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Expression of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma and the Surrounding Liver: Correlation with Angiographically Assisted CT

Masayuki Kanematsu1,2, Shinji Osada3, Nozomi Amaoka3, Satoshi Goshima1, Hiroshi Kondo1, Hironori Nishibori1, Hiroki Kato1, Masayuki Matsuo1, Ryujiro Yokoyama2, Hiroaki Hoshi1 and Noriyuki Moriyama4

1 Department of Radiology, Gifu University School of Medicine, Gifu 501-1193, Japan.
2 Department of Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193, Japan.
3 Department of Surgical Oncology, Gifu University School of Medicine, Gifu 501-1193, Japan.
4 Department of Diagnostic Radiology, National Cancer Center Hospital, Tsukiji 104-0045, Japan.



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Fig. 1. Schematic shows electrophoretic bands in Western blotting and their corresponding electrophoretic histograms with different concentrations of vascular endothelial growth factor (VEGF) solution in control study. Concentration of VEGF solution and area under histogram showed very high direct correlation (r = 0.97, p < 0.0001).

 


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Fig. 2A. Correlation between size of hepatocellular carcinoma (HCC) in millimeters and vascular endothelial growth factor (VEGF) expression index of HCC. Scattergram shows moderate direct correlation (r = 0.51, p = 0.021) between size of HCC in millimeters and VEGF expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively.

 


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Fig. 2B. Correlation between size of hepatocellular carcinoma (HCC) in millimeters and vascular endothelial growth factor (VEGF) expression index of HCC. Scattergram shows high direct correlation (r = 0.66, p = 0.0015) between size of HCC in millimeters and difference in VEGF expression index.

 


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Fig. 3A. Correlation between contrast-enahancement index of hepatocellular carcinoma (HCC) and vascular endothelial growth factor (VEGF) expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively. Scattergram shows moderate inverse correlation (r = –0.57, p = 0.017) between contrast enhancement indexes of HCCs on CT hepatic arteriography and VEGF of HCC.

 


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Fig. 3B. Correlation between contrast-enahancement index of hepatocellular carcinoma (HCC) and vascular endothelial growth factor (VEGF) expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively. Scattergram shows high inverse correlation (r = –0.80, p = 0.0001) between contrast enhancement indexes of HCCs on CT hepatic arteriography and difference in VEGF expression index.

 


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Fig. 3C. Correlation between contrast-enahancement index of hepatocellular carcinoma (HCC) and vascular endothelial growth factor (VEGF) expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively. Scattergram shows marginal moderate direct correlation (r = 0.44, p = 0.076) between contrast enhancement indexes of surrounding liver on CT hepatic arteriography and VEGF expression index of surrounding liver.

 


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Fig. 3D. Correlation between contrast-enahancement index of hepatocellular carcinoma (HCC) and vascular endothelial growth factor (VEGF) expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively. Scattergram shows high inverse correlation (r = –0.71, p = 0.0013) between contrast enhancement index of surrounding liver on CT hepatic arteriography and difference in VEGF expression index.

 


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Fig. 3E. Correlation between contrast-enahancement index of hepatocellular carcinoma (HCC) and vascular endothelial growth factor (VEGF) expression index of HCC. Straight line and two curves in graph indicate regression line and 95% confidence interval, respectively. Scattergram shows moderate inverse correlation (r = –0.51, p = 0.023) between contrast enhancement indexes of HCCs on CT during arterial portography and difference in VEGF expression index.

 


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Fig. 4A. 74-year-old woman with moderately differentiated 2-cm hepatocellular carcinoma (HCC) showing weak vascular endothelial growth factor (VEGF) expression in right inferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. CT hepatic arteriogram shows intense homogeneous hepatic artery enhancement in HCC (arrow).

 


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Fig. 4B. 74-year-old woman with moderately differentiated 2-cm hepatocellular carcinoma (HCC) showing weak vascular endothelial growth factor (VEGF) expression in right inferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. Schematic shows electrophoretic bands and their corresponding histograms. For calibration, 1.25 mg/mL of VEGF solution was used. Areas of histogram were 480 pixels for calibration band, 761 pixels for HCC band, and 2,375 pixels for surrounding liver band. VEGF expression index was 1.59 in HCC and 4.95 in surrounding liver, giving difference in VEGF expression index of –3.36. Note that electrophoretic peak adjacent to that of liver is due to expression of irregular protein.

 


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Fig. 5A. 64-year-old man with well-differentiated 4.6-cm hepatocellular carcinoma (HCC) showing weak vascular endothelial growth factor (VEGF) expression in right posteroinferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was B. CT hepatic arteriogram shows moderate hepatic artery enhancement with mild heterogeneity in HCC (arrow).

 


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Fig. 5B. 64-year-old man with well-differentiated 4.6-cm hepatocellular carcinoma (HCC) showing weak vascular endothelial growth factor (VEGF) expression in right posteroinferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was B. Schematic shows electrophoretic bands and their corresponding histograms. For calibration, 1.25 mg/mL of VEGF solution was used. Areas of histogram were 902 pixels for calibration band, 1,101 pixels for HCC band, and 1,638 pixels for surrounding liver band. VEGF expression index was 1.22 in HCC and 1.82 in surrounding liver, giving difference in VEGF expression index of –0.60. Note that electrophoretic peaks adjacent to those of HCC and liver are due to expression of irregular protein.

 


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Fig. 6A. 77-year-old woman with moderately differentiated 6.8-cm hepatocellular carcinoma (HCC) showing moderate vascular endothelial growth factor (VEGF) expression in lateral segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. CT hepatic arteriogram shows moderate hepatic artery enhancement with moderate heterogeneity in HCC (arrow).

 


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Fig. 6B. 77-year-old woman with moderately differentiated 6.8-cm hepatocellular carcinoma (HCC) showing moderate vascular endothelial growth factor (VEGF) expression in lateral segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. Schematic shows electrophoretic bands and their corresponding histograms. For calibration, 1.25 mg/mL of VEGF solution was used. Areas of histogram were 312 pixels for calibration band, 1,654 pixels for HCC band, and 738 pixels for surrounding liver band. VEGF expression index was 5.30 in HCC and 2.37 in surrounding liver, giving difference in VEGF expression index of 2.93. Note that electrophoretic peak adjacent to that of liver is due to expression of irregular protein.

 


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Fig. 7A. 57-year-old man with poorly differentiated 5.8-cm hepatocellular carcinoma (HCC) showing strong vascular endothelial growth factor (VEGF) expression, dominantly in anteroinferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. CT hepatic arteriogram shows mild hepatic artery enhancement with moderate heterogeneity in HCC (arrow). Note that central area of HCC exhibits water density with no enhancement, presumably due to tumor necrosis.

 


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Fig. 7B. 57-year-old man with poorly differentiated 5.8-cm hepatocellular carcinoma (HCC) showing strong vascular endothelial growth factor (VEGF) expression, dominantly in anteroinferior segment of liver with chronic type C viral hepatitis. Child-Pugh grade was A. Schematic shows electrophoretic bands and their corresponding histograms. For calibration, 1.25 mg/mL of VEGF solution was used. Areas of histogram were 376 pixels for calibration band, 3,485 pixels for HCC band, and 1,395 pixels for surrounding liver band. VEGF expression index was 9.27 in HCC and 3.71 in surrounding liver, giving difference in VEGF expression index of 5.56. Note that electrophoretic peaks adjacent to those of HCC and liver are due to expression of irregular protein.

 

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