喉癌肿瘤组织中内皮素-1的表达及意义
摘要
目的：研究内皮素-1(ET-1)在喉癌组织中的表达及其表达在不同类型喉组织，不同临床分期的喉癌组织中是否有差异。并初步探讨ET-1在喉癌的发病机制中的作用，为进一步研究喉癌患者术前术后血清中内皮素-1的表达及意义提供理论来源，为今后深入研究ET及其受体与喉癌的相关性提供理论依据。
方法：随机选取30例喉癌患者肿瘤标本，其中TNM分期：Ⅰ期5例，Ⅱ期19例，Ⅲ期6例，Ⅳ期0例；10例手术安全切缘外正常黏膜作为正常对照组。另随机抽取20例喉良性病变手术病例为良性病变组，其中10例为声带小结，10例为声带息肉。采用免疫组织化学SP法分别检测30例喉癌组织、20例喉良性病变组织及10例喉正常黏膜组织中ET-1的表达及不同喉癌临床分期的组织中ET-1的表达，按照每一视野阳性细胞数＞5％以上确定为阳性的标准，运用完全随机设计多个独立样本比较的H检验法及两个独立样本比较的Mann-Whitney U检验方法来分析以上各组织间表达是否有统计学差异。
结果：喉癌组织阳性表达率93.3％(28／30)，喉良性病变组织阳性表达率90％(18／20)，喉正常组织阳性表达率60％(6／10)。采用HMIAS-2000彩色病理图文分析系统，自动测量阳性区域的面积，并以此来代表待测组织阳性染色程度得到以下结果：喉癌组织阳性染色面积比的均值为47.85％，其中临床
Objective: To explore the expression of Endothelin-l(ET-l) in laryngeal carcinoma. To compare the expression in different tissue and different clinical stage. To approach the contribution that endothelin-1 educing in pathogenesy of the laryngeal carcinoma. This study could provide a theory source to research the expression of Endothelin-1 (ET-1) in laryngeal carcinoma patient blood serum; This study could provide a theory to lucubrate ET and ET receptor in future.
Method: To select the tumor sample of 30 laryngeal carcinoma at random. TNM Staging:5 case of I stage ,19 case of II stage, 6 case of III stage. 10 case of the normal mucosa out of operation cutting edge as normal control group,20 larynx benign lesion operation case as benign lesion group. Immunohistochemical (SP) method was use to detect the expression of Endothelin-1 in 30 cases of laryngeal carcinoma,20 cases of laryngeal benign lesion and 10 cases of normal laryngeal mucousa. Immunohistochemical (SP) method was use to detect the expression in different clinical staging laryngeal carcinoma again. Kruskal-Wallis H test and Mann-Whitney U test were used to analysis if there were statistical contrast of ET-1 expression in every tissue.
Result: According to the standard that masculine cell population exceed 5%, we get the result: The expression of ET-1 in laryngeal carcinoma tissue was
方法：随机选取30例喉癌患者肿瘤标本，其中TNM分期：Ⅰ期5例，Ⅱ期19例，Ⅲ期6例，Ⅳ期0例；10例手术安全切缘外正常黏膜作为正常对照组。另随机抽取20例喉良性病变手术病例为良性病变组，其中10例为声带小结，10例为声带息肉。采用免疫组织化学SP法分别检测30例喉癌组织、20例喉良性病变组织及10例喉正常黏膜组织中ET-1的表达及不同喉癌临床分期的组织中ET-1的表达，按照每一视野阳性细胞数＞5％以上确定为阳性的标准，运用完全随机设计多个独立样本比较的H检验法及两个独立样本比较的Mann-Whitney U检验方法来分析以上各组织间表达是否有统计学差异。
结果：喉癌组织阳性表达率93.3％(28／30)，喉良性病变组织阳性表达率90％(18／20)，喉正常组织阳性表达率60％(6／10)。采用HMIAS-2000彩色病理图文分析系统，自动测量阳性区域的面积，并以此来代表待测组织阳性染色程度得到以下结果：喉癌组织阳性染色面积比的均值为47.85％，其中临床
Objective: To explore the expression of Endothelin-l(ET-l) in laryngeal carcinoma. To compare the expression in different tissue and different clinical stage. To approach the contribution that endothelin-1 educing in pathogenesy of the laryngeal carcinoma. This study could provide a theory source to research the expression of Endothelin-1 (ET-1) in laryngeal carcinoma patient blood serum; This study could provide a theory to lucubrate ET and ET receptor in future.
Method: To select the tumor sample of 30 laryngeal carcinoma at random. TNM Staging:5 case of I stage ,19 case of II stage, 6 case of III stage. 10 case of the normal mucosa out of operation cutting edge as normal control group,20 larynx benign lesion operation case as benign lesion group. Immunohistochemical (SP) method was use to detect the expression of Endothelin-1 in 30 cases of laryngeal carcinoma,20 cases of laryngeal benign lesion and 10 cases of normal laryngeal mucousa. Immunohistochemical (SP) method was use to detect the expression in different clinical staging laryngeal carcinoma again. Kruskal-Wallis H test and Mann-Whitney U test were used to analysis if there were statistical contrast of ET-1 expression in every tissue.
Result: According to the standard that masculine cell population exceed 5%, we get the result: The expression of ET-1 in laryngeal carcinoma tissue was
引文
[01] Yanagisawa M, Kurihara H, Tomobe Y et al. A novel potent vaso constrictor peptide by vascular endothelial cells. Nature, 1988;33,2:411-415.
[02] 刘玉春，王春玲，朱平先等．内皮素-1与肿瘤的血管生成．医学综述 2003．9(1)，32-33．
[03] 李长忠，孙亚红，刘波．内皮素与肿瘤的关系．国外医学肿瘤学分册．2003，30(5)，360-362．
[04] Economos K. Endothelin-1 gene expression and biosynthesis in human endometrial HEC-1A cancer cells. Cancer Res. 1992.52:554.
[05] Baley PA. Endothelin messenger RNA and receptor are differentinlly expressed in cultured human breast epithelial and stromal cells. J Clin Invest. 1990.85:1320.
[06] Kusuhara M. Production of endothelin in human cancer cell line. Cancer Res. 1990.50:3257.
[07] Inoue A, Yanagisawa M, Kimura S et al. The human endothelin family:three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA. 1989;86:2863.
[08] Bagnato A, Catt KJ. Endothelins as autocrine regulators of tumor cell growth[J].Trends Endocrinol Metab, 1998,9:378-383.
[09] E Asham, A Shankar, M Loizidou, S Fredericks et al. Increased endothelin-1 in colorectal cancer and reduction of tumour growth by rtareceptor antagonism[J]. British Journal of Cancer, 2001, 85(11): 1759-1763.
[10] Lahav R, Heffner G. Pattersenph an endothelin receptor bantagonist inhibirs growth and induces cell death in vitro and in vivo cell lines[J]. Cancer Res, 1999, 50:3257-3261.
[11] Donatella Del Bufalo, Marco varmi, Debora Sslani et al. Endothelin-1 protects ovarian carcinoma cells against paclitaxel-induced apoptosis: requirement for activation[J]. Molecular pharmacology, 2002, 61(3): 524-532.
[12] Rosano L, Spinella F, Di Castro V, et al. Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells. Cancer Res. 2005 15;65(24):11649-57.
[13] Egidy G, Juillerat Jeanneret L , Jeannin JF , et al . Modulation of human colon tumor-stromal interactions by the endothelin system[J] . Am J Pathol , 2000 , 157 (6) : 1863-1874.
[14] Ali H, Loizidou M, Dashwood M, et al. Stimulation of colorectal cancer cell line growth by ET-1 and its inhibition by ET(A) antagonists. Gut, 2000, 47: 685-688.
[15] Arun C, London NJ, Hemingway DM. Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer. Int J Biol Markers. 2004; 19(1) : 32-7.
[16] Ferrari-Bravo A, Franciosi C, Lissoni P, et al. Effects of oncological surgery on endothelin-1 secretion in patients with operable gastric cancer. Int J Biomarkers, 2000, 15: 56-57.
[17] Teng XJ, Shen ZX, Xiang JJ, et al. Peripheral plasma Big endothelin -1 levels in patients with gastric carcinoma undergoing radical gastrectomy and its relationship with tumor recurrence. Zhonghua Wei Chang Wai Ke Za Zhi. 2006;9(1):34-7.
[18] Lucie Peduto Eberl, Olivier Valdenaire, Valerie Saintgiorgio et al. Endothelin receptor blockade potentiates Fasl-induced apoptosis in rat colon carcinoma cells[J]. Int J Cancer 2000, 86:182-187.
[19] Spinella S, Laura Rosano, Valeriana Di Castro et al. Endothelin-1 induces vascular endothelial growth factor-1 in ovarian carcinoma cells[J]. J Biol Chem, 2002,277:27850-27855.
[20] SchreyM P, Patel KV, Tezap sidis N et al. Bombesin and Glucocorticoids stium late human breast cancer cells to produced endothelin, a paracrinem itogen for breast stromal cells. Cancer Res, 1992; 52: 1786.
[21] Chen J, Fabry B, Schiffrin EL, et al. Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells[J]. Am J Physiol Cell Physiol, 2001, 280(6): C1475-1484.
[22] 谭浩翔，李良庆，张声。内皮素—1与肿瘤血管生成的关系[J] 世界肿瘤杂志 2004，03(01)，100-103。
[23] Cruz A, Parnot C, Ribatti D, et al. Endothelin-1, a regulator of angiogenesis in the chick chorioallantoic memberane[J]. J Vasc Res, 2001,38(6):536-545.
[24] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor-no pathway[J]. Arterioscler Thromb Vasc Biol, 2001,21(10):1598-1603.
[25] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor no pathway[J]. Arterioscler Thromb Vasc Biol. 2001, 21(10):1598-1603.
[26] Oikawa T, Kusuhara M, Ishikawa S et al. Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. Br J Cancer 1994;69:1059-1064.
[27] Bhargava S, Stummeyer T, Hotz B, et al. Selective inhibition of endothelin receptor A as an anti-angiogenic and anti-proliferative strategy for human pancreatic cancer. J Gastrointest Surg. 2005; 9 (5): 703-709.
[28] Kar S, Yousern SA, Carr BI et al. Endothlin-1 expression by human hepatocellular carcinoma. Biochem Biophys Res Commun, 1995; 216(2): 514-519.
[29] Chen CY, Lu CL, Chang FY, et al. Delayed gastrointestinal transit in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2002;17(12):1254-1259.
[30] Mathieu MN, Chevillard C. Endothelin-1 and ETA receptor subtype are expressed in the gastric HGT-1 cell line. J Cardiovase Pharmacol, 1995;26(suppl3):508-509.
[31] Pagotto U, Arzberger T, Hopfner U et al. Expression and localization of endothelin-1 and endothelin receptors in human meningiomas: Evidence for a role in tumoral growth. J Clin Invest, 1995:96(4): 2017-2025.
[32] Yamashila J, Ogawa M. Nommura K, et al. Interleukin 6 stimulates the production of immunoreactive endothelin-1 in human breast cancer cells. Cancer Res, 1993; 53(3):464-467.
[33] Hagemann T, Binder C, Binder L, et al. Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells. DNA Cell Biol. 2005;24(ll):766-776.
[34] Rossi G, Belloni AS, Alberlin G et al. Endothelin-1 and its receptors A and B in human aldosteroneproducing adenomas. Hypertension, 1995;25(4):342-347.
[35] Giaid A, Hamid QA, Springall DR et al. Detection of endothelin immunoreactivity and mRNA inpulmonary tumors J Pathology. 1990;162:15-22.
[36] Battistini B, Chailler P, D' Orleans-Juste P, et al. Growth regulatory properties of endothelins[J].Peptides,1993,14(2): 385-399.
[37] 杨晓燕，刘林英，戚好文等．肺癌组织中内皮素1阳性表达及定量分析．中华结核和呼吸杂志，1998，21(2)：111-113．
[1] Yanagisawa M, Kurihara H, Tomobe Y et al. A novel potent vaso constrictor peptide by vascular endothelial cells. Nature, 1988; 33,2:411-415.
[2] 谭浩翔，李良庆，张声．内皮素-1与肿瘤血管生成的关系[J] 世界肿瘤杂志 2004，03(01)，100-103。
[3] Cruz A, Parnot C, Ribatti D, et al. Endothelin-1,a regulator of angiogenesis in the chick chorioallantoic memberane[J]. J Vasc Res, 2001,38(6):536-545.
[4] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor no pathway[J]. Arterioscler Thromb Vasc Biol. 2001,21 (10):1598-1603.
[5] Ishibashi M, Fujita M, Nagai K, et al. Production and secretion of endothelin by hepatocellular carcinoma. J Clin Endocrinol Metab, 1993,76;378-383.
[6] Nakamuta M, Ohashi M, Tabata S et al. High plasma concentration of endothelin like immunoreuctivities in patients with hepatocelllular carcinoma. AM J Gastrcenterol, 1993;88(2):248-252.
[7] Oikawa T, Kusuhara M, Ishikawa S et al. Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. Br J Cancer 1994;69:1059-1064.
[8] Kar S, Yousern SA, Carr BI et al. Endothlin-1 expression by human hepatocellular carcinoma. Biochem Biophys Res Commun, 1995;216 (2):514-519.
[9] Mathieu MN, Chevillard C. Endothelin-1 and ETA receptor subtype are expressed in the gastric HGT-1 cell line. J Cardiovase Pharmacol, 1995;26(suppl3):508-509.
[10] Pagotto U, Arzberger T, Hopfner U et al. Expression and localization of endothelin-1 and endothelin receptors in human meningiomas: Evidence for a role in tumoral growth. J Clin Invest, 1995;96(4) :2017-2025.
[11] Yamashila J, Ogawa M. Nommura K, et al. Interleukin 6 stimulates the production of immunoreactive endothelin-1 in human breast cancer cells. Cancer Res, 1993;53(3):464-467.
[12] Rossi G, Belloni AS, Alberlin G et al. Endothelin-1 and its receptors A and B in human aldosteroneproducing adenomas. Hyper- tension, 1995;25(4): 342-347.
[13] Giaid A, Hamid QA, Springall DR et al. Detection of endothelin immunoreactivity and mRNA inpulmonary tumors J Pathology. 1990; 162:15-22.
[14] Cohen AJ, Gilman LB, Miller YE et al. Endothelin receptor expression in lung cancer cell lines and bronchial epithelial cell lines. FASEBJ 1997;11:A3221.
[15] Ahmed SI, Thompson J, Coulson JM, et al. Studies on the expression of endothelin, its receptor subtypes, and converting enzymes in lung cancer and in human bronchial epithelium. AM J Respir cell Mol Biol, 2000;22(4): 422-431.
[16] Asham EH, Shankar A, Loizidou M, et al Increased endothelin-1 in colorectal cancer and reduction of tumor growth by ETA receptor antagonism. Br J Cancer, 2001:85:1755-1763.
[17] Peduto-Eberl L. Endothelin receptor blockade potentiates Fasl-induced apoptosis in rat colon carcinoma cells. Int J Cancer 2000;86:182-187.
[18] Egidy G, Juillerat-Jeanneret L, Jiannin J, et al. Modulation of human colon tumor-stromal interactions by the endothelial system. AM J Pathol, 2000;157:1863-1874.
[19] Carducei M. Atrasentan and endothelin-receptor antagonist for refractory and enocarcinomas: safety and pharmacokinetics. J Clin Oucol, 2002;20:2171-2180.
[20] Kusuhura M, Yamaguchi K, Nagasaki K et al. Production of endothelin in human cancer cell lines. Cancer Res, 1990;50:32~57.
[21] Itoh K, Goseki N, Yoshino K, et al. Changes in endothelin in human plasma after surgery: preliminary report. Nippon-Gesa-GakkaiZasshi, 1990;91:296.
[22]．郭艳，石梅，韩良辅等．放疗前后恶性肿瘤患者血清含量的检测及其临床意义[J] 第四军医大学学报 2002：23(16)。
[23] Nakagawa H. Effects of endothelin-1 on choroidal vessels-2. Study using indocyanine green videoangiography[J]. Nippon Ganka Gakkai Zasshi, 2001;105(5):301-307.
[24] Li Q, Grimelius L, Hong A, et al. Characterisation of endothelin-1 related protein in human adrenal cortex and in cortical lesions[J]. Histochem Cell Biol,1999;111(1):33-37.
[25] Rai A, Gulati A. Evidence for the involvement of ET(B) receptors in ET-1-induced changes in blood flow to the rat breast tumor [J].Cancer Chemother Pharmacol, 2003;51(1):21-28.
[02] 刘玉春，王春玲，朱平先等．内皮素-1与肿瘤的血管生成．医学综述 2003．9(1)，32-33．
[03] 李长忠，孙亚红，刘波．内皮素与肿瘤的关系．国外医学肿瘤学分册．2003，30(5)，360-362．
[04] Economos K. Endothelin-1 gene expression and biosynthesis in human endometrial HEC-1A cancer cells. Cancer Res. 1992.52:554.
[05] Baley PA. Endothelin messenger RNA and receptor are differentinlly expressed in cultured human breast epithelial and stromal cells. J Clin Invest. 1990.85:1320.
[06] Kusuhara M. Production of endothelin in human cancer cell line. Cancer Res. 1990.50:3257.
[07] Inoue A, Yanagisawa M, Kimura S et al. The human endothelin family:three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA. 1989;86:2863.
[08] Bagnato A, Catt KJ. Endothelins as autocrine regulators of tumor cell growth[J].Trends Endocrinol Metab, 1998,9:378-383.
[09] E Asham, A Shankar, M Loizidou, S Fredericks et al. Increased endothelin-1 in colorectal cancer and reduction of tumour growth by rtareceptor antagonism[J]. British Journal of Cancer, 2001, 85(11): 1759-1763.
[10] Lahav R, Heffner G. Pattersenph an endothelin receptor bantagonist inhibirs growth and induces cell death in vitro and in vivo cell lines[J]. Cancer Res, 1999, 50:3257-3261.
[11] Donatella Del Bufalo, Marco varmi, Debora Sslani et al. Endothelin-1 protects ovarian carcinoma cells against paclitaxel-induced apoptosis: requirement for activation[J]. Molecular pharmacology, 2002, 61(3): 524-532.
[12] Rosano L, Spinella F, Di Castro V, et al. Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells. Cancer Res. 2005 15;65(24):11649-57.
[13] Egidy G, Juillerat Jeanneret L , Jeannin JF , et al . Modulation of human colon tumor-stromal interactions by the endothelin system[J] . Am J Pathol , 2000 , 157 (6) : 1863-1874.
[14] Ali H, Loizidou M, Dashwood M, et al. Stimulation of colorectal cancer cell line growth by ET-1 and its inhibition by ET(A) antagonists. Gut, 2000, 47: 685-688.
[15] Arun C, London NJ, Hemingway DM. Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer. Int J Biol Markers. 2004; 19(1) : 32-7.
[16] Ferrari-Bravo A, Franciosi C, Lissoni P, et al. Effects of oncological surgery on endothelin-1 secretion in patients with operable gastric cancer. Int J Biomarkers, 2000, 15: 56-57.
[17] Teng XJ, Shen ZX, Xiang JJ, et al. Peripheral plasma Big endothelin -1 levels in patients with gastric carcinoma undergoing radical gastrectomy and its relationship with tumor recurrence. Zhonghua Wei Chang Wai Ke Za Zhi. 2006;9(1):34-7.
[18] Lucie Peduto Eberl, Olivier Valdenaire, Valerie Saintgiorgio et al. Endothelin receptor blockade potentiates Fasl-induced apoptosis in rat colon carcinoma cells[J]. Int J Cancer 2000, 86:182-187.
[19] Spinella S, Laura Rosano, Valeriana Di Castro et al. Endothelin-1 induces vascular endothelial growth factor-1 in ovarian carcinoma cells[J]. J Biol Chem, 2002,277:27850-27855.
[20] SchreyM P, Patel KV, Tezap sidis N et al. Bombesin and Glucocorticoids stium late human breast cancer cells to produced endothelin, a paracrinem itogen for breast stromal cells. Cancer Res, 1992; 52: 1786.
[21] Chen J, Fabry B, Schiffrin EL, et al. Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells[J]. Am J Physiol Cell Physiol, 2001, 280(6): C1475-1484.
[22] 谭浩翔，李良庆，张声。内皮素—1与肿瘤血管生成的关系[J] 世界肿瘤杂志 2004，03(01)，100-103。
[23] Cruz A, Parnot C, Ribatti D, et al. Endothelin-1, a regulator of angiogenesis in the chick chorioallantoic memberane[J]. J Vasc Res, 2001,38(6):536-545.
[24] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor-no pathway[J]. Arterioscler Thromb Vasc Biol, 2001,21(10):1598-1603.
[25] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor no pathway[J]. Arterioscler Thromb Vasc Biol. 2001, 21(10):1598-1603.
[26] Oikawa T, Kusuhara M, Ishikawa S et al. Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. Br J Cancer 1994;69:1059-1064.
[27] Bhargava S, Stummeyer T, Hotz B, et al. Selective inhibition of endothelin receptor A as an anti-angiogenic and anti-proliferative strategy for human pancreatic cancer. J Gastrointest Surg. 2005; 9 (5): 703-709.
[28] Kar S, Yousern SA, Carr BI et al. Endothlin-1 expression by human hepatocellular carcinoma. Biochem Biophys Res Commun, 1995; 216(2): 514-519.
[29] Chen CY, Lu CL, Chang FY, et al. Delayed gastrointestinal transit in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2002;17(12):1254-1259.
[30] Mathieu MN, Chevillard C. Endothelin-1 and ETA receptor subtype are expressed in the gastric HGT-1 cell line. J Cardiovase Pharmacol, 1995;26(suppl3):508-509.
[31] Pagotto U, Arzberger T, Hopfner U et al. Expression and localization of endothelin-1 and endothelin receptors in human meningiomas: Evidence for a role in tumoral growth. J Clin Invest, 1995:96(4): 2017-2025.
[32] Yamashila J, Ogawa M. Nommura K, et al. Interleukin 6 stimulates the production of immunoreactive endothelin-1 in human breast cancer cells. Cancer Res, 1993; 53(3):464-467.
[33] Hagemann T, Binder C, Binder L, et al. Expression of endothelins and their receptors promotes an invasive phenotype of breast tumor cells but is insufficient to induce invasion in benign cells. DNA Cell Biol. 2005;24(ll):766-776.
[34] Rossi G, Belloni AS, Alberlin G et al. Endothelin-1 and its receptors A and B in human aldosteroneproducing adenomas. Hypertension, 1995;25(4):342-347.
[35] Giaid A, Hamid QA, Springall DR et al. Detection of endothelin immunoreactivity and mRNA inpulmonary tumors J Pathology. 1990;162:15-22.
[36] Battistini B, Chailler P, D' Orleans-Juste P, et al. Growth regulatory properties of endothelins[J].Peptides,1993,14(2): 385-399.
[37] 杨晓燕，刘林英，戚好文等．肺癌组织中内皮素1阳性表达及定量分析．中华结核和呼吸杂志，1998，21(2)：111-113．
[1] Yanagisawa M, Kurihara H, Tomobe Y et al. A novel potent vaso constrictor peptide by vascular endothelial cells. Nature, 1988; 33,2:411-415.
[2] 谭浩翔，李良庆，张声．内皮素-1与肿瘤血管生成的关系[J] 世界肿瘤杂志 2004，03(01)，100-103。
[3] Cruz A, Parnot C, Ribatti D, et al. Endothelin-1,a regulator of angiogenesis in the chick chorioallantoic memberane[J]. J Vasc Res, 2001,38(6):536-545.
[4] Iglarz M, Silvestre JS, Duriez M, et al. Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis in rat hindlimbs through activation of vascular endothelial growth factor no pathway[J]. Arterioscler Thromb Vasc Biol. 2001,21 (10):1598-1603.
[5] Ishibashi M, Fujita M, Nagai K, et al. Production and secretion of endothelin by hepatocellular carcinoma. J Clin Endocrinol Metab, 1993,76;378-383.
[6] Nakamuta M, Ohashi M, Tabata S et al. High plasma concentration of endothelin like immunoreuctivities in patients with hepatocelllular carcinoma. AM J Gastrcenterol, 1993;88(2):248-252.
[7] Oikawa T, Kusuhara M, Ishikawa S et al. Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells. Br J Cancer 1994;69:1059-1064.
[8] Kar S, Yousern SA, Carr BI et al. Endothlin-1 expression by human hepatocellular carcinoma. Biochem Biophys Res Commun, 1995;216 (2):514-519.
[9] Mathieu MN, Chevillard C. Endothelin-1 and ETA receptor subtype are expressed in the gastric HGT-1 cell line. J Cardiovase Pharmacol, 1995;26(suppl3):508-509.
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