The proteasome subunit PSMA7 located on the 20q13 amplicon was found to be differentially expressed in colorectal cancer by semiquantitative RT-PCR. PSMA7 mRNA was overexpressed in 37.5% (12/32) colorectal cancer tissues while it was either of a low level or not expressed in matched normal mucosa. The aim of this study was to examine the PSMA7 protein expression in 62 colorectal cancer primary sites, 34 lymph node metastatic sites and 13 liver metastatic sites by immunohistochemistry and clarify the correlations of this expression with the clinicopathological parameters. PSMA7 high expression was detected in 38.8% (24/62) colorectal cancer primary sites, 52.9% (18/34) lymph node metastatic sites and 100% (13/13) liver metastatic sites but not in the normal colorectal tissues. The PSMA7 high expression was significantly correlated with liver metastasis (P=0.028). Survival was significantly lower in patients with a PSMA7 high expression than in those with a PSMA7 low expression (P=0.0012). Moreover, in multivariate analysis, the PSMA7 expression demonstrated an independent prognostic factor (P=0.004, relative risk 5.057; 95% confidence interval, 1.682-15.201). These results indicated that PSMA7 may play an important role in colorectal cancer progression and provide a unique target site for the development of therapeutic drugs. The evaluation of PSMA7 expression in primary colorectal cancer at the time of surgery may be a valuable tool for defining patients with a high risk of developing liver metastasis. Materials and methods Patients and tissue samples. A total of 62 patients with colorectal adenocarcinoma who underwent surgery from

AIM:Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1) and vascular endothelial growth factor (VEGF). However, the roles of TGFβ1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-β1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-β1 and its receptor CD105 in gastric malignant tumors. METHODS:The expressions of TGF-β1 and CD105 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-β1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Immunohistochemistry (DS-ABC). RESULTS:Among the 55 cases of gastric carcinoma tissues, 30 were positive for TGF-β1 (54.55 %). The MVD of TGF-β1 strong positive group (++~+++ 23.22±5.8) was significantly higher than that of weak positive group (+17.56±7.2) and negative group (-17.46±3.9) (q=4.5, q=5.3207, respectively, P<0.01). In the areas of high expression of TGF-β1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1 %). The expressions of both VEGF and CD105 (MVD) were related with the depth of invasion (F=5.438, P<0.05; F=4.168, P=0.05), lymph node metastasis (F=10.311, P<0.01; F=20.282, P<0.01) and Dukes stage (F=6.196, P<0.01; F=10.274, P<0.01), but not with histological grade (F=0.487, P>0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P<0.01). CONCLUSION:Over-expression of TGF-β1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors. CD105, as a receptor of TGF-β1, can regulate the biological effect of TGF-β1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.

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TXBcl-XL, an anti-apoptotic protein of Bcl-2 family, is overexpressed in colon cancers. To determine Bcl-XL's potential feasibility as a therapeutic target, we constructed a recombinant adenovirus that expressed a U6 promoter-driven small hairpin RNA (shRNA) targeting Bcl-XL (Ad/Bcl-XL shRNA) and evaluated the vector's ability to induce RNA interference in vivo and alter apoptosis induction in colon cancer cells and tumours. Ad/Bcl-XL shRNA effectively knocked down Bcl-XL expression in colon cancer cells and decreased their viability. Treatment with Ad/Bcl-XL shRNA but not control vectors led to dramatically increased cleavage of cellular apoptosis-related enzymes caspase-9, caspase-3 and poly (ADP-ribose) polymerase. Ad/Bcl-XL shRNA also significantly suppressed the growth of subcutaneous tumours derived from DLD1 cells in a nude mouse model and did so without causing any obvious damage to normal tissues or normal human fibroblasts. Together, our results support the feasibility of using adenovirusmediated RNA interference therapy targeting Bcl-XL against colon cancers and warrant further studies of its safety and efficacy. ' 2007 Wiley-Liss, Inc.