Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Tratamentos com Preservação do Órgão/métodos , Neoplasias Retais/cirurgia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: COX-2 and E-cadherin, involved in invasion and metastasis, are molecules critical for gastric carcinogenesis. A relationship between them is documented in non-small cell lung and prostate cancer. We present novel evidence of a relationship between COX-2 and E-cadherin expression in gastric cancer. METHODS: Using qPCR and Western blots analysis on celecoxib and PGE2 treated and untreated gastric cancer cell lines derived from tumours of the intestinal type (MKN45, MKN28, AGS3, MKN7) and immunohistochemistry of 178 gastric cancers on tissue microarrays (TMA), we examined the COX-2/E-cadherin relationship. RESULTS: Down-regulation of COX-2 by celecoxib led to up-regulation of E-cadherin mRNA and protein levels in conventional gastric cancer cell lines, whereas expression was down regulated in the early-onset gastric cancer (EOGC) cell line. Immunohistochemistry on TMAs of 178 gastric cancers showed no correlation between COX-2 and E-cadherin expression in the conventional or early gastric cancer groups. CONCLUSION: The results suggest that COX-2 has an impact on transcriptional regulation of E-cadherin in gastric cancer and our findings further highlight the intriguing nature of EOGCs which appear to have a molecular phenotype distinct from conventional gastric cancer. In addition, our findings also suggest that reduction of COX-2 using nonsteroidal anti-inflammatory drugs in gastric cancer chemoprevention may only be relevant for older patients.
Assuntos
Caderinas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idade de Início , Western Blotting , Caderinas/genética , Celecoxib , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/farmacologia , Análise Mutacional de DNA , Dinoprostona/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Países Baixos/epidemiologia , Pirazóis/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Sulfonamidas/farmacologia , Análise Serial de TecidosRESUMO
It has been reported that interleukin-1beta (IL-1B) genes play a crucial role in the genetic predisposition to gastric cancer although there is no information about their role in different subtypes of gastric cancer. We performed single nucleotide polymorphism analysis of IL-1B in 241 gastric cancers including early onset gastric cancers (EOGC), conventional gastric cancers, and gastric stump cancers (GSCs) as well as 100 control patients, using real-time polymerase chain reaction and sequence analysis. The C allele was present in 60% of EOGCs, 59% of conventional gastric cancers, and 90% of GSCs, compared to 62% in the control group. Interestingly, there was no difference between early onset and conventional gastric cancer with respect to the IL-1B -31T>C polymorphism distribution. A statistically significant difference in the presence of the C allele compared to the control group was found in patients with gastric stump cancer (p = 0.008) with the T allele conferring protection against gastric stump cancer. In summary, we have shown that the IL-1B -31C allele promoter polymorphism is significantly associated with gastric stump cancer compared to the control group. Although several molecular differences have been identified between conventional gastric cancer and early onset gastric cancer, the IL-1B -31 allele distribution is similar between these two groups.
