CD147、MMP-9、VEGF在垂体瘤中的表达及与生物学行为关系的研究
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摘要
目的
研究CD147、基质金属蛋白酶-9及血管内皮生成因子在垂体腺瘤中的蛋白质表达,探讨CD147、MMP-9及VEGF与垂体腺瘤侵袭发生的相关性以及它们之间的内在联系。
方法
1.标本来源
收集2006、2～2007、4期间山东省立医院神经外科的垂体腺瘤手术标50例,其中男性26例,女性24例,年龄18～71岁,平均年龄38.3±1.3岁;所有病例诊断均有术后的免疫组化病理证实。依据影像学提示肿瘤侵犯海绵窦或有骨质破坏,和/或术中观察肿瘤对周围骨质、海绵窦有/无侵犯等情况分为侵袭性组(29例)和非侵袭性组(21例),根据分泌功能分类:功能性垂体腺瘤(泌乳素腺瘤15例、生长激素腺瘤6例、促肾上腺腺瘤2例、多功能腺瘤8例)和无功能性垂体腺瘤(19例)。
2.免疫组化染色方法
采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(S-P)法,按标准实验流程,检测CD147、MMP-9、VEGF在侵袭性和非侵袭性垂体瘤中的蛋白质表达。
3.结果判定标准
CD147以肿瘤细胞质或胞膜出现黄色或黄褐色颗粒为阳性,MMP-9以肿瘤细胞胞质内出现棕黄色颗粒为阳性,VEGF以肿瘤细胞浆出现棕黄色颗粒为阳性。在高倍视野(×400)下,每张切片随机观察5个视野的肿瘤细胞,计算200个肿瘤细胞免疫反应阳性的细胞百分比,根据CD147、MMP-9及VEGF反应阳性细胞显色强度及范围进行评价:①阴性(一):无阳性细胞染色;②弱阳性(+):阳性细胞小于25%或显色浅;③中度阳性(++):阳性细胞在26%～50%或染色略深;④强阳性(+++):阳性细胞大于50%或显色深。
结果
1、免疫组化显色结果:
1)、CD147在侵袭性和非侵袭性垂体腺瘤中强阳性表达率分别为51.7%和23.8%,阳性表达率分别为93.1%和52.4%,两组比较差异均具有统计学意义(x~2=3.95,P＜0.05和x~2=11.07,P＜0.05)。
2)、MMP-9在侵袭性和非侵袭性垂体腺瘤中的强阳性表达率分别为58.6%和14.3%,阳性表达率分别为86.2%和42.9%,两组比较差异具有统计学意义(x~2=9.98,P＜0.05和x~2=10.52,P＜0.05)。
3)、VEGFF在侵袭性和非侵袭性垂体腺瘤中强阳性表达率为62.1%和19.1%,阳性表达率为96.6%和57.1%,两组比较差异具有统计学意义(x~2=9.15,P＜0.05和x~2=11.82,P＜0.05)。
2、相关分析:Pearson相关分析显示,侵袭性垂体腺瘤中CD147与MMP-9表达成正相关(r_s=0.373,P＜0.05),CD147与VEGF表达成正相关(r_s=0.509,P＜0.01),MMP-9与VEGF表达成正相关(r_s=0.781,P＜0.01);而非侵袭性垂体腺瘤组中CD147、MMP-9与VEGF的蛋白质表达无相关性(P＞0.05)。
结论
1、CD147、MMP-9、VEGF在侵袭性与非侵袭性垂体腺瘤中的表达有显著性差异。侵袭性垂体腺瘤中CD147、MMP-9、VEGF蛋白表达较非侵袭性垂体腺瘤显著增高。
2、垂体腺瘤的侵袭性生长可能与CD147、MMP-9、VEGF高表达有关,在肿瘤侵袭生长过程中,CD147与MMP-9的产生有关,VEGF与MMP-9的产生有关,CD147与VEGF的生长有关,共同促进垂体腺瘤侵袭性生长。
3、CD147、MMP-9、VEGF可以作为判断垂体腺瘤侵袭性生长的有效指标。
4、患者性别及垂体腺瘤有无分泌功能与垂体腺瘤侵袭性发生率无关。
Objective
The aim is to study the protein expression of CD147、MMP-9 and VEGF in pituitary adenomas, and to study the biological relationship between CD147、MMP-9、VEGF and the invasiveness of pituitary adenomas, and to evaluate the clinical significance.
Method
1、Patient Selection
Tissue samples were obtained from patients who underwent surgery in Shandong Provincial Hospital from February, 2006 to April, 2007. The total number of tissue samples was 50, including 26 males and 24 females with an average age of 38.3±1.3. All diagnoses of these cases were verified by immunohistochemical pathology. According to the illustration of images and observation in operations, cases were divided into 29 invasive cases (PRL 5 cases, GH 6 cases, ACTH 2 ones , and multifuctional adenomas 8 cases)and 21 noninvasive cases(19 cases); according to secreting function, cases were divided into 31 functional cases and 19 nonfunctional cases.
2、Immunohistochemistry
The protein expression of CD147, MMP-9 and VEGF were detected by the S-P method with ultrasensitive S-P kit.
3、Result determination
The positive staining of CD147 is yellow or yellow brown particles located in cytoplasm or cellular membrane. The positive staining of MMP-9 or VEGF is yellow brown particles located in cytoplasm. 5 fields at a magnification of 400 X at every slice were observed at random .The percentage of positive staining cells in 200 tumor cells was calculated. The results were evaluated by staining intense and extent in positive cells:①negative(-): no staining;②weak positive(+):the number of positive cells < 25% or slight staining;③mild positive(++):the number of positive cells from 26% to 50% or mild staining;④strong positive(+++): the number of positive cells > 50% or deep staining.
Results
The rates of intense positive expression of CD147 in invasive and noninvasive cases were 54% and 20.7% respectively; the rates of total positive expression were 96.8% and 51.4%; and there were statistic significance in the two teams respectively( P<0.05). The rates of intense positive expressoin of MMP-9 in invasive and noninvasive ones were 58.6% and 14. 3% respectively; the total positive expression were 86. 2% and 42. 9% respectively; and there were statistic significance in the two teams respectively( P<0.05). The rates of intense positive expressoin of VEGF in invasive and noninvasive ones were 62.1% and 19.1% respectively; the total positive expression were 96.6% and 57.1% respectively; and there were statistic significance in the two teams respectively( P<0.05). There was a significant positive correlation among protein expression of CD147, MMP-9 and VEGF in invasive cases; but there were not significant correlation in noninvasive cases. And the incidence of the invasiveness has no significant difference with the sexulty of patients and secretion of adenomas .
Conclusion
The protein expression of CD147, MMP-9 and VEGF may play important roles in the invasiveness of pituitary adenomas and may be useful markers to predict the invasiveness. The invasiveness growth of adenomas may has connection with high protein expression of CD147, MMP-9 and VEGF. During invasive growth , there are some correlation among CD147, MMP-9 and VEGF; reciprocal promotion between CD147 and MMP-9,MMP-9 and VEGF. And the incidence of the invasiveness has no significant difference with the sexulty of patients and secretion of adenomas .
研究CD147、基质金属蛋白酶-9及血管内皮生成因子在垂体腺瘤中的蛋白质表达,探讨CD147、MMP-9及VEGF与垂体腺瘤侵袭发生的相关性以及它们之间的内在联系。
方法
1.标本来源
收集2006、2～2007、4期间山东省立医院神经外科的垂体腺瘤手术标50例,其中男性26例,女性24例,年龄18～71岁,平均年龄38.3±1.3岁;所有病例诊断均有术后的免疫组化病理证实。依据影像学提示肿瘤侵犯海绵窦或有骨质破坏,和/或术中观察肿瘤对周围骨质、海绵窦有/无侵犯等情况分为侵袭性组(29例)和非侵袭性组(21例),根据分泌功能分类:功能性垂体腺瘤(泌乳素腺瘤15例、生长激素腺瘤6例、促肾上腺腺瘤2例、多功能腺瘤8例)和无功能性垂体腺瘤(19例)。
2.免疫组化染色方法
采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(S-P)法,按标准实验流程,检测CD147、MMP-9、VEGF在侵袭性和非侵袭性垂体瘤中的蛋白质表达。
3.结果判定标准
CD147以肿瘤细胞质或胞膜出现黄色或黄褐色颗粒为阳性,MMP-9以肿瘤细胞胞质内出现棕黄色颗粒为阳性,VEGF以肿瘤细胞浆出现棕黄色颗粒为阳性。在高倍视野(×400)下,每张切片随机观察5个视野的肿瘤细胞,计算200个肿瘤细胞免疫反应阳性的细胞百分比,根据CD147、MMP-9及VEGF反应阳性细胞显色强度及范围进行评价:①阴性(一):无阳性细胞染色;②弱阳性(+):阳性细胞小于25%或显色浅;③中度阳性(++):阳性细胞在26%～50%或染色略深;④强阳性(+++):阳性细胞大于50%或显色深。
结果
1、免疫组化显色结果:
1)、CD147在侵袭性和非侵袭性垂体腺瘤中强阳性表达率分别为51.7%和23.8%,阳性表达率分别为93.1%和52.4%,两组比较差异均具有统计学意义(x~2=3.95,P＜0.05和x~2=11.07,P＜0.05)。
2)、MMP-9在侵袭性和非侵袭性垂体腺瘤中的强阳性表达率分别为58.6%和14.3%,阳性表达率分别为86.2%和42.9%,两组比较差异具有统计学意义(x~2=9.98,P＜0.05和x~2=10.52,P＜0.05)。
3)、VEGFF在侵袭性和非侵袭性垂体腺瘤中强阳性表达率为62.1%和19.1%,阳性表达率为96.6%和57.1%,两组比较差异具有统计学意义(x~2=9.15,P＜0.05和x~2=11.82,P＜0.05)。
2、相关分析:Pearson相关分析显示,侵袭性垂体腺瘤中CD147与MMP-9表达成正相关(r_s=0.373,P＜0.05),CD147与VEGF表达成正相关(r_s=0.509,P＜0.01),MMP-9与VEGF表达成正相关(r_s=0.781,P＜0.01);而非侵袭性垂体腺瘤组中CD147、MMP-9与VEGF的蛋白质表达无相关性(P＞0.05)。
结论
1、CD147、MMP-9、VEGF在侵袭性与非侵袭性垂体腺瘤中的表达有显著性差异。侵袭性垂体腺瘤中CD147、MMP-9、VEGF蛋白表达较非侵袭性垂体腺瘤显著增高。
2、垂体腺瘤的侵袭性生长可能与CD147、MMP-9、VEGF高表达有关,在肿瘤侵袭生长过程中,CD147与MMP-9的产生有关,VEGF与MMP-9的产生有关,CD147与VEGF的生长有关,共同促进垂体腺瘤侵袭性生长。
3、CD147、MMP-9、VEGF可以作为判断垂体腺瘤侵袭性生长的有效指标。
4、患者性别及垂体腺瘤有无分泌功能与垂体腺瘤侵袭性发生率无关。
Objective
The aim is to study the protein expression of CD147、MMP-9 and VEGF in pituitary adenomas, and to study the biological relationship between CD147、MMP-9、VEGF and the invasiveness of pituitary adenomas, and to evaluate the clinical significance.
Method
1、Patient Selection
Tissue samples were obtained from patients who underwent surgery in Shandong Provincial Hospital from February, 2006 to April, 2007. The total number of tissue samples was 50, including 26 males and 24 females with an average age of 38.3±1.3. All diagnoses of these cases were verified by immunohistochemical pathology. According to the illustration of images and observation in operations, cases were divided into 29 invasive cases (PRL 5 cases, GH 6 cases, ACTH 2 ones , and multifuctional adenomas 8 cases)and 21 noninvasive cases(19 cases); according to secreting function, cases were divided into 31 functional cases and 19 nonfunctional cases.
2、Immunohistochemistry
The protein expression of CD147, MMP-9 and VEGF were detected by the S-P method with ultrasensitive S-P kit.
3、Result determination
The positive staining of CD147 is yellow or yellow brown particles located in cytoplasm or cellular membrane. The positive staining of MMP-9 or VEGF is yellow brown particles located in cytoplasm. 5 fields at a magnification of 400 X at every slice were observed at random .The percentage of positive staining cells in 200 tumor cells was calculated. The results were evaluated by staining intense and extent in positive cells:①negative(-): no staining;②weak positive(+):the number of positive cells < 25% or slight staining;③mild positive(++):the number of positive cells from 26% to 50% or mild staining;④strong positive(+++): the number of positive cells > 50% or deep staining.
Results
The rates of intense positive expression of CD147 in invasive and noninvasive cases were 54% and 20.7% respectively; the rates of total positive expression were 96.8% and 51.4%; and there were statistic significance in the two teams respectively( P<0.05). The rates of intense positive expressoin of MMP-9 in invasive and noninvasive ones were 58.6% and 14. 3% respectively; the total positive expression were 86. 2% and 42. 9% respectively; and there were statistic significance in the two teams respectively( P<0.05). The rates of intense positive expressoin of VEGF in invasive and noninvasive ones were 62.1% and 19.1% respectively; the total positive expression were 96.6% and 57.1% respectively; and there were statistic significance in the two teams respectively( P<0.05). There was a significant positive correlation among protein expression of CD147, MMP-9 and VEGF in invasive cases; but there were not significant correlation in noninvasive cases. And the incidence of the invasiveness has no significant difference with the sexulty of patients and secretion of adenomas .
Conclusion
The protein expression of CD147, MMP-9 and VEGF may play important roles in the invasiveness of pituitary adenomas and may be useful markers to predict the invasiveness. The invasiveness growth of adenomas may has connection with high protein expression of CD147, MMP-9 and VEGF. During invasive growth , there are some correlation among CD147, MMP-9 and VEGF; reciprocal promotion between CD147 and MMP-9,MMP-9 and VEGF. And the incidence of the invasiveness has no significant difference with the sexulty of patients and secretion of adenomas .
引文
[1]Turner H E,Nagy Z,Esiri M M,et al.Role of matrix metalloproteinase -9 in pituitary tumor behavior[J].Clin Endocorinol Metab,2000,85(8):2931-2935.
[2]王翦,刘运生.MMP及TIMP在垂体腺瘤中的表达及与侵袭性关系[J].湖南医科大学学报,2004,29(6):647-650.
[3]Veikkola T,Alitalo K.VEGFs,receptors and angiogenesis[J].Semin C ancer Biol,1999,9:211-220.
[4]Anthony P,Heaney,Gregory A et al.Early involvement of estrogen i nduced pituitary tumor transforming gene and Hardy J,Vezina JL.Tra nssphenoidal neurosurgery of intracranial neoplasm[J].Adv Neurol,1976,15:261-273.
[5]Knosp E,Stiner E,Kitz K,et al.Pituitary adenomas with invasiono f the cavernous sinus space a magnetic resonance imaging classifica tion compared with surgical findings[J].Neurosurgery,1993,Oct;33(4):610-7;discussion 617-8.
[6]Shimizu M,Saitoh Y,Itch H.Immunohistochemical staining of Haraso ncogene in normal,benign,and malignant human pancreatic tissue[J].Hum Pathol,1990,21:601-612.
[7]Jefferson G.Extrasellar extensions of pituitary adenomas:Preside nt's address[J].Pro R Soc Med,1940,33:433-458.
[8]Scheithauer B W,Kovacs K T,Laws E R Jr,et al.Pathology of invas ire pituitary tumors with special reference to functional classific ation[J].Neurosurg,1986,65:733-744.
[9]Kawamoto H,Uozumi T,Kawamoto K,et al.Analysis of the growth rat e and cavernous sinus invasion of pituitary adenomas[J].Acta Neuro chir(Wien),1995,136:37-43.
[10]Thaper K,Kovacs K,Scheithauer B W et al.Proliferative activity an d invasiveness among pituitary adenomas and carcinomas:an analysi s using the M-IB-1 antibody[J].Neurosurgery,1996,38(1):99-107.
[11]Tomita T.Matrix metalloproteinases and tissue inhibitors of metal loproteinases in thyroid C-cells and medullary thyroid carcinomas [J].Histopathology,1997,31(2):150-156.
[12]Bode W,Fernandez Catalan C,Grams F,et al.Insights into MMP-TIM P interactions[J].Ann N Y Acad Sci,1999,878:73-91.
[13]任祖渊.侵袭性垂体腺瘤的研究现状及展望.中华神经外科杂志.2000.16(增 刊):112-115.
[14]龚俊扬.侵袭性垂体腺瘤及其研究进展.国外医学神经病学神经外科分册,2000,27:27-28.
[15]Miyajima Y,Nakano R,Mori matsu M,et al.Analysis of expression of matrix metalloproteinase-2 and -9 in hypopharyngeal squamous cell carcinoma by in situhybridization[J].Ann Otol-Rhinol-Larvnglo.1995,104:678-684
[16]Bode W,Fernandez Catalan C,Grams F,et al.Insights into MMP-TIM P interactions[J].Ann N Y Acad Sci,1999,878:73-91.
[17]Seandel M,Noack-Kunmnann K,Zhu D,et al.Growth factor induced angiogenesis in vivo requires specific cleavage of fibrillar type Ⅰ collagen[J].Blood,2001,97(8):2323-2332.
[18]John A,Tuszynski G.The role of MMPs in tumor angiogenesis and tu mor metastasis[J].Pathol Oncol Res,2001,7(1):14.
[19]Curran S,Murray GI.Matrix metalloproteinases in tumour invasion and metastasis[J].Pathol,1999,189(3):300-308.
[20]Heaney AP,Horwitz GA,Wang Z,et al.Early involvement of estroge ninduced pituitary tumor transforming gene and fibroblast growth fact or expression in prolactinoma pathogenesis.Nat Med,1999,5(11):1317-1321.
[21]Kawamoto H,Uozumi T,Kamamtot K,et al.Type Ⅳ collagenase activ ity and cavenous sinus invasion in human pituitary adenomas[J].Ac ta Neurochir(Wien),1996;138(4):390-395.
[22]Turner H E,Nagy Z,Esiri M M,etal.Roleofm atrix metalloproteinase-9 in pituitary tumor behavior[J].JClin Endocorinol Metab,2000,85(8):2931-2935.
[23]Vu TH,Shipley J M,Bergers G,et al.MMP-9/gelatinase B is a key r egulation of growth plate angiogenesis and apoptosis of hypertroph ic chondrocytes[J].Cell,1998,93(3):411-422.
[24]Bergers G,Brekken R,Mc Mahon G,et al.Matrixm etalloproteinase-9triggers the angiogenic switch during carcinogenesis[J].Nat Cell Biol,2005,10:737-744.
[25]RiedelF,Gotte K,Schwalb J,et al.Expression of 92-kDa type Ⅳ colla genase correlateswith angiogenic markers and poor survivalin head and neck squam ouscellcarcinoma[J].Int J Oncol,2000,17(6):1099-1105.
[26]IedelF,Gotte K,Bergler W,et al.Inverse correlation of apoptotic and angiogenic markers in squam ouscell carcinoma of the head andn eck[J]. Oncol Rep, 2001,8(3):471-476.
[27]Senger D R, Galli S J, Dvorak A M, et al. Tumor cells secrea VPF that promotes accumulation of ascites fluid. Science, 1983 (219) :983.
[28]Houck KA, Ferrara N, Winer J, et al. The vascular endo thelial growth factor family: indentification of a fourth molecular species and characterization of alternative splicing of RNA[J]. Mol Endocrinol, 1991; 5(12): 1806-1814.
[29]Papoutsi M , Kurz H , Schachtele C, et al. Induction of the blood-Brain-barrier marker neurothelin/ HT7 in endo2 the lial cells by a variety of tumors in chick embryos[J ].Histochem Cell Biol ,2000, 113(2) :105.
[30]Sameshima T, Nabeshima K, Toole B P, et al. Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors[J]. Virchows Arch ,2006 ,442(6) : 577.
[31]Mitsumoto Y, Watanabe A ,Miyauchi , et al. Stimulation of the regrow th of MMP damaged dopaminergic fibers by the treatment of mesencep halic cultures with basigin[J].J Neural Transm ,2001 ,108 (10) : 1127.
[32]Lanckura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on mela noma cells and imluccs tumors cell invasion by stimulating product ion of matrix metalloproteinases by libroblasts[J]. Int J Cancer, 2002, 99(4): 520-528.
[33]Ellerbroek S. M, Stack M.S. Membrane associated matrix metalloprote inases in metastasis[J]. Bioessays, 1999, 21:940-949.
[34]Stetler Stevenson W .G Matrix metalloproteinases and tumor invasio n from correlation and causality to the clinic Semin[J]. Cancer Biol,1996,7:147-154.
[35]Bergers G,Brekken R,Mc Mahon G, et al.Matrixm etalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J]. Nat Cell Biol,2000, 10:737-744.
[36]Kim I, Kim HG, Moon SO, et al.Angiopoietin-1 inducesendothelial cells prouting through the activation of focaladhesion kinase and plasm insecretin[J].CircRes, 2000, 86(9):952-959.
[37]Fang J, ShingY, W iederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotypein a tumor mode l[J].Proc Natl Acad SciUSA, 2000, 97(8):3884-3889.
[38]Liang L, Major T, Bocan T. Characteriation of the promoter of human extracellular matrix metalloproteinases inducer(EMMPRIN).GENE, 2002, 282(1-2): 75-86.
[1]李存孝,范清宇.CD147结构和功能及其与肿瘤关系的研究进展[J].现代肿瘤医学,2005,13(3):422-424.
[2]Biswas C,Zhng Y,Decastro R et al.The human tumor cell-derived collagenase stimulatory factor(Renamed EMMPRIN)is a member of the immunoglobulin[J].Cancer Res,1995:55:434-439.
[3]李吉,陈翔.CD147及其与肿瘤关系的研究及进展[J].国外医学肿瘤学分册.2003,30(4):258-261.
[4]Guo H,Majmudar G,Jensen T C,et al.Characterization of the human EMMPRIN,a tumor cell surface inducer of matrix metalloproteinases [J].Gene,1998,220(122):99-108.
[5]金伯泉.白细胞分化抗原[M]见:金伯泉主编,细胞和分子免疫学[M].第2版,北京:科学出版社 2001:4.
[6]Lanckura T,Chen X,Kanzaki T.Basigin(CD147)is expressed on m elanoma cells and imluccs tumors cell invasion by stimulating prod uction of matrix metalloproteinases by libroblasts[J].Int J Cancer,2002,99(4):520-528
[7]Chen X,Kanekura T,Tsuyama S,et al.Ultrastructural localization of basigin in normal human epidermis[J].Histochem Cell Biol,2001,115(6):465-470.
[8]Renno T,Wilson A,Dunkel C,et al.A role for CD147 in thymic devel opmen[J].J Immunol,2002,168(10):4946.
[9]Saxena DK,Oh Oka T,Kadomatsu K,et al.Behaviour of a sperm surf ce transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice[J].Reproduction,2002,123 3) : 435-444.
[10]Ochrietor J D, Moroz T P, Clamp M F, et al. Inactivation of the basigin gene impairs normal retinal development and maturation[J] . Vision Res, 2002, 42 (4) : 447-453.
[11] Papoutsi M, Kurz H, Schachtelec C, et al. Induction of the blood-brain-barrier marker neurothelin/HT7 in endothelial cell by a variety of tumors in chick embryos[J] . Histochem Cell Biol, 2000, 113 (2) : 105-113.
[12]Sameshima T, Nabeshima K, Toole B P, et al. Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: astudy using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors[J]. Virchows Arch ,2003,442(6) : 577.
[13]Mitsumoto Y, Watanabe A ,Miyauchi ,et al. Stimulation of the regrowth of MMP damaged dopaminergic fibers by the treatment of mesencephalic cultures with basigin[J]. Neural Transm ,2001 , 108(10):1127.
[14]Kanekura T, Chen X, Kanzaki T. Basigi(CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts[J] . Int J Cancer 2002 (99): 4520-528.
[15]Decastro R, Zhang Y, Guo H , et al. Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer[J]. Invest Dermatol, 1996, 106 (6) : 2160-1265.
[16]Guo H, Li R, Zucker S , et al. EMMPRIN (CD147) , an inducer of matrix metalloproteinases synthesis, also binds interstitial colagenase to the tumor cell surface[J] . Cancer Res, 2000, 60: 888-891.
[17]Broods P C, Stromblad S, Sanders L C, et al. Localization of matrix metalloproteinase MMP-2 to the surface of inasive cells by interaction with integrin αvβ3 [J] . Cell, 1996, 85 (5) : 683-693.
[18]Yoshiad S, Shibata M, Yamamoto S, et al. Homoligomer formation by asigin, and immunoglobulin superfamily member, via its N-terminal immunoglobulin domain[J] . Eur J Biochem, 2000, 267 (14) : 4372-4380.
[19]Kuno N, Kadomatsu K, Fan Q W , et al. Female steriling in miclacking the basigin gene which encode a transmember glycoprotei belonging to the IGSF[J]. FEBS Lett, 1998, 425 (2) : 191-194.
[20]Igakura T, Kadomatsu K, Kaname T, et al. A mill mutation basigin, and immunoglobulin superfamily member, indicates it important roles in periimplantation development and spermatogenesis[J].Dev Biol ,1998,194(2):152-165.
[21]Berditchevski F,Chang S,Bodovova J,et al.Generation of monoclonal antibodies to integrin-associated proteins.Evidence that alpha 3 beta 1 compexes with EMMPRIN/Basigin/OX247PM6[J].Biol Chem,1997,272(46):29174-29180.
[22]陈志南,刘彦仿抗人肝细胞癌单克隆抗体的产生及相应抗原P60免疫组化定位研究[J]单克隆抗体通讯,1989;27(1):33-36.
[23]郭晓楠,陈志南.肝癌膜相关抗原HA618G为CDl47分子的鉴定[J].肿瘤防治研究,2000,27(1):7-10.
[24]Sun JX,Hemler ME.Regulation of MMP-Ⅰ and MMP-2 production through CDI47/extracellular matrix metalloproteinase inducer Interactions[J].Cancer Res.2001:61:2276-2281.
[25]Guo H.Zucker S,Gordon M K,et al.Stimulation of matrix metalloprote inase Production by recombinant extracellular matrix metalloprotei nase inducer from transfected Chinese Hamster Ovary Cell[J].Biol Chem,1997;272(1):24-27.
[26]Lim M,Martinez T,Jablous D,et al.Tumor-derived EMMPRIN(extrac llular metalloproteinase inducer)stimulates collagenase transcri tion through MAPK p38[J].FEES Lett.1998:441(1):88-92.
[27]Broods P C,Stromblad S,Sanders LC,et al.Localization of matrix metalloproteinase MMP -2 to the surface of inasive cells by interaction with integrin α ν β3[J].Cell,1996,85(5):683-693.
[28]Liang L,Major T,Bocan T.Characterization of the promoter of Human extracellular matrix metalloproteinase inducer(EMMPRIN)[J].Gene,2002,282(122):75-86.
[29]Kasinrerk W,Tokrasinwit N,Phunpae P.CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell in U937 via LFA-1/ICAM-1 pathway[J].Immunology,1999,96(2):184-192.
[30]Jiang J L,Zhou Q,Yu M K,et al.The involvement of HAb18G/CD147 in regulation of store-operated calcium entry and metastasis of human hepatoma cells[J].Biol Chem,2001,276(50):46870-46877.
[31]Stemlicht M D,Werb Z.How matrix metalloproteinase regulate cell behavior[J].Annr Rev Cell Biol,2001,17:463.
[32]John A,Tuszynski G.The role of MMPs in tumor angiogenesis and tumor metastasis[J].Pathol Oncol Res,2001,7(1):14.
[33]Gun H.Li R,Zucker S,et al.EMMPRIN(CD147),an iducer of matrix metalloproteinases synthesis,also binds interstitial collagenase to the tumor cell surface[]]. Cancer Res, 2000; 60: 888-891.
[34]Zucker S.Drews M.Conner C, et al.Tissue inhibitor of metalloprotein ase-2(TIMP-2)binds to the catalytic domain of the cell surface receptor, membrane type-1 matrix metalloproteinase I(MT-MMP)[J]. Biol Chem ,1998,273:1216-1222.
[35]Polette M, Gilles C. Marchand V, et al. Tumor collagenase stimulatory factor(TCSF)expression and localization inhuman lung and breast cancers[J]. Histochem Cytochem. 1997, 45(5):703-709.
[36]Kasinrerk W .Tokrasinwit N, Phunpae P. CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell line U1937 via LFA-I/ICAM-I pathway[J]. Immunology. 1999,96(2): 184-192.
[37]Liang L, Major T, Bocan T. Characterization of the promoter of human extracellular matrix metalloproteinase inducer(EMMPRIN)[J]. Gene. 2002: 282(1-2):75-86.
[38]Cheng J, Ire T, Munskata R, et al. Biosynthesis of basement membrane molecules by salivary adnoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study. Virchows Arch(B), 1995, 426(6): 577.
[39]Giese A , Westphal M. Glioma invasion in the central nervous system [J].Neurosurgery. 1996 Aug; 39(2): 235-252.
[40]Nabeshima K, Lane W S, Biswas C. Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor[J].Arch Biochem Biophys, 1991(285): 90-96.
[41]Nakano A, Tani E, Miyazaki K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas[J].Neurosurg. 1995 Aug: 83 (2 ) : 298-307.
[42]Sameshima T, Nabeshima K, Toole BP, et al. Glioma cell extracellular matrix metallo proteinase inducer(EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in cocultures with brain-derived fibroblasts [J].Can cer Lett, 2000, 157 (2): 177-184.
[43]Sameshima T, Nabeshima K, Toole BP, et al. Expression of emmprin CD147 a cell surface inducer of matrix metalloproteinases in normal human brain and gliomas[J]. Int J Cancer. 2000 Oct: 88 (1) :21-27.
[44]Itoh T, Tanioka M, Yoshida H, et al.Reduced angiogenesis and tumor progression in gelatinase A-deficient mice[J]. Caner Res. 1998 Mar, 58(5): 1048-1051.
[45]Liu weiping , KUNISHIO Katsuzo, MATSUMOTO Yoshihito , et al . Matrix metal loproteinase 2 expression in invasive pituitary adenomas [J]. Chin Neurosury Dis Res, 2003, 2(1):7-11.
[46]Steward WP, Thomas AI, Marimastat : the clinical development of a matrix metalloproteinase inhibitor[J]. Expert Opin Investing Drups. 2000,9(12): 2913-2922.
[47]Kruger EA, Figg WD. TNP-470: an angiogenesis inhibitor in clinical development for cancer [J].Expert Opin Investing Drugs. 2000, 9(6):1383-1396.
[48]Liang L, Major T, Bocan T.Characteriation of the promoter of human extracellular matrix metalloproteinases inducer(EMMPRIN).GENE, 2002, 282(1-2): 75-86.
[2]王翦,刘运生.MMP及TIMP在垂体腺瘤中的表达及与侵袭性关系[J].湖南医科大学学报,2004,29(6):647-650.
[3]Veikkola T,Alitalo K.VEGFs,receptors and angiogenesis[J].Semin C ancer Biol,1999,9:211-220.
[4]Anthony P,Heaney,Gregory A et al.Early involvement of estrogen i nduced pituitary tumor transforming gene and Hardy J,Vezina JL.Tra nssphenoidal neurosurgery of intracranial neoplasm[J].Adv Neurol,1976,15:261-273.
[5]Knosp E,Stiner E,Kitz K,et al.Pituitary adenomas with invasiono f the cavernous sinus space a magnetic resonance imaging classifica tion compared with surgical findings[J].Neurosurgery,1993,Oct;33(4):610-7;discussion 617-8.
[6]Shimizu M,Saitoh Y,Itch H.Immunohistochemical staining of Haraso ncogene in normal,benign,and malignant human pancreatic tissue[J].Hum Pathol,1990,21:601-612.
[7]Jefferson G.Extrasellar extensions of pituitary adenomas:Preside nt's address[J].Pro R Soc Med,1940,33:433-458.
[8]Scheithauer B W,Kovacs K T,Laws E R Jr,et al.Pathology of invas ire pituitary tumors with special reference to functional classific ation[J].Neurosurg,1986,65:733-744.
[9]Kawamoto H,Uozumi T,Kawamoto K,et al.Analysis of the growth rat e and cavernous sinus invasion of pituitary adenomas[J].Acta Neuro chir(Wien),1995,136:37-43.
[10]Thaper K,Kovacs K,Scheithauer B W et al.Proliferative activity an d invasiveness among pituitary adenomas and carcinomas:an analysi s using the M-IB-1 antibody[J].Neurosurgery,1996,38(1):99-107.
[11]Tomita T.Matrix metalloproteinases and tissue inhibitors of metal loproteinases in thyroid C-cells and medullary thyroid carcinomas [J].Histopathology,1997,31(2):150-156.
[12]Bode W,Fernandez Catalan C,Grams F,et al.Insights into MMP-TIM P interactions[J].Ann N Y Acad Sci,1999,878:73-91.
[13]任祖渊.侵袭性垂体腺瘤的研究现状及展望.中华神经外科杂志.2000.16(增 刊):112-115.
[14]龚俊扬.侵袭性垂体腺瘤及其研究进展.国外医学神经病学神经外科分册,2000,27:27-28.
[15]Miyajima Y,Nakano R,Mori matsu M,et al.Analysis of expression of matrix metalloproteinase-2 and -9 in hypopharyngeal squamous cell carcinoma by in situhybridization[J].Ann Otol-Rhinol-Larvnglo.1995,104:678-684
[16]Bode W,Fernandez Catalan C,Grams F,et al.Insights into MMP-TIM P interactions[J].Ann N Y Acad Sci,1999,878:73-91.
[17]Seandel M,Noack-Kunmnann K,Zhu D,et al.Growth factor induced angiogenesis in vivo requires specific cleavage of fibrillar type Ⅰ collagen[J].Blood,2001,97(8):2323-2332.
[18]John A,Tuszynski G.The role of MMPs in tumor angiogenesis and tu mor metastasis[J].Pathol Oncol Res,2001,7(1):14.
[19]Curran S,Murray GI.Matrix metalloproteinases in tumour invasion and metastasis[J].Pathol,1999,189(3):300-308.
[20]Heaney AP,Horwitz GA,Wang Z,et al.Early involvement of estroge ninduced pituitary tumor transforming gene and fibroblast growth fact or expression in prolactinoma pathogenesis.Nat Med,1999,5(11):1317-1321.
[21]Kawamoto H,Uozumi T,Kamamtot K,et al.Type Ⅳ collagenase activ ity and cavenous sinus invasion in human pituitary adenomas[J].Ac ta Neurochir(Wien),1996;138(4):390-395.
[22]Turner H E,Nagy Z,Esiri M M,etal.Roleofm atrix metalloproteinase-9 in pituitary tumor behavior[J].JClin Endocorinol Metab,2000,85(8):2931-2935.
[23]Vu TH,Shipley J M,Bergers G,et al.MMP-9/gelatinase B is a key r egulation of growth plate angiogenesis and apoptosis of hypertroph ic chondrocytes[J].Cell,1998,93(3):411-422.
[24]Bergers G,Brekken R,Mc Mahon G,et al.Matrixm etalloproteinase-9triggers the angiogenic switch during carcinogenesis[J].Nat Cell Biol,2005,10:737-744.
[25]RiedelF,Gotte K,Schwalb J,et al.Expression of 92-kDa type Ⅳ colla genase correlateswith angiogenic markers and poor survivalin head and neck squam ouscellcarcinoma[J].Int J Oncol,2000,17(6):1099-1105.
[26]IedelF,Gotte K,Bergler W,et al.Inverse correlation of apoptotic and angiogenic markers in squam ouscell carcinoma of the head andn eck[J]. Oncol Rep, 2001,8(3):471-476.
[27]Senger D R, Galli S J, Dvorak A M, et al. Tumor cells secrea VPF that promotes accumulation of ascites fluid. Science, 1983 (219) :983.
[28]Houck KA, Ferrara N, Winer J, et al. The vascular endo thelial growth factor family: indentification of a fourth molecular species and characterization of alternative splicing of RNA[J]. Mol Endocrinol, 1991; 5(12): 1806-1814.
[29]Papoutsi M , Kurz H , Schachtele C, et al. Induction of the blood-Brain-barrier marker neurothelin/ HT7 in endo2 the lial cells by a variety of tumors in chick embryos[J ].Histochem Cell Biol ,2000, 113(2) :105.
[30]Sameshima T, Nabeshima K, Toole B P, et al. Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: a study using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors[J]. Virchows Arch ,2006 ,442(6) : 577.
[31]Mitsumoto Y, Watanabe A ,Miyauchi , et al. Stimulation of the regrow th of MMP damaged dopaminergic fibers by the treatment of mesencep halic cultures with basigin[J].J Neural Transm ,2001 ,108 (10) : 1127.
[32]Lanckura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on mela noma cells and imluccs tumors cell invasion by stimulating product ion of matrix metalloproteinases by libroblasts[J]. Int J Cancer, 2002, 99(4): 520-528.
[33]Ellerbroek S. M, Stack M.S. Membrane associated matrix metalloprote inases in metastasis[J]. Bioessays, 1999, 21:940-949.
[34]Stetler Stevenson W .G Matrix metalloproteinases and tumor invasio n from correlation and causality to the clinic Semin[J]. Cancer Biol,1996,7:147-154.
[35]Bergers G,Brekken R,Mc Mahon G, et al.Matrixm etalloproteinase-9 triggers the angiogenic switch during carcinogenesis [J]. Nat Cell Biol,2000, 10:737-744.
[36]Kim I, Kim HG, Moon SO, et al.Angiopoietin-1 inducesendothelial cells prouting through the activation of focaladhesion kinase and plasm insecretin[J].CircRes, 2000, 86(9):952-959.
[37]Fang J, ShingY, W iederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotypein a tumor mode l[J].Proc Natl Acad SciUSA, 2000, 97(8):3884-3889.
[38]Liang L, Major T, Bocan T. Characteriation of the promoter of human extracellular matrix metalloproteinases inducer(EMMPRIN).GENE, 2002, 282(1-2): 75-86.
[1]李存孝,范清宇.CD147结构和功能及其与肿瘤关系的研究进展[J].现代肿瘤医学,2005,13(3):422-424.
[2]Biswas C,Zhng Y,Decastro R et al.The human tumor cell-derived collagenase stimulatory factor(Renamed EMMPRIN)is a member of the immunoglobulin[J].Cancer Res,1995:55:434-439.
[3]李吉,陈翔.CD147及其与肿瘤关系的研究及进展[J].国外医学肿瘤学分册.2003,30(4):258-261.
[4]Guo H,Majmudar G,Jensen T C,et al.Characterization of the human EMMPRIN,a tumor cell surface inducer of matrix metalloproteinases [J].Gene,1998,220(122):99-108.
[5]金伯泉.白细胞分化抗原[M]见:金伯泉主编,细胞和分子免疫学[M].第2版,北京:科学出版社 2001:4.
[6]Lanckura T,Chen X,Kanzaki T.Basigin(CD147)is expressed on m elanoma cells and imluccs tumors cell invasion by stimulating prod uction of matrix metalloproteinases by libroblasts[J].Int J Cancer,2002,99(4):520-528
[7]Chen X,Kanekura T,Tsuyama S,et al.Ultrastructural localization of basigin in normal human epidermis[J].Histochem Cell Biol,2001,115(6):465-470.
[8]Renno T,Wilson A,Dunkel C,et al.A role for CD147 in thymic devel opmen[J].J Immunol,2002,168(10):4946.
[9]Saxena DK,Oh Oka T,Kadomatsu K,et al.Behaviour of a sperm surf ce transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice[J].Reproduction,2002,123 3) : 435-444.
[10]Ochrietor J D, Moroz T P, Clamp M F, et al. Inactivation of the basigin gene impairs normal retinal development and maturation[J] . Vision Res, 2002, 42 (4) : 447-453.
[11] Papoutsi M, Kurz H, Schachtelec C, et al. Induction of the blood-brain-barrier marker neurothelin/HT7 in endothelial cell by a variety of tumors in chick embryos[J] . Histochem Cell Biol, 2000, 113 (2) : 105-113.
[12]Sameshima T, Nabeshima K, Toole B P, et al. Correlation of emmprin expression in vascular endothelial cells with blood-brain-barrier function: astudy using magnetic resonance imaging enhanced by Gd-DTPA and immunohistochemistry in brain tumors[J]. Virchows Arch ,2003,442(6) : 577.
[13]Mitsumoto Y, Watanabe A ,Miyauchi ,et al. Stimulation of the regrowth of MMP damaged dopaminergic fibers by the treatment of mesencephalic cultures with basigin[J]. Neural Transm ,2001 , 108(10):1127.
[14]Kanekura T, Chen X, Kanzaki T. Basigi(CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts[J] . Int J Cancer 2002 (99): 4520-528.
[15]Decastro R, Zhang Y, Guo H , et al. Human keratinocytes express EMMPRIN, an extracellular matrix metalloproteinase inducer[J]. Invest Dermatol, 1996, 106 (6) : 2160-1265.
[16]Guo H, Li R, Zucker S , et al. EMMPRIN (CD147) , an inducer of matrix metalloproteinases synthesis, also binds interstitial colagenase to the tumor cell surface[J] . Cancer Res, 2000, 60: 888-891.
[17]Broods P C, Stromblad S, Sanders L C, et al. Localization of matrix metalloproteinase MMP-2 to the surface of inasive cells by interaction with integrin αvβ3 [J] . Cell, 1996, 85 (5) : 683-693.
[18]Yoshiad S, Shibata M, Yamamoto S, et al. Homoligomer formation by asigin, and immunoglobulin superfamily member, via its N-terminal immunoglobulin domain[J] . Eur J Biochem, 2000, 267 (14) : 4372-4380.
[19]Kuno N, Kadomatsu K, Fan Q W , et al. Female steriling in miclacking the basigin gene which encode a transmember glycoprotei belonging to the IGSF[J]. FEBS Lett, 1998, 425 (2) : 191-194.
[20]Igakura T, Kadomatsu K, Kaname T, et al. A mill mutation basigin, and immunoglobulin superfamily member, indicates it important roles in periimplantation development and spermatogenesis[J].Dev Biol ,1998,194(2):152-165.
[21]Berditchevski F,Chang S,Bodovova J,et al.Generation of monoclonal antibodies to integrin-associated proteins.Evidence that alpha 3 beta 1 compexes with EMMPRIN/Basigin/OX247PM6[J].Biol Chem,1997,272(46):29174-29180.
[22]陈志南,刘彦仿抗人肝细胞癌单克隆抗体的产生及相应抗原P60免疫组化定位研究[J]单克隆抗体通讯,1989;27(1):33-36.
[23]郭晓楠,陈志南.肝癌膜相关抗原HA618G为CDl47分子的鉴定[J].肿瘤防治研究,2000,27(1):7-10.
[24]Sun JX,Hemler ME.Regulation of MMP-Ⅰ and MMP-2 production through CDI47/extracellular matrix metalloproteinase inducer Interactions[J].Cancer Res.2001:61:2276-2281.
[25]Guo H.Zucker S,Gordon M K,et al.Stimulation of matrix metalloprote inase Production by recombinant extracellular matrix metalloprotei nase inducer from transfected Chinese Hamster Ovary Cell[J].Biol Chem,1997;272(1):24-27.
[26]Lim M,Martinez T,Jablous D,et al.Tumor-derived EMMPRIN(extrac llular metalloproteinase inducer)stimulates collagenase transcri tion through MAPK p38[J].FEES Lett.1998:441(1):88-92.
[27]Broods P C,Stromblad S,Sanders LC,et al.Localization of matrix metalloproteinase MMP -2 to the surface of inasive cells by interaction with integrin α ν β3[J].Cell,1996,85(5):683-693.
[28]Liang L,Major T,Bocan T.Characterization of the promoter of Human extracellular matrix metalloproteinase inducer(EMMPRIN)[J].Gene,2002,282(122):75-86.
[29]Kasinrerk W,Tokrasinwit N,Phunpae P.CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell in U937 via LFA-1/ICAM-1 pathway[J].Immunology,1999,96(2):184-192.
[30]Jiang J L,Zhou Q,Yu M K,et al.The involvement of HAb18G/CD147 in regulation of store-operated calcium entry and metastasis of human hepatoma cells[J].Biol Chem,2001,276(50):46870-46877.
[31]Stemlicht M D,Werb Z.How matrix metalloproteinase regulate cell behavior[J].Annr Rev Cell Biol,2001,17:463.
[32]John A,Tuszynski G.The role of MMPs in tumor angiogenesis and tumor metastasis[J].Pathol Oncol Res,2001,7(1):14.
[33]Gun H.Li R,Zucker S,et al.EMMPRIN(CD147),an iducer of matrix metalloproteinases synthesis,also binds interstitial collagenase to the tumor cell surface[]]. Cancer Res, 2000; 60: 888-891.
[34]Zucker S.Drews M.Conner C, et al.Tissue inhibitor of metalloprotein ase-2(TIMP-2)binds to the catalytic domain of the cell surface receptor, membrane type-1 matrix metalloproteinase I(MT-MMP)[J]. Biol Chem ,1998,273:1216-1222.
[35]Polette M, Gilles C. Marchand V, et al. Tumor collagenase stimulatory factor(TCSF)expression and localization inhuman lung and breast cancers[J]. Histochem Cytochem. 1997, 45(5):703-709.
[36]Kasinrerk W .Tokrasinwit N, Phunpae P. CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell line U1937 via LFA-I/ICAM-I pathway[J]. Immunology. 1999,96(2): 184-192.
[37]Liang L, Major T, Bocan T. Characterization of the promoter of human extracellular matrix metalloproteinase inducer(EMMPRIN)[J]. Gene. 2002: 282(1-2):75-86.
[38]Cheng J, Ire T, Munskata R, et al. Biosynthesis of basement membrane molecules by salivary adnoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study. Virchows Arch(B), 1995, 426(6): 577.
[39]Giese A , Westphal M. Glioma invasion in the central nervous system [J].Neurosurgery. 1996 Aug; 39(2): 235-252.
[40]Nabeshima K, Lane W S, Biswas C. Partial sequencing and characterization of the tumor cell-derived collagenase stimulatory factor[J].Arch Biochem Biophys, 1991(285): 90-96.
[41]Nakano A, Tani E, Miyazaki K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas[J].Neurosurg. 1995 Aug: 83 (2 ) : 298-307.
[42]Sameshima T, Nabeshima K, Toole BP, et al. Glioma cell extracellular matrix metallo proteinase inducer(EMMPRIN) (CD147) stimulates production of membrane-type matrix metalloproteinases and activated gelatinase A in cocultures with brain-derived fibroblasts [J].Can cer Lett, 2000, 157 (2): 177-184.
[43]Sameshima T, Nabeshima K, Toole BP, et al. Expression of emmprin CD147 a cell surface inducer of matrix metalloproteinases in normal human brain and gliomas[J]. Int J Cancer. 2000 Oct: 88 (1) :21-27.
[44]Itoh T, Tanioka M, Yoshida H, et al.Reduced angiogenesis and tumor progression in gelatinase A-deficient mice[J]. Caner Res. 1998 Mar, 58(5): 1048-1051.
[45]Liu weiping , KUNISHIO Katsuzo, MATSUMOTO Yoshihito , et al . Matrix metal loproteinase 2 expression in invasive pituitary adenomas [J]. Chin Neurosury Dis Res, 2003, 2(1):7-11.
[46]Steward WP, Thomas AI, Marimastat : the clinical development of a matrix metalloproteinase inhibitor[J]. Expert Opin Investing Drups. 2000,9(12): 2913-2922.
[47]Kruger EA, Figg WD. TNP-470: an angiogenesis inhibitor in clinical development for cancer [J].Expert Opin Investing Drugs. 2000, 9(6):1383-1396.
[48]Liang L, Major T, Bocan T.Characteriation of the promoter of human extracellular matrix metalloproteinases inducer(EMMPRIN).GENE, 2002, 282(1-2): 75-86.
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