BackgroundHepatocellular carcinoma (HCC) is a malignancy with poor survival outcome. New treatment options for the disease are needed. In this study, we identified and evaluated tumor vascular PLVAP as a therapeutic target for treatment of HCC.MethodsGenes showing extreme differential expression between paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP was identified as one of such genes with potential to serve as a therapeutic target for treatment of HCC. 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.ResultsPLVAP 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. Infusion of recombinant monoclonal anti-PLVAP Fab-TF into the main 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.ConclusionsThe 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 and potentially avoid the drawback of high viscosity of chemoembolic emulsion for TACE to improve therapeutic outcome. Anti-PLVAP Fab-TF may become a viable therapeutic agent in patients with advanced disease and compromised liver function.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-815) contains supplementary material, which is available to authorized users.

Shannon information in the genomes of all completely sequenced prokaryotes and eukaryotes are measured in word lengths of two to ten letters. It is found that in a scale-dependent way, the Shannon information in complete genomes are much greater than that in matching random sequences--thousands of times greater in the case of short words. Furthermore, with the exception of the 14 chromosomes of Plasmodium falciparum, the Shannon information in all available complete genomes belong to a universality class given by an extremely simple formula. The data are consistent with a model for genome growth composed of two main ingredients: random segmental duplications that increase the Shannon information in a scale-independent way, and random point mutations that preferentially reduces the larger-scale Shannon information. The inference drawn from the present study is that the large-scale and coarse-grained growth of genomes was selectively neutral and this suggests an independent corroboration of Kimura's neutral theory of evolution.

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Shannon information in the genomes of all completely sequenced prokaryotes and eukaryotes are measured in word lengths of two to ten letters. It is found that in a scale-dependent way, the Shannon information in complete genomes are much greater than that in matching random sequences -thousands of times greater in the case of short words. Furthermore, with the exception of the 14 chromosomes of Plasmodium falciparum, the Shannon information in all available complete genomes belong to a universality class given by an extremely simple formula. The data are consistent with a model for genome growth composed of two main ingredients: random segmental duplications that increase the Shannon information in a scale-independent way, and random point mutations that preferentially reduces the larger-scale Shannon information. The inference drawn from the present study is that the large-scale and coarse-grained growth of genomes was selectively neutral and this suggests an independent corroboration of Kimura's neutral theory of evolution.