HMSH2 and HMSH6 gene expression profiles in colorectal adenocarcinoma in patients up to 50 years of age

Lynch syndrome, previously called hereditary non-polyposis colorectal cancer (HNPCC), is a major mortality threat. It is an autosomal dominant disease which is caused by a germline mutation in the DNA mismatch repair (MMR), especially in patients aged up to 50 years. Such mutation more frequently occurs in the hMSH2 gene (38-40%) and less frequently in the hMSH6 gene (14-16%). These mutations, when associated with the patient's lifestyle, may reveal a considerable variability in the disease manifestations, such as the degrees of penetrance and clinical aggressiveness. The aim of this study is to analyze the expression of DNA MMR genes, and correlate this expression with the clinical and anatomopathological findings of the neoplasia in patients aged between 39 and 49 years. A total of 45 patients were included: (48.9%) males and (51.1%) females, and they all underwent resection of a colorectal adenocarcinoma. The tissue microarray technique was used to analyze the relative and absolute expression of hMSH2 and hMSH6. Amsterdam II criteria for the diagnosis of HNPCC were obtained from the data provided by medical records and interviews with patients. hMSH2 and hMSH6 was expressed in all patients, which correlated between each other (RHO = 0.669 and p < 0.001) but not to age. There is a positive correlation between the expressions of males (RHO = 0.673 and p = 0.001) and females (RHO = 0.006 and p < 0.001). It is possible to evaluate the expression of MMR genes in embedded anatomopathological samples. Gene expressions correlated between each other and to the sex of the patients, but no difference in relation to age. (C) 2016 Elsevier Masson SAS. All rights reserved.State Civil Servant Hosp IAMSPE, Sao Paulo, BrazilABC Med Sch, Oncol Hematol Discipline, Sao Paulo, BrazilUniv Paulista, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Chem & Pharmaceut Sci, Sao Paulo, BrazilAv Principe de Gales 821, BR-09060650 Santo Andre, SP, BrazilAv Ibirapuera,981-2 Andar, BR-04029000 Sao Paulo, SP, BrazilInstitute of Chemical and Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), Diadema, São Paulo, BrazilWeb of Scienc

Pancreatic islet allograft in spleen with immunossuppression with cyclosporine. Experimental model in dogs Alotransplante de ilhotas pancreáticas no baço com imunossupressão com ciclosporina. Modelo experimental em cães

PURPOSE: To study the functional behavior of the allograft with immunosuppression of pancreatic islets in the spleen. METHODS: Five groups of 10 Mongrel dogs were used: Group A (control) underwent biochemical tests; Group B underwent total pancreatectomy; Group C underwent total pancreatectomy and pancreatic islet autotransplant in the spleen; Group D underwent pancreatic islet allograft in the spleen without immunosuppressive therapy; Group E underwent pancreatic islet allograft in the spleen and immunosuppression with cyclosporine. All of the animals with grafts received pancreatic islets prepared by the mechanical-enzymatic method - stationary collagenase digestion and purification with dextran discontinuous density gradient, implanted in the spleen. RESULTS: The animals with autotransplant and those with allografts with immunosuppression that became normoglycemic showed altered results of intravenous tolerance glucose (p < 0.001) and peripheral and splenic vein plasmatic insulin levels were significantly lower (p < 0.001) in animals that had allografts with immunosuppression than in those with just autotransplants. CONCLUSIONS: In the animals with immunosupression with cyclosporine subjected to allograft of pancreatic islets prepared with the mechanical-enzymatic preparation method (stationary collagenase digestion and purification with dextran discontinuous density gradient), the production of insulin is decreased and the response to intravenous glucose is altered.<br>OBJETIVO: Avaliar o comportamento funcional do alotransplante com imunossupressão de ilhotas pancreáticas no baço. MÉTODOS: Foram utilizados cinco grupos de 10 cães mestiços: grupo A (controle) submetido aos exames bioquímicos; grupo B, submetido à pancreatectomia total; grupo C (autotransplante) submetido à pancreatectomia total e autotransplantação de ilhotas pancreáticas no baço; grupo D, submetido à alotransplantação de ilhotas pancreáticas no baço sem terapia imunossupressiva; grupo E, submetido à alotransplantação de ilhotas no baço e imunossupressão com ciclosporina. Todos os animais transplantados receberam ilhotas pancreáticas isoladas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran e foram implantadas no baço. RESULTADOS: Animais autotransplantados e alotransplantados com imunossupressão que se tornaram normoglicêmicos apresentaram testes de tolerância à glicose intravenosa alterados (p<0,001) e o nível de insulina plasmática periférica e na veia esplênica foram significantemente menores (p<0,001) nos animais alotransplantados com imunossupressão em relação aos autotransplantados. CONCLUSÃO: Nos animais submetidos ao alotransplante de ilhotas pancreáticas com imunossupressão com ciclosporina e preparadas pelo método mecânico-enzimático, digestão estacionária com colagenase e purificação com gradiente de densidade descontínua de dextran, a produção de insulina está diminuída e a resposta à sobrecarga de glicose intravenosa alterada