Essay Example on The main findings of our study are that in pediatric patients with HLB and HCC

1 the peritumoral DRs positive for paracrine factors such as VEGF DRs VEGFD DRs ANGPT1 DRs and PDGFC DRs stained with EpCAM are observed in HBL and HCC 2 ANGPT1 DRs correlates closely with Ki67 DRs in HBL 3 Angiogenic maker expression of CD34 in DRs area is positively correlated with number of CD34 vessel and area of CD34 in intratumoral area in pediatric patient with liver tumors 4 There are positive correlation within DRs positive for paracrine factors Effects of age preoperative chemotherapy and gender of pediatric patients on DRs positive for paracrine factors are identified in this study 5 AS for relationship between DR for PF and tumor grade In the course of chronic cholestatic liver diseases cholangiocyte proliferation aims to repair and compensate for the anatomic and functional loss of injured ducts 1 In fact proliferating cholangiocytes display enhanced secretory activities by which they compensate for the impaired function of injured cells 2 4 In these pathologies HPC activation contributes to DRs 5 6 DRs is thought to arise due to a complex interaction between hepatocytes hepatic progenitor cells hepatic stellate cells and extracellular matrix as well as inflammatory cells and endothelial cells 7 In liver diseases condition it is known that DRs occurs in cholestatic diseases in inflammatory diseases and in conditions with massive loss of parenchyma 8 9 Furthermore a study suggests an important role of VEGFs in support the expansion of HPC niche by an autocrine and paracrine effects on neighboring cells stimulating the proliferation of HPCs and endothelial cells 11 

These aspects could have important implication in liver diseases processes and carcinogenesis In addition It is reported that the positive association of ductular reactions with poor prognosis of adult HCC 12 Based on these reports we hypothesized that DRs which express paracrine factors are correlated with angiogenesis and tumoral proliferation According to recent studies PDGF C may use paracrine mechanisms to modulate endothelial cells and perhaps other non parenchymal cells including hepatic satellite cells by inducing other growth factors that act on these liver cells 13 14 Our results show that PDGFC DRs is positively correlated with proliferation of tumor cell in overall liver tumor group while there are no correlations in each HBL and HCC Table 3 It remains to be determined whether PDGF C acts directly or through paracrine effects to induce progression of tumors in this study In adults sustained angiogenesis is pathological and characteristic of malignancy where the formation of a neovasculature is essential for tumor growth and development 15 17 One of the signals linking ductal and arterial development in the liver is VEGF which cooperates with ANGPT 1 18 Besides two studies previously reported that VEGF D showed angiogenic activity on endothelial cells as well as mitogenic and motogenic activity on tumor derived cells and suggested VEGF D can be a c fos effector for tumor malignancy 19 20 However relationships are still not clear among these angiogenic factors DRs and liver tumors in pediatric patients 

In this study although there are no significant correlation between VEGF DRs and perspectives of angiogenesis and proliferation of tumor cells we observed that the group of VEGFD DRs above 50 show higher the number of vessel with CD34 positive staining in peritumoral area compared to the group of VEGFD DRs below 50 The group of ANGPT 1 DRs above 50 show a greater area of CD34 positive staining in peritumoral area compare to the group of ANGPT 1 DRs below 50 Table 6 Moreover ANGPT 1 DRs in HCC the group of ANGPT 1 DRs above 50 show a greater area of Ki67 positive staining in intratumoral area compare to the group have ANGPT 1 DRs below 50 Nevertheless the negative correlations between ANGPT 1 DRs and area of CD34 positive staining in peritumoral area between ANGPT 1 DRs and area of CD34 positive staining in intratumoral area are identified as well in this study Table 4 Although the expression of ANGPTs in intratumoral area was not tested in this study it also has been reported that the expression of ANGPTs is greater in HCC tissues than in noncancerous liver tissues and it is more intense in hypervascular HCC than in HCC that does not show hypervascularity ANGPT 2 expression is upregulated with tumor dedifferentiation 

These results suggest it is the balance of ANGPT 1 and ANGPT 2 expression that regulates the vascular development of HCC 21 22 Therefore to clarify the relationships among ANGPT 1 DRs and angiogenesis and proliferation of tumor cell it is needed to investigate that the level of ANGPT 1 and ANGPT 2 expression in both peritumoral DRs and intratumoral area for future work Finally cholangiocyte proliferation occurs virtually in all pathologic conditions of liver injury where it is associated with inflammation regeneration and repair thus conditioning the evolution of liver damage Interestingly proliferating cholangiocytes secrete different cytokines growth factors neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells 10 Our finding positive correlation between Ki67 DRs and proliferation in intratumoral area in HBL Table 3 imply these perspective of DRs in status of liver damage including liver tumors In conclusion our study demonstrates that the peritumoral DRs positive for paracrine factors are observed in HBL and HCC and positive correlations within DRs positive for paracrine factors are identified It is also supported that the DRs correlated closely with severity of fibrosis and Inflammation in pediatric patients with liver tumor and grade of tumor Therefore our results suggest DRs positive for paracrine factors play a potential role in liver diseases and tumor progression as a paracrine manner in pediatric patients with liver tumors