Epithelial (E)-cadherin and its associated cytoplasmic proteins (␣-, ␤-, and ␥-catenins) are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor͞invasion suppressor role for E-cadherin, and loss of expression, as well as mutations, has been described in a number of epithelial cancers. To investigate whether E-cadherin gene (CDH1) mutations occur in colorectal cancer, we screened 49 human colon carcinoma cell lines from 43 patients by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. In addition to silent changes, polymorphisms, and intronic variants in a number of the cell lines, we detected frameshift single-base deletions in repeat regions of exon 3 (codons 120 and 126) causing premature truncations at codon 216 in four replication-errorpositive (RER؉) cell lines (LS174T, HCT116, GP2d, and GP5d) derived from 3 patients. In LS174T such a mutation inevitably contributes to its lack of E-cadherin protein expression and function. Transfection of full-length E-cadherin cDNA into LS174T cells enhanced intercellular adhesion, induced differentiation, retarded proliferation, inhibited tumorigenicity, and restored responsiveness to the migratory effects induced by the motogenic trefoil factor 2 (human spasmolytic polypeptide). These results indicate that, although inactivating E-cadherin mutations occur relatively infrequently in colorectal cancer cell lines overall (3͞43 ‫؍‬ 7%), they are more common in cells with an RER؉ phenotype (3͞10 ‫؍‬ 30%) and may contribute to the dysfunction of the E-cadherin-catenin-mediated adhesion͞sig-naling system commonly seen in these tumors. These results also indicate that normal E-cadherin-mediated cell adhesion can restore the ability of colonic tumor cells to respond to trefoil factor 2.

These results provide further evidence that in colorectal cancer there is a widespread deregulated expression of cell-cell and cell-matrix adhesion molecules. Changes in the expression and function of adhesion molecules which regulate growth and differentiation may play a role in the behaviour of colorectal cancer.

Our numerical results are in good agreement with in vivo measurements reported in the literature, demonstrating the potential of our model for prediction of oxygen distribution and intravascular oxygen tension profiles in the retinal arterial network. This paves the way for investigating the effects of parameter variation, simulating cases not available from experimental studies.

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The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement.