© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 447-454, Copyright © 1998 by Oxford University Press
J Yoneda, H Kuniyasu, MA Crispens, JE Price, CD Bucana and IJ Fidler
BACKGROUND: By the time patients are diagnosed with ovarian carcinoma,
peritoneal dissemination of the tumor often has occurred. The progressive
growth and spread of ovarian carcinoma depend, in part, on the formation of
an adequate blood supply. We determined whether the expression of genes
that regulate distinct steps in angiogenesis (i.e., the formation of new
blood vessels) was associated with the pattern and progressive growth of
human ovarian carcinomas implanted in the peritoneal cavity of nude mice.
METHODS: Five different human ovarian carcinomas were injected individually
into the peritoneal cavity of female NCr-nu/nu nude mice. The expression of
basic fibroblast growth factor, vascular endothelial growth factor/vascular
permeability factor (VEGF/VPF), interleukin 8 (IL-8), and collagenase type
IV (MMP-2 [matrix metalloproteinase-2] and MMP-9) was determined by
northern blot analysis, in situ hybridization of messenger RNA, and
immunohistochemical analysis. Blood vessel distribution and density,
macrophage infiltration pattern, and stromal reaction were determined by
immunohistochemical analysis with specific antibodies. RESULTS: Three of
the carcinomas produced both solid lesions and ascitic tumors, whereas the
remaining two produced only solid lesions. Two of the carcinomas produced
rapidly progressive disease, two produced slow disease, and one produced
intermediate disease. The formation of ascites was directly associated with
expression of VEGF/ VPF, and survival was inversely associated with
expression of IL-8. In rapidly growing tumors, the number of blood vessels
was high throughout the lesion; in contrast, in slow-growing tumors, most
vessels (and infiltrating macrophages) were located at the periphery.
CONCLUSIONS: The expression of various genes that regulate angiogenesis in
human ovarian carcinomas is associated with the pattern of the disease and
its progression. Therefore, targeting specific genes that regulate
angiogenesis could offer new approaches to the treatment of ovarian cancer.
ARTICLES
Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice
Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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L. Xu and I. J. Fidler Acidic pH-induced Elevation in Interleukin 8 Expression by Human Ovarian Carcinoma Cells Cancer Res., August 1, 2000; 60(16): 4610 - 4616. [Abstract] [Full Text]
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J. A. Belperio, M. P. Keane, D. A. Arenberg, C. L. Addison, J. E. Ehlert, M. D. Burdick, and R. M. Strieter CXC chemokines in angiogenesis J. Leukoc. Biol., July 1, 2000; 68(1): 1 - 8. [Abstract] [Full Text]
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C. J. Bruns, C. C. Solorzano, M. T. Harbison, S. Ozawa, R. Tsan, D. Fan, J. Abbruzzese, P. Traxler, E. Buchdunger, R. Radinsky, et al. Blockade of the Epidermal Growth Factor Receptor Signaling by a Novel Tyrosine Kinase Inhibitor Leads to Apoptosis of Endothelial Cells and Therapy of Human Pancreatic Carcinoma Cancer Res., June 1, 2000; 60(11): 2926 - 2935. [Abstract] [Full Text] [PDF]
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J. Fujimoto, H. Sakaguchi, I. Aoki, and T. Tamaya Clinical Implications of Expression of Interleukin 8 Related to Angiogenesis in Uterine Cervical Cancers Cancer Res., May 1, 2000; 60(10): 2632 - 2635. [Abstract] [Full Text]
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Y. Yokoyama, M. Dhanabal, A. W. Griffioen, V. P. Sukhatme, and S. Ramakrishnan Synergy between Angiostatin and Endostatin: Inhibition of Ovarian Cancer Growth Cancer Res., April 1, 2000; 60(8): 2190 - 2196. [Abstract] [Full Text]
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K. Inoue, J. W. Slaton, S. J. Kim, P. Perrotte, B. Y. Eve, M. Bar-Eli, R. Radinsky, and C. P. N. Dinney Interleukin 8 Expression Regulates Tumorigenicity and Metastasis in Human Bladder Cancer Cancer Res., April 1, 2000; 60(8): 2290 - 2299. [Abstract] [Full Text]
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S. Yano, R. S. Herbst, H. Shinohara, B. Knighton, C. D. Bucana, J. J. Killion, J. Wood, and I. J. Fidler Treatment for Malignant Pleural Effusion of Human Lung Adenocarcinoma by Inhibition of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Phosphorylation Clin. Cancer Res., March 1, 2000; 6(3): 957 - 965. [Abstract] [Full Text]
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L. Xu, K. Xie, N. Mukaida, K. Matsushima, and I. J. Fidler Hypoxia-induced Elevation in Interleukin-8 Expression by Human Ovarian Carcinoma Cells Cancer Res., November 1, 1999; 59(22): 5822 - 5829. [Abstract] [Full Text] [PDF]
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Z. Duan, A. J. Feller, R. T. Penson, Bruce. A. Chabner, and M. V. Seiden Discovery of Differentially Expressed Genes Associated with Paclitaxel Resistance Using cDNA Array Technology: Analysis of Interleukin (IL) 6, IL-8, and Monocyte Chemotactic Protein 1 in the Paclitaxel-resistant Phenotype Clin. Cancer Res., November 1, 1999; 5(11): 3445 - 3453. [Abstract] [Full Text] [PDF]
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Q. Shi, J. L. Abbruzzese, S. Huang, I. J. Fidler, Q. Xiong, and K. Xie Constitutive and Inducible Interleukin 8 Expression by Hypoxia and Acidosis Renders Human Pancreatic Cancer Cells More Tumorigenic and Metastatic Clin. Cancer Res., November 1, 1999; 5(11): 3711 - 3721. [Abstract] [Full Text] [PDF]
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J. W. Slaton, P. Perrotte, K. Inoue, C. P. N. Dinney, and I. J. Fidler Interferon-{{alpha}}-mediated Down-Regulation of Angiogenesis-related Genes and Therapy of Bladder Cancer Are Dependent on Optimization of Biological Dose and Schedule Clin. Cancer Res., October 1, 1999; 5(10): 2726 - 2734. [Abstract] [Full Text] [PDF]
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J. R. Wiener, K. Nakano, R. P. Kruzelock, C. D. Bucana, R. C. Bast Jr., and G. E. Gallick Decreased Src Tyrosine Kinase Activity Inhibits Malignant Human Ovarian Cancer Tumor Growth in a Nude Mouse Model Clin. Cancer Res., August 1, 1999; 5(8): 2164 - 2170. [Abstract] [Full Text] [PDF]
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B. B. Moore, D. A. Arenberg, K. Stoy, T. Morgan, C. L. Addison, S. B. Morris, M. Glass, C. Wilke, Y. Y. Xue, S. Sitterding, et al. Distinct CXC Chemokines Mediate Tumorigenicity of Prostate Cancer Cells Am. J. Pathol., May 1, 1999; 154(5): 1503 - 1512. [Abstract] [Full Text] [PDF]
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