(44.192.112.123) 您好!臺灣時間:2021/03/09 00:51
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:鄭文芳
研究生(外文):Wen-Fang Cheng
論文名稱:血管新生及血管內皮細胞生長因子在子宮頸癌之研究
論文名稱(外文):Angiogenesis and Vascular Endothelial Growth Factor in Cervical Cancer
指導教授:謝長堯謝長堯引用關係謝豐舟謝豐舟引用關係
指導教授(外文):Chang-Yao HsiehFon-Jou Hsieh
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:133
中文關鍵詞:血管內皮細胞生長因子
外文關鍵詞:Vascular Endothelial Growth Factor
相關次數:
  • 被引用被引用:0
  • 點閱點閱:204
  • 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:0
  • 收藏至我的研究室書目清單書目收藏:1
中文摘要
子宮頸癌是國人婦女惡性腫瘤發生率排名第一位的疾病。子宮頸癌的治療在第一期及第二期初以手術治療為主,雖然其治療已有不錯的成果,仍有百分之二十的婦女因此病而復發進而死亡。關於子宮頸癌的預後及轉移研究為數雖多,但主要在探討子宮頸腫瘤細胞本身的生物特徵。本研究嘗試由腫瘤血管新生及其生長因子之角度切入,以能量都卜勒超音波經體內的觀察,提供腫瘤血管新生可以作為疾病嚴重度和轉移的預測指標。進一步闡述能量都卜勒超音波在組織學與細胞生物學上的基礎,也發現血管內皮細胞生長因子可以作為子宮頸癌病人術後復發的重要指標。最後更研究血管內皮細胞生長因子,除了促進血管內皮細胞分裂之外,也有抗細胞凋亡之功能。這些發現為子宮頸癌的分子生物學研究及其臨床治療,提供了一個重要的方向。
首先我們在104及35位接受手術的子宮頸癌病人,發現彩色都卜勒超音波測得的血流訊號和腫瘤血管新生具有關聯。雖然彩色都卜勒超音波測得的腫瘤內動脈血管阻力係數無法作為量化子宮頸癌血管新生的指標,但有無可測得的腫瘤內動脈血管阻力係數可作為子宮旁組織侵犯和骨盆腔淋巴結轉移的排除篩檢工具。以能量都卜勒超音波測得的腫瘤內血管係數則可作為量化子宮頸癌腫瘤血管新生的指標。
接著我們發現在90位接受手術的子宮頸癌病人,其疾病的嚴重度和轉移的能力可以利用血管係數、顯微血管密度和細胞質中內皮細胞生長因子濃度反應出來。此外經能量都卜勒超音波測得的血管係數具有其在組織學上及細胞生物學上的基礎,因為以Sperman相關分析顯示血管係數、顯微許管密度和細胞質中內皮細胞生長因子濃度分別呈現正相關性。當腫瘤內血管係數 >12時必須高度懷疑子宮頸癌病人有淋巴結轉移的可能性,放射線治療可能比手術治療對這些病人要來得適當。
為了瞭解血管內皮細胞生長因子在子宮頸癌所扮演的角色,我們收集了135例具有完整臨床追蹤資料且經手術切除其子宮頸癌的病人。其中位數追蹤時間為27.0個月。子宮頸癌腫瘤組織比正常子宮頸組織有明顯地較高的細胞質中血管內皮細胞生長因子濃度(154.0 versus 0.0 pg /mg protein, P<0.001)。當以多變項危險模式分析時,只有過量表達血管內皮細胞生長因子(危險比例9.92, P=0.001)仍然是統計上獨立的危險因子。病人有過量表達細胞質中血管內皮細胞生長因子蛋白質濃度者有顯著地較差的無病存活期間(log-rank-test, P=0.004)。子宮頸癌腫瘤內細胞質中血管內皮細胞生長因子的濃度高低不但可以反應出子宮頸癌的嚴重性,也是子宮頸癌病人預後的危險因子。
血管內皮細胞生長因子除了促進內皮細胞細胞分裂之外,是否還有其他的功能呢? 利用臍靜脈血管內皮細胞的實驗模式,我們發現缺乏生長因子和血清時,大部分的臍靜脈血管內皮細胞會造成細胞凋亡。絕大多數的凋亡細胞是從培養皿中分離而懸浮於培養液中。我們發現血管內皮細胞生長因子可以抑制臍靜脈血管內皮細胞失去生長因子的細胞凋亡的比例。當臍靜脈血管內皮細胞在沒有任何內皮細胞生長因子和血清的M199溶液中時,其Mcl-1蛋白質表達明顯地下降。當接受血管內皮細胞生長因子的刺激後,其Mcl-1的蛋白質表達量在第1個小時就立刻升高。血管內皮細胞生長因子可能經由調節Mcl-1的表達對臍靜脈血管內皮細胞造成抑制細胞凋亡的效果。血管內皮細胞生長因子不但具有促進內皮細胞分裂的能力更有延緩細胞凋亡的功能。
論文總結:
第一、能量都卜勒超音波測得的腫瘤內血管係數不但可作為量化子宮頸癌腫瘤血管新生的指標也有其臨床上的應用價值。此外血管係數亦具有組織學上及細胞生物學上的基礎。
第二、血管內皮細胞生長因子在臨床上可以作為子宮頸癌病人預後的危險因子,在功能上它更有延緩細胞凋亡的功能。
第三、從臨床的觀察到病理組織至臍靜脈血管內皮細胞的實驗模式,證明了腫瘤血管新生和血管內皮細胞生長因子在子宮頸癌扮演了相當重要的角色。
ABSTRACT
Cervical cancer is the most frequent neoplasm of women in Taiwan. The primary treatment of cervical cancer with stages I and IIa is surgery. Although the result of treatment for these patients is good, about 20% of these cervical cancer patients are expected to die of the disease due to recurrence. There were many studies on the prognosis and metastasis of cervical cancer, but most of them focused on the biologic characteristics of cervical cancer cells. This study tried to evaluate the prognosis and metastasis of cervical cancer with tumor angiogenesis and its related growth factors. Tumor angiogenesis assessed by power Doppler ultrasound with “in vivo” observation could be a predictive parameter of disease severity and metastatic potential. Furthermore, we elucidated the histologic and cellular biologic bases of power Doppler ultrasound. Besides, vascular endothelial growth factor could be an important parameter for the recurrence of cervical cancer patients after surgery. Finally, we evaluated vascular endothelial growth factor not only promotes mitosis of endothelial cell but also has the function of anti-apoptosis. These findings provide an important guide for studying the molecular biology and clinical treatment of cervical cancer.
First we found that the blood flow signal assessed by color and power Doppler ultrasound had correlated with tumor angiogenesis in 104 and 35 cervical cancer patients undergoing surgery. Although the intratumoral arterial resistance index could not be the parameter to quantitate angiogenesis of cervical cancer, the detectable or undetectable intratumoral arterial resistance index could be a negative screening tool for parametrial invasion and pelvic lymph node metastasis. Vascularity index assessed by power Doppler ultrasound and quantitative imaging system could be a new parameter to quantitate tumor angiogenesis of cervical cancer.
Second, we found that the disease severity and metastatic ability could be reflected by vascularity index, microvessel density and cytosol vascular endothelial growth factor in 90 cervical cancer patients undergoing surgery. The vascularity index assessed by power Doppler ultrasound had its histologic and cellular biologic bases because the vascularity index, microvessel density and cytosol vascular endothelial growth factor revealed positive correlation by Sperman correlation analyses, respectively. Cervical cancer patients whose intratumoral vascularity index is higher than 12, lymph node metastasis should be highly suspected. Radiation rather than surgery seems to be a suitable therapy for these patients.
For understanding the role of vascular endothelial growth factor on cervical cancer, we collected 135 cervical cancer patients with surgery and complete clinical follow-up. The median time of follow-up was 27.0 months. The concentrations of cytosol vascular endothelial growth factor in cervical cancer tissues showed significantly higher than those in normal cervical tissues (154.0 versus 0.0 pg/mg protein, P <0.001)。Only over-expressed vascular endothelial growth factor is the independent risk factor (hazard ratio 9.92, P=0.001) by multivariate hazard model analysis. Patients with over-expressed vascular endothelial growth factor had significantly poorer disease-free interval (log-rank-test, P=0.004)。Cytosol vascular endothelial growth factor in cervical cancer tissues not only could reflect the severity of cervical cancer but also be a risk factor for prognosis of early-staged cervical cancer patients.
Is there any other function for vascular endothelial growth factor except promoting the mitosis of endothelial cell ? The human umbilical vein endothelial cell (HUVEC) was used as a model system to study the survival effect of vascular endothelial growth factor. We demonstrated that most of the HUVECs underwent apoptosis when serum and endothelial growth factor were deprived from the culture medium. Most apoptotic HUVECs became detached from the culture dishes. We found that vascular endothelial growth factor could inhibit the apoptotic percentage of HUVECs upon growth factor withdrawl. The Mcl-1 protein levels in HUVECs significantly decreased in the medium without serum and endothelial growth factor. When stimulated by vascular endothelial growth factor, the protein level of Mcl-1 in HUVECs was immediately elevated within one hour treatment. Vascular endothelial growth factor might regulate the expression of Mcl-1 to inhibit apoptosis of HUVECs. Vascular endothelial growth factor not only promote the mitotic ability of endothelial cell, but also have the ability of delaying apoptosis.
Conclusions:
1. Intratumoral vascularity index assessed by power Doppler ultrasound could be the parameter for quantitating angiogenesis of cervical cancer and has its histologic and cellular biologic bases. Vascularity index also has its value for clinical application.
2. Vascular endothelial growth factor clinically could be a risk factor of cervical cancer patients and it has the function of delaying cell apoptosis.
3. Tumor angiogenesis and vascular endothelial growth factor play important roles in cervical cancer from clinical observation to histopathology and experimental model of HUVECs.
封面
誌謝
目錄
表目錄
圖目錄
中文摘要
英文摘要
第一章緒言
一.本論文之研究背景
二.本論文研究之動機及目的
第二章彩色及能量都卜勒超音波(color and power Doppler ultrasound)在子宮頸癌的應用和腫瘤血重新生的關係
一.前言
二.材料與方法
三.結果
四.討論
五.結論
六.中文摘要
七.英文摘要
第三章 腫瘤內血管係數(vascularity index)與血管內皮細胞 生長因子(vascular endothelial growth factor)及子宮頸癌疾病致病力之關係
一.前言
二.材料與方法
三.結果
四.討論
五.結論
六.中文摘要
七.英文摘要
第四章 子宮頸癌之血管內皮細胞生長因子與子宮頸疾病侵襲力及其預後之關係
一.前言
二.材料與方法
三.結果
四.討論
五.結論
六.中文摘要
七.英文摘要
第五章 血管內皮細胞生長因子與細胞凋亡(apoptosis)的關係
一.前言
二.材料與方法
三.結果
四.討論
五.結論
六.中文摘要
七.英文摘要
第六章 論文總結
第七章
第八章 參考文獻
發表之相關論文
參考文獻
Abulafia O, Triest WE, Sherer DM, Hansen CC, Chezzi F. Angiogenesis in endometrial hyperplasia and stage I endometrial carcinoma. Obstet Gynecol 1995;86:479-85.
Araki S, Shimada Y, Kaji K, Hayashi H. Apoptosis of vascular endothelial cells by fibroblast growth factor deprivation. Biochem Biophys Res Commun 1990;168:1194-200.
Atkovar G, Uzel O, Ozsahin M, Koca S, Sahinler I, Okkan S, Uzel R. Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors. Radiother Oncol 1995;35:198-205.
Auerbach W, Auerbach R. Angiogenesis inhibition: a review. Pharmacol Ther 1994;63:265-311.
Berkman RA, Merrill MJ, Reinhold WC, Monacci WT, Saxena A, Clark WC, Robertson JT, Ali IU, Oldfield EH. Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin
Invest 1993;91:153-9.
Berse B, Brown LF, Van De Water L, Dvorak HF, Senger DR. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell 1992;3:211-20.
Bicknell R, Harris AL. Novel growth regulatory factors and tumor angiogenesis. Eun J Cancer 1991;27:781-5.
Boise LH, Gonzalez-Garicia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB. Bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993;74:597-608.
Boocock CA, Charnock-Jones DS, Sharkey AM, McLaren J, Barker PJ, Wright KA, Twnetyman PR, Smith SK. Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst 1995;87:506-16.
Bosari S, Lee AKC, Delellis RA, Wiley BD, Heatley G, Silverman ML. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 1992;23:755-61.
Brem SS, Gullino PM, Medina D. Angiogenesis:a marker for neoplastic transformation of mammary papillary hyperplasia. Science (Washington DC) 1977;195:880-2.
Brem SS, Jonsen HM, Gulluno PM. Angiogenesis as a marker of preneoplastic lesions of the human breast .Cancer (phila) 1978;41:239-44.
Brown LF, Berse B, Jackman RW, Togazzi K, Manseau EJ, Dvorak HF, Senger DR. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 1993a;143:1255-62.
Brown LF, Berse B, Jackman RW, Togazzi K, Manseau EJ, Senger DR, Dvorak HF. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 1993b;53:4727-35.
Brown LF, Berse B, Jackman RW, Tognazzi K, Guidi AJ, Dvorak HF, Senger DR, Connolly JL, Schnitt SJ. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 1995;26:86-91.
Bude RO, Rubin JM. Power Doppler sonography. Radiology 1996;200:21-3.
Burghardt E, Pickel H, Haas J, Lahousen M. Prognostic factors and operative treatment of stage IB to IIB cervical cancer. Am J Obstet Gynecol 1987;156:988-96.
Chao JR, Wang JM, Lee SF, Peng HW, Lin YH, Chou CH, Li JC, Huang HM, Chou CK, Kuo ML, Yen JJY, Yang-Yen HF. Mcl-1 is an immediate-early gene activated by the GM-CSF signaling pathway and one component of the GM-CSF viability responses. Mol Cell Biol 1998;18:4883-98.
Charnock-Jones DS, Sharkey A, Rajput-Williams J, Burch D, Schofield J, Fountain S, Boobock CA, Smith SK. Identification and localization of alternatively spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod 1993;48:1120-8.
Charnock-Jones DS, Sharkey AM, Boocock CA, Ahmed A, Plevin R, Ferrara N, Smith SK. Vascular endothelial growth factor receptor localization and activation in human trophoblast and choriocarcinoma cells. Biol Reprod 1994;51:524-30.
Chittenden T, Harrington EA, O’Conner R, Flemington C, Lutz RJ, Evan GI, Guild BC. Induction of apoptosis by the Bcl-2 homologue Bak. Nature 1995 ; 374 : 733-6.
Cho A, Courntman DW, Langille BL. Apoptosis (programmed cell death) in arteries of the neonatal lamb. Cir Res 1995;76:168-75.
Chodak Gw, Haudenschild C, Gittes RF, Folkman J. Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder. Ann Surg 1980;192:762-71.
Claffey KP, Senger DR, Speigelman BM. Structural requirements for dimerization, glycosylation, secretion, and biological function of VPF/VEGF. Biochem Biophys Acta 1995;1246:1-9.
Cockerill GW, Gamble JR, Vads MA. Angiogenesis: models and modulators. Int Rev Cytol 1995;159:113-60.
Collins, Connolly DT, Williams TJ. Characterization of the increase in vascular permeability induced by vascular permeability factor in vivo. Br J Pharmacol 1993;109:195-9.
Crum R, Szabo S, Folkman J. A new class of steroid inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 1985;230:1375-8.
Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1990;38:352-7.
Dobbs SP, Hewett PW, Johnson IR, Carmichael J, Murray JC. Angiogenesis is associated with vascular endothelial growth factor expression in cervical intraepithelial neoplasia. Br J Cancer 1998;76;1410-5.
Dock W, Grabenwoger F, Metz V, Eibenberger K, Farres MT. Tumor vascularization: assessment with duplex sonography. Radiology 1991;181:241-4.
Dvorak HF, Orenstein NS, Carvalho AC, Churchill WH, Dvorak AM, Galli SJ, Feder J, Bitzer AM, Rypysc J, Giovinco P. Induction of a fibrin-gel investment: an early event in line 10 hepatocarcinoma growth mediated by tumor-secreted products. J Immunol 1979;122:166-74.
Evan G, Littlewood T. A matter of life and cell death. Science 1998;281:1317-22.
Farrow SN, Brown R. New members of the Bcl-2 family and their protein partners , Curr Opin Genet Dev 1996 ; 6 : 45-9.
Ferrara N, Henzel WL. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Comm 1989;161:851-8.
Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocrine Res 1992;13:18-32.
Ferrara N, Heinsohn H, Waldner CE, Bunting S, Thomas GR. The regulation of blood-vessel growth by vascular endothelial growth factor. Ann NY Acad Sci 1995;752:246-56.
Folkman J, Cole P, Zimmerman S. Tumor behavior in isolated perfused organs: in vitro growth and metastasis of biopsy material in rabbit thyroid and canine intestinal segment. Am Surg 1966;164:491-502.
Folkman J. Tumor angiogenesis: therapeutic implications. New Engl J Med 1971;285:1182-6.
Folkman J. Angiogenesis. In Biology of endothelial cells. Jaffe EA ed. Boston: Martinus-Nijhoff 1984, pp 412-28.
Folkman J. Angiogenic factors. Science 1987;235:442-5.
Folkman J, Watson K, Ingber D, Hanahan D. Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 1989a;339:58-61.
Folkman J. Tumor angiogenesis, in Holland F, Frei IIII E, Bast Jr RC, Kufe DW, Morton DL, Weichselbaum RR (eds.): Cancer Medicine. Philadelphia, PA, Lea and Febiger, 1989b, pp 153-170.
Folkman J. What is the evidence that tumors are angiogenesis-dependent ? J Natl Cancer Inst 1990;82:4-6.
Folkman J. Intratumoral microvascular density as a prognostic factor in cancer. Am J Pathol 1995a;147:9-19.
Folkman J. Seminars in Medicine of the Beth Israel hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med 1995b;333:1757-63.
Fregene TA, Khanuja PS, Noto AC, Gehani SK, Van Egmont EM, Luz DA, Pienta KJ. Tumor-associated angiogenesis in prostate cancer. Anticancer Res 1993;13:2377-81.
Garcia I, Martinou I, Tsujimoto Y, Martinou JC. Prevention of programmed cell death of sympathetic neurons by the Bcl-2 proto-oncogene. Science 1992; 258 : 302-4.
Geng WJ, Libby P. Evidence for apoptosis in advanced human atheroma: co-localization with interleukin-1b-converting enzyme. Am J Pathol 1995;147:251-6.
Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994;330:1431-7.
Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J. Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 1972;136:261-76.
Gimbrone MA Jr, Cotran RS, Leapman SB, Folkman J. Tumor growth and neovascularization: an experimental model using the rabbit cornea. J Natl Cancer Inst 1974;52:413-27.
Gonzalez-Gonzalez D, Ketting BW, van-Bunningen B, van-Dijk JD. Carcinoma of the uterine cervix stage IB and IIA: results of postoperative irradiation in patients with microscopic infiltration in the parametrium and/or lymph node metastasis. Int J Radiat Biol Phys 1989;16:389-95.
Gothlin JH, Hoiem L. Percutaneous fine-needle biopsy of radiographically normal lymph nodes in the staging of prostatic carcinoma. Radiology 1981;141:351-4.
Guidi AJ, Abu-Jawdeh G, Berse B, Jackman RW, Tognazzi K, Dvorak HF, Brown LF. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst 1995;87:1237-45.
Hamada K, Alemany R, Zhang WW, Hittelman WH, Lotan R, Roth JA, Mitchell MF. Adenovirus-mediated transfer of a wild-type p53 Gene and induction of apoptosis in cervical cancer. Cancer Res 1996;56:3047-54.
Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis. Am J Pathol 1995;147:267-77.
Hart IR, Saini A. Biology of tumor metastasis. Lancet 1992;339:1453-7.
Hata K, Hata T, Kitao M. Intratumoral peak systolic velocity as a new possible predictor for detection of adnexal malignancy. Am J Obstet Gynecol 1995;172:1496-1500.
Hatch KD, Cervical cancer. In: Berek JS, Hacker NF, editors. Practical gynecologic oncology. Baltimore: Williams and Wilkins, 1994;243-83.
Hawkins MJ. Clnical trials of angiogenic agents. Curr Opin Oncol 1995;7:90-3.
Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer 1984;49:405-13.
Horak ER, Leek R, Klenk N, Lejeune S, Smith K, Stuart N, Greenall M, Stepneiwska K, Harris AL. Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of nodal metastasis and survival in breast cancer. Lancet 1992;340:1120-4.
Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 1990;348:334-6.
Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrin 1991;5:1806-14.
Houck KA, Leung DW, Rowland AM, Winer J, Forrera N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992;267:26031-7.
Hsieh CY, Wu CC, Chen TM, Chen CA, Chen CL, Hsieh FJ. Clinical significance of intratumoral blood flow in cervical carcinomas assessed by color Doppler ultrasound. Cancer 1995;75:2518-22.
Hsieh FJ , Wu CC, Lee CN, Chen TM, Chen CA, Chen FC, Hsieh CY. Vascular patterns of gestational trophoblastic tumors by color Doppler ultrasound. Cancer 1994a;74:2361-5.
Hsieh FJ, Wu CC, Chen CA, Chen CM, Hsieh CY, Chen HY. Correlation of uterine hemodynamics with chemotherapy response in gestational trophoblastic tumors. Obstet Gynecol 1994b;83:1021-5.
Isner JM, Kearney M, Bortman S, Passeri J. Apoptosis in human atherosclerosis and restenosis. Circulation 1995;91:2703-11.
Kainz C, Speisen P,Wanner C , Obermair A, Tempfer C, Sliutz G, Reinthaller A, Breitenecker G. Prognistic value of Tumor microvessel density in cancar of the uterine cervix.Stage IB to IIB. Anticancer Res 1995;15:1549-52.
Kamura T, Tsukamoto N, Tsuruchi N Akazawa K, Nakano H. Multivariate analysis of the histopathologic prognostic factors of cervical cancer patients undergoing radical hysterectomy. Cancer 1992;69:181-6.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Karsan A, Yee E, Kaushansky K, Harlan JM. Cloning of a human Bcl-2 homologue: inflammatory cytokines induce human A1 in cultured endothelial cells. Blood 1996;87:3089-96.
Katoh O, Takahashi T, Oguri T, Kuramoto K, Mihara K, Kobayashi M, Hirata S, Watanabe H. Vascular endothelial growth factor inhibits apoptotic death in hematopoitic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor. Cancer Res 1998;58:5565-9.
Kiefer J, Okret S, Jondal M, McConkey DJ. Functional glucocorticoid receptor expression is required for cAMP-mediated apoptosis in a human leukemic T cell line. J Immunol 1995;155:4525-8.
Korsmeyer SJ. Regulators of cell death. Trends Genet 1995 ; 11 : 101-5.
Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci USA 1993;90:3516-20.
Kurjak A, Shalan H, Sosic A, Benic S, Zudenigo D, Kupesic S, Predanic M. Endometrial carcinoma in postmenopausal women: evaluation by transvaginal color Doppler ultrasonography. Am J Obstet Gynecol 1993;169:1597-603.
Lai CH, Chang HC, Cang TC, Hsueh S, Tang SG. Prognostic factors and impacts of adjuvant therapy in early-stage cervical carcinoma with pelvic node metastases. Gynecol Oncol 1993;51:390-6.
Lencioni R, Pinto F, Armillotta N, Bartolozzi C. Assessment of tumor vascularity in hepatocellular carcinoma: comparison of power Doppler ultrasound and color Doppler ultrasound. Radiology 1996 201:353-8.
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is secreted angiogenic mitogen. Science 1989;246:1306-9.
Lin EY, Orlofsky A, Wong H-G, Reed JC, Prystowsky MB. A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood 1996;87:983-92.
Lin HH, Cheng WF, Chan KWA, Chang DW, Chen CK, Huang SC. Risk factors for recurrence in patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation. Obstet Gynecol 1996;88:274-9.
Liotta L, Kleinerman J, Saidel G. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 1974;34:997-1004.
Lomo J, Smeland EB, Karjewaski SW, Reed JC, Blomhoff HK. Expression of the Bcl-2 homologue Mcl-1 correlates with survival of peripheral blood B lymphocytes. Cancer Res 1996;56:40-3.
Morri K, Tanaka R, Washiyama K, Kumanishi T, Kuwano R. Expression of vascular endothelial growth factor in capillary hemangioblastoma. Biochem Biophys Res Commun 1993;194:749-55.
Nunez G , London L , Hockenbery D , Alexander M , Mckearn JP , Korsmeyer SJ. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 1990 ; 144 : 3602-10.
Obermair A, Kucera E, Mayerhofer K, Speirser P, Seifert M, Czerwenka K, Kaider A, Leodolter S, Kainz C, Zellinger R. Vascular endothelial growth factor (VEGF) in human breast cancer: correlation with disease-free survival. Int J Cancer 1997;74:455-8.
Obermair A, Wanner C, Bilgi S, Speirser P, Kaider A, Reinthaller A, Leodolter S, Gitsch G. Tumor angiogenesis in stage IB cervical cancer: correlation of microvessel density with survival. Am J Obstet Gynecol 1998;178:314-9.
Olson TA, Mohanrai D, Carson LF, Ramakrishnan S. Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res 1994;54:276-80.
Oltvai ZN , Milliman CL , Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog , Bax , that accelerates programmed cell death. Cell 1993;74:609-19.
Park J, Keller GA, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extravascular matrix-bound VEGF. Mol Biol Cell 1993;4:1317-26.
Perez CA, Kurman RJ, Stehman FB, Thigpen JT. Uterine cervix. In: Hoskins WJ, Perez CA, Young RC. Principles and practice of gynecologic oncology. Philadelphia: J.B. Lippincott, 1993;591-662.
Peterson F. Annual report on the results of treatment in gynecological cancer. Stockholm: International Federation of Gynecology and Obstetrics; 1994.
Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359:845-8.
Plate KH, Breier G, Millauer B, Ullrich A, Risau W. Up-regulation of vascular endothelial growth factor and its receptors in an rat glioma model of tumor angiogenesis. Cancer Res 1993;53:5822-7.
Plate KH, Breier G, Weich HA, Mennel HD, Risau W. Vascular endothelial growth factor and glioma angiogenesis: coordinate induction VEGF receptors, distributionof VEGF protein and possible in vivo regulatoryu mechanisms. Int J Cancer 1994;59:520-9.
Pober JS , Cotran RS. Cytokines and endothelial cell biology. Physiol Res 1990;70:427-51.
Ponten J, Adami HO, Bergstrpm R, Dillner J, Friberg LG, Gustafsson L, Miller AB, Parkin DM, Trichopoulos D. Strategies for global control of cervical cancer. Int J Cancer 1995; 60:1-26.
Raff MC , Barres BA , Burne JF , Coles HS , Ishizaki Y , Jacobson MD. Programmed cell death and the control of cell surrival : lessons from the nerrous system. Science 1993 ; 262 : 695-700.
Ramos I, Fernandez LA, Morse SS, Fortune KL, Taylor KJ. Detection of neovascular signals in a 3 day Walker 256 rat carcinoma by Doppler ultrasound. Ultra in Med & Biol 1988;14:123-6.
Reed J. Bcl-2 and the regulation of programmed cell death. J Cell Biol 1994;124:1-6.
Rechsteiner, Rogers SW. PEST sequences and regulation by proteolysis. Trend Biochem Sci 1996;21:267-71.
Reynolds JE, Yang T, Qian L, Jenkinson D, Zhou P, Estaman A, Criag RW. Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells. Cancer Res 1994;4:6348-52.
Risau W. Differentiation of endothelium. FASEB 1995a;9:926-33.
Risau W, Flamme I. Vasculogenesis. Annu Res Cell Del Biol 1995b;11:73-91.
Ruoslahti E, Reed JC. Anchorage dependence. integrins, and apoptosis. Cell 1994;77:477-8.
Samoto K, Ikezaki K, Ono M, Shono T, Kohno K, Kuwano M, Fukui M. Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 1995;55:1189-93.
Sato K, Terada K, Sugiyama T, Takakashi S, Saito M, Moriyama M, Kakinuma H, Suzuki Y, Kato M, Kato T. Frequent overexpression of vascular endothelial growth factor gene in human renal cell carcinoma. J Exp Med 1994;173:355-60.
Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983-5.
Senger DR, Perruzzi CA, Feder J, Dvorak HF. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 1986;46:5629-32.
Senger DR, Dvorak HF. Vascular permeability factor in astrocytomas and other tumors. In: P.M. Black and L. Lampson (eds): Astrocytomas: Diagnosis, Treatment, and Biology. Blackwell Scientific Publications, London, 1993; pp250-60.
Sentman CL , Shutter JR , Hockenbery D , Kanagawa O , Korsmeyer SJ. Bcl-2 inhibit multiple forms of apoptosis but not negative selection in thymocytes. Cell 1991 ; 67 : 879-88.
Sevin BU, Nadji M, Lampe B, Lu Y, Hilsenbeck S, Koechi OR, Averette HE. Prognostic factors of early stage cervical cancer treated by radical hysterectomy. Cancer 1995;76:1978-86.
Shepherd JH. Staging announcement: FIGO staging of gynecological cancers; cervical and vulva. Int J Gynecol Cancer 1995;5:319.
Sheth S, Hamper UK, McCollum ME, Caskey CI, Rosenshein NB, Kurman RJ. Endometrial blood flow analysis in postmenopausal women: can it help differentiate benign from malignant causes of endometrial thickening ? Radiology 1995;195:661-5.
Smith-McCune K and Weidner N. Demonstration and characterization of the angiogenic properties of cerrical dysplasia .Cancer Res 1994;54:800-4.
Smith-McCune K, Zhu Y, Darragh T. Angiogenesis in histologically benign squamous mucosa is a sensitive marker for nearby cervical intraepithelial neoplasia. Angiogenesis 1998;2:135-142.
Spyridopoulos I, Brogi E, Kearney M, Sullivan AB, Cetrulo C, Isner JM, Losordo W. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-a: balance between growth and death signals. J Mol Cell Cardiol 1997;29:1321-30.
Srivastava A, Laidler P, Davies RP, Horgan K, Hughes LE. The prognostic significance of tumor vascularity in intermediate-thickness (0.76-4.0mm thick) skin melanoma: a quantitative histologic study. Am J Pathol 1988;133:419-23.
Steller H. Mechanisms and genes of cellular suicide. 1995 ; 267 : 1445-9.
Strarkey JR, Crowle PK, Taubenberger S. Mast-cell-deficient W/W mice exhibit a decreased rate of tumor angiogenesis. Int J Cancer 1988;42:48-52.
Strasser A, Harris AW, Cory S. Bcl-2 transgene inhibits T cell death and perturbs thymic seif-censorship. Cell 1991;67:889-99.
Subak LL, Hricak H, Bethan P, Azizi L, Stern JL. Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. Obstet Gynecol 1995;86:43-50.
Sugihara T, Kaul SC, Mitsui Y, Wadhwa R. Enhanced expression of multiple forms of VEGF is associated with spontaneous immortalization of murine fibroblasts. Biochem Biophys Acta 1994;1224:365-70.
Takahashi A, Sasaki H, Kim SJ, Tobisu, Kakizoe T, Tsukamoto T, Kumamoto Y, Sugimura T, Terada M. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 1994;54:4233-7.
Tannock I. Population of kinetics in a transplanted mouse mammary tumor. Cancer Res 1970;30:2470-6.
Thompson CB. Apoptosis in the pathogenesis and Treatment of disease. Science 1995 ; 267 : 1456-1462.
Tischer E, Mitchell R, Hortman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266:26031-7.
Toi M, Kashitane J, Tominaga T. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer 1993;55:371-4.
Toi M, Hoshina S, Takayanagi T, Tominaga T. Association of vascular endothelial growth factor expression with tumor angiogenesis and early relapse in primary breast cancer. Jpn J Cancer Res 1994;85:1045-9.
Toi M, Kondo S, Suzuki S, Yamamoto Y, Inada K, Imazawa T, Taniguchi T, Tominaga T. Quantitative analysis of vascular endothelial growth factor in primary breast cancer. Cancer 1996;77:1101-6.
Tokumo K, Kodama J, Seki N, et al. Different angiogenic pathways in human cervical cancers. Gynecol Oncol 1998;68:38-44.
Tsujimoto Y , Croce CM. Analysis of the structure , transcripts , and protein products of bcl-2, the gene involved in human fallicular lumphoma. Proc Natl Acad Sci USA 1986 ; 83 : 5214-8.
Umezawa A, Maruyama T, Inazawa J, Imai SI, Takano T, Hata JI. Induction of mcl-1/EAT1, Bcl-2 related gene, by retinoic acid or heat shock in the human embryonal carcinoma cells, NCR-G3. Cell structure and Function 1996;21:143-50.
Valentin L, Sladkevicius P, Marsal K. Limited contribution of Doppler velocimetry to the differential diagnosis of extrapelvic tumors. Obstet Gynecol 1994;83:425-33.
van Bommel PF, van Lindert AC, Kock HC, Leers WH, Neijt JP. A review of prognostic factors in early-stage carcinoma of the cervix (FIGO IB and IIA) and implications for treatment strategy. Eur J Obstet Gynecol Reprod Biol 1987;26:69-84.
van Nagell JR, Greenwell N, Powell DF, Donaldson ES, Hanson MB, Gay EC. Microinvasive carcinoma of the cervix. Am J Obstet Gynecol 1983;145:981-91.
Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988;335:440-2.
Veis DJ, Sentman CL, Bach EA, Korsmeyer SJ. Expression of the Bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. J Immunol 1993;151:2546-54.
Vinores S, Kuchles M, Mahlow J, Chiu C, Green W, Campochiaro P. Blood-ocular barrier breakdown in eyes with ocular melanoma. A potential role for vascular endothelial growth factor/ vascular permeability factor. Am J Pathol 1995;147:1289-97.
Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8.
Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-staged breast carcinoma. J Natl Cancer Inst 1992;84:1875-87.
Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 1993;143:401-9.
Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 1995;36:169-80.
Werner-Wasik M, Schmid CH, Bornstein L, Ball HG, Smith DM, Madoc-Jones H. Prognostic factors for local and distant recurrence in stage I and II cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32:1309-17.
Williams GT , Smith CA , McCarthy NJ , Grimes EA. Apoptosis : final control point in cell biology. Trends cell Biol 1992 ; 2 : 263-7.
Wiggins DL, Granai CO, Steinhoff MM, Calabresi P. Tumor angiogenesis as a prognostic factor in cervical carcinoma. Gynecol Oncol 1995;56:353-6.
Wizigmann-Voos S, Breier G, Risau W, Plate KH. Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res 1995;55:1358-64.
Wu CC, Lee CN, Chen TM, Shyu MK, Hsieh CY, Chen HY, Hsieh FJ. Incremental angiogenesis assessed by color Doppler ultrasound in the tumorigenesis of ovarian neoplasm. Cancer 1994a;73:1251-6.
Wu CC, Lee CN, Chen TM, Lai JI, Hsieh CY, Hsieh FJ. Factors contributing to the accuracy in diagnosing ovarian malignancy by color Doppler ultrasound. Obstet Gynecol 1994b;84:605-8.
Yang T, Kozopas KM, Craig RW. The intracellular distribution and pattern of expression of Mcl-1 overlap with, but not identical to, theses of Bcl-2. J Cell Biol 1995a;128:1173-84.
Yang EL , Zha J , Jackel J , Boise LH , Thompson CB , Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-xL and Bcl-2 , displaces Bax and promotes cell death. Cell 1995b; 80 : 285-291.
Yeo TK, Senger DR, Dvorak HF, Freter L, Yeo KT. Glycosylation is essential for efficient secretion but not for permeability-enhancing activity of vascular permeability factor (vascular endothelial growth factor). Biochem Biophys Res Commun 1991;179:1568-75.
Zhou P, Qian L, Kozopas KM, Craig RW. Mcl-1, a Bcl-2 family member, delays the death of hematopoitic cell under a variety of apoptosis-inducing conditions. Blood 1997;89:630-643.
發表之相關論文
Cervical cancer
1. Cheng WF, Lee CN, Chu JS, Chen CA, Chen TM, Huang KT, Hsieh CY, Hsieh FJ. Vascularity index as a new parameter for the in vivo assessment of angiogenesis for cervical carcinoma. Cancer 1999;58:561-7.
2. Cheng WF, Lee CN, Chen CA, Chu JS, Kung CCS, Hsieh CY, Hsieh FJ. Comparison of “in vivo” and “in vitro” methods for evaluating angiogenesis and their clinical application in cervical carcinoma. Angiogenesis in press
3. Cheng WF, Chen CA, Lee CN, Chen TM, Hsieh FJ, Hsieh CY. Vascular endothelial growth factor in cervical carcinoma. Obstetrics and Gynecology 1999;93:761-5.
Endometrial cancer
4. Cheng WF, Chen TM, Chen CA, Wu CC, Huang KT, Hsieh CY, Hsieh FJ. Clinical application of intratumoral blood flow study in endometrial carcinoma. Cancer 1998;82:1881-6.
5. Cheng WF, Chen CA, Lee CN, Chen TM, Huang KT, Hsieh CY, Hsieh FJ. Preoperative ultrasound study in predicting lymph node metastasis for endometrial cancer patients. Gynecol Oncology 1998; 71:424-7.
Ovarian cancer
6. Chen CA, Cheng WF, Lee CN, Chen TM, Kung CCS, Hsieh FJ, Hsieh CY. Serum vascular endothelial growth factor in epithelial ovarian neoplasms: correlation with patient survival. Gynecol Oncology in press
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
1. 王國恭 (民85).早產.當代醫學,23(6),470-475。
2. 雲小瓊 (民84) .早產兒之營養評估及因應之道.醫院藥學,12,83-87。
3. 雲小瓊 (民84) .早產兒之營養評估及因應之道.醫院藥學,12,83-87。
4. 楊玉娥 (民85).經產婦於產後初期角色轉變過程中的經驗歷程.護理研究,4,397-407。
5. 曾英芬、陳俞君、范惠珍、謝生蘭(民87).母親在早產兒住院初期的居家照顧需求與母育信心.護理研究,6(2),163-174。
6. 曾英芬、陳俞君、范惠珍、謝生蘭(民87).母親在早產兒住院初期的居家照顧需求與母育信心.護理研究,6(2),163-174。
7. 楊玉娥 (民85).經產婦於產後初期角色轉變過程中的經驗歷程.護理研究,4,397-407。
8. 王國恭 (民85).早產.當代醫學,23(6),470-475。
9. 10. 衛民:----政府規範、集體協商或勞工參與_____二十一世紀台灣勞資關係模式分析。勞資關係月刊14(1):6-25,1995。
10. 10. 衛民:----政府規範、集體協商或勞工參與_____二十一世紀台灣勞資關係模式分析。勞資關係月刊14(1):6-25,1995。
11. 9. 詹火生:從勞動基準法擴大適用談勞資關係。中國勞工986卷:8-9,1998。
12. 9. 詹火生:從勞動基準法擴大適用談勞資關係。中國勞工986卷:8-9,1998。
13. 滕儒錚、鄒國英、江伯倫、謝貴雄 (民85) 早產兒的視網膜病變.當代醫學,23,187-193。
14. 滕儒錚、鄒國英、江伯倫、謝貴雄 (民85) 早產兒的視網膜病變.當代醫學,23,187-193。
15. 劉瓊宇 (民76).支持早產兒父母親的探討.護理雜誌,34(2),59-63。
 
系統版面圖檔 系統版面圖檔