Skip to main content
Top
Published in: Journal of Gastroenterology 7/2012

01-07-2012 | Original Article—Alimentary Tract

Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival

Authors: Hong-Qing Xi, Xiao-Song Wu, Bo Wei, Lin Chen

Published in: Journal of Gastroenterology | Issue 7/2012

Login to get access

Abstract

Background

EphA3, a member of the Eph receptor tyrosine kinases, plays important roles in tumor angiogenesis and progression. However, the function of EphA3 in solid tumors has not been widely studied. We aimed to explore EphA3 expression in gastric carcinoma and analyze its role as a potential prognostic factor.

Methods

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess EphA3 mRNA in a normal gastric mucosa cell line and carcinoma cell lines. Immunohistochemistry for EphA3 and vascular endothelial growth factor (VEGF) was performed in 318 cases of gastric carcinoma. CD34 immunohistochemical staining was used for microvessel density (MVD) counting. Western blotting was used to analyze EphA3 expression in the cell lines and to determine the expression of EphA3 and VEGF in 75 cases of gastric carcinoma and matched normal mucosa.

Results

EphA3 mRNA and protein expression was significantly higher in gastric cancer than that in normal mucosa (all P < 0.001). EphA3 was significantly correlated with TNM stage and poor prognosis (all P < 0.001). Multivariate analysis showed that EphA3 had an independent effect on survival (P = 0.037). EphA3 was positively correlated with VEGF (P < 0.001), and MVD (P < 0.001). According to Western blot analysis, both EphA3 and VEGF expression were significantly higher in carcinoma than that in normal mucosa (all P < 0.001). A positive correlation was observed between EphA3 and VEGF expression in cancer (P < 0.001, r = 0.513).

Conclusions

EphA3 may play important roles in the angiogenesis and prognosis of gastric carcinoma, and thus may become a useful target for therapeutic intervention and a potential indicator for clinical assessment of tumor prognosis.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
2.
go back to reference Wikkinson DG. Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci. 2001;2:155–64.CrossRef Wikkinson DG. Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci. 2001;2:155–64.CrossRef
3.
4.
go back to reference Clifford N, Smith LM, Powell J, Gattenlöhner S, Marx A, O’Connor R. The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration. J Cell Biochem. 2008;105:1250–9.PubMedCrossRef Clifford N, Smith LM, Powell J, Gattenlöhner S, Marx A, O’Connor R. The EphA3 receptor is expressed in a subset of rhabdomyosarcoma cell lines and suppresses cell adhesion and migration. J Cell Biochem. 2008;105:1250–9.PubMedCrossRef
5.
go back to reference Anon. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell. 1997;90:403–4. Anon. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell. 1997;90:403–4.
6.
go back to reference Wang J, Dong Y, Wang X, Ma H, Sheng Z, Li G, et al. Expression of EphA1 in gastric carcinomas is associated with metastasis and survival. Oncol Rep. 2010;24:1577–84.PubMed Wang J, Dong Y, Wang X, Ma H, Sheng Z, Li G, et al. Expression of EphA1 in gastric carcinomas is associated with metastasis and survival. Oncol Rep. 2010;24:1577–84.PubMed
7.
go back to reference Nakamura R, Kataoka H, Sato N, Kanamori M, Ihara M, Igarashi H, et al. EPHA2/EFNA1 expression in human gastric cancer. Cancer Sci. 2005;96:42–7.PubMedCrossRef Nakamura R, Kataoka H, Sato N, Kanamori M, Ihara M, Igarashi H, et al. EPHA2/EFNA1 expression in human gastric cancer. Cancer Sci. 2005;96:42–7.PubMedCrossRef
8.
go back to reference Yuan W, Chen Z, Wu S, Ge J, Chang S, Wang X, et al. Expression of EphA2 and E-cadherin in gastric cancer: correlated with tumor progression and lymphogenous metastasis. Pathol Oncol Res. 2009;15:473–8.PubMedCrossRef Yuan W, Chen Z, Wu S, Ge J, Chang S, Wang X, et al. Expression of EphA2 and E-cadherin in gastric cancer: correlated with tumor progression and lymphogenous metastasis. Pathol Oncol Res. 2009;15:473–8.PubMedCrossRef
9.
go back to reference Wang J, Li G, Ma H, Bao Y, Wang X, Zhou H, et al. Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. Hum Pathol. 2007;38:1649–56.PubMedCrossRef Wang J, Li G, Ma H, Bao Y, Wang X, Zhou H, et al. Differential expression of EphA7 receptor tyrosine kinase in gastric carcinoma. Hum Pathol. 2007;38:1649–56.PubMedCrossRef
10.
go back to reference Yu G, Gao Y, Ni C, Chen Y, Pan J, Wang X, et al. Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer. J Cancer Res Clin Oncol. 2011;137:73–80.PubMedCrossRef Yu G, Gao Y, Ni C, Chen Y, Pan J, Wang X, et al. Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer. J Cancer Res Clin Oncol. 2011;137:73–80.PubMedCrossRef
11.
go back to reference Holder N, Klein R. Eph receptors and ephrins: effectors of morphogenesis. Development. 1999;126:2033–44.PubMed Holder N, Klein R. Eph receptors and ephrins: effectors of morphogenesis. Development. 1999;126:2033–44.PubMed
12.
go back to reference Surawska H, Ma PC, Salgia R. The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev. 2004;15:419–33.PubMedCrossRef Surawska H, Ma PC, Salgia R. The role of ephrins and Eph receptors in cancer. Cytokine Growth Factor Rev. 2004;15:419–33.PubMedCrossRef
13.
go back to reference Heroult M, Schaffner F, Augustin HG. Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Exp Cell Res. 2006;312:642–50.PubMedCrossRef Heroult M, Schaffner F, Augustin HG. Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Exp Cell Res. 2006;312:642–50.PubMedCrossRef
15.
go back to reference Smith LM, Walsh PT, Rüdiger T, Cotter TG, Mc Carthy TV, Marx A, et al. EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Exp Cell Res. 2004;292:295–303.PubMedCrossRef Smith LM, Walsh PT, Rüdiger T, Cotter TG, Mc Carthy TV, Marx A, et al. EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion. Exp Cell Res. 2004;292:295–303.PubMedCrossRef
16.
go back to reference Hafner C, Schmitz G, Meyer S, Bataille F, Hau P, Langmann T, et al. Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers. Clin Chem. 2004;50:490–9.PubMedCrossRef Hafner C, Schmitz G, Meyer S, Bataille F, Hau P, Langmann T, et al. Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers. Clin Chem. 2004;50:490–9.PubMedCrossRef
17.
go back to reference Wimmer-Kleikamp SH, Lackmann M. Eph-modulated cell morphology, adhesion and motility in carcinogenesis. IUBMB Life. 2005;57:421–31.PubMedCrossRef Wimmer-Kleikamp SH, Lackmann M. Eph-modulated cell morphology, adhesion and motility in carcinogenesis. IUBMB Life. 2005;57:421–31.PubMedCrossRef
18.
go back to reference Bae HJ, Song JH, Noh JH, Kim JK, Jung KH, Eun JW, et al. Low frequency mutation of the ephrin receptor A3 gene in hepatocellular carcinoma. Neoplasma. 2009;56:331–4.PubMedCrossRef Bae HJ, Song JH, Noh JH, Kim JK, Jung KH, Eun JW, et al. Low frequency mutation of the ephrin receptor A3 gene in hepatocellular carcinoma. Neoplasma. 2009;56:331–4.PubMedCrossRef
19.
go back to reference Xi HQ, Zhao P. Clinicopathological significance and prognostic value of EphA3 and CD133 expression in colorectal carcinoma. J Clin Pathol. 2011;64:498–503.PubMedCrossRef Xi HQ, Zhao P. Clinicopathological significance and prognostic value of EphA3 and CD133 expression in colorectal carcinoma. J Clin Pathol. 2011;64:498–503.PubMedCrossRef
20.
go back to reference Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.PubMedCrossRef Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82:4–6.PubMedCrossRef
21.
go back to reference Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 1999;13:1055–66.PubMedCrossRef Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 1999;13:1055–66.PubMedCrossRef
22.
go back to reference de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992;255:989–91.PubMedCrossRef de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992;255:989–91.PubMedCrossRef
23.
go back to reference Lazăr D, Tăban S, Raica M, Sporea I, Cornianu M, Goldiş A, et al. Immunohistochemical evaluation of the tumor neoangiogenesis as a prognostic factor for gastric cancers. Rom J Morphol Embryol. 2008;49:137–48.PubMed Lazăr D, Tăban S, Raica M, Sporea I, Cornianu M, Goldiş A, et al. Immunohistochemical evaluation of the tumor neoangiogenesis as a prognostic factor for gastric cancers. Rom J Morphol Embryol. 2008;49:137–48.PubMed
24.
go back to reference Tsutsui S, Kume M, Era S. Prognostic value of microvessel density in invasive ductal carcinoma of the breast. Breast Cancer. 2003;10:312–9.PubMedCrossRef Tsutsui S, Kume M, Era S. Prognostic value of microvessel density in invasive ductal carcinoma of the breast. Breast Cancer. 2003;10:312–9.PubMedCrossRef
25.
go back to reference Lackner C, Jukic Z, Tsybrovskyy O, Jatzko G, Wette V, Hoefler G, et al. Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer. Virchows Arch. 2004;445:160–7.PubMedCrossRef Lackner C, Jukic Z, Tsybrovskyy O, Jatzko G, Wette V, Hoefler G, et al. Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer. Virchows Arch. 2004;445:160–7.PubMedCrossRef
26.
go back to reference Raspollini MR, Amunni G, Villanucci A, Baroni G, Boddi V, Taddei GL. Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma. Int J Gynecol Cancer. 2004;14:815–23.PubMedCrossRef Raspollini MR, Amunni G, Villanucci A, Baroni G, Boddi V, Taddei GL. Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma. Int J Gynecol Cancer. 2004;14:815–23.PubMedCrossRef
27.
go back to reference Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer. 2006;51:143–58.PubMedCrossRef Bremnes RM, Camps C, Sirera R. Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. Lung Cancer. 2006;51:143–58.PubMedCrossRef
28.
go back to reference Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R, et al. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56:2671–6.PubMed Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T, Horiuchi T, Muraoka R, et al. Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res. 1996;56:2671–6.PubMed
29.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods. 2001;25:402–8.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods. 2001;25:402–8.PubMedCrossRef
30.
go back to reference Xi HQ, Zhao P, Han WD. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. World J Gastroenterol. 2010;16:1644–8.PubMedCrossRef Xi HQ, Zhao P, Han WD. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma. World J Gastroenterol. 2010;16:1644–8.PubMedCrossRef
31.
go back to reference Matsubara J, Yamada Y, Nakajima TE, Kato K, Hamaguchi T, Shirao K, et al. Clinical significance of insulin-like growth factor type 1 receptor and epidermal growth factor receptor in patients with advanced gastric cancer. Oncology. 2008;74:76–83.PubMedCrossRef Matsubara J, Yamada Y, Nakajima TE, Kato K, Hamaguchi T, Shirao K, et al. Clinical significance of insulin-like growth factor type 1 receptor and epidermal growth factor receptor in patients with advanced gastric cancer. Oncology. 2008;74:76–83.PubMedCrossRef
32.
go back to reference Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, et al. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006;27:1060–1.PubMedCrossRef Wood LD, Calhoun ES, Silliman N, Ptak J, Szabo S, Powell SM, et al. Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum Mutat. 2006;27:1060–1.PubMedCrossRef
33.
go back to reference Hansen S, Grabau DA, Sørensen FB, Bak M, Vach W, Rose C. Vascular grading of angiogenesis: prognostic significance in breast cancer. Br J Cancer. 2000;82:339–47.PubMedCrossRef Hansen S, Grabau DA, Sørensen FB, Bak M, Vach W, Rose C. Vascular grading of angiogenesis: prognostic significance in breast cancer. Br J Cancer. 2000;82:339–47.PubMedCrossRef
34.
go back to reference Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992;84:1875–87.PubMedCrossRef Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992;84:1875–87.PubMedCrossRef
35.
go back to reference Dodelet VC, Pasquale EB. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene. 2000;19:5614–9.PubMedCrossRef Dodelet VC, Pasquale EB. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene. 2000;19:5614–9.PubMedCrossRef
36.
go back to reference Clevers H, Batlle E. EphB/EphrinB receptors and Wnt signaling in colorectal cancer. Cancer Res. 2006;66:2–5.PubMedCrossRef Clevers H, Batlle E. EphB/EphrinB receptors and Wnt signaling in colorectal cancer. Cancer Res. 2006;66:2–5.PubMedCrossRef
37.
go back to reference Boyd AW, Ward LD, Wicks IP, Simpson RJ, Salvaris E, Wilks A, et al. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J Biol Chem. 1992;267:3262–7.PubMed Boyd AW, Ward LD, Wicks IP, Simpson RJ, Salvaris E, Wilks A, et al. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. J Biol Chem. 1992;267:3262–7.PubMed
38.
go back to reference Wicks IP, Wilkinson D, Salvaris E, Boyd AW. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc Natl Acad Sci USA. 1992;89:1611–5.PubMedCrossRef Wicks IP, Wilkinson D, Salvaris E, Boyd AW. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. Proc Natl Acad Sci USA. 1992;89:1611–5.PubMedCrossRef
39.
go back to reference Dottori M, Down M, Huttmann A, Fitzpatrick DR, Boyd AW. Cloning and characterization of EphA3 (Hek) gene promoter: DNA methylation regulates expression in hematopoietic tumor cells. Blood. 1999;94:2477–86.PubMed Dottori M, Down M, Huttmann A, Fitzpatrick DR, Boyd AW. Cloning and characterization of EphA3 (Hek) gene promoter: DNA methylation regulates expression in hematopoietic tumor cells. Blood. 1999;94:2477–86.PubMed
40.
go back to reference Fox BP, Tabone CJ, Kandpal RP. Potential clinical relevance of Eph receptors and ephrin ligands expressed in prostate carcinoma cell lines. Biochem Biophys Res Commun. 2006;342:1263–72.PubMedCrossRef Fox BP, Tabone CJ, Kandpal RP. Potential clinical relevance of Eph receptors and ephrin ligands expressed in prostate carcinoma cell lines. Biochem Biophys Res Commun. 2006;342:1263–72.PubMedCrossRef
41.
go back to reference Tomoda M, Maehara Y, Kakeji Y, Ohno S, Ichiyoshi Y, Sugimachi K. Intratumoral neovascularization and growth pattern in early gastric carcinoma. Cancer. 1999;85:2340–6.PubMedCrossRef Tomoda M, Maehara Y, Kakeji Y, Ohno S, Ichiyoshi Y, Sugimachi K. Intratumoral neovascularization and growth pattern in early gastric carcinoma. Cancer. 1999;85:2340–6.PubMedCrossRef
42.
go back to reference Senger DR, Connolly DT, Van de Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factors. Cancer Res. 1990;50:1774–8.PubMed Senger DR, Connolly DT, Van de Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factors. Cancer Res. 1990;50:1774–8.PubMed
43.
go back to reference Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84:1470–8.PubMedCrossRef Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84:1470–8.PubMedCrossRef
44.
go back to reference Zhang H, Wu J, Meng L, Shou CC. Expression of vascular endothelial growth factor and its receptors KDR and Flt-1 in gastric cancer cells. World J Gastroenterol. 2002;8:994–8.PubMed Zhang H, Wu J, Meng L, Shou CC. Expression of vascular endothelial growth factor and its receptors KDR and Flt-1 in gastric cancer cells. World J Gastroenterol. 2002;8:994–8.PubMed
45.
go back to reference Iordache S, Saftoiu A, Georgescu CV, Ramboiu S, Gheonea DI, Filip M, et al. Vascular endothelial growth factor expression and microvessel density–two useful tools for the assessment of prognosis and survival in gastric cancer patients. J Gastrointest Liver Dis. 2010;19:135–9. Iordache S, Saftoiu A, Georgescu CV, Ramboiu S, Gheonea DI, Filip M, et al. Vascular endothelial growth factor expression and microvessel density–two useful tools for the assessment of prognosis and survival in gastric cancer patients. J Gastrointest Liver Dis. 2010;19:135–9.
46.
go back to reference Lee SA, Choi SR, Jang JS, Lee JH, Roh MH, Kim SO, et al. Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by endoscopic submucosal dissection. Dig Dis Sci. 2010;55:1955–63.PubMedCrossRef Lee SA, Choi SR, Jang JS, Lee JH, Roh MH, Kim SO, et al. Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by endoscopic submucosal dissection. Dig Dis Sci. 2010;55:1955–63.PubMedCrossRef
47.
go back to reference Chen CN, Cheng YM, Lin MT, Hsieh FJ, Lee PH, Chang KJ. Association of color Doppler vascularity index and microvessel density with survival in patients with gastric cancer. Ann Surg. 2002;235:512–8.PubMedCrossRef Chen CN, Cheng YM, Lin MT, Hsieh FJ, Lee PH, Chang KJ. Association of color Doppler vascularity index and microvessel density with survival in patients with gastric cancer. Ann Surg. 2002;235:512–8.PubMedCrossRef
48.
go back to reference Zheng H, Tsuneyama K, Cheng C, Takahashi H, Cui Z, Nomoto K, Murai Y, Takano Y. Expression of KAI1 and tenascin, and microvessel density are closely correlated with liver metastasis of gastrointestinal adenocarcinoma. J Clin Pathol. 2007;60:50–6.PubMedCrossRef Zheng H, Tsuneyama K, Cheng C, Takahashi H, Cui Z, Nomoto K, Murai Y, Takano Y. Expression of KAI1 and tenascin, and microvessel density are closely correlated with liver metastasis of gastrointestinal adenocarcinoma. J Clin Pathol. 2007;60:50–6.PubMedCrossRef
49.
go back to reference Nakamoto M, Bergemann AD. Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis. Microsc Res Tech. 2002;59:58–67.PubMedCrossRef Nakamoto M, Bergemann AD. Diverse roles for the Eph family of receptor tyrosine kinases in carcinogenesis. Microsc Res Tech. 2002;59:58–67.PubMedCrossRef
50.
go back to reference Brantley-Sieders D, Parker M, Chen J. Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des. 2004;10:3431–42.PubMedCrossRef Brantley-Sieders D, Parker M, Chen J. Eph receptor tyrosine kinases in tumor and tumor microenvironment. Curr Pharm Des. 2004;10:3431–42.PubMedCrossRef
51.
go back to reference Cheng N, Brantley D, Fang WB, Liu H, Fanslow W, Cerretti DP, et al. Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors. Neoplasia. 2003;5:445–56.PubMed Cheng N, Brantley D, Fang WB, Liu H, Fanslow W, Cerretti DP, et al. Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors. Neoplasia. 2003;5:445–56.PubMed
52.
go back to reference Brantley DM, Cheng N, Thompson EJ, Lin Q, Brekken RA, Thorpe PE, et al. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002;21:7011–26.PubMedCrossRef Brantley DM, Cheng N, Thompson EJ, Lin Q, Brekken RA, Thorpe PE, et al. Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 2002;21:7011–26.PubMedCrossRef
53.
go back to reference Dobrzanski P, Hunter K, Jones-Bolin S, Chang H, Robinson C, Pritchard S, et al. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res. 2004;64:910–9.PubMedCrossRef Dobrzanski P, Hunter K, Jones-Bolin S, Chang H, Robinson C, Pritchard S, et al. Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res. 2004;64:910–9.PubMedCrossRef
Metadata
Title
Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival
Authors
Hong-Qing Xi
Xiao-Song Wu
Bo Wei
Lin Chen
Publication date
01-07-2012
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 7/2012
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0549-4

Other articles of this Issue 7/2012

Journal of Gastroenterology 7/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.