Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG-100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95 percent) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85 percent) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer

Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA extraction. Patients had never been submitted to chemotherapy or radiotherapy, nor did they have any other diagnosed cancer. None of the gastric cancer samples presented methylated DNA sequences for ANAPC1 and TP53. CDKN2A methylation was not detected in any normal gastric mucosa; however, the CDKN2A promoter was methylated in 30.4 percent of gastric cancer samples, with 35 percent methylation in diffuse-type and 26.9 percent in intestinal-type cancers. CDKN2A methylation was associated with the carcinogenesis process for ~30 percent diffuse-type and intestinal-type compared to non-neoplastic samples. Thus, ANAPC1 and TP53 methylation was probably not implicated in gastric carcinogenesis in our samples. CDKN2A can be implicated in the carcinogenesis process of only a subset of gastric neoplasias.

Valvoplastia mitral percutânea por baläo, resultados imediatos e complicaçöes / Percutaneous mitral balloon valvuloplasty. Immediate results and complications

Foram estudados os resultados obtidos em 156 procedimentos de valvoplastia mitral percutânea por baläo (VMPB) realizados em 153 pacientes, no período de 6 de julho de 1987 a 31 de maio de 1993. A idade do grupo foi de 37,62 +/_ 13,76 anos. Foram 126 procedimentos (80,8 por cento) em mulheres (idade média 37,30 +/_ 13,00 anos) e 30 procedimentos (19,2 por cento) em homens (idade média de 38,93 +/_ 16,74 anos) p= 0,568181). A classe funcional (CF) de NYHA foi II em 12 procedimentos (7,7 por cento), I em 118(75,6 por cento) e IV EM 26(16,7 por cento). Em 131 procedimentos (84,0 por cento) os pacientes estavam em ritmo sinusial e em 25 (16,0 por cento) estavam em fibrilaçäo atrial. O escore ecocardiográfico variou de 4 a 14 pontos com média 7,7 +/_ 1,7 pontos, entre 4 a 9 pontos situou-se 90,4 por cento dos pacientes. Foram efetivados com dados pré e pós VMPB, 139 procedimentos e houve sucesso, área valvar mitral (AVM) 1,5 centímetros ao quadrado pós VMPB, em 131 procedimentos. Quando medida pela ccardiografia AVM pré VMPB foi de 0,9 +/_ 0,2 cm ao quadrado e após VMPB 1,8 +/_ 0,3 cm ao quadrado (p<0,000001) e quando medida por métodos hemodinâmicos foi de 0,9 +/_ 0,2 cm ao quadrado pós VMPB (p<0,000001). A pressäo pulmonar média caiu de 41 +/_ 15 mmHg 27 +/_ 11 mmHg pós VMPB (p<0,000001) e o gradiente mitral médio caiu de 22 +/_ 7 mmHg para 6 +/_ 5 mmHg (p<0,000001). Foram utilizados baläo único de 20 mm (4 procedimentos), duplo baläo (7 procedimentos), baläo de Inoue (4 procedimentos) e baläo nio de baixo perfil (131 procedimentos). Dos 139 procedimentos pré VMPB, em 121 a valva mitral (VM) era competente e em 18 havia regurgitaçäo mitral (RM) de 1+. Após a VMPB a VM era competente em 91 e havia RM de 1+ em 39, de 3+ em 4 e de 4+ em 1. Houve complicaçäo em 10 procedimentos, sendo insuficiência mitral grave IM em 5 (3 ou 4+), acidente vascular cerebral (AVC) em 3 e tamponamento cardíaco em 2. Dos 10,2 evoluíram para óbito, um após tamponamento cardíaco por perfuraçäo de ventrículo esquerdo e utr por descerebraçäo após AVC. Conclui-se que a VMPB foi um procedimento efetivo, com alto grau de suceso nos procedimentos efetivados e com baixo percentual de complicaçöes.