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Many pathological processes including wound healing, chronic inflammation and cancer require angiogenesis, i.e., the formation of new vasculature in the lesions. Accumulating evidence indicates that angiogenesis is crucial for both chronic inflammation and the growth of malignant tumors with the participation of diverse cytokines, chemokines and growth factors. It is nevertheless believed that differences exist in angiogenesis between cancer and chronic inflammatory diseases. The aim of this review is to outline the characteristics of angiogenesis in chronic inflammation and cancer. A better understanding of the angiogenic processes may facilitate the design of more effective therapies for chronic inflammation and cancer.

Background & Objective: EphrinB2 is a novel angiogenic factor. EphrinB2 and its receptor EphB4 express in several kinds of tumor cells,and correlate with tumorigenesis and neoangiogenesis. This study was designed to explore the characteristics of EphB4 and EphrinB2 protein expression in astrocytomas., Methods: Double labelling immunofluorescence was used to detect co-expression of EphB4/EphrinB2 with glial fibrilary acid protein (GFAP)or CD34 protein in 35 fresh glioma specimens, and 2 kinds of human glioma cell lines (CHG-5,and SHG-44)., Results: EphB4/EphrinB2 and CD34 proteins co-expressed in some tumor stromal microvessels, and mainly localizing in endothelial cells. Co-expression of EphB4/EphrinB2 and GFAP proteins was also noticed in tumor cells,and 2 glioma cell lines. In poorly-differentiated SHG-44 cells, the average fluorescence intensity of EphB4 was 72.48+/-33.78,and that of EphrinB2 was 96.80+/-36.98, both higher than those in well-differentiated CHG-5 cells (56.7+/-21.7, and 53.6+/-18.8). But the green fluorescence intensity of GFAP in SHG-44 cells was 22.3+/-15.3, while in CHG-5 cells was 47.5+/-16.7., Conclusion: Expressions of EphB4 and EphrinB2 proteins may be related to differentiation degree of tumor cells.

Objective: To investigate the biological effects of ectopic overexpression of glial fibrillary acidic protein (GFAP) in human malignant glioma cell line, and to explore new method of differentiation induction gene therapy for gliomas., Methods: A eukaryotic expression vector containing 1.1 kb GFAP cDNA fused with green fluorescent protein (GFP) gene, pIRGFP-GFAP, was transfected into human SHG-44 glioma cell line by lipofectamine. The expression of GFAP/GFP gene and their proteins were detected by fluorescent real-time monitoring, in situ hybridization, Western blot and immunocytochemistry. Flow cytometry, soft agar colony formation and other methods were used to measure the effects of exogenous GFAP expression on cell cycle progression, morphology and growth features of the transfected glioma cells., Results: The expressions of GFAP mRNA and its protein were markedly increased in SHG-44 cells upon stable transfection with pIRGFP/GFAP vector. Profound morphological changes in these cells were also observed, including the formation of abundant, stellate and thin cytoplasmic processes and a reduction of atypia. Cell proliferation rate and its tumorigenecity on soft agar were markedly reduced. In addition, cell cycle analysis revealed a percentage decrease of cell populations at G0/G1 and G2/M phases., Conclusions: Ectopic overexpression of GFAP gene could significantly suppress the growth of SHG-44 malignant glioma cells along with an induction of differentiation. These results imply that forced over-expression of GFAP gene may provide a new strategy for glioma therapy.

Objective: To clarify the clinicopathologic significance of immunohistochemistry for proliferative activity and oncoprotein expression in astrocytic tumors., Study Design: Ninety-seven cases of brain astrocytic tumors with histologic grading and follow-up data were investigated with immunohistochemistry and image analyzer to detect the expression of proliferating cell nuclear antigen (PCNA), silver-binding nucleolar organizer regions (AgNORs) and several oncoproteins., Results: PCNA was significantly related to AgNORs, grading and prognosis of astrocytomas. The frequency of mutant p53 protein expression was higher in grade 2-4 astrocytomas than in grade 1. Epidermal growth factor (EGF) (37.1%), EGF receptor (83.5%) and p21ras (42.3%) expression levels were related to neither the grade nor prognosis of the tumors. The positive ratios of p53 antibodies were higher in grades 2-4 than in grade 1, and the intensities correlated with PCNA but not with prognosis., Conclusion: Aberrations of c-erbB-2, p21ras, EGF and EGF receptor might be early events in the initiation and progression of astrocytomas, whereas p53 overexpression is involved in all the stages. Immunohistochemical detection had no prognostic value. PCNA could be important to the evaluation of astrocytoma malignancy.

Objective: To investigate the correlation of angiogenic factor expression levels with the degrees of malignancy and vascularity and their clinicopathologic significance in astrocytomas., Study Design: Factor VIII-related antigen (FVIII-RAg) was used as the marker of endothelia and basic fibroblast growth factor (bFGF); FGF receptor (FGFR)-1 and vascular endothelial growth factor (VEGF) were qualitatively and quantitatively detected with immunohistochemistry and image analysis in 61 brain astrocytomas. The correlation with tumor grades, angiogenesis and prognosis was studied., Results: Measurement of FVIIIRAg expression could describe endothelial proliferation and vascularity, which were related to grade of tumor and prognosis. bFGF and VEGF expression levels in neoplastic astrocytes and endothelia were significantly different in various grades of astrocytoma. These angiogenic factors affected the positive reaction areas and integral optical densities of FVIII-RAg as well as survival time. In contrast, the expression of FGFR-1 was related to neither bFGF nor FVIIIRAg and had no significant effect on tumor malignancy., Conclusion: Positive regulation by bFGF and autocrine/paracrine VEGF contributes to the growth and angiogenesis of astrocytomas. Measurement of endothelial cell proliferation with FVIIIRAg in tumor stroma and quantitative detection of angiogenic factor levels in neoplastic cells had prognostic value in brain astrocytomas. The results also indicate that inhibiting bFGF and VEGF expression and/or blocking their effects could be a very useful therapeutic strategy for malignant gliomas.

The localization of S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin as well as the relations between immunohistochemical reactions, grading and prognoses in 243 gliomas were investigated. In astrocytomas, both GFAP and S-100 protein were decreased along with the increase of tumor grades while the vimentin content was coincidently increased. The intensity of GFAP were negatively related to that of vimentin. Typical neoplastic oligodendroglial cells were known to be devoid of glial filaments and negative to GFAP and vimentin, anyhow, in the sporadic tumor cells, positive reaction to both GFAP and vimentin were identified, and these cells were considered to be either the astrocytes or the transitional cells between astrocytes and oligodendrocytes. Difference of the survival rates in cases with various gradings or intensities against S-100 protein and GFAP stainings were noticed. The results suggested that vimentin and GFAP may exist either independently or coexist synchronously in the astrocytomas as the markers, expressing the anaplasia stages of astrocytes. S-100 protein is considered to be an important indicator for both differentiation and prognosis of this tumor.