跳到主要內容

臺灣博碩士論文加值系統

(44.192.115.114) 您好!臺灣時間:2023/09/29 12:58
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:黃金仁
論文名稱:以微陣列分析法探討猿病毒腫瘤抗原氮端區段抑制神經膠原致癌基因表現之分子機轉
論文名稱(外文):Microarray approach toward the molecular mechanism of transcriptional suppression of HER2/neu by the N-terminal domain of SV40 large Tantigen
指導教授:高銘欽高銘欽引用關係
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:80
中文關鍵詞:神經膠原致癌基因猿病毒腫瘤抗原氮端區段維甲酸受體微陣列維甲酸誘導基因
外文關鍵詞:HER2/neuSV40 LT425RARMicroarrayRIG1
相關次數:
  • 被引用被引用:0
  • 點閱點閱:161
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
神經膠原致癌基因調控失常而致過度表現常引起許多人類的癌症,臨床報告顯示其與癌細胞轉移與預後不良有密切的關係。本實驗室之前證實猿病毒腫瘤抗原氮端1-178個胺酸部位 (猿病毒腫瘤抗原氮端區段 LT425) 在神經膠原致癌基因過度表現的卵巢癌及乳癌細胞中能有效作為腫瘤轉形的抑制劑。然而,對於猿病毒腫瘤抗原氮端區段抑制神經膠原致癌基因過度表現的機轉仍不清楚。本論文採用微陣列分析法試圖找出與猿病毒腫瘤抗原氮端區段抑制神經膠原致癌基因過度表現相關的基因。經微陣列實驗結果顯示共有1685個基因表現增加,而有114個基因表現降低,其中經文獻交叉搜尋比對結果發現RARRES3基因有可能參與猿病毒腫瘤抗原氮端區段抑制腫瘤生長的作用,西方墨點實驗也證實此項推測,因此,本論文提出初步假說如下:猿病毒腫瘤抗原氮端區段可能直接活化RARRES3基因而引發腫瘤抑制效應,或者也可能經由活化維甲酸胞核受體後再活化RARRES3基因而引發腫瘤抑制效應。

It has been known that HER2/neu is overexpressed in a wide variety of human cancers and shown to be associated with increased metastasis and poor prognosis. We have demonstrated that the N-terminal domain of SV40 large T antigen (LT425) can act as a transforming suppressor of the HER2/neu oncogene in human ovarian and breast cancer cells. However, the repression mechanism of HER2/neu by LT425 is still unknown In this study, by using the microarray approach, we have made an attempt at finding genes related to the suppression of HER2/neu by LT425. Among 6000 known human genes, 1685 genes were found to be up-regulated while 114 genes were down-regulated in LT425-transfected ovarian cancer cells. In addition, through the microarray data comparison and related literature search, the RARRES3 gene was demonstrated to be the most possible one which involves in the LT425-mediated transcriptional repression of HER2/neu oncogene. The elevated level of RARRES3 protein in LT425-transfeced ovarian cancer cells was further elucidated by Western blot analysis. Therefore, a preliminary hypothesis was proposed that LT425 may directly activate the expression of RARRES3 gene leading to the repression of HER2/neu oncogene. It may also be possible that LT425 stimulates the binding of RAR with RA followed by activating RARRES3 gene expression and causes tumor suppressing effects.

目 錄
目錄………………………………………………………………………….……..Ⅰ
表目錄………………………………………………………………………….…..Ⅲ
圖目錄…………………………………………………………………….………..Ⅳ
縮寫表……………………………………………………………………….……..Ⅴ
中文摘要…………………………………………………………………….……..Ⅵ
英文摘要…………………………………………………………………….……..Ⅶ
第一章、 緒論
壹、 神經膠原致癌基因……………………………………….….……..1
貳、 神經膠原致癌基因與癌症………………………………..………..3
參、 目前針對HER2/neu的治療方法…………………………..……...4
肆、 猿病毒腫瘤抗原……………………………………………..……..7
伍、 微陣列分析……………………………………………….….……..8
陸、 維甲酸細胞核受體……………………………………….….…….10
柒、 TIG3/RIG1基因之發現及相關研究…….……………….….……14
捌、 研究背景及目的………………………..………………….….…...15
第二章、 材料與方法………………………………...…………………..………16
第一節、 實驗材料與儀器………………………………………….………..16
壹、 細胞株…………………………………………………….………..16
貳、 抗體……………………………………………………….………..16
參、 化學藥品試劑與其他耗材……………………………….………..16
肆、 儀器………………………………………………………….……..17
第二節、 實驗方法…………………………………………………….……..18
壹、 細胞解凍及處理…………………………………………………..18
貳、 總量RNA抽取………………………...……………………...….23
參、 微陣列分析實驗………………………………………….……….24
肆、 蛋白質萃取…………………………………………………..........27
伍、 蛋白質濃度測定………………………………………………......28
陸、 西方墨點法………………………………………………………..28
柒、 維甲酸處理細胞及檢測RAR核受體與TIG3/RIG1之蛋白表
現量………………………………………………………………..30
第三章、 結果……………………………………………………………….…...32
壹、 以Trizol方法抽取RNA………………………………………….32
貳、 微陣列資料分析……………………….……………………….…32
參、 RARRES3 (TIG3) 基因之篩選,研究及初步假說……….…….33
肆、 以西方墨點法測定RIG1/TIG3在卵巢癌細胞中蛋白質表現量.34
伍、 以西方墨點法測定RAR-β在卵巢癌細胞中蛋白質表現量…...34
陸、 以西方墨點法測定RAR-α在卵巢癌細胞中蛋白質表現量…...35
柒、 以西方墨點法測定caspase-3在卵巢癌細胞中蛋白質表現量…35
第四章、 討論……………………………………………………………………36
第五章、 結論……………………………………………………………………42
表…………………………………………………………………………………..43
圖…………………………………………………………………………………..47
參考文獻…………………………………………………………………………..55
附錄一……………………………………………………………………………..63
附錄二……………………………………………………………………………..72
表目錄
表一、 SKOV3.ip1卵巢癌細胞在穩定轉染LT425基因後經微陣列測定
比較基因表現量大於或等於1.95的基因……………………………..43
表二、 SKOV3.ip1卵巢癌細胞在穩定轉染LT425基因後經微陣列測定
分析比較基因表現量小於0.5的基因…………………………………44
表三、 在SKOV3.ip1-LT425-29及SKOV3.ip1-LT425-31兩個細胞株中
接受LT425上升調控的微陣列分析結果……………………………..45
表四、 HER2/neu、LT425與TIG3/RIG1之間的相互關聯性…...…………...46
圖目錄
圖 2-1. 實驗流程圖……………………………………………………………….47
圖 3-1. 利用Trizolz方法抽取RNA後之電泳圖……………………..……..….48
圖 3-2. LT425抑制HER2/neu之初步假說………..………….…………….…...49
圖 3-3. 以西方墨點法分析 p185 及 RIG 1 於卵巢癌細胞珠中的表現….…..50
圖 3-4. 以西方墨點法分析 p185 及 RAR-β 於卵巢癌細胞珠中的表現…...51
圖 3-5. 以西方墨點法分析p185與RAR-α 於卵巢癌細胞珠中的表現……..52
圖 3-6. 以西方墨點法分析caspase-3 於卵巢癌細胞珠中的表現………...…...53
圖 3-7. 根據本論文實驗結果提出LT425抑制HER2/neu基因表現之假說.....54

參考文獻
Afshari CA, Nuwaysir EF and Barrett JC (1999) Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res. 59: 4759-4760.
Bargamn CI, Hung MC, Weinberg RA (1986) The neu oncogene encodes an epidermal-growth-factor receptor-related protein. Nature 319: 216-230.
Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twad-dell T, Henderson IC, Norton L (1996) Phase II study of weekly intravenous recombinant humanized anti-p185 HER2 monoclonal antibody in patients with HER2/neu-overexpressing meta.
Baselga J, Seidman AD, Rosen PP and Norton L (1997) HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology 11:43—48.
Baselga J, Norton L, Albanell J, Kim YM and Mendelsohn J (1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhance the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 58:2825-2831
Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P, McKenzie S, Yin S and Bast RC (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 50: 4087—4091.
Berg JM (1989) DNA binding specificity of steroid receptor. Cell 57: 1065-1089.
Brown M, McCormack M, Zinn KG, Farrell MP, Bikel I, Livingston DM (1986) A recombinant murine retrovirus for simian virus 40 large T cDNA transforms mouse fibroblasts to anchorage-independent growth. Journal of Virology 60:290-3.
Cgambon P (1996) A decad of molecular biology of retinoic acid receptors. FASEB J. 10:940-954.
Chakravrti D, LaMorte VJ, Nelson MC, Nakajima T, Schulman IG, Juguilon H, Montminy M, Evans RM (1996) Role of CBP/p300 in nuclear receptor signaling. Nature 383: 99-103.
Challberg MD and Kelly TJ (1989) Animal virus DNA replication. Ann. Rev. Biochem. 58: 671-717.
Chuang TC, Yu YH, Lin YS, Kao MC (2002) The N-terminal domain of SV40 large T represses the HER2/neu-mediated transformation and metastatic potential in breast cancer. FEBS Letters 511: 46-50.
Chung YL, Sheu ML, Yang SC, Lin CH and Yen SH (2002) Resistance to tamoxifen-induced apoptosis is associated with direct interactionbetween HER2/neu and cell membrane estrogen receptor in breast cancer. Int. J. Cancer 97: 306-312.
Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Paton V, Shak S, Lieberman G and Slamon D (1998) Efficacy and safety of Herceptin (Humanized anti-HER2 antibody) as a single agent in 222 woman with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc. Am. Soc. Clin. Oncol. 17:97A.
Coussen L, Yang-Feng TL and Liao YC (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 230: 1132-1139.
Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J and Francke U (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230: 1132-9.
De Luca LM (1991) Retinoids and their receptors in differentiation, embryogenesis, and neoplasia. FASEB J. 5:2924-2932.
DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA and Trent JM (1996) Use of a cDNA microarray to analyze gene expression patterns in human cancer. Nature Genet. 14: 457-460.
DeRisi JL, Iyer VR and Brown PO (1997) Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278: 680-686.
D'Emilia J, Bulovas K, D'Ercole K, Wolf B, Steel GJr and Summerhayes IC (1989) Expression of the c-erbB-2 gene product (p185) at different stages of neoplastic progression in the colon. Oncogene 4: 1233-1239.
Dickman S (1998) Antibodies stage a comeback in cancer treatment. Science 280:1196-1197.
Drebin JA, Link VC, Stern DF, Weinberg RA and Greene MI (1985) Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 41:695-706.
Evans RM (1988) The steroid and thyroid receptor supperfamily. Science 240: 889-895.
Fanning, E. and Knippers, R. 1992. Structure and function of simian virus 40 large tumor antigen. Ann. Rev. Biochem. 61, 55-85.
Fiers W, Contreras, Haegemen R, Rogiers R, Voorde V, Heuverswyn HV, Herreweghe JV, Volckaert G and Ysebaert M (1978) Complete nucleotide sequence of SV40 DNA. Nature 273, 113-120.
Fukushige SI, Matsubara KI, Yoshida M, Sasaki M, Suzuki T, Semba K, Toyoshima K and Yamamoto T (1986) Locolization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol. Cell. Biol. 6: 955-958.
Grunt T, Dittrich E, Ofterdinger M, Schneider SM, Dittrich C and Huber H (1998) Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells. Br. J. Cancer 78:79-87.
Gu K, Mes-Masson AM, Gauthier J and Saad F (1996) Overexpression of HER-2/neu in human prostate cancer and begin hyperplasia. Cancer Lett. 99: 185-9.
Hajnal A, Klemenz R, Schafer R (1994) Subtraction cloning of H-rev107, a gene specifically expressed in H-ras resistant fibroblasts. Oncogene 9: 479-90.
Haynes NM, Smyth MJ, Kershaw MH, Trapani JA and Darcy PK (1999) Fas-lignd-mediated lysis of erbB2-overexpressing tumor cellsby redirected cytotoxic T lymphocyte. Cancer Immunol. Immunother. 47: 278-286.
Hazan R, Margolis B, Dombalagian M, Ullrich A, Zilberstein A and Schlessinger J (1990) Identification of autophosphoylation sites of HER-2/neu. Cell. Growth. Differ. 1: 3-7.
Hortobagyi GN, Ueno NT, Xia W, Zhang S, Wolf JK, Putnam JB, Weiden PL, Willey JS, Carey,M, Branham DL, Payne JY, Tucker SD, Bartholomeusz C, Kilbourn RG, De Jager RL, Sneige N, Katz RL, Anklesaria P, Ibrahim NK, Murray JL, Theriault RL, Valero V, Gershenson DM, Bevers MW, Huang L, Lopez-Berestein G, Hung MC (2001) Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial. Journal of Clinical Oncology. 19:3422-33.
Hou L, Shi D, Tu SM (1992) Oral cancer progression and c-erbB-2/neu proto-oncogene expression. Cancer Lett. 65: 215-220.
Hudziak RM, Lewis GD, Winget M, Fendly BM, Shepard HM, Ullrich A (1989) p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Molecular & Cellular Biology. 9:1165-72.
Huang SL, Shyu RY, Yeh MY, Jiang SY (2000) Cloning and characterization of novel retinoid-inducible gene 1 (RIG1) deriving from human gastric cancer cells. Mol. Cell. Endocrinol. 159: 15-24.
Huang SL, Shyu RY, Yeh MY, Jiang SY (2002) The retinoid-inducible gene 1: effect on apoptosis and mitogen-activated kinase signal pathway. Antiancer Res. 22: 799-804
Hung MC, Yan DH and Zhao X (1989) Amplification of the proto-neu oncogene facilitates oncogenic activation by a single point mutation. Proc. Natl. Acad. Sci. USA 86: 2545-2548.
Hung MC, Zhang X, Yan DH, Zhang HZ, He GP, Zhang TQ and Shi DR (1992) Aberrant expression of the c-erbB-2/neu protooncogene in overian cancer. Cell. 62: 1165-1175.
Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JCF, Trent JM, Staudt LM, Hudson Jr. J, Boguski MS, Lashkari D, Shalon D, Botstein D and Brown PO (1999) The transcriptional program in the response of human fibroblasts to serum. Science 283: 83-87.
Kao MC, Liu GY, Chuang TC, Lin YS, Wuu JA and Law SL (1998) The N-terminal 178-amino-acid domain only of the SV40 large T antigen acts as a transforming suppressor of the HER-2/neu oncogene. Oncogene. 16, 547-554.
Kastner P, Krust A, Mendelsohn C, Garnier JM, Zelent A, Leroy P, Staub A, Chambon P (1990) Murine isoforms of retinoic acid receptor with specific patterns of expression. Proc Natl Acad Sci USA 87: 2700-2704.
King CR, Kraus MH, Aaronson SA (1985) Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 229: 947-976.
Kraus MH, Issing W, Miki T, Popescu NC and Aaronson SA (1989) Isola-tion and characterization of erbB3, a third member of the erbB/ epidermal growth factor receptor family: evidence for overexpres-sion in a subset of human mammary tumors. Proc Natl Acad Sci USA 86: 9193—9197.
Krupitza G, Hulla W, Harant H, Dittrich E, Huber H. Grunt T and Dittrich C (1995) Retinoic acid induced death of ovarian cancinoma cell correlates with c-myc stimulation. Int J Cancer 61: 649-657.
Lacroix H, Iglehart JD, Skinner MA and Kraus MH (1989) Overexpression of erbB-2 or EGF receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastases. Oncogene. 4:145-51.
Leroy P, Nakshatri H, Chambon P (1991) Mouse retinoic acid 2 isoform is transcribed from a promoter that contains a retinoic acid response element. Proc Natl Acad Sci USA 88:10138-10142.
Lin, Y. C., Peng, J. M. and Wang, W. B. 2000. The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene. Oncogene. 19:2704-13.
Manfredi JJ & Prives C (1994) The transforming activity of Simian Virus 40 largy tumor antiagen. Biochimica et Biophysica Acta. 1198: 65-83.
Marchionni MA (1995) neu tack on neurequlin. Nature 378: 334-335.
Matin A and Hung MC (1993) Negative regulation of the Neu promoter by the SV40 large T antigen. Cell Growth & Differentiation 4: 1051-1056.
Matin A and Hung MC (1994) The retinoblastoma gene product, Rb, represses neu expression trough two regions within the neu regulatory sequence. Oncogene 9 :1333-1339.
Mitra AB, Murty VV, Pratap M, Sodhani P, Chaganti RS (1994) ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. Cancer Res. 54: 637-639.
Monier R (1986) The Papovaviridae. Salzman NP. (Ed.). pp.247-294, Plenum Press, New York.
Naar AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK, Rosenfeld MG (1991) The orientation and spcing of core DNA-binding motifs dictate selective transcriptional response to three nuclear receptors. Cell 65: 1267-1279.
Nagpal S, Zelent A, Chambon P (1992) RAR-β4, a retinoicacid receptor isoform is generated from RAR-β2 by alternative splicing and usage of a CUG initiator codon. Proc Natl Acad Sci USA 89: 2718-2722.
Noonberg SB, Scott GK, Hunt CA, Hogan ME and Benz CC (1994) Inhibition oftranscription factor binding to the HER2 promoter by triple-forming oligodeoxyribonucleotides. Gene 149: 123-126.
Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recom-binant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol. 16:2659—2671.
Pietras RJ, Pegram MD, Finn RS, Maneval DA and Slamon DJ (1998) Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER2 receptor and DNA-reactive grugs. Oncogene 17:2235-2249.
Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG and Shoyab M (1993) Ligand-specific activation of HER4/p180 erbB4 , a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci USA 90:1746—1750.
Rao GN, Ney E and Herbert RA (1999) Changes associated with delay of mammary cancer by retinoid analogues in transgenic mice bearing c-neu oncogene. Breast Cancer Res. Tret. 56: 241-254.
Reddy VB, Thimmappaya B, Dhar R, Subramanian KN, Zain BS, Pan J, Ghosh PK, Celma ML and Weissman SM (1978) The genome of simian virus 40. Science 200: 494-502.
Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D and Brown PO (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nature Genet. 24: 227-235.
Salzman NP, Natarajan V and Selzer GB (1986) The Papovaviridae. Saltzman NP (Ed.), pp. 27-98. Plenum Press, New York.
Semba K, Kamata N, Toyoshima K, Yamamoto T (1985) A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-crbB-l/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc. Natl. Acad. Sci. USA. 82: 6497-6501.
Sers C, Emmenegger U, Husmann K, Bucher K. Andres AC, Schafer R (1997) Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 intumor cell lines and experimental tumors. J Cell Biol 136: 935-944.
Shepard HM, Lewis GD, Sarup JC, Fendly BM, Maneval D, Mordenti J, Figari I, Kotts CE, Palladino Jr MA, Ullrich A and Slamon D (1992) Monoclonal antibody therapy of human cancer: Taking the HER2 prutooncogene to the clinic. J. Clin. Immunol. 11:117-127.
Schena M, Shalon D, Davis RW and Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467-470.
Schulze A and Downward J (2001) Navigating gene expression using microarrays-a technology review. Nature Cell Biology 3: E190-5.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177—182.
Slamon DJ, Godolphin W and Jones LA (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707-712.
Slamon D, Leyland-Jones B and Shank S (1998) Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic breast cancer (HER21/MBC) markedly increases anticancer activity: a randomized, multina-tional controlled phase III trial. Proc Am Soc Clin Oncol 17:98a.
Suen TC and Hung MC (1991) c-Myc reverses neu-induced transformed morphology by transcriptional repression. Mol. Cell. Biol. 11: 354-362.
Thor AD, Schwartz LH, Koerner FC, Edgerton SM, Skates SJ, Yin S, McKenzie SJ, Panicali DI, Marks PJ, Fingert HJ and Wood WC (1989) Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up. Cancer Res. 49:7147-7152.
Tsuchiya T, Ueyama Y, Tamaoki N, Yamaguchi S and Shibuya M (1989) Co-amplification of c-myc and c-erbB-2 oncogenes in a poorly differentiated human gastric cancer. Jpn. J. Cancer Res. 80:920-923.
Williams TM, Weiner DB, Greene MI and Maguire HC Jr (1991) Expression of c-erbB-2 in human pancreatic adenocarcinomas. Pathobiology. 59, 46-52.
Wright C, Angus B, Nicholson S, Sainsbury JR C, Cairns J, Gullick WJ, Kelly P, Harris AL and Horne CH W (1989) Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res. 49:2087-2090.
Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T & Toyoshima K (1986) Similarity of protein encoded by the human c-erbB2 gene to epidermal growth factor receptor. Nature 319, 230-234.
Yan DH, Wen Y, Spohn B, Choubey D, Gutterman JU, Hung MC (1999) Reduced growth rate and transformation phenotype of the prostate cancer cells by an interferon-inducible protein, p202. Oncogene 18 : 807-11.
Yokota J, Yamamoto T, Miyajima N (1988) Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue. Oncogene 2: 283-287.
Yoo GH, Hung MC, Lopez-Berestein G, LaFollette S, Ensley JF, Carey M, Batson E, Reynolds TC, Murray JL (2001) Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer. Clinical Cancer Research. 7:1237-45.
Yu D, Suen TC, Yan DH, Chang LS & Hung MC (1990) Transcriptional repression of the neu protooncogene by the adenovirus 5 E1A gene products. Proc. Natl. Acad. Sci. USA 87, 4499-4503.
Zeillinger R, Kury F, Czerwenka K, Kubista E, Sliutz G, Knogler W, Huber J, Zielinski C, Reiner G, Jakesz R, Staffen A, Reiner A, Wrba F and Spona J (1989) HER-2 amplification, steroid receptors and epidermal growth factor receptor in primary breast cancer. Oncogene 4:109-114.
Zhang L, Chang CJ, Bacus SS & Hung MC (1995) Suppressed transformation and differentiation of HER-2/neu-overexpressing breast cancer cells by emodin. Cancer Res. 55, 3890-3896.
Zhang L and Hung MC (1996) Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotheraputic drugs by trrosine kinase inhibitor emodin. Oncogene 12, 571-576.
Zhang XK, Lehmann J, Hoffmann B, Dawson M, Cameron J, Graupner G, Hermann T, Tran P, Pfahl M (1992) Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature 358: 587-591.
Zhang L, Lau YK, Xia W, Hortobagyi GN, Hung MC (1999) Tyrosine kinase inhibitor emodin suppresses growth of HER2/neu-overex-pressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. Clin Cancer Res 5:343— 353.
Zhau HE, Zhang X, von Eschenbach AC, Scorsone K, Babaian RJ, Ro JY, Hung MC (1990) Amplification and expression of the c-erb B-2/neu proto-oncogene in human bladder cancer. Mol. Carcinogenesis 3: 254-257.
吳孟勳 (2001) 國防醫學院生物化學研究所碩士論文:人類RIG1基因啟動區維甲酸反應序列之鑑定與分析。
莊子超 (2002) 國防醫學院生命科學研究所博士論文:神經膠原致癌基因標的癌症基因治療之研究。

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 陳振貴、張火木。「大專生的休閒生活與現代價值觀的建立」。技術及職業教育雙月刊 第35期(民85年10月)http://gopher.cc.ntnu.edu.tw/tvc/www/35.htm#n37(民90.12.19)
2. 梁朝雲。「從數位媒體的發展談校園媒體服務」。研習資訊 16卷1期(民88.02),http://www.iest.edu.tw/issue/j1/16-2.htm(民90.12.19)
3. 黃翠嫩。「推展視聽媒體在教學上的應用—以台灣大學圖書館多媒體服務中心推展活動為例」。大學圖書館3卷3期。http://www.lib.ntu.edu.tw/pub/univj/uj3-3/uj3-3_4.htm(民90.01.27)
4. 羅綸新。「多媒體的應用」。教學科技與媒體9(1993.06),頁50-55。
5. 林勤敏。「美國公共圖書館視聽教育觀摩考察心得」。書苑 v30(民85年10月),頁49-55。
6. 葉榮木、張素惠。「從學習的觀點探索現代教學科技與教學改革」。教學科技與媒體49(2000.02),頁2-8。
7. 梁朝雲。「在學青少年網路使用行為分析及輔導方案」,教育資料與圖書館學 39卷1期(2001.09),頁51-55。
8. 梁朝雲,劉守信。「青少年網路行為與輔導策略─以新竹世在學青少年為例」。教學科技與媒體55(2001.03),頁72-91。
9. 王麗卿。「教學媒體在設計科系教學上的應用─台南女子技術學院之現況調查研究」。視聽教育雙月刊 第42卷2期(2000.10),頁12-22。
10. 王麗卿。「幻燈片教學媒體在設計教學上的運用及成效」。視聽教育雙月刊 第40卷5期(1999.04),頁21-26。
11. 柯志恩。「認知導向的媒體選擇」。教學科技與媒體2(1992),頁37-40。
12. 鄭美珠。「視聽資料處理」。佛教圖書館館訊 第17期(民88年3月),頁29-38。
13. 黃信捷。「視聽資料媒體的管理與維護」。佛教圖書館館訊 第17期(民88年3月),頁13-28。
14. 李世忠。「大學資源中心的功能探討:以淡江大學教學科技組為例」。教學科技與媒體v 43 (1999年2月),頁44-50。
15. 趙文心。「大學圖書館非書資料室釋義」。視聽教育雙月刊第四十一卷第三期(民88年12月),頁9-19。