Transforming growth factor ß repressor, SnoN, is overexpressed in human gastrointestinal stromal tumors.

PURPOSE: The transforming growth factor bgr; (TGF-ß)/ Smad pathway is implicated in the development of interstitial cells of Cajal. The aim of this study was to examine the role of this pathway in human gastrointestinal stromal tumors (GISTs). METHODS: The expression of TGF-ß receptor II (TßRII), phosphorylated Smad2 (p-Smad2), SnoN, p21(WAF17sol;CIP1) and p27(KIP1) was examined by immunohistochemistry in 30 hu-man GISTs in relation to prognostic factors. RESULTS: TßRII was expressed in 76.9% of the cases. All cases were positive for p-Smad2 and SnoN, with significantly higher expression levels in small intestinal compared to gastric GISTs. Downregulation of p21(WAF1/CIP1) and p27(KIP1) was found in 78.6% and 46.4% of the cases respectively, while cytoplasmic expression of p27(KIP1) was also noted in 50% of GISTs. CONCLUSIONS: TGF-ß/Smad pathway may contribute to GIST pathogenesis. SnoN overexpression and low levels of p21(WAF1)/CIP1 and p27(KIP1) may be of importance in GISTs.

ILK over-expression in human colon cancer progression correlates with activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway.

Integrin-linked kinase (ILK) has been implicated in the development and progression of several human malignancies. However, the role of ILK in human colon cancer progression is not well established, neither have its possible in vivo downstream effectors in the disease been identified. We studied, by immunohistochemistry, ILK, beta-catenin, E-cadherin, p-Akt and p-FKHR protein expression in 125 primary colon carcinomas and 45 corresponding lymph node metastases. ILK was expressed in 98.4% of the primary tumours and in 100% of metastatic lesions. The levels of ILK expression correlated strongly with tumour invasion, tumour grade and stage and were significantly higher in metastatic tumours. Activation of beta-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway correlated significantly with both ILK expression and tumour progression parameters. In conclusion, our results suggest that ILK may have an important role in progression of human colon cancer, possibly through in vivo regulation of beta-catenin, E-cadherin and Akt pathways. Our study also provides some evidence implicating p-FKHR in human colon carcinogenesis and ILK signalling.

Expression of the licensing factors, Cdt1 and Geminin, in human colon cancer.

Licensing of chromatin for replication is an evolu-tionarily conserved step in the control of cell division and genomic integrity. Proteins that participate in licensing have been recently documented to denote the proliferative state of cells and they have been proposed as diagnostic and prognostic markers in human cancer. Cdt1 was recently discovered as an important licensing factor, that is inhibited by Geminin. In the present study we analyzed Cdt1 and Geminin expression in human colon cancer. We showed that Cdt1 protein is highly expressed in human neoplastic lesions of the colon while its cell-cycle phase-specific expression profile appears preserved during human carcinogenesis. Similarly, Geminin, Cdt1's inhibitor, is also overexpressed in colon carcinomas and its expression correlates with significant clinicopathological parameters of the disease. Moreover, both Cdt1 and Geminin expression are severely downregulated upon differentiation of Caco-2 cells, an in vitro model of intestinal epithelial differentiation.

A three-dimensional breast software phantom for mammography simulation.

This paper presents a methodology for three-dimensional (3D) computer modelling of the breast, using a combination of 3D geometrical primitives and voxel matrices that can be further subjected to simulated x-ray imaging, to produce synthetic mammograms. The breast phantom is a composite model of the breast and includes the breast surface, the duct system and terminal ductal lobular units. Cooper's ligaments, the pectoral muscle, the 3D mammographic background and breast abnormalities. A second analytical x-ray matter interaction modelling module is used to generate synthetic images from monoenergetic fan beams. Mammographic images of various synthesized breast models differing in size, shape and composition were produced. A preliminary qualitative assessment performed by three radiologists and a quantitative evaluation study using fractal and grey-level histogram analysis were conducted. A comparative study of extracted features with published data has also been performed. The evaluation results indicated good correlation of characteristics between synthetic and actual radiographs. Applications foreseen are not only in the area of breast imaging experimentation but also in education and training.