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With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both α-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC. [Copyright &y& Elsevier]

Nonsteroidal anti-inflammatory drugs (NSAIDs) have a preventive effect against colorectal cancer. Although inhibition of cyclooxygenase-2 plays a crucial role in the suppression of tumors, precise mechanisms of their action remain to be disclosed. To identify genes involved in the growth-suppressive effect of NSAIDs, we utilized cDNA microarray containing 23,040 genes and analyzed time-dependent alteration of gene expression in response to sulindac or aspirin in NSAIDs-sensitive SW480 and SW948 colon-cancer cells as well as in relatively resistant SNU-C4 cells. Consequently we identified 112 genes with commonly altered expression by sulindac and 176 with commonly altered expression by aspirin in the three lines. Addition of sulindac and that of aspirin altered expression levels of 130 and 140 genes, respectively, in SW480 and SW948 cells but not in SNU-C4 cells. These data may lead to a better understanding of growth-suppressive effects on colonic epithelium, and may provide clues for identifying novel therapeutic and/or preventive molecular targets of colon cancer. [Copyright &y& Elsevier]