Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling.

BACKGROUND: The characterization of differentially expressed genes between cancerous and normal tissues is an important step in the understanding of tumorigenesis. Global gene expression profiling with microarrays has now offered a powerful tool to measure the changes of thousands of genes in any carcinoma tissues in an effort to identify these key disease-related genes. To compare the gene expression of a primary liver carcinoma, metastatic carcinoma to the liver, and normal liver, the authors analyzed tissue from six primary hepatocellular carcinomas (HCCs), five colorectal adenocarcinoma metastases to the liver, and eight normal livers. METHODS: Samples were processed from total RNA to fragmented cRNA and hybridized onto Affymetrix GeneChip(R) expression arrays. Analyses were performed to determine the consensus pattern of gene expression for primary liver carcinoma, metastatic liver carcinoma, and normal liver tissue and their changes in expression level. RESULTS: In hepatocellular carcinoma, 842 genes were overexpressed, and 393 genes were underexpressed in comparison with genes of normal liver tissue. Of note, 7 of the 20 most increased identified known genes previously have been associated with liver carcinoma or other types of cancers. The 13 additional identified genes until now have not previously shown strong association with cancers. Furthermore, the authors identified 42 genes and 24 expressed sequence tags that are expressed at a significant level in both HCC and metastastic tumors, presenting a list of marker genes indicative of cancerous liver tissue. CONCLUSIONS: In this study, genes that can be involved in the production of and maintenance of hepatic carcinomas were identified. These data offer new insight into genes that are potentially important in the pathogenesis of liver carcinoma, as well as additional targets for new strategies for cancer therapy and treatment.

Candida albicans adherence to a human oesophageal cell line.

The oesophageal epithelium appears to be one of the primary cell targets of Candida albicans in AIDS patients. To study this interaction, we have established an in vitro adherence assay using a human epithelial oesophageal cell line (HET1-A). When yeast cells were grown in 500 mM D-galactose, adherence increased significantly over cultures prepared in 500 mM D-glucose. In addition to HET1-A cells, adherence of the organism grown in D-galactose to human buccal epithelial cells and a murine alveolar macrophage cell line was also higher. Adherence of yeast cells to HET1-A cells was partially inhibited in the presence of D-glucosamine or N-acetyl-D-glucosamine, but not with D-mannose, D-glucose, L-fucose or D-galactose. Attachment to HET1-A cells was studied using scanning and transmission electron microscopy. Partial phagocytosis of adhering yeast cells was observed occasionally within the first 90 min following infection, as evidenced by the formation of HET1-A pseudopodia in instances of close contact with yeast cells. The influence of D-galactose on cell surface proteins was studied by analysing beta-mercaptoethanol-extracted proteins from yeast cells grown in either 500 mM D-galactose or D-glucose. From D-galactose-grown cells only, a glycoprotein of approximately 190 kDa was observed in Aurodye-stained SDS-PAGE gels and in Western blots using an immunoglobulin fraction (IgG) prepared from sera of rabbits infected with the organism. These studies demonstrate that C. albicans adheres to human oesophageal cells and may utilize cell surface proteins whose synthesis is nutritionally regulated.