Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: An immunohistochemical study

Chow, Nan Haw; Hsu, Ping I.; Lin, Xi Zhang; Yang, Hsiao Bai; Chan, Shih Huang; Cheng, Kuo-Sheng; Huang, Shih Ming; Su, Ih Jen

doi:10.1016/s0046-8177(97)90179-9

Cited by 107 publications

(55 citation statements)

References 28 publications

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“…[32][33][34] The hepatic VEGF level in chronic liver diseases has been shown to increase with disease progression. 35,36 Recently, it has been reported that VEGF expression was significantly increased in the experimental liver fibrosis model. 37 VEGF stimulated HSC activation and sinusoidal capillarization.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

et al. 2001

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The renin-angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor ␤ 1 (TGF-␤ 1 ) expression via AT-II type 1 receptor (AT 1 -R) in vitro. The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT 1 -R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibrosis development. These inhibitory effects of PE and CA were also found in the on-going liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the ␣ smooth muscle actin (␣-SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF-␤ 1 protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT-II increased the TGF-␤ 1 mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT-II and AT 1 -R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti-liver fibrosis therapy. (HEPATOLOGY 2001; 34:745-750.)

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Section: Discussionmentioning

confidence: 99%

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

et al. 2001

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“…Therefore, the VEGF expression sites in HCC tissues are thought to be evaluable in immunohistochemical study alone, though there has been only one publication on this issue. 47 The present study drew special attention to the relationship between the histological grades of HCC and VEGF, and we examined VEGF expression in various types of HCCs, including small-sized and well-differentiated HCCs, sarcomatous HCCs, and single HCC nodules with histological variety, which all have not been previously investigated in detail. HCCs that consisted of cancerous tissues of two different histological grades in a single tumor nodule would be best suited to the studies on the relationship between histological grades and VEGF expression.…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor in human hepatocellular carcinoma

et al. 1998

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RIN YAMAGUCHI, HIROHISA YANO, AKIHIRO IEMURA, SACHIKO OGASAWARA, MAKOTO HARAMAKI, AND MASAMICHI KOJIRO Vascular endothelial growth factor (VEGF) is thought to take an important role in tumor angiogenesis. The present study examined VEGF expression immunohistochemically in hepatocellular carcinomas (HCCs) in various histological grades and sizes. In HCCs that were composed of cancerous tissues of single histological grade, VEGF expression was the highest in well-differentiated HCCs, followed by moderately differentiated HCCs, and then poorly differentiated HCCs. VEGF positivity gradually decreased with the increase in tumor size. In the nodules larger than 3.0 cm, 36.8% were VEGF-negative. In HCCs consisting of cancerous tissues of two different histological grades, the expression was less intensive in the higher-grade HCC component. VEGF was not expressed in sarcomatous areas, while VEGF was expressed in the surrounding HCC tissues. The expression was also remarkable in the noncancerous tissues in which inflammatory cell infiltration was apparent. VEGF expression was also examined in six HCC cell lines. 5,6 and angiogenin 7 are known to promote tumor angiogenesis, and growth factors are thought to be the most important. Vascular endothelial growth factor (VEGF) was first described by Senger et al. 8 and Ferrara et al. 9 VEGF is the most intriguing factor in regard to tumor angiogenesis. 8,10 It selectively acts on the endothelial cells that express VEGF receptor, i.e., fms-like tyrosine kinase 1 (flt-1) or KDR/flk-1, 11,12 whereas the other angiogenesis factors, such as basic fibroblast growth factor (bFGF), which does not possess signal peptide, show no specificity. 13 There are four known splicing variants of human VEGF, i.e., VEGF 121 , VEGF 165 , VEGF 189 , and VEGF 206 . They possess signal peptide. VEGF 121 and VEGF 165 are exported from the cells, while VEGF 189 and VEGF 206 are predominantly cell-associated. 14,15 VEGF has been reported to possess various biological activities, e.g., it increases vascular permeability, 8,15 exerts mitogenic effects on endothelial cells, 9,15 stimulates the proliferation and migration of endothelial cells, 16,17 induces the expression of interstitial collagenase, 16 and promotes macrophage migration. 18 Its expression in mRNA level has been confirmed in various organs, such as the lung, kidney, adrenal gland, heart, liver, and gastric mucosa; and in malignant tumors, brain tumor, bladder cancer, kidney cancer, ovarian cancer, gastric cancer, colon cancer, breast cancer, and hepatocellular carcinoma (HCC). [19][20][21][22][23][24][25][26][27] HCC is generally considered as a hypervascular tumor, but its vascularity varies widely according to tumor size and histological grade. In small-sized and well-differentiated HCCs, artery-like vessels are not well developed, 28,29 and capillarization of blood space (sinusoid of HCC) is incomplete. [30][31][32] These HCCs are often undetectable by angiography. [32][33][34] On the other hand, in moderately or poorly differentiated HCC...

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“…In total, there were four tissue OS studies (Chow et al, 1997;Jeng et al, 2004a;Deli et al, 2005;Sheen et al, 2005), six tissue DFS studies (Jeng et al, 2004a;Sheen et al, 2005;Guo et al, 2006;Wada et al, 2006;Zhang et al, 2006;Ho et al, 2007), seven serum OS studies (Poon et al, 2001(Poon et al, , 2004a(Poon et al, , b, 2007Chao et al, 2003;Kim et al, 2004;Jeng et al, 2004b;Treiber et al, 2006), and five serum DFS studies (Poon et al, 2001(Poon et al, , 2007Chao et al, 2003;Jeng et al, 2004b;Treiber et al, 2006). Pooled HRs were then calculated for all groups.…”

Section: Summary Estimates Of Primary Studiesmentioning

confidence: 99%

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

et al. 2009

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Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC. Its overall test performance remains unclear, however. The aim was to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of VEGF as a predictor of survival in patients with treated HCC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios were calculated. A total of 16 studies were included for meta-analysis (8 for tissue and 8 for serum). Methodological analysis indicated a trend for higher study quality with serum studies as compared to tissue-based investigations. Four distinct groups were pooled for analysis: tissue overall survival ( n =251), tissue disease-free survival ( n =413), serum overall survival ( n =579), and serum disease-free survival ( n =439). High tissue VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26–3.68) and disease-free (HR=1.69, 95% CI: 1.23–2.33) survival. Similarly, high serum VEGF levels predicted poor overall (HR=2.35, 95% CI: 1.80–3.07) and disease-free (HR=2.36, 95% CI 1.76–3.16) survival. A high degree of inter-study consistency was present in three of four groups analysed. Tissue and serum VEGF levels appear to have significant predictive ability for estimating overall survival in HCC and may be useful for defining prognosis in HCC.

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Expression of vascular endothelial growth factor in normal liver and hepatocellular carcinoma: An immunohistochemical study

Cited by 107 publications

References 28 publications

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats

Expression of vascular endothelial growth factor in human hepatocellular carcinoma

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

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