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Endocan is differentially expressed in the endothelium of HCC blood vessels, being absent from the sinusoids of both peritumoral non-malignant and healthy liver tissue; thus, immunohistochemistry for endocan helps visualize HCC vasculature (Huang et al., 2009). Endocan-positive microvessel density (MVD), unlike CD34-positive MVD, was shown to be predictive of poor survival, and high expression of endocan by tumoral endothelial cells correlated with the angiogenic and invasive potential of the tumor (Huang et al., 2009; L. Y. Chen et al., 2010). In a recent study, endocan production by tumoral hepatocytes has also been reported, and silencing of endocan has been shown to inhibit tumor cell growth and

*PG-100* is the PG form of macrophage colony-stimulating factor and, as such, is a 'part-time' PG that may exist in a GAG-less or CS/DS-substituted form, the latter exhibiting less than 1% of cytokine activity compared with the non-PG variant (Schwarz et al., 1990; Partenheimer et al. 1995). PG-100 was first discovered in the conditioned medium of osteosarcoma cells, and later found to be produced by other cell types including endothelia (Nelimarkka et al., 1997). PG-100 was only faintly immunostained in the normal liver, whereas in active fibrosis it was strongly visualized in bile duct epithelia, and thus proposed as a marker of ductular reaction (Högemann et al., 1997). The significance of this elevated

**3. Outlook: PGs in future therapies of chronic liver disease and HCC** 

level of evidence (*in vitro*, *in vivo*) is also indicated in the table.

remarkable promise, but these apparently have a longer way ahead.

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PGs are emerging therapeutic targets in inflammatory, fibrogenic and malignant diseases. As a summary to this review, in **Table 2** we have collected some (however, by no means all) current attempts to exploit the multiple actions of PGs for countering the progression of chronic liver disease and HCC. Such experiments may involve delivery of PGs with supposed therapeutic effect, inhibition of those known to promote the pathologic process, modulation of HS structure, or application of HS-mimicking molecules. Some PGs expressed in the liver may be well-studied therapeutic targets in other organs or tumor types (e.g. perlecan, heparanase), yet have not been included in the list because their therapeutic potential has not been addressed specifically in the context of liver disease. The

Therapeutic approaches targeting glypican-3 have reached closest to human application; some phase I clinical trials have been completed or are underway. Several other PGs show

Publication of this article was supported by the grants Nos. 67925 and 100904 from the

Abid, M. R., Yi, X., Yano, K., Shih, S. C. & Aird, W. C. (2006). Vascular endocan is

preferentially expressed in tumor endothelium. *Microvascular Research*, Vol.72,

migration *in vitro* (Kang et al., 2011).

expression remains to be clarified.

**4. Acknowledgement** 

**5. References** 

Hungarian Scientific Research Fund (OTKA).


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**9** 

*India* 

**Chemically Induced Hepatocellular** 

**Factor II and Raf Gene Signaling** 

Biswajit Mukherjee\*, Miltu Kumar Ghosh and Chowdhury Mobaswar Hossain

**Carcinoma and Stages of Development** 

*Department of Pharmaceutical Technology, Jadavpur University, Kolkata* 

**with Biochemical and Genetic Modulation:** 

**A Special Reference to Insulin-Like-Growth** 

The liver, the largest organ in the body, predominantly functions as a biochemical laboratory where metabolism takes place. It has both endocrine and exocrine functions; and is also involved in numerous metabolic activities and acting as a storage depot. Once the nutritional substances and other chemicals such as drugs, carcinogens etc. reach in liver, they are metabolized by hepatic enzymes. The organ is located on the right side of the abdomen just beneath the diaphragm in human. Liver is a solid organ consisting of several lobes. Each lobe is constituted with numerous lobules which are in general hexagonal in shape (Figure 1). The center of each lobule is occupied by the central vein and the periphery of the lobule is delineated by a close arrangement of hepatic artery, portal vein, and bile duct; called "portal triads". The portal triads appear at the vertices of the hexagonal lobules. The vessels generated from the portal triads ramify and distribute along the sides of the lobule, and open into the sinusoids which have thin epithelial lining, a discontinuous layer of fenestrated endothelial cells. The liver has different types of cells. Oval cells are generally found near the portal triad. This rare cell-type has been claimed as hepatic stem cells by some researchers (Zamule et al., 2011). However, the major cell-type in liver is the polygonal hepatic parenchymal cells (hepatocytes). Hepatic lobules are made up of more than 80% hepatocytes which have an average size of 25 and occupy 70-90% of liver mass, depending on the species. They have clear cell membrane; sometimes with two nuclei. They have large deposits of glycogen, often with lipid droplets and basophilic materials. They also contain other cellular organelles such as mitochondria, rough endoplasmic reticulum (granular) and smooth endoplasmic reticulum (agranular), golgi apparatus, and lysosomes. The hepatocytes are arranged in stacks of anastomosing plates, separated by an anastomosing

**1. Introduction** 

 \*

Corresponding Author

**1.1 Liver and its physiology** 

