Expression of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma: Correlation with Radiologic Findings
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Angiogenesis is the process whereby new blood vessels develop from the preexisting vasculature. It takes place physiologically during embryonic development, during the normal growth of tissues and the wound healing, and during the female reproductive cycle (i.e., ovulation, menstruation, and placental development) as well as during the pathologic growth and metastatic spread of malignant neoplasms (Folkman, 1971). A variety of humoral agents need to be activated to generate a neovascular blood supply or angiogenesis in the human body, and vascular endothelial growth factor (VEGF) is one of the most important humoral agents to be activated to ensure the growth of the vascular endothelium.
Various types of hepatocellular nodules with malignant potential are known to develop in livers with chronic liver damage: they are large regenerative nodules, low-grade dysplastic nodules, high-grade dysplastic nodules, well-differentiated hepatocellular carcinoma (HCC), and moderately or poorly differentiated HCC (International Working Party, 1995). In the process of HCC development, the expression of proangiogenetic factors such as VEGF appears to play an important role. The expression of this factor in HCC tissues has been considered to be associated with tumor size or histological tumor grade (Yamaguchi et al., 1998). Even in the nontumorous liver parenchyma, VEGF is expressed by sinusoidal endothelial cells and hepatocytes (Yamane et al., 1994).
KeywordsDysplastic Nodule Hepatic Nodule Surrounding Liver Arterial Portography Hepatocellular Nodule
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- El-Assal, O.N., Yamanoi, A., Soda, Y., Yamaguchi, M., Igarashi, M., Yamamoto, A., Nabika, T., and Nagasue, N. 1998. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology 27: 1554–1562.PubMedCrossRefGoogle Scholar
- Hayashi, M., Matsui, O., Ueda, K., Kawamori, Y., Kadoya, M., Yoshikawa, J., Gabata, T., Takashima, T., Nonomura, A., and Nakanuma, Y. 1999. Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium. Am. J. Roentgenol. 172: 969–976.Google Scholar
- International Working Party. 1995. Terminology of nodular hepatocellular lesions. Hepatology 22: 983–993.Google Scholar
- Jeng, K.S., Sheen, I.S., Wang, Y.C., Gu, S.L., Chu, C.M., Shih, S.C., Wang, P.C., Chang, W.H., and Wang, H.Y. 2004. Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection? World J. Gastroenterol. 10: 676–681.PubMedGoogle Scholar
- Kanematsu, M., Hoshi, H., Imaeda, T., Murakami, T., Inaba, Y., Yokoyama, R., and Nakamura, H. 1997. Detection and characterization of hepatic tumors: value of combined helical CT hepatic arteriography and CT during arterial portogra-phy. Am. J. Roentgenol. 168: 1193–1198.Google Scholar
- Kanematsu, M., Osada, S., Amaoka, N., Goshima, S., Kondo, H., Nishibori, H., Kato, H., Matsuo, M., Yokoyama, R., Hoshi, H., and Moriyama, N. 2004b. Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver: correlation with angi-ographically assisted CT. Am. J. Roentgenol. 183: 1585–1593.Google Scholar
- Kanematsu, M., Osada, S., Amaoka, N., Goshima, S., Kondo, H., Kato, H., Nishibori, H., Yokoyama, R., Hoshi, H., and Moriyama, N. 2005. Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver and correlation with MRI findings. Am. J. Roentgenol. 184: 832–841.Google Scholar
- Kwak, B.K., Shim, H.J., Park, E.S., Kim, S.A., Choi, D., Lim, H.K., Park, C.K., Chung, J.W., and Park, J.H. 2001. Hepatocellular carcinoma: correlation between vascular endothelial growth factor level and degree of enhancement by multiphase contrast-enhanced computed tomography. Invest. Radiol. 36: 487–492.PubMedCrossRefGoogle Scholar
- Mise, M., Arii, S., Higashituji, H., Furutani, M., Niwano, M., Harada, T., Ishigami, S., Toda, Y., Nakayama, H., Fukumoto, M., Fujita, J., and Imamura, M. 1996. Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumors. Hepatology 23: 455–464.PubMedCrossRefGoogle Scholar
- Monacci, W.T., Merrill, M.J., and Oldfield, E.H. 1993. Expression of vascular permeability factor/vascular endothelial factor in normal rat tissues. Am. J. Physiol. 264: 995–1002.Google Scholar
- Morgan, B., Thomas, A.L., Drevs, J., Hennig, J., Buchert, M., Jivan, A., Horsfield, M.A., Mross, K., Ball, H.A., Lee, L., Mietlowski, W., Fuxuis, S., Unger, C., O'Byrne, K., Henry, A., Cherryman, G.R., Laurent, D., Dugan, M., Marme, D., and Steward, W.P. 2003. Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK222584, an inhibitor of the vascular endothe-lial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two phase I studies. J. Clin. Oncol. 21: 3955–3964.PubMedCrossRefGoogle Scholar
- Scarfo, L.M., Weller, P.F., and Farber, H.W. 2001. Induction of endothelial cell cytoplasmic lipid bodies during hypoxia. Am. J. Physiol. Heart Circ. Physiol. 280: 294–301.Google Scholar
- Semelka, R.C., Shoenut, J.P., Kroeker, M.A., Greenberg, H.M., Simm, F.C., Minuk, G.Y., Kroeker, R.M., and Micflikier, A.B. 1992. Focal liver disease: comparison of dynamic contrast-enhanced CT and T2-weighted fat-suppressed, FLASH, and dynamic gadolinium-enhanced MR imaging at 1.5 T. Radiology 184: 687–694.PubMedGoogle Scholar
- Suzuki, K., Hayashi, N., Miyamoto, Y., Yamamoto, M., Ohkawa, K., Ito, Y., Sasaki, Y., Yamaguchi, Y., Nakase, H., Noda, K., Enomoto, N., Arai, K., Yamada, Y., Yoshihara, H., Tujimura, T., Kawano, K., Yoshikawa, K., and Kamada, T. 1996. Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res. 56: 3004–3009.PubMedGoogle Scholar
- Viglietto, G., Maglione, D., Rambaldi, M., Cerutti, J., Romano, A., Trapasso, F., Fedele, M., Ippolito, P., Chiappetta, G., and Botti, G. 1995. Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11: 1569–1579.PubMedGoogle Scholar
- Yamane, A., Seetharam, L., Yamaguchi, S., Gotoh, N., Takahashi, T., Neufeld, G., and Shibuya, M. 1994. A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1). Oncogene 9: 2683–2690.PubMedGoogle Scholar