-Context -Search of tumors markers that allow treatment with higher survival rates, and indicate the response to treatment and recurrence of cancer -Objective -To analyze the immunoexpression of the proteins p53, bcl-2 and Ki-67 in colorectal adenocarcinoma and correlate them with the clinical-pathological prognostic factors. Method -Tissue microarray paraffin blocks were made from colorectal adenocarcinoma tissue resected from 82 patients who had undergone surgery but not chemotherapy or radiotherapy, at "Hospital São Paulo", São Paulo, SP, Brazil, between 2002 and 2005. Thin sections (4 μm) were subjected to immunohistochemical reactions, and immunoexpression staining scores were obtained. The scores were correlated with the degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The study variables were analyzed using the chi-square and Kaplan-Meier tests to investigate associations with the markers. The significance of the differences between the curves of the diseasefree interval and survival was analyzed using the Logrank and Wilcoxon tests. Results -The immunohistochemical expression of p53 was positive in 70 tumors (85.4%) and negative in 12 (14.6%). The expression of bcl-2 was positive in 26 (31.7%) and negative in 56 (68.3%). The expression of Ki-67 was positive in 62 (75.6%) and negative in 20 (24.4%). There was no statistically significant correlation between the expressions of these markers separately or in conjunction, in relation to the degree of cell differentiation, staging, disease-free interval, survival and specific mortality. In relation to recurrence, there was a statistically significant correlation with positive expression of Ki-67 (P = 0.035). Conclusion -The immunohistochemical expression of Ki-67 in colorectal cancer is associated with recurrence of this disease. HEADINGS -Colorectal neoplasms. Adenocarcinoma. Immunohistochemistry. Tumor suppressor protein p53. Proto-oncogene proteins c-bcl-2. Bcl-2 homologous antagonist-killer protein.
PURPOSE: To analyze the expression of metalloproteinase-1, metalloproteinase-7 and vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma, and to correlate these with the clinical-pathological prognostic factors. METHODS: Tumor tissue from 82 patients was fixed in formalin and embedded in paraffin blocks. These samples were analyzed by means of the streptavidin-biotin immunohistochemical method, using the tissue microarray technique. Marker positivity was evaluated using categorical scores that determined cutoff percentages of stained tumor cells. Protein tissue expression was correlated with the variables of degree of cell differentiation, staging, disease-free interval, recurrence, survival and specific mortality. The Fisher exact and Kaplan-Meier tests were used to assess associations between the markers and the study variables. The log-rank and Wilcoxon tests were used to assess the significance of differences between curves of disease-free interval and survival. RESULTS: All tumors were positive for metalloproteinase-1; 50 (61%) were positive and 32 (39%) were negative for metalloproteinase-7; and 60 (74.1%) were positive and 21 (25.9%) were negative for VEGF. Correlation of marker expression, both in groups and individually, did not show statistical significance in relation to the degree of cell differentiation, staging, disease-free interval, survival or specific mortality. Recurrence showed a statistically significant correlation with positive expression of the three markers, when analyzed as a group (p = 0.038). CONCLUSION: The associated expression of metalloproteinase-1, metalloproteinase-7 and VEGF in colorectal adenocarcinoma is related to the incidence of disease recurrence.
RESUMO: A metaloproteinase-1 (MMP-1) e a metaloproteinase-7 (MMP-7) são proteinases da matriz extracelular (MEC), zincodependentes, envolvidas no processo inicial da carcinogênese por permitirem a invasão tumoral na célula e promover o processo INTRODUÇÃOA invasão celular de um tecido pode ocorrer durante vários estágios, sejam fisiológicos ou patológi-cos. Existem barreiras que se opõem ao movimento de invasão tecidual, como as membranas basais, a matriz estromal e a junção entre as células. Acredita-se que um mecanismo comum para a quebra destas barreiras, seja a atuação de enzimas proteolíticas. Os tipos de proteinases envolvidas dependem do tipo de tecido envolvido e das circunstâncias encontradas na matriz. Não obstante, existem três classes de proteinases (matriz metaloproteinases -MMP, serina proteinases e cisteína proteinases) que têm distribuição alterada, aumento na expressão e/ou atividade, envolvidas na remodelação da matriz, facilitando a invasão tumoral. Algumas evidências sugerem que proteinases, especificamente as MMPs, estão envolvidas nos estados iniciais da progressão tumoral 1 .A carcinogênese e o desenvolvimento do cân-cer colorretal são processos de várias etapas, caracterizadas por mudanças progressivas na quantidade ou atividade de proteínas que regulam a proliferação, diferenciação e sobrevida celular, e são mediados por mecanismos genéticos e epigenéticos 2, 3 . Uma seqüên-cia ordenada de eventos não aleatórios leva ao desenvolvimento do câncer colorretal (CCR), passando o epitélio por transformação invasiva 4 , sendo a progressão do epitélio intestinal normal até o desenvolvimento do carcinoma invasivo estimada entre 7 e 12 anos 5 . A membrana basal e a matriz extracelular representam duas barreiras físicas à invasão maligna, e suas degradações pelas MMPs têm papel fundamental na progressão tumoral e disseminação das metástases 4,[6][7][8][9][10][11] .
The surgical block was sent to pathological exam, which showed it to be a mature sacrococcygeal teratoma. A good clinical evolution took place after resection.
OBJETIVO: A presente investigação teve como objetivo implantar um esfíncter artificial de silicone ( C C - Silimed® ) em colostomias terminais, em cães, e analisar a continência às fezes sólidas e líquidas, como também as complicações advindas do procedimento. MÉTODOS: Foram utilizados 13 cães mestiços, 11 machos e 2 fêmeas, com peso que variou entre 16 e 30kg, média de 22,5 + 4,3kg. Foram construídas colostomias terminais dotadas do C C - Silimed®, que eram ativados por um período de 8 horas diariamente. Os animais eram observados durante 15 semanas. A continência alcançada era demonstrada radiologicamente através de enema baritado. RESULTADOS: A pressão no sistema variou entre 60 e 80cm de água, média de 74,8 + 5,0cm. O volume de fluido que era introduzido no reservatório oscilou entre 5 e 8ml, média de 6,9 + 0,8ml. A continência foi alcançada em todos os animais, mas ocorreu escape fecal esporádico nos cães, durante esforços físicos. Infecção da ferida operatória aconteceu em três cães ( 23,1% ) e obstrução intestinal em ( 7,7% ). CONCLUSÃO: O esfíncter artificial de silicone ( C C - Silimed® ) mostrou-se efetivo na continência para fezes sólidas e líquidas. Assim sendo, abre uma expectativa para seu emprego clínico, em tempo futuro, em indivíduos portadores de colostomia definitiva.
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