This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takano, S. Articles by Nose, T. Search for Related Content PubMed PubMed Citation Articles by Takano, S. Articles by Nose, T.

Concentration of Vascular Endothelial Growth Factor in the Serum and Tumor Tissue of Brain Tumor Patients¹

Department of Neurosurgery, Soujinkai Hospital, 1467 Oka, Fujishiro, Kitasoumagun, Ibaraki 300-15 [S. T., T. M., S. S.]; Division of Neurological Surgery, Tsukuba University School of Medicine, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305 [Y. Y., T. N.]; and Tsukuba Research Laboratory, Toagosei Co., Ltd., 2 Ohkubo, Tsukuba, Ibaraki 300-33 [S. K., H. S.], Japan

Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytoma, low grade astrocytoma, meningioma, malignant lymphoma, and metastatic brain tumor as well as normal brain. VEGF concentration in the tissue of glioblastomas was significantly higher than that in other types of tumors as well as normal brain. Although VEGF concentration of the serum was not correlated with that of the tissue, VEGF concentrations of glioblastoma cyst fluid were 200–300-fold higher than those of serum in the patients. VEGF concentration in the tumors was significantly correlated with the vascularity measured by counting vessels stained with von Willebrand factor antibody. VEGF protein localized to the cytoplasm of tumor cells and vasculature in gliomas, predominantly in the peripheral microvessel "hot spots" as well as around the necrosis in glioblastomas. VEGF immunopositivities were well reflected with VEGF concentration determined by ELISA. VEGF ELISA demonstrated time-dependent increase of the VEGF concentration in the serum-free conditioned medium of various glioma cell lines. The conditioned medium with high VEGF concentration induced endothelial cell migration. These observations suggest that VEGF represents a useful marker and measurable element of glioblastoma angiogenesis. The measurement of VEGF concentration by ELISA in tumor and tumor cyst fluid may allow for the assessment of vascularity in gliomas.

¹ This work was supported in part by Grant-in-Aid 06671372 from the Japanese Ministry of Education, Science, and Culture (to Y. Y.).

² To whom requests for reprints should be addressed.

Received 9/12/95. Accepted 3/ 1/95.

This article has been cited by other articles:

				E. Karathanasis, S. Suryanarayanan, S. R. Balusu, K. McNeeley, I. Sechopoulos, A. Karellas, A. V. Annapragada, and R. V. Bellamkonda Imaging Nanoprobe for Prediction of Outcome of Nanoparticle Chemotherapy by Using Mammography Radiology, February 1, 2009; 250(2): 398 - 406. [Abstract] [Full Text] [PDF]

				P. J. Dickinson, B. K. Sturges, R. J. Higgins, B. N. Roberts, C. M. Leutenegger, A. W. Bollen, and R. A. LeCouteur Vascular Endothelial Growth Factor mRNA Expression and Peritumoral Edema in Canine Primary Central Nervous System Tumors Vet. Pathol., March 1, 2008; 45(2): 131 - 139. [Abstract] [Full Text] [PDF]

				F.J. Wippold II, M. Lammle, F. Anatelli, J. Lennerz, and A. Perry Neuropathology for the Neuroradiologist: Palisades and Pseudopalisades AJNR Am. J. Neuroradiol., November 1, 2006; 27(10): 2037 - 2041. [Abstract] [Full Text] [PDF]

				D. B. Kirpotin, D. C. Drummond, Y. Shao, M. R. Shalaby, K. Hong, U. B. Nielsen, J. D. Marks, C. C. Benz, and J. W. Park Antibody Targeting of Long-Circulating Lipidic Nanoparticles Does Not Increase Tumor Localization but Does Increase Internalization in Animal Models. Cancer Res., July 1, 2006; 66(13): 6732 - 6740. [Abstract] [Full Text] [PDF]

				D. A. Reardon, J. A. Quinn, J. J. Vredenburgh, S. Gururangan, A. H. Friedman, A. Desjardins, S. Sathornsumetee, J. E. Herndon II, J. M. Dowell, R. E. McLendon, et al. Phase 1 Trial of Gefitinib Plus Sirolimus in Adults with Recurrent Malignant Glioma Clin. Cancer Res., February 1, 2006; 12(3): 860 - 868. [Abstract] [Full Text] [PDF]

				Y. Cao, C. I. Tsien, Z. Shen, D. S. Tatro, R. Ten Haken, M. L. Kessler, T. L. Chenevert, and T. S. Lawrence Use of Magnetic Resonance Imaging to Assess Blood-Brain/Blood-Glioma Barrier Opening During Conformal Radiotherapy J. Clin. Oncol., June 20, 2005; 23(18): 4127 - 4136. [Abstract] [Full Text] [PDF]

				B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Neuro-oncol, April 1, 2005; 7(2): 134 - 153. [Abstract] [PDF]

				M. M. Dikov, J. E. Ohm, N. Ray, E. E. Tchekneva, J. Burlison, D. Moghanaki, S. Nadaf, and D. P. Carbone Differential Roles of Vascular Endothelial Growth Factor Receptors 1 and 2 in Dendritic Cell Differentiation J. Immunol., January 1, 2005; 174(1): 215 - 222. [Abstract] [Full Text] [PDF]

				P. Mukherjee, L. E. Abate, and T. N. Seyfried Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors Clin. Cancer Res., August 15, 2004; 10(16): 5622 - 5629. [Abstract] [Full Text] [PDF]

				S. Lu, D. Ahn, G. Johnson, M. Law, D. Zagzag, and R. I. Grossman Diffusion-Tensor MR Imaging of Intracranial Neoplasia and Associated Peritumoral Edema: Introduction of the Tumor Infiltration Index Radiology, July 1, 2004; 232(1): 221 - 228. [Abstract] [Full Text] [PDF]

				Y.-H. Zhou, F. Tan, K. R. Hess, and W. K. A. Yung The Expression of PAX6, PTEN, Vascular Endothelial Growth Factor, and Epidermal Growth Factor Receptor in Gliomas: Relationship to Tumor Grade and Survival Clin. Cancer Res., August 1, 2003; 9(9): 3369 - 3375. [Abstract] [Full Text] [PDF]

				M. L. Falchetti, F. Pierconti, P. Casalbore, N. Maggiano, A. Levi, L. M. Larocca, and R. Pallini Glioblastoma Induces Vascular Endothelial Cells to Express Telomerase in Vitro Cancer Res., July 1, 2003; 63(13): 3750 - 3754. [Abstract] [Full Text] [PDF]

				D. J. Brat and T. B. Mapstone Malignant Glioma Physiology: Cellular Response to Hypoxia and Its Role in Tumor Progression Ann Intern Med, April 15, 2003; 138(8): 659 - 668. [Full Text] [PDF]

				K. L. Jones, H. F. Krous, J. Nadeau, B. Blackbourne, H. R. Zielke, and D. Gozal Vascular Endothelial Growth Factor in the Cerebrospinal Fluid of Infants Who Died of Sudden Infant Death Syndrome: Evidence for Antecedent Hypoxia Pediatrics, February 1, 2003; 111(2): 358 - 363. [Abstract] [Full Text] [PDF]

				S. Takano, K. Tsuboi, A. Matsumura, and T. Nose Anti-vascular endothelial growth factor antibody and nimustine as combined therapy: Effects on tumor growth and angiogenesis in human glioblastoma xenografts Neuro-oncol, January 1, 2003; 5(1): 1 - 7. [Abstract] [PDF]

				B. C. Cooper, J. M. Ritchie, C. L. W. Broghammer, J. Coffin, J. I. Sorosky, R. E. Buller, M. J. C. Hendrix, and A. K. Sood Preoperative Serum Vascular Endothelial Growth Factor Levels: Significance in Ovarian Cancer Clin. Cancer Res., October 1, 2002; 8(10): 3193 - 3197. [Abstract] [Full Text] [PDF]

				T. Morimoto, M. Aoyagi, M. Tamaki, Y. Yoshino, H. Hori, L. Duan, T. Yano, M. Shibata, K. Ohno, K. Hirakawa, et al. Increased Levels of Tissue Endostatin in Human Malignant Gliomas Clin. Cancer Res., September 1, 2002; 8(9): 2933 - 2938. [Abstract] [Full Text] [PDF]

				M. A. Lafleur, M. M. Handsley, V. Knauper, G. Murphy, and D. R. Edwards Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs) J. Cell Sci., January 9, 2002; 115(17): 3427 - 3438. [Abstract] [Full Text] [PDF]

				M. M. Dikov, T. Oyama, P. Cheng, T. Takahashi, K. Takahashi, T. Sepetavec, B. Edwards, Y. Adachi, S. Nadaf, T. Daniel, et al. Vascular Endothelial Growth Factor Effects on Nuclear Factor-{{kappa}}B Activation in Hematopoietic Progenitor Cells Cancer Res., March 1, 2001; 61(5): 2015 - 2021. [Abstract] [Full Text]

				B. A. Teicher, K. Menon, E. Alvarez, E. Galbreath, C. Shih, and M. Faul Antiangiogenic and Antitumor Effects of a Protein Kinase C{beta} Inhibitor in Human T98G Glioblastoma Multiforme Xenografts Clin. Cancer Res., March 1, 2001; 7(3): 634 - 640. [Abstract] [Full Text]

				D. J. Brat and E. G. Van Meir Glomeruloid Microvascular Proliferation Orchestrated by VPF/VEGF : A New World of Angiogenesis Research Am. J. Pathol., March 1, 2001; 158(3): 789 - 796. [Full Text] [PDF]

				L. D. Ke, Y.-X. Shi, S.-A. Im, X. Chen, and W. K. A. Yung The Relevance of Cell Proliferation, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor Production to Angiogenesis and Tumorigenicity in Human Glioma Cell Lines Clin. Cancer Res., June 1, 2000; 6(6): 2562 - 2572. [Abstract] [Full Text]

				B. Almand, J. R. Resser, B. Lindman, S. Nadaf, J. I. Clark, E. D. Kwon, D. P. Carbone, and D. I. Gabrilovich Clinical Significance of Defective Dendritic Cell Differentiation in Cancer Clin. Cancer Res., May 1, 2000; 6(5): 1755 - 1766. [Abstract] [Full Text] [PDF]

				G. Stockhammer, W. Poewe, S. Burgstaller, F. Deisenhammer, A. Muigg, S. Kiechl, E. Schmutzhard, H. Maier, S. Felber, P. Schumacher, et al. Vascular endothelial growth factor in CSF: A biological marker for carcinomatous meningitis Neurology, April 25, 2000; 54(8): 1670 - 1676. [Abstract] [Full Text] [PDF]

				N. Sato, G. Sze, I. A. Awad, C. M. Putman, T. Shibazaki, and K. Endo Parenchymal Perianeurysmal Cystic Changes in the Brain: Report of Five Cases Radiology, April 1, 2000; 215(1): 229 - 233. [Abstract] [Full Text]

				L. Hefler, C. Tempfer, A. Obermair, K. Frischmuth, G. Sliutz, A. Reinthaller, S. Leodolter, and C. Kainz Serum Concentrations of Vascular Endothelial Growth Factor in Vulvar Cancer Clin. Cancer Res., October 1, 1999; 5(10): 2806 - 2809. [Abstract] [Full Text] [PDF]

				D. I. Gabrilovich, T. Ishida, S. Nadaf, J. E. Ohm, and D. P. Carbone Antibodies to Vascular Endothelial Growth Factor Enhance the Efficacy of Cancer Immunotherapy by Improving Endogenous Dendritic Cell Function Clin. Cancer Res., October 1, 1999; 5(10): 2963 - 2970. [Abstract] [Full Text] [PDF]

				M. D. Balbay, C. A. Pettaway, H. Kuniyasu, K. Inoue, E. Ramirez, E. Li, I. J. Fidler, and C. P. N. Dinney Highly Metastatic Human Prostate Cancer Growing within the Prostate of Athymic Mice Overexpresses Vascular Endothelial Growth Factor Clin. Cancer Res., April 1, 1999; 5(4): 783 - 789. [Abstract] [Full Text] [PDF]

				P. Salven, A. Orpana, and H. Joensuu Leukocytes and Platelets of Patients with Cancer Contain High Levels of Vascular Endothelial Growth Factor Clin. Cancer Res., March 1, 1999; 5(3): 487 - 491. [Abstract] [Full Text] [PDF]

				J.-P. Theurillat, J. Hainfellner, A. Maddalena, J. Weissenberger, and A. Aguzzi Early Induction of Angiogenetic Signals in Gliomas of GFAP-v-src Transgenic Mice Am. J. Pathol., February 1, 1999; 154(2): 581 - 590. [Abstract] [Full Text] [PDF]

				Y. S. Lin, C. Nguyen, J.-L. Mendoza, E. Escandon, D. Fei, Y. G. Meng, and N. B. Modi Preclinical Pharmacokinetics, Interspecies Scaling, and Tissue Distribution of a Humanized Monoclonal Antibody against Vascular Endothelial Growth Factor J. Pharmacol. Exp. Ther., January 1, 1999; 288(1): 371 - 378. [Abstract] [Full Text]

				D. Gabrilovich, T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, and D. P. Carbone Vascular Endothelial Growth Factor Inhibits the Development of Dendritic Cells and Dramatically Affects the Differentiation of Multiple Hematopoietic Lineages In Vivo Blood, December 1, 1998; 92(11): 4150 - 4166. [Abstract] [Full Text] [PDF]

				J. Ambati, K. V. Chalam, D. K Chawla, C. T. D'Angio, E. G. Guillet, S. J. Rose, R. E. Vanderlinde, and B. K. Ambati Elevated {gamma}-Aminobutyric Acid, Glutamate, and Vascular Endothelial Growth Factor Levels in the Vitreous of Patients With Proliferative Diabetic Retinopathy Arch Ophthalmol, September 1, 1997; 115(9): 1161 - 1166. [Abstract] [PDF]

				K. Sato, M. Miyakawa, N. Onoda, H. Demura, T. Yamashita, M. Miura, T. Kasajima, K. Yamazaki, and T. Obara Increased Concentration of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Cyst Fluid of Enlarging and Recurrent Thyroid Nodules J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1968 - 1973. [Abstract] [Full Text] [PDF]

				M. S. Pepper Manipulating Angiogenesis: From Basic Science to the Bedside Arterioscler Thromb Vasc Biol, April 1, 1997; 17(4): 605 - 619. [Abstract] [Full Text]