Gene expression profiling of 18 hepatocellular carcinoma and adjacent non-tumorous liver tissue
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ABSTRACT: These paired HCC and non-tumorous liver tissues were used to determine highly dfferentially expressed genes in HCC and non-tumorous liver tissue. Hepatocellular carcinoma (HCC) is a malignancy with poor survival outcome. Genes showing extreme differential expression between paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP was identified as a gene specifically expressed in vascular endothelial cells of HCC but not in non-tumorous liver tissues. This finding was confirmed by RT-PCR analysis of micro-dissected cells and immunohistochemical staining of tissue sections. A recombinant monoclonal anti-PLVAP Fab fragment co-expressing extracellular domain of human tissue factor (TF) was developed. The potential therapeutic effect and toxicity to treat HCC were studied using a Hep3B HCC xenograft model in SCID mice. Infusion of recombinant monoclonal anti-PLVAP Fab-TF into the tumor feeding artery induced tumor vascular thrombosis and extensive tumor necrosis at doses between 2.5 µg and 12 µg. Tumor growth was suppressed for 40 days after a single treatment. Systemic administration did not induce tumor necrosis. Little systemic toxicity was noted for this therapeutic agent. The results of this study suggest that anti-PLVAP Fab-TF may be used to treat HCC cases for which transcatheter arterial chemoembolization (TACE) is currently used, but without major drawbacks of TACE. Anti-PLVAP Fab-TF may improve therapeutic outcome and be a viable therapeutic agent in patients with more advanced disease and compromised liver function.
ORGANISM(S): Homo sapiens
PROVIDER: GSE60502 | GEO | 2015/01/01
SECONDARY ACCESSION(S): PRJNA258424
REPOSITORIES: GEO
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