(3.238.186.43) 您好!臺灣時間:2021/02/26 12:22
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:鄭雅文
研究生(外文):Ya-wen Cheng
論文名稱:探討子宮內膜異位症與血管新生因子表現的關係
論文名稱(外文):Angiogenic factors in endometriosis: evaluation of four candidate genes expressions and their relation with the severity and extent of the disease
指導教授:王妙媛王妙媛引用關係
指導教授(外文):Nancy M. Wang
學位類別:碩士
校院名稱:國立彰化師範大學
系所名稱:生物技術研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:70
中文關鍵詞:子宮內膜異位症血管新生血管新生因子生物晶片即時定量聚合酶連鎖反應
外文關鍵詞:endometriosisangiogenesismicroarrayVEGF-BTIMP-1ENGRPS27areal-time PCR
相關次數:
  • 被引用被引用:0
  • 點閱點閱:202
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:13
  • 收藏至我的研究室書目清單書目收藏:0
子宮內膜異位症是婦科常見疾病,其好發率為全球婦女的6至10%。此疾病造成月經疼痛、骨盆疼痛、性交疼痛、不孕症,以及其他非特異性的症狀。子宮內膜異位症的成因相當複雜且不明確,唯一廣泛接受的假說為經血逆流。之前研究指出子宮內膜異位症為血管新生疾病,而且在子宮內膜異位症病人的腹水中,含有大量的血管新生因子。本篇研究的主要目的為找出和形成子宮內膜異位症有關的血管新生因子; 先利用生物晶片篩檢出在子宮內膜異位症組織會大量表現的血管新生因子,其因子為VEGF-B、 TIMP-1、 ENG以及 RPS27a。於是,總共收集72個子宮內膜異位症的檢體,再應用real-time PCR評估此四個血管新生因子的表現量。
我們的結果顯示,在血管新生之生物晶片中,VEGF-B、 TIMP-1、 ENG以及 RPS27a在子宮內膜異位症組織中表現量增加0.95、1.45、1.98及1.53倍。根據病人病歷分析,子宮內膜異位症的分級、CA-125濃度和身體質量指數與正常人沒有差異。應用於real-time PCR,在子宮內膜異位症的組織中,58% (42/72)的病例其ENG的表現量增加以及57% (41/72)的病例其RPS27a的表現量增加2.22倍和1.47倍,而VEGF-B及TIMP-1分別有25% (18/72)和28% (20/72)的病例會表現量增加2.85倍和0.71倍。另外在血液內白血球中,此四個基因的表現量皆比正常白血球低。之後觀察病歷與子宮內膜異位症的關係,發現子宮內膜異位症輕度與重度等級的病人及骨盆疼痛中,ENG與RPS27a會大量表現,但是在其他病症中,例如:經痛、不孕症、子宮內膜異位囊腫的位置、子宮沾粘及子宮後壁沾粘,此四個基因表現量沒有差異。根據此篇研究結果,子宮內膜異位症為血管新生的疾病,ENG確實會大量表現於血管新生中的子宮內膜異位的組織,而RPS27a的表現促使子宮內膜異位的組織大量增生,此兩個血管新生因子有可能成為診斷子宮內膜異位症的生物標記,進而發展血管新生的治療來抑制子宮內膜異位症。
Endometriosis is a common female reproduction disease and the incidence of endometriosis is 6-10% worldwide. Its symptoms include dysmenorrhoea, pelvic pain, especially menstrual cycle, dyspareunia, even infertility and nonspecific symptoms. The cause of this disease is still unknown. The most widely accepted hypothesis for the development of endometriosis is retrograde menstruation. Previous studies have suggested that endometriosis is an angiogenic disease. The peritoneal fluid of women with endometriosis contains more angiogenic factors than that of women without the disease. Thus, the aim of this study is to search for angiogenic factors which participate in endometriosis pathogenesis pathway. In this study, several candidates VEGF-B, TIMP-1, ENG and RPS27a were identified which were found over expressed in endometriosis by microarray. These four genes expressed 0.95, 1.45, 1.98 and 1.53 fold higher in endometriosis than control. Real-time PCR was used to quantitate expressions of these factors from 72 endometriotic tissues collected in this study. Among these factors, ENG and RPS27a were found strongly expressed in endometriosis (58%, 42/72 and 57%, 41/72 respectively). VEGF-B and TIMP-1 were down regulated in endometriosis (25%, 18/72 and 28%, 20/72 respectively). These four genes expressed 2.85, 0.71, 2.22 and 1.47 fold higher in endometriosis than control. However, we failed to detect these genes’ expression in leukocyte. In addition, no correlation was found between these genes. The CA-125 concentration, BMI and AFS score were not significant differences between endometriois and normal control. ENG and RPS27a were over expressed in stage III, IV and pain of patients. Others clinic characteristics, dysmenorrhea, adhesion, infertility, the location of endometrioma and cul-de-sac obliteration, were not associated these genes expressons. In conclusion, endometriosis is an angiogenic disease where ENG, is an angiogenic biomarker and RPS27a may promote endometriotic cells growth. They are potential biomarkers for diagnosis and to develop a new therapy for angiogenesis of endometriosis.
Chapter 1 Introduction......................1
1. Endometriosis............................1
2. Symptoms of endometriosis................1
3. Diagnosis of endometriosis...............2
4. Stage of endometriosis...................2
5. Treatment of endometriosis...............3
6. Causes of endometriosis..................3
7. Angiogenesis with endometriosis..........5
8. Gene expression in endometriosis.........6
9. VEGF-B...................................7
10. TIMP-1..................................8
11. ENG.....................................10
12. RPS27a..................................11
13. Specific aims...........................11
Chapter 2 Materials and methods.............12
1. Patients and samples collection..........12
2. DNA extraction of frozen tissues.........12
3. RNA extraction of frozen tissues.........13
4. DNA and RNA extraction of leukocyte......14
5. Synthesis of cDNA........................15
6. cDNA microarray..........................16
7. VEGF-B, TIMP-1, ENG and RPS27a expression using real time PCR....................................16
8. Statistic analysis.......................18
Chapter 3 Results...........................19
1. Characteristics and clinical features of women with endometriosis...............................19
2. Angiogenesis microarray with endometriosis and without endometriosis...............................20
3. Expressions of VEGF-B, TIMP-1, ENG and RPS27a in tissue with real-time PCR..........................21
4. Expressions of VEGF-B, TIMP-1, ENG and RPS27a in tissue related with clinical characteristics of endometriosis........22
5. Expressions of VEGF-B, TIMP-1, ENG and RPS27a in blood leukocyte with real-time PCR................28
Chapter 4 Discussions.......................30
1. The relationship between staging of endometriosis and other clinical characteristics..............30
2. ENG up-regulated expression is associated with angiogenesis for endometriosis.............30
3. RPS27a up-regulated expression is associated with angiogenesis for endometriosis............31
4. TIMP-1 down-regulated expression is associated with angiogenesis for endometriosis............32
5. VEGF-B expression is not associated with angiogenesis for endometriosis.........................33
Chapter 5 References......................35
Chapter 6 Figures.........................44
1.The results of angiogenesis macroarray...44
2.The standard curve of VEGF-B...........45
3.The standard curve of TIMP-1...........46
4.The standard curve of RPS27a...........47
5.The standard curve of ENG..............48
6.The distribution of mRNA expression of four genes in 72 endometriosis patients...................49
7.The distribution of mRNA expression of four genes in 13 leukocyte blood..........................50
Chapter 7 Tables..........................51
1.The values of gene expression array comparing endometriotic tissues with normal endometrium.....51
2.Oligonucleotide primers for real-time PCR study of VEGF-B, TIMP-1, RPS27a, endoglin and ACTB (β-actin)....52
3.Primers efficiencies and annealing temperatures for real-time PCR study of VEGF-B, TIMP-1, RPS27a, ENG and ACTB (β-actin).............53
4.Basic characteristics of patients with endometriosis.....54
5.Summary of clinical and pathological characteristic in endometriosis patients..........55
6.Comparison of characteristics of patients with endometriosis and normal controls........56
7.mRNA expression of the four genes in endometriosis patients.............57
8.The values of gene expression comparing endometriotic tissues with normal endometrium by real-time PCR.......58
9.mRNA expression of four genes in endometriosis patients and normal................59
10.VEGF-B expression in endometriosis according to clinical characteristics of patents...........60
11.TIMP-1 expression in endometriosis according to clinical characteristics of patents..........61
12.ENG expression in endometriosis according to clinical characteristics of patents..........62
13.RPS27a expression in endometriosis according to clinical characteristics of patents..........63
14.mRNA expression of the four genes in blood leukocyte by real-time PCR.......................64
15.mRNA expression of the APN in endometriosis patients and normal patients.....................65
Chapter 8 Appendix........................66
American Fertility Society. Classification of endometriosis. Fertil Steril. 1979; 32: 633-45.
Becker CM, Amato RJ. Angiogenesis and antiangiogenic therapy in endometriosis. Microvasc Res. 2007; 74: 121-30.
Bachman KE, Herman JG, Corn PG, Merlo A, Costello JF, Cavenee WK, et al. Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. Cancer Res. 1999; 59: 798-802.
Bodey B, Bodey Jr B, Siegel SE, Kaiser HE. Over-expression of endoglin (CD105): a marker of breast carcinoma-induced neovascularization. Anticancer Res. 1998; 18: 3621-8.
Cramer DW. Epidemiology of endometriosis in adolescents. In: Wilson EA, ed. Endometriosis. New York: Alan Liss, 1987: 5-8.
Cheng YM, Wang ST, Chou CY. Serum CA-125 in preoperative patients at high risk for endometriosis. Obstet Gynecol. 2002; 99: 375-80.
Charnock-Jones DS, Sharkey AM, Rajput-Williams J, Burch D, Schofield JP, Fountain SA, et al. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod. 1993; 48: 1120-8.
Calabrò L, Fonsatti E, Bellomo G, Alonci A, Colizzi F, Sigalotti L, et al. Differential levels of soluble endoglin (CD105) in myeloid malignancies. J Cell Physiol. 2003; 194: 171-5.
Cullen TS. Adenomyoma of the rectovaginal septum. J Ameri Medl Asso. 1914; 62: 835-9.
Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, et al. Matrix metalloproteinases generate angiostatin: effects on neovascularization. JImmunol. 1998; 161: 6845-52.
Dulaimi E, Ibanez de Caceres I, Uzzo RG, Al-Saleem T, Greenberg RE, Polascik TJ, et al. Promoter hypermethylation profile of kidney cancer. Clin Cancer Res. 2004; 10: 3972-9.
Donnez J, Smoes P, Gillerot S. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998; 13: 1686-90.
DeClerck YA. Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloprotein- ases in cancer. Eur J Cancer. 2000; 36: 1258-68.
Dizerega GS, Barber DL, Hodgen GD. Endometriosis: role of ovarian steroids in initiation, maintenance, and suppression. Fertil Steril. 1980; 33: 649-53.
Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J. 2003; 17: 984-92.
Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002; 2: 161-74.
Electron K, Miao P, Emily R, Quan-Yang D, Orlo H, Alex M. Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms. Surgery. 2005; 138: 1102-10.
Fanton JW, Golden JG. Radiation-induced endometriosis in Maccaca mulatta. Radiat Res. 1991; 126: 141-6.
Findlay JK. Angiogenesis in reproductive tissues. J Endocrinol. 1986; 111: 357-66.
Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol. 2002; 29: 10-4.
Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt- receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature. 1995; 376: 66-70.
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. EndocrRev. 1997; 18: 4-25.
Fernandez HA, Kallenbach K, Seghezzi G, Grossi, E, Colvin S, chneider R, et al. Inhibition of endothelial cell migration by gene transfer of tissue inhibitor of metalloproteinases-1. J Surg Res. 1999; 82: 156-62.
Giudice LC, Kao LC. Endometriosis. Lancet. 2004; 364: 1789-99.
Gordon, JD, Shifren JL, Foulk RA, Taylor RN, Jaffe RB. Angiogenesis in the human female reproductive tract. Obst Gynecol Surv. 1995; 50: 688-97.
Gasson JC, Bersch N, Golde DW. Characterization of purified human erythroid potentiating activity. Prog Clin Biol Res. 1985; 184: 95-104.
Gougos A, Letarte M. Identification of a human endothelial cell antigen with monoclonal antibody 44G4 produced against a pre-B leukemic cell line. J Immunol. 1988; 141: 1925-33.
Gargett CE, Lederman FL, Lau TM. Lack of correlation between vascular endothelial growth factor production and endothelial cell. Hum Reprod. 1999; 14: 2080-8.
Greene J, Wang M, Liu YE, Raymond LA, Rosen C, Shi YE. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem. 1996; 271: 30375-80.
Houston DE. Evidence for the risk of pelvic endometriosis by age, race, and socioeconomic status. Epidemiol Rev. 1984; 6: 167-91.
Halme JA, Hammond MG, Hulka JF, Raj S, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984; 64: 333-7.
Healy DL, Rogers PA, Hii L, Wingfield M. Angiogenesis: a new theory for endometriosis. Hum Reprod Update. 1998; 5: 736-40.
Hyder SM, Nawaz Z, Chiappetta C, Stancel GM. Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res. 2000; 60: 3183-90.Hayrabedyan S, Kyurkchiev S, Kehayov I. Endoglin (cd105) and S100A13 as markers of active angiogenesis in endometriosis. Reprod Biol. 2005; 5: 51-67.
Koninckx PR, Braet P, Kennedy SH, Barlow DH. Dioxin pollution and endometriosis in Belgium. Hum Reprod. 1994; 9: 1001-2.
Kim SH, Choi YM, Chae HD, Kim KR, Kim CH, Kang BM. Increased expression of endoglin in the eutopic endometrium of women with endometriosis. Fertil Steril. 2001; 76: 918-22.
Kirschner LS, Stratakis CA. Structure of the human ubiquitin fusion gene Uba80 (RPS27a) and one of its pseudogenes. Biochem Biophys Res Commun. 2000; 270: 1106-10.
Kaku T, Hirakawa T, Kamura T, Amada S, Kinukawa N, Kabayashi H, et al. Angiogenesis in adenocarcinoma of the uterine cervix. Cancer. 1998; 83: 1384-90.
Ko Y, Hahn T, Lu H, Ma ZL, Chen J, Rothe M et al. A novel component of the ubiquitin pathway, ubiquitin carboxyl extension protein 1 is overexpressed in prostate cancer. Int J Mol Med. 2005; 15: 183-96.
Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of the peritoneal fluid. Hum Reprod Update. 1998; 4: 741-51.
Lessey BA. Medical management of endometriosis and infertility. Fertil Steril. 2000; 73: 1089-96.
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246: 1306-9.
Lastres P, Bellon T, Cabañas C, Sanchez-Madrid F, Acevedo A, Gougos A, et al. Regulated expression on human macrophages of endoglin, an Arg-Gly-Asp containing surface antigen. Eur J Immunol. 1992; 22: 393-7.
Li XF, Gregory J, Ahmed A. Immunolocalisation of vascular endothelial growth factor in human endometrium. Growth Factors. 1994; 11: 277-82.
Louise H, Stephen C, Clement L, Kaylon L, Kevin G, Brian D, et al. Antiangiogenicagents are effective inhibitors of endometriosis. J Clini Endocrinol Metab. 2003; 88: 2889-99.
Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N, et al. Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer. 2000; 89: 122-6.
Leibovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001; 75: 1-10.
Li G, Fridman R, Kim HR. Tissue inhibitor of metalloproteinase- 1 inhibits apoptosis of human breast epithelial cells. Cancer Res. 1999; 59: 6267-75.
Lafleur MA, Handsley MM, Knauper V, Murphy G, Edwards D R. Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs). J Cell Sci. 2002; 115: 3427-38.
Luparello C, Avanzato G, Carella C, Pucci-Minafra I. Tissue inhibitor of metalloprotease (TIMP)-1 and proliferative behaviour of clonal breast cancer cells. Breast Cancer Res Treat. 1999; 54: 235-44.
Mueller, M.D, Vigne JL, Minchenko A, Lebovic DI, Leitman DC, Taylor RN. Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta. Proc Natl Acad Sci. 2000; 97: 10972-7.
Mettler L, Salmassi A, Schollmeyer T, Schmutzler AG, Pungel F, Jonat W. Comparison of c-DNA microarray analysis of gene expression between eutopic endometrium and ectopic endometrium (endometriosis). J Assist Reprod Genet. 2007; 24: 249-58.
Meden H, Marx D, Roegglen T, Schauer A, Kuhn W. Overexpression of the oncogene c-erbB-2 (HER2/neu) and response to chemotherapy in patients with ovarian cancer. Int J Gynecol Pathol. 1998; 17: 61-5.
Meden H, Fattahi-Meibodi A. CA 125 in benign gynecological conditions. Int J Biol Markers.1998; 13: 231-7.
Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O. Organ-specific endoglin (CD105) expression in the angiogenesis of human cancers. Pathol Int. 2006; 56: 717-23.
McColl BK, Stacker SA, Achen MG. Molecular regulation of the VEGF family-inducers of angiogenesis and lymphangiogenesis. APMIS. 2004; 112: 463-80.
McCarty MF, Baker CH, Bucana CD, Fidler IJ. Quantitative and qualitative in vivo angiogenesis assay. Int J Oncol. 2002; 21: 5-10.
Mizumoto H, Saito T, Ashihara K, Nishimura M, Takehara M, Tanaka R et al. Expression of matrix metalloproteinases in ovarian endometriomas: immunohistochemical study and enzyme immunoassay. Life Sci. 2002; 71: 259-73.
Nap AW, Groothuis PG, Demir AY, Evers JL, Dunselman GA. Pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004; 18: 233-44.
Olive DL, Lindheim SR, Pritts EA. New medical treatments for endometriosis. Best Pract Res Clin Obstet Gynecol. 2004; 18: 319-28.
Oosterlynck DJ, Meuleman C, Sobis, H, Vandeputte M, Koninckx PR. Angiogenic activity of peritoneal fluid from women with endometriosis. Fertil Steril. 1993; 59: 778-82.
Olofsson B, Pajusola K, Kaipainen A, Euler G, Joukov V, Saksela O, et al. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci. 1996; 93: 2576-81.
Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci. 1998; 95: 11709-14.
Oosterlynck DJ, Meuleman C, Sobis H, Vandeputte M, Koninckx PR. Angiogenic activity of peritoneal fluid from women with endometriosis. Fertil Steril. 1993; 59: 778-82.
Ozlem E, Cagatay TM. Anıl Onan, Mehmet E, Haldun G, Omur A. CD105 expression is an independent predictor of survival in patients with endometrial cancer. GynecolOncol. 2006; 103: 1007-11.
Piva M, Horowitz GM, Sharpe-Timms KL. Interleukin-6 differentially stimulates haptoglobin production by peritoneal and endometriotic cells in vitro: a model for endometrium-peritoneum interaction in endometriosis. J Clin Endocrinol Metab. 2001; 86: 2553-61.
Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A, et al. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000; 60: 722-7.
Rier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. Endometriosis in rhesus monkeys (Maccaca mulatta) following chronic exposure to 2, 3, 7, 8-tetrachlorodibenzo- p- dioxin. Fundam Appl Toxicol. 1993; 21: 431-41.
Reed MJ, Koike T, Sadoun E, Sage EH, Puolakkainen P. Inhibition of TIMP1 enhances angiogenesis in vivo and cell migration in vitro. Microvasc Res. 2003; 65: 9-17.
Rangel R, Sun Y, Guzman-Rojas L, Ozawa MG, Sun J, Giordano RJ, et al. Impaired angiogenesis in aminopeptidase N-null mice. Proc Natl Acad Sci. 2007; 104: 4588-93.
Redman KL, Rechsteiner M. Extended reading frame of a ubiquitin gene encodes a stable, conserved, basic protein. J Biol Chem. 1988; 263: 4926-31.
Ruggero D, Pandolfi PP. Does the ribosome translate cancer? Nat Rev Cancer. 2003; 3: 179-92.
Seli E, Senturk LM, Bahtiyar OM, Kayisli UA, Arici A. Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen. Fertil Steril. 2001; 75: 1172-6.
Sensky TE, Liu DT. Endometriosis: associations with menorrhagia, infertility and oral contraceptives. Int J Gynaecol Obstet. 1980; 17: 573-6.
Simpson JL, Elias S, Malinak LR, Buttram VC Jr. Heritable aspects of endometriosis, I: genetic studies. Am J Obstet Gynecol. 1980; 137: 327-31.
Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obst Gynecol. 1927; 14: 442-69.
Silvestre JS, Tamarat R, Ebrahimian TG, Le-Roux A, Clergue M, Emmanuel F, et al. Vascular endothelial growth factor-B promotes in vivo angiogenesis. Circ Res. 2003; 93: 114-23.
Sharpe-Timms KL, Keisler LW, McIntush EW, Keisler DH. Tissue inhibitor of metalloproteinase-1 concentrations are attenuated in peritoneal fluid and sera of women with endometriosis and restored in sera by gonadotropin-releasing hormone agonist therapy. Fertil Steril. 1998; 69: 1128-34.
Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, et al. Failure of blood-island formation and vasculogenesis in flk-1- deficient mice. Nature. 1995; 376: 62-6.
Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis. 2006; 9: 225-30.
Salgado KB, Toscani NV, Silva LL, Hilbig A, Barbosa-Coutinho LM. Immunoexpression of endoglin in brain metastasis secondary to malignant melanoma: evaluation of angiogenesis and comparison with brain metastasis secondary to breast and lung carcinomas. Clin Exp Metastasis. 2007; 24: 403-10.
Stracke JO, Hutton M, Stewart M, Pendas AM, Smith B, Lopez-Otin C, et al. Biochemical characterization of the catalytic domain of human matrix metalloproteinase 19. Evidence for a role as a potent basement membrane degrading enzyme. J Biol Chem. 2000; 275: 14809-16.
Tsudo T, Harada T, Iwabe T, Tanikawa M, Nagano Y, Ito M, et al. Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues. Fertil Steril. 2000; 73: 205-11.
Torry DS, Holt VJ, Keenan JA, Harris G, Caudle MR, Torry RJ. Vascular endothelial growth factor expression in cycling human endometrium. Fertil Steril. 1996; 66: 72-80.
Takahashi N, Kawanishi-Tabata R, Haba A, Tabata M, Haruta Y, Tsai H, et al.Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res. 2001; 7: 524-32.
Valle RF, Sciarra JJ. Endometriosis: treatment strategies. Ann NY Acad Sci. 2003; 997: 229-39.
Vinatier D, Dufour P, Oosterlynck D. Immunological aspects of endometriosis. Hum Reprod Update. 1996; 2: 371-84.
Wild A, Ramaswamy A, Langer P, Celik I, Fendrich V, Chaloupka B, et al. Frequent methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene in pancreatic endocrine tumors. J Clin Endocrinol Metab. 2003; 88: 1367-73.
Wong JM, Mafune K, Yow H, Rivers EN, Ravikumar TS, Steele GD Jr, et al. Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene. Cancer Res. 1993; 53: 1916-20.
Yu WH, Yu S, Meng Q, Brew K, Woessner Jr JF. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J Biol Chem. 2000; 275: 31226-32.
Zeitoun K, Takayama K, Sasano H, Suzuki T, Moghrabi N, Andersson S, et al. Deficient 17beta-hydroxysteroid dehydrogenase type 2 expression in endometriosis: failure to metabolize 17 beta-estradiol. J Clin Endocrinol Metab. 1998; 83: 4474-80.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔