There have been considerable recent advances towards a better understanding of the complex cellular and molecular network underlying liver fibrogenesis. Recent data indicate that the termination of fibrogenic processes and the restoration of deficient fibrolytic pathways may allow the reversal of advanced fibrosis and even cirrhosis. Therefore, efforts have been made to better clarify the cellular and molecular mechanisms that are involved in liver fibrosis. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis, complemented by other sources of matrix-producing cells, including portal fibroblasts, fibrocytes and bone marrow-derived myofibroblasts. These cells converge in a complex interaction with neighboring cells to provoke scarring in response to persistent injury. Defining the interaction of different cell types, revealing the effects of cytokines on these cells and characterizing the regulatory mechanisms that control gene expression in activated HSCs will enable the discovery of new therapeutic targets. Moreover, the characterization of different pathways associated with different etiologies aid in the development of disease-specific therapies. This article outlines recent advances regarding the cellular and molecular mechanisms involved in liver fibrosis that may be translated into future therapies. The pathogenesis of liver fibrosis associated with alcoholic liver disease, non-alcoholic fatty liver disease and viral hepatitis are also discussed to emphasize the various mechanisms involved in liver fibrosis.

Conclusions-These findings support the suggestion that MVD is a reliable prognostic marker in SCC of the oesophagus. Moreover, MCD may have a role in the angiogenesis of these tumours and might be responsible for their aggressive behaviour. (J Clin Pathol 2001;54:940-944)

Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis.

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Recently, considerable attention has been focused on the role of the small heat-shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis.