh and inflammatory reaction (evaluated histologically and by COX2 immunochemistry). Results: The PMS group had the lowest adhesion area (63.1%) and grade 1 adhesions. The ePTFE and PM groups presented almost the total area of their surface covered by adherences (99.8% and 97.7% respectively) The group ePTFE had the highest percentage of area without incorporation (42%; p

Background GIST is the most common mesenchymal tumor of gastrointestinal tract and is more frequent in stomach. Its main mutations affect KIT and PDGFRA genes. Full genetic analysis panels are currently used to study mutations in GIST and other tumors. Considering that in gastric GIST KIT gene mutations in exon 11 are sensitive to IM whereas PDGFRΑ gene mutations in exon 18 (D842V) are resistant to the same drug, the aim of this study is to focus on these two molecular targets as a short alternative panel for predicting therapeutic response in gastric GIST which might optimize resources. Methods The genotypes of 38 cases of primary GIST were determined by performing bidirectional DNA sequencing. Results Exon 11 of KIT gene showed mutations in 65.3% and the exon 18 of PDGFRA gene showed 9% of cases. So it was possible to determine a subgroup of tumors which presented mutations in KIT exon 11 and PDGFRA exon 18. Conclusion Considering all of the foregoing analyzed globally, the application of short panel has impact on the cost and time of release of results to the physician, allowing a rapid approach to patients eligible for treatment with the target therapy.

Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.

Esophageal cancer is a highly aggressive neoplasm. In Brazil, it is the sixth most frequent among men and fifteenth among women. The most common type is squamous cell carcinoma (SCC), responsible for 96% of cases. Twenty-eight specimens of Esophael squamous cell carcinoma (ESCC) were obtained by surgery procedures.The tissues were fixed in formalin and embedded in paraffin. In each case, all available hematoxylin and eosin stained sections were examined and a representative block was selected. The ages of these patients ranged from 40 to 93 years, with a mean age of 60 years. Results: The histological grade of tumors was 4 well-differentiated, 19 moderately differentiated and 5 poorly differentiated. Expression of Cox-2 and VEGF in ESCC was demonstrated in 23 (82,14%) and 13 (44,43%) cases, respectively. Adjacent normal mucosa was positive in 11 (39,29%) samples and 9 (32,15%) samples for Cox-2 and VEGF, respectively. No relationship between the expression of Cox-2 and VEGF with the clinicopathological parameters, including gender, age, surgical margin, lymph node status and tumor differentiation. The median follow-up period was 60 months. Survival analysis of patients with ESCC showed no relationship with the expression of Cox-2 and VEGF. Conclusion: VEGF and Cox-2 are expressed in ESCC. Cox-2, VEGF, play a significant role in the origin and development of ESCC and the inhibitors of these proteins could prove to be an important therapeutic tool in the control of this disease.

The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis.For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate.The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p 0.05) among groups.In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.

BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue.

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.

Sporadic colorectal cancer (CRC) is a consequence of the accumulation of genetic and epigenetic alterations that result in the transformation of normal colonic epithelial cells to adenocarcinomas. Studies have indicated that a common event in the tumorigenesis of CRC is the association of global hypomethylation with discrete hypermethylation at the promoter regions of specific genes that are involved in cell cycle regulation, DNA repair, apoptosis, angiogenesis, adhesion and invasion. The present study aimed to investigate the epigenetic changes (DNA methylation) in 24 candidate genes in CRC. A total of 10 candidate hypermethylated (HM) and unmethylated (UM) genes were identified that may be useful epigenetic markers for non-invasive CRC screening. The five genes that had the highest average UM percentages in the control group were MLH1 (71.7%), DKK2 (69.6%), CDKN2A (68.4%), APC (67.5%) and hsa-mir-342 (67.4%). RUNX3 (58.9%), PCDH10 (55.5%), SFRP5 (52.1%), IGF2 (50.4%) and Hnf1b (50.0%) were the five genes with the highest average HM percentages in the test group. In summary, the present preliminary study identified the methylation profiles of normal and cancerous colonic epithelial tissues, and provided the groundwork for future large-scale methylation studies.

Background: Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. Aim: To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Methods: Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Results: Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Conclusion: Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlich's neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and late scarring by fibroblasts and FGF. RESUMO Racional: A cicatrização é fenômeno biológico inato, e a carcinogênese adquirido, mas com elementos humorais e celulares comuns. A carcinogênese interfere de forma negativa na cicatrização. Objetivo: Avaliar as modificações histológicas nas cicatrizes laparotômicas de camundongos Balb/c sadios como controles, e com a neoplasia de Ehrlich, em suas diferentes formas de apresentação. Métodos: Foram utilizados 54 camundongos, divididos em três grupos de 18 animais cada um. O primeiro era controle; o segundo com a neoplasia de Ehrlich em sua forma ascítica; e o terceiro na forma subcutânea. Sete dias após a inoculação do tumor, todos os 54 camundongos foram submetidos à laparotomia e reoperados no sétimo dia de pós-operatório, com ressecção da cicatriz e posterior eutanásia. As cicatrizes foram encaminhadas para estudo histológico com técnicas imunoistoquímicas para avaliar Cox-2 (ciclo-oxigenase 2), VEGF (fator de crescimento do endotélio vascular) e FGF (fator de crescimento dos fibroblastos) e analisadas de forma semiquantitativana tanto na cicatriz laparotômica como na parede abdominal mais distante do local operado. Resultados: Avaliando o peso, observou-se a correta inoculação do tumor e o aumento de peso no grupo com a neoplasia na modalidade ascítica. Os estudos histológicos mostraram que os grupos com a neoplasia apresentaram maior presença da Cox-2 em relação ao controle, estatisticamente significante. No estudo da Cox-2 da parede abdominal foi o local em que o grupo ascítico apresentou a diferença mais expressiva. O VEGF não apresentou diferenças significantes entre os três grupos, independentemente do local estudado. O FGF teve aumento significante nos animais com neoplasia. Conclusão: Os achados histológicos encontrados tanto na cicatriz das laparotomias quanto na parede abdominal mostraram que com a neoplasia de Ehrlich houve resposta inflamatória exacerbada, traduzida por expressão mais intensa da Cox-2 e maior proliferação fibroblástica, traduzida por expressão mais intensa do FGF, ou seja, estimulou tanto as reações inflamatórias imediatas, observadas nas reações da Cox-2, como nas cicatriciais tardias com os fibroblastos e o FGF.

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1–Sham/saline solution, G2–CAE/control, G3–acetic acid/control, G4–curative- CAE treatment and G5–preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value

PURPOSE: To evaluate the immunohistochemical expression of p16, Ki-67, p53 and Bcl-2 proteins in gastrointestinal stromal tumors (GIST); to assess the possible association between these variables and clinical and histopathological factors of cancer; and to check for prognostic value of these variables (survival and recurrence). METHODS: A sample of 55 patients treated surgically for GIST in three hospitals was studied. The surgically excised tumors were confirmed as GIST by KIT, vimentin, desmin S100 protein, CD117, 1A4 and CD34 assessment in paraffin blocks. RESULTS: Only 9 (16%) cases of GIST were positive for p53, p16 was positive among 43.6%; 80% of GISTs showed staining for Bcl-2. The proliferative index (expressed as the proportion of positive cells) assessed by immunohistochemical expression of Ki-67 was high in 49% of cases. Elevated Ki-67 scores were associated to high histological grade (p=0.0026) and mitosis index, MI (p=0.0001). High Ki-67 index was associated to death. Expression of p53, p16 and Bcl-2 did not correlate to morphological or clinical variables. CONCLUSIONS: Ki-67 immunohistochemical evaluation should be included in preoperative evaluation of GIST biopsies or surgical specimens as a prognostic tool for clinical staging; and all other proteins studied (Bcl-2, p53 and p16) did not play a role in GIST metabolic or carcinogenic process, remaining without prognostic value.OBJETIVO: Avaliar a expressão imunoistoquímica de p16, Ki-67, p53 e Bcl-2 proteínas em tumores gastrointestinais estromais (GIST); determinar a possível associação entre essas variáveis e fatores clínicos e histopatológicos de câncer, e para verificar o valor prognóstico destas variáveis (sobrevivência e recorrência). MÉTODOS: Uma amostra de 55 pacientes tratados cirurgicamente para GIST em três hospitais foi estudada. Os tumores extirpados cirurgicamente foram confirmados como GIST por KIT, vimentina, proteína desmina S100, CD117, 1A4 e avaliação de CD34 em blocos de parafina. RESULTADOS: Apenas nove (16%) casos de GIST foram positivos para p53, p16 foi positiva em 43,6%, 80% dos GIST apresentaram coloração para Bcl-2. O índice proliferativo (expresso como a proporção de células positivas), avaliado pela expressão imunoistoquímica de Ki-67, foi elevado em 49% dos casos. Escores de Ki-67 elevados foram associados com alto grau histológico (p=0,0026) e índice de mitose, MI (p=0,0001). Alto índice de Ki-67 foi associado à morte. Expressão da p53, p16 e Bcl-2 não se correlacionou com as variáveis morfológicas ou clínicas. CONCLUSÕES: A avaliação imunoistoquímica de Ki-67 deve ser incluída na avaliação pré-operatória de biópsias ou peças cirúrgicas de GIST como uma ferramenta prognóstica para o estadiamento clínico, e todas as outras proteínas estudadas (Bcl-2, p53 e p16) não desempenharam um papel no processo metabólico ou carcinogênico em GIST, mantendo-se sem valor prognóstico.

Objective Since the first data from a patient with colorectal adenocarcinoma are obtained by biopsy, this study evaluated the accuracy of diagnosis by biopsy as compared with the diagnostic potential of the surgical specimen, considering the histological type, grade of differentiation, and immunohistochemical expression of p53. Methods. The specimens were obtained from 80 patients assisted at Hospital São Paulo. The biopsy and surgical specimen sections were stained by hematoxylin–eosin and immunohistochemistry and compared by 3 pathologists blinded to the evaluations. Results. The accuracy for the histological types was 88%. The grade of differentiation presented an accuracy of 70% with Kappa = .48. The expression of protein p53 exhibited an accuracy of 68% with Kappa = .22. Conclusion. The preoperative biopsy of colorectal adenocarcinoma presented good accuracy compared with histopathological examination of the surgical specimen, but with weak to moderate effective degree of agreement between the results.

Objective: To determine the expression of p53, p16 and Ki-67 and its relevance in survival and cell differentiation. Methods: Fifteen duodenopancreatectomized patients were included. Immunohistochemical expression of p53, p16 and Ki-67 was determined in paraffin embedded tumor blocks. The relation of these expressions with different variables was studied. Results: Ninety-three per cent of tumors showed expression of p53 and p16. Ki-67 was expressed in 86.66% of tumors (labeling index – LI 11.91 ± 9.47). The presence of combined alterations was not related to significant differences in tumor type, stage or survival; similar results were obtained analyzing isolated expressions. When groups of p16 and Ki-67 expressions where created, the median survival was not significant. However, there was a slightly better survival in patients with focal expression of p16 (median survival 20.75 versus 14.34), when compared to patients with diffuse expression. Conclusion: The overexpression of p53, p16 and Ki-67 was not related to survival or tumor grade, when comparing isolated or combined expressions. RESUMO Objetivo: Determinar a expressão de p53, p16 e Ki-67 e sua relevância na sobrevida e diferenciação celular. Métodos: Foram incluídos 15 pacientes submetidos a duodenopancreatectomia. A expressão imunohistoquímica de p53, p16 e Ki-67 foi determinada em blocos tumorais embebidos em parafina. Foi estudada a relação dessas expressões com as variáveis. Resultados: Noventa e três por cento dos tumores apresentaram expressão de p53 e p16. Ki-67 estava expresso em 86,66% dos tumores (índice proliferativo – IP 11,91 ± 9,47). A presença de alterações combinadas não estava relacionada a diferenças significativas no tipo tumoral, no estágio ou na sobrevida; resultados semelhantes foram obtidos com a análise de expressões isoladas. Quando foram criados os grupos de expressões de p16 e Ki-67, a sobrevida mediana não era significativa. Entretanto, havia uma sobrevida discretamente melhor nos pacientes com expressão focal do p16 (sobrevida mediana 20,75 versus 14,34) em comparação com pacientes com expressão difusa. Conclusão: A superexpressão das proteínas p53, p16 e Ki-67 não estava relacionada à sobrevida ou ao grau tumoral quando se compararam as expressões isoladas ou combinadas.

Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice. The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment. Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG). Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p = 0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p = 0.052. We have not found any difference among metastasis development in the groups (p = 0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p = 0.041). Patients with positive or negative p53 tumors had similar survival (p = 0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p = 0.069). The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.

The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF- α. Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF-kB, TNF- and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF- α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration. Keywords: Grape juice - NF-kappa B - TNF-α - iNOS - carcinogenesis

PURPOSE: To quantify the degree of angiogenesis by conventional method (microvessel density, MVD) and computerized method (endothelial area, EA), and to evaluate their relationships with the prognosis of patients operated on for colorectal adenocarcinoma. METHODS: Tumoral angiogenesis was studied by means of an immunohistochemical technique, using CD 34, on 126 patients; to quantify the angiogenesis, MVD (defined as number of microvessels per mm²) and EA measurement (defined as the area occupied by EA in the microscope field). A computerized method, IMAGELab software was utilized to quantify endothelial area. RESULTS: The mean number of microvessels was 128.6 MV/mm² (SD = 44.5) and the mean EA was 4.3% (SD = 2.1). The Pearson method demonstrated a low correlation coefficient between MVD and EA (r = 0.429). No relationship between MVD and EA was observed with regard to relapse-free interval and overall survival. CONCLUSION: The histological analysis of angiogenesis expression in patients with colorectal adenocarcinoma can be performed either by computer-assisted image analysis of endothelial area or by conventional microvessels counting. Both methods did not show any significant relationship between these angiogenesis parameters with relapse-free interval and overall survival.OBJETIVO: Quantificar a intensidade da angiogênese pelo método convencional (densidade microvasal, DMV) e pelo método informatizado, área endothelial (AE) e avaliar a sua correlação com o prognóstico de doentes operados por adenocarcinoma colorretal. MÉTODOS: A angiogênese tumoral foi investigada por meio de técnica imuno-histoquímica, utilizando-se CD-34, em 126 doentes; para quantificar a angiogênese, a microdensidade vascular, definida como o número de microvasos por mm² e a medida da área endotelial, definida como a área ocupada pelo endotélio vascular identificada no campo microscópico foram empregadas. Um programa computadorizado, o IMAGELab foi empregado para a quantificação da área endothelial. RESULTADOS: A media do número de microvasos foi de 128,6 MV/mm ² (d esvio padrão de 44,5). O método do coeficiente de Pearson demonstrou uma baixa correlação entre a DMV e a AE (r=0,429). Nenhuma correlação entre a DMV e AE com o intervalo livre de doença e tempo global de sobrevida foi observada. CONCLUSÃO: A análise histológica da expressão angiogênica em doentes com adenocarcinoma colorretal pode ser realizada tanto da forma informatizada, na quantificação da área endotelial, como pela convencional, na contagem dos microvasos. Ambos métodos não demonstraram relação estatisticamente significante entre estes parâmetros de angiogênese e o intervalo livre de doença e a sobrevida global.

Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

PURPOSE: To evaluate the effects of maternal remote ischemic preconditioning (IPCr) in the colonic mucosa of newborn rats subjected to hypoxia and reoxygenation.METHODS:Newborn Wistar rats were divided into three groups. Control Group (CG), Hypoxia and Reoxygenation Group (HRG) and Remote Ischemic Preconditioning Group (IPCrG). Hypoxia and reoxygenation was performed 2x per day, with an interval of 6 hours, on the 1st, 2nd and 3rd days of life, with 10 minutes of CO2 at 100%, followed by 10 minutes O2 at 100%(HRG/IPCrG). The maternal IPCr was performed 24 hours before delivery by applying a rubber band tourniquet to the left hind limb (IPCrG). Segments of the colon underwent histological (HE) and immunohistochemical analysis for caspase-3 and COX - 2.RESULTS: The histological findings showed no intestinal mucosal damage in the CG group and severe lesions in HRG that was attenuated in the IPCrG (p

Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). Results The calprotectin levels exhibited significant reductions (P = 0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (PTNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.

The aim of this study was to analyze the immunoexpression of (Smac) DIABLO, AIF, cytochrome c, Ki-67 and cleaved caspase-3 in gastric cancer. A tissue microarray (TMA) paraffin block was constructed using gastric adenocarcinoma tissue and adjacent normal adjacent mucosa from 87 patients who had not previously undergone radiotherapy or chemotherapy. Immunohistochemistry was used to evaluate the protein levels. Samples were positive for (Smac) DIABLO in 37 (45.6%) and 37 (46.8%), for AIF in 31 (36.9%) and 36 (45.6%), for cytochrome c in 60 (68.9%) and 44 (54.4%), for Ki-67 in 63 (72.4%) and 52 (61.9%) and for cleaved caspase-3 in 21 (24.1%) and 3 (3.4%) cases of tumor and adjacent normal tissues, respectively. Our results suggest that increased expression of Ki-67 and cleaved caspase-3 could contribute to carcinogenesis. The expression of these proteins indicates an attempt of cells to maintain tissue homeostasis.

In spite its relative rarity, gallbladder adenocarcinoma is a neoplasm who presents an aggressive biologic behavior. The single curative treatment has been radical surgical resection with free margin. Prognostic factors has been studied because are very important to identify long-term survival patients which may benefit of aggressive surgical resection.To evaluate long-term prognostic predictors from gallbladder cancer.The medical records of all patients that presented confirmed histological diagnosis of gallbladder adenocarcinoma operated over a 14 year period were identified and retrospectively reviewed. Uni and multivariate analysis was done.Total sample was 100 patients. Median age was 71 years (34 to 93). There were 17 men and 83 women. Lesion distribution according to TNM stage system was: I (n=22), II (n=59), III (n=6), IV (n=4) and unknown (n=9). Fifty two patients underwent radical resection (R0) while 48 to palliative surgery (R1-R2). Overall major morbidity was 14%, while postoperative surgical mortality rate (30th postoperative day) was 12 %. Five-year survival rate was 28% while median of survival was 10 months. Multivariate analysis identified six prognostic factors: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort (after 2002) and hilar lymphadenectomy.Prognostic factors were: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort and hilar lymphadenectomy.