IPATIMUP is a private non-profit research organization whith the following main goals: Research in human pathology, with particular emphasis on oncobiology. Training of graduate students, technicians, residents and specialists in Pathology. Diffusion of scientific knowledge and teaching of undergraduate students. Providing sophisticated diagnostic expertise in the different fields covered by the Institute - Pathology , Oncobiology and Population Genetics.

Gastric carcinoma (GC) is the second leading cause of cancer-related death in the world. Patients infected with Helicobacter pylori, a stomach colonizing bacteria, are at increased risk for developing GC. Persistent inflammation elicited by H. pylori and intensified via the cytokine cascade, leads to chronic atrophic gastritis, hypochlorhydria and GC. However, progression towards GC, occurs only in some patients and seems to depend on both bacterial and host factors. Under INCA, we want to: Identify Human cytokine and inflammation-related gene polymorphisms associated with increased risk of progression to H. pylori-associated GC; Assess the influence of H. pylori virulence on genetic predisposition to the development of GC. This project will involve high-throughput genotyping technology. This topic will be investigated in close collaboration with other members of the INCA consortium in order to extend the concept of identification of genetic susceptibility factors to all other models of cancer inducing infections.

Machado JC, Oliveira C, Carvalho R, Soares P, Berx G, Caldas C, Seruca R, Carneiro F, Sobrinho-Simões M. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene 20: 1525-1528, 2001. Machado JC, Pharoah P, Sousa S, Carvalho R, Oliveira C, Figueiredo C, Amorim A, Seruca R, Caldas C, Carneiro F, Sobrinho-Simões M. Interleukin 1 beta and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 121: 823-829, 2001. Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, Capelinha AF, Quint W, Caldas C, van Doorn LJ, Carneiro F, Sobrinho-Simões M. Helicobacter pylori and interleukin-1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94: 1680-1687, 2002. Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, Alves CC, Campos ML, van Doorn LJ, Caldas C, Seruca R, Carneiro F, Sobrinho-Simões M. A pro-inflammatory genetic profile increases the risk of chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125: 364-371, 2003. Suriano G, Oliveira MJ, Huntsman D, Mateus AR, Ferreira P, Casares F, Oliveira C, Carneiro F, Machado JC, Mareel M, Seruca R. E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells. Hum Mol Genet 12: 3007-3016, 2003. Regalo G, Canedo P, Suriano G, Resende C, Campos ML, Oliveira MJ, Figueiredo C, Rodrigues-Pereira P, Blin N, Seruca R, Carneiro F, Machado JC. C/EBPbeta is over-expressed in gastric carcinogenesis and is associated with COX-2 expression. J Pathol 210: 398-404, 2006. Oliveira MJ, Costa AC, Costa AM, Henriques L, Suriano G, Atherton JC, Machado JC, Carneiro F, Seruca R, Mareel M, Leroy A, Figueiredo C. Helicobacter pylori induces gastric epithelial cell invasion in a C-Met and type IV secretion system dependent manner. J Biol Chem 281:34888-34896, 2006. Canedo P, Castanheira-Vale AJ, Lunet N, Pereira F, Figueiredo C, Gioia-Patricola L, Canzian F, Moreira H, Suriano G, Barros H, Carneiro F, Seruca R, Machado JC. The interleukin-8 -251*T/*A polymorphism is not associated with risk for gastric carcinoma development in a Portuguese population. Eur J Cancer Prev (in press). Costa B, Ferreira P, Costa S, Canedo P, Oliveira P, Silva A, Pardal F, Suriano G, Machado JC, Lopes JM, Reis RM. Association between functional EGF+61 polymorphism and glioma risk. Clin Cancer Res (in press).