BACKGROUND Akt/protein kinase B (PKB), which is included in phosphatidyl inositol‐3‐OH kinase (PI3K) signaling, controls many intracellular processes, such as the suppression of apoptosis and the promotion of the cell cycle. Therefore, the authors investigated phosphorylated Akt (Ser473) in colorectal carcinomas to reveal the role of PI3K signaling during the development of colorectal carcinoma. METHODS Expression of phosphorylated Akt (Ser473) in two colon carcinoma cell lines (DLD‐1 and Colo205) and 65 human colorectal carcinomas was analyzed using western blotting and immunohistochemistry, respectively. Growth inhibition and induction of apoptosis caused by LY294002, a specific inhibitor of PI3K, were also examined in these cell lines. In tumor samples, the level of cell proliferation activity (Ki‐67) and number of apoptotic bodies (single stranded DNA) were determined by counting positive cells. RESULTS LY294002 significantly affected the proliferation and apoptosis of Colo205 cells, suggesting an association with the low phosphorylation level of Akt protein. Immunohistochemic analysis showed that 46% of the tumors had a high level of expression of phosphorylated Akt with a close association with Ki‐67 proliferative activity (P < 0.001) and the number of apoptotic bodies (P < 0.001). Akt phosphorylation was also correlated with some clinicopathologic parameters of the malignancies, including depth of invasion, infiltration to venous vessels, lymph node metastasis, and clinicopathologic stage. CONCLUSIONS The phosphorylated Akt level can monitor cell growth and resistance to apoptosis, indicating that activation of Akt plays an important role during the progression of colorectal carcinomas by helping promote cell growth and rescue cells from apoptosis. These findings also suggest the possibility of using LY294002 for treatment of colorectal carcinoma. Cancer 2002;94:3127–34. © 2002 American Cancer Society. DOI 10.1002/cncr.10591

Background-Toll-like receptors (TLRs)

Results showed the up-regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.

Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.