WT1在卵巢癌中的表达及其反义核酸诱导卵巢癌细胞凋亡的实验研究
|
摘要
目的研究WT1在上皮性卵巢癌组织中的表达及其反义核酸在体内、体外实验中对卵巢癌细胞增殖和凋亡的影响,探讨WT1基因的临床病理学意义和其反义核酸应用于卵巢癌治疗研究的可能性。方法检测各种不同病理类型卵巢组织及经紫杉醇治疗后裸鼠卵巢癌皮下移植瘤组织中WT1和相关凋亡基因的表达,应用WT1反义寡核苷酸转染卵巢癌SKOV_3细胞株,检测、观察转染前后卵巢癌细胞体内、体外增殖和凋亡的改变。结果上皮性卵巢癌、尤其是浆液性囊腺癌组织中WT1的表达明显高于其它组织学类型,且与临床分期、组织学分级相关。经紫杉醇治疗后的裸鼠卵巢癌皮下移植瘤组织中WT1表达下降,同时出现凋亡。WT1反义寡核苷酸转染后的卵巢癌SKOV_3细胞株生长缓慢,早期即发生凋亡,且体外成瘤能力降低。结论WT1在上皮性卵巢癌中高表达,可作为临床诊断的辅助性指标,其生物学效应是通过调节细胞的增殖和凋亡过程来实现的,可能成为卵巢癌治疗新的生物学靶点。
Objectives To study the expression of WT1 protein in ovarian carcinoma and the effect of WT1 ASODN inducing proliferation and apoptosis of SKOV_3 in vitro and in vivre.Methods Expression of WT1 and gene correlated with apoptosis were studied in all kinds of ovarian tissues and nude mouse transplanted tumor treated with Taxol. The WT1 ASODN was transferred into SKOV_3 cells.Investigate the changes in expression levels of WT1 protein and cell proliferation and apoptosis in ovarian epithelial after transfection.Results The positive expression rate of WT1 in ovarian epithelial carcinomas,especially in serous carcinomas,was statistically higher than those in other histologic subtypes.There were closed relationship between the expression of WT1 and clinical stage,histological grades,but no relationship with lymph node metastasisand ascites. Low lever of WT1 and apoptosis occurred were detected in nude mice during Taxol treatments.The growth of the ovarian cancer cell lines SKOV_3 transfected by WT1 ASODN became significantly slow and its activity reduced.Apoptosis were found in early stage.The tumorigenic ability of the SKOV_3 transfected by WT1 ASODN was decreased.Conclusion The overexpression of WT1 gene might be the biomolecular markers for the clinical diagnosis of ovarian epithelial tumors,especially serous carcinomas.WT1 may play an important role in regulate the proliferation and Apoptosis of ovarian cancer cell lines SKOV_3. WT1 will become a new diagnosis and therapeutic target in ovarian epithelial carcinoma.
Objectives To study the expression of WT1 protein in ovarian carcinoma and the effect of WT1 ASODN inducing proliferation and apoptosis of SKOV_3 in vitro and in vivre.Methods Expression of WT1 and gene correlated with apoptosis were studied in all kinds of ovarian tissues and nude mouse transplanted tumor treated with Taxol. The WT1 ASODN was transferred into SKOV_3 cells.Investigate the changes in expression levels of WT1 protein and cell proliferation and apoptosis in ovarian epithelial after transfection.Results The positive expression rate of WT1 in ovarian epithelial carcinomas,especially in serous carcinomas,was statistically higher than those in other histologic subtypes.There were closed relationship between the expression of WT1 and clinical stage,histological grades,but no relationship with lymph node metastasisand ascites. Low lever of WT1 and apoptosis occurred were detected in nude mice during Taxol treatments.The growth of the ovarian cancer cell lines SKOV_3 transfected by WT1 ASODN became significantly slow and its activity reduced.Apoptosis were found in early stage.The tumorigenic ability of the SKOV_3 transfected by WT1 ASODN was decreased.Conclusion The overexpression of WT1 gene might be the biomolecular markers for the clinical diagnosis of ovarian epithelial tumors,especially serous carcinomas.WT1 may play an important role in regulate the proliferation and Apoptosis of ovarian cancer cell lines SKOV_3. WT1 will become a new diagnosis and therapeutic target in ovarian epithelial carcinoma.
引文
[1] Call KM, Glaster T, Ito CY, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. CELL,1990,60 :509-520.
[2] Gessler, M. Poustka A, Covenee W, et al. Homozygous deletion in Wilms' tumors of a zinc-finger gene identified by Chromosome jumping. Nature. 1990, 343:774-778.
[3] Pritehard jones K, Fleming S, Davidson D, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature, 1990,346 (6280): 194-197.
[4] Miwa H, Beran M, Saunders GF, et al. Expression of the tumor gene (WT1) in human leukemia.Leukmia, 1992;6:405-408.
[5] Sugiyama H. Wilms' tumor gene WT1: its oncogenic function and clinical application [J]. Int J Hematol, 2001, 73 (2): 177-187.
[6]曹泽毅主编．北京．人民卫生出版社．1999年．
[7] Wadler S. New developments in treatment of ovarian cancer. Expert Opin Investig Drugs,2001,10(6):1167-1172.
[8] Werness BA, Eltabbkh GH. et al. Familial ovarian cancer and early ovarian cancer: biologic and clinical features. Int J Gynecol Pathol,2001,20(1):48-63.
[9] Markman M, Kennedy A, Webster K, et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol. 2001;19(7): 1901-1905.
[10] Gerenlee RT. et al. Cancer statistics. CA Cancer J. Clin, 2001,51(1):15 -36.
[11] Rubina S. Ismail, Rae Lynn Balduin, Junguo Fang, et al. Differential Gene Expression between Normal and Tumor-derived Ovarian Epithelial Cells. Cancer Research, 2000(23):6744-6749.
[12] Harber A, Bukler J, Glaser T, et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of wilm's tumor. Cell, 1990, 6(7):1257-1269.
[13] Lee TH, Lwu S, Kim J, et al. Inhibition of Wilms Tumor 1 Transactivation by B one Morrow ZincFinger2 ,a NPvel Transcripitional Repressor. J Biol Chem, 2002,277: 44826-44837.
[14] Larsson SH, Charlien JP, Miyayawa K, et al. Subnuclear localization of WT1 in splicing localization of domains is regulated by alternative splicing. Cell, 1995;81:391- 401.
[15] Inoue K, Sugiyama H, Ogawa H, et al. WT1 as a new prognostic factor and new maker for the detection of minimal residual disease in acute leukemica. Blood, 1994;84:3071 - 3079.
[16] Frainer GC, Patmasiriwat P, Zhong XH, et al. Expression of the tumor suppressor geneWT1 in both human and mouse bone marrow. Blood, 1995; 86: 4704-4706.
[17] Siberstein GB, Van Horn K, Strickland P, et al. Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA. 1997, 94(15):8132-8137.
[18] David M, Ella E, Chirag B, et al. Wilms tumor suppression gene WT1 is expressed in primary breast tumors despite tumor-specifit promoter methylation. Cancer Res, 2001,61, 921-925.
[19] Sekiya M, Adachi M, Hinoda Y, et al. Down regulation of Wilms' tumor gene (WT1) during myelomoonocytic diferentiation in HL-60 cells. Blood, 1994,83(7): 1876-1882.
[20] Phelan SA, Lindberg C, Call KM, et al. Wilms' tumor gene WT1 mRNA is down regulated during induction of erythroid and megakaryocytic diferentiation of K562 cells. Cell Growth Differ, 1994,5 (6) :677-686.
[21] Miyagi T, Ahuja H, Kubota T, et al. Expression of the candidate Wilm's tumor gene, WT1, in human leukemia cells. Leukemia, 1993,7(7):970-977.
[22] Wang ZY, Qiu QQ, Deuel TF. The Wilms' tumor gene product WT1 activates or supresses transcription through separate functional domains. J Biol Chem, 1993, 268(13):9172-9175
[23] Hylander B, Repasky E, Shrikant P, et al. Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol. 2006 Apr; 101(1): 12-17
[24] Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol 2001;116(2):246-252.
[25] Al-Hussaini M, Stockman A, Foster H, McCluggage WG. WT-1 assist in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid carcinoma. Histopathology 2004; 44(2): 109-115.
[26] Acs G, Pasha T, Zhang PJ. WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary and endometrium. Int J Gynecol Pathol 2004; 23(2): 110-118.
[27] Shimizu M, Toki T, Takagi Y, et al. Immunohistochemical detection of the Wilms tumor gene (WT1) in epithelial ovarian tumors. Int J Gynecol Pathol 2000; 19(2): 158-163.
[28] Wirote N, Jitti H, Chavaboon D, et al. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. BMC Cancer. 2006,6: 90
[26] Laux DE. Hypermethylation of the Wilms tumor suppressor gene CpG island in human breast carcinomas. Breast cancer Res Treat. 1999,56:35-43.
[27] Huang TH. Identification of DNA methylation markers for human breast carcinomas using the methylation-sensitive restriction fingerprinting technique. Cancer Res. 1997,57:1030-1034.
[28] Evron E. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet, 2001,357:1335-1336.
[29] Tornos C, Soslow R, Chen S, et al. Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.Am J Surg Pathol, 2005 Nov;29(11): 1482-1489.
[30] Goldstein NS, Uzieblo A. WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas. Am J Clin Pathol, 2002 Apr;l 17(4):541-545.
[31] Oka Y. Human cytotoxic T-lymphocyte responaes specific for peptides of the wild-type Wilms tumor gene (WT1) product. Immunogenetics,2000,51:99-107.
[32] Ohminami H. HLA class I- restricted lysis of leukemia cells by a CD8 cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood, 2000,95:286-293.
[33] Oka Y. Cancer immunotherapy targeting Wilms tumor gene WTI product. J immunol,2000,164:1873-1880.
[34] GAO L. Selective elimination of leukemac CD34 progenitor cells by cytotoxic T-lymphocyte specific for WTI. Bllod,2000,95:2198-2203.
[1]Zhou H,Kuang J,Zhong L,et al.Tumor amplified kinase STK15/BTAK induces centrosome amplification,aneuploidy and transformation.NatGenet,1998,20:189-193.
[2]McGuire WP,Rowinsky EK,Rosenshein NB,et al.Taxol:a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms.Ann Intern Med,1989,111:273-277.
[3]李文锦,钱和年,吕文英.人卵巢上皮性癌裸鼠皮下移植瘤模型和腹水瘤模型的建立[J].中 华妇产科杂志,1993, 28(1): 38.
[4] Meihua Sui, Feng Chen, Zhi Chen, Weimin Fan. Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors .Int.J.Cancer 2006,119:712-717.
[5] Herr I,Ucur E,Herzer K,et al. Glucocorticoid corteatment induces apoptosis resistance toward cancer therapy in carcinomas[J]. Cancer Res,2003,63 (12) :112-120.
[6] Zhu X, Sui M, Fan W. Invitro and in vivo characterizations of tetrandrine on the reversal of P-glycoprotein-mediated drug resistance to paclitaxel[J].Anticancer Res,2005,25 (38) : 1953-1962.
[7] 江希明，郑数，丁仁瑞主编.肿瘤生物学.浙江科学技术出版社1990.231-250.
[8] Sui L, Tokuda M, Ohno M, et al. The concurrent expression of p27kip1 and cyclin D1 in epithelial ovarian tumors. Gynecol Oncol 1999,73:202-209.
[9] Davy M, Mossige J, Johannessen JV. Heterologous growth of human ovarian cancer. Acta Obstet Gynecol Scand, 1977,56:55-59.
[10] Fu X, Hofman RM. Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anti-cancer Res ,1993,13:283-288.
[11] Astoul P, Colt HG, Wang X, et al. Metastatic human pleural ovarian cancer model constructed by orthotopic implantation of fresh histologically intact patient carcinoma in nude mice. Anticancer Res,1993,13(6A):1999-2006.
[12] Fidler IJ, Yano S, Zhang RD, et al. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol,2002,3(1):53-57.
[13] Qiu C, Wu H, He H, Qiu W. A cervical lymph node metastatic model of human tongue carcinoma: Serial and orthotopic transplantation of histologically intact patient specimens in nude mice. J Oral Maxillofac Surg,2003, 61(6):696-700.
[14] Tang ZY, Sun FX, Tian J, et al. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential. World J Gastroenterol,2001,7(5): 597-601.
[15] Adelman DC, Erickson KL, Gershwin ME. Macrophage-mediated inhibition of melanoma cell growth in nude mice. Exp Cell Biol.l983,51(3):165-171.
[16] Taillandier L, Antunes L, Angioi-Duprez KS. Models for neuro-oncological preclinical studies:solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci. Methods,2003.125(1-2):147-157.
[17] Euhus DM, Cler L , Shivapurkar N, et al. Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk. J Natl Cancer Inst,2002,94(11):858-860.
[19] Haldar S, Chintapalli J, Croce CM. Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res, 1996,Mar 15:56(6): 1253 -1255.
[20] Scatena CD, Stewart ZA, Mays D, Tang LJ, Keefer CJ, Leach SD, Pietenpol JA . Mitotic phosphorylation of Bcl-2 during normal cell cycle progression and Taxol-induced growth arrest. J B iol Chem,1998,Nov 13; 273(46) :30777-30784.
[21] Haldar S, Basu A, Croce CM. Serine-70 is one of the critical sites for drug-induced Bcl-2 phosphorylation in cancer cells. Cancer Res.l998,Apr 15;58(8): 1609-1615.
[22] Haldar S, Jena N, Croce CM. Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA.1995,May9;92(10):4507-4511.
[23] Manthey CL, Perera PY, Vogel SN. Taxol provides a second signal for murine macrophage tumoricidal activity. J Immunol, 1994; 152(2):825-831.
[24] 梅兴国，鲁明波。紫杉醇的抗癌作用及治疗其它疾病的潜力。国外医学药学分册,1996,2 3(3): 136-140.
[25] Mei ZZ, Sun ZX. Inhibitor of apoptosis proteins and the regulation of apoptosis. Foreign M edical Science of Genetics, 1999,22(6):281.
[1]Kronenwett R,Haas R.Antisense strategies for the treatment of hematological malignancies and solid tumors[J].Annals of Hematology,1998;77,1-12.
[2]Rosenberg SA,Aebersold P,Cornetta K,et al.Gene transfer into humans-immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction.N Engl J Med,1990,323:570.
[3]Hung WC,Huang JS,Chuang LY.Antisense oligodeoxynucleotides targeted against different reigions of cyclin D mRNA may exert different inhibitory effects on cell growth and gene expression.Biochem Biophys Res Commun 1996;220:719-723.
[4]Piroll KF,Hao Z,Rait A,et al.Evidence supporting a signal transduction pathway leading to the radio-resistant phenotype in human tumor cells.Biochem Biophys Res Commun 1997;230(1):196-201.
[5]Gautschio O,Tschopp S,Olie RA,et al.Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins.J Natl Cancer Inst,2001,93(6):463-471.
[6]Hung MC,Hortobagyi GN,Ueno NT.Development of clinical trial of EIA gene therapy targeting HER-2/neu-overexpressing breast and ovarian cancer.Adv Exp Med Bio,2000,465:171-180.
[7]Kim CK,Haider KhH,Choi SH.Nonviral vector for efficient gene transfer to human ovarian adenocarcinoma cells.Gynecol Oncol,2002,84(1):85-93.
[8]Wang ZY,Gaggero A,Rubartelli A,et al.Expression of interleukin- 18 in human ovarian carcinoma and normal ovarian epithelium:evidence for defective processing in tumor cells[J].Int J Cancer,200298(6):873-878.
[9]Lechanteur C,Princen F,Lo Bue S,et a 1.HSV-1 thymidine kinase gene therapy for peritoneal carcinomatosis[J].Adv Exp Med bio1,1998,451:115-119.
[10]Qian HN,Liu GZ,Cao SJ,et al.The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-gamma genes.Int J Gynecol Cancer[J],2002 12(1):80 -85.
[11]Guha C,Guha U,Tribius S,et al.Antisense ATM gene therapy:a strategy to increase the radiosensitivity of human tumors.Gene Ther,2000;7(10):852-858.
[12]Raizada MK,Francis SC,Wang HW,et al.Targeting of the renin-angiotensin system by antisense gene therapy:a possible strategy for the long-term control of hypertension.J Hypertens.2000;19(4):353-362.
[13]Kristian P,Ame O,Mats S,et al.Inhibition of platelet-deried Growth Factor Receptor reduces interstitial hypertension and increase transcapillary transport in tumor.Cancer Res,2001;61:2929-2934.
[14]Skimisdotir I,Sorbe B,Scidal T.The growth factor receptors HER-2/neu and EGFR,their relationship,and their effects on the prognosis in early stage(FIGO Ⅰ -Ⅱ) epithelial ovarian carcinoma.Int J Gynecol Cancer,2001 11(2):119-129.
[15]Institute of Experimental Dermatology,University of Munster,Munster,Germany.Growth inhibition of human mammary carcinoma by liposomal hexadecyl-phocholine:participation of activated macrophages in the antitumor mechanism[J].Int J Cancer,2001,92:426-433.
[16]Fletcher JC.Evolution of ethical debate about human gene therapy.Human Gene Therapy,1990,1(1):55-68.
[17]Galderisi U,Bernard G.Antisense inhibitory effects:a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides.J cell Biochem,1997,74:31-37.
[18]董凡,金由辛.寡聚脱氧核苷酸的结构和抗降解特性的研究.中国生物化学和分子生物学报,1998,14(1):62 64.
[19]Oberbauer R.Not nonsense but antisense- applications of antisense oligonucleotides in diferent fields of medicine[J].Wiener klinische wochenschrift,1997,109(2):40-46.
[20]Marcusson EG,Yacyshyn BR,Shanahan WJ,et al.Preclinical and clinical pharmacology of antisense oligonucleotides[J].Molecular Biothechnology,1999,12(1);1-11.
[21]Blay J.Technology evaluation:gEM-231,Hybridon Inc[J].Current Opinion in molecular therapeutics,2000,2(4):468-472.
[22]Ferkol T,Perales JC,Eckman E,et al.Gene transfer into airway epithelium of animals by targeting the polymeric immunoglobulin receptor[J].Journal of Clinical Investigation,1995,95:493-502.
[23]Agrawal S,Zhang X,Lit Z,et al.Absorption,tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleolide following orala dministration[J].Biochemical Pharmacology, 1995;50:571-576.
[24] Saison-BT, Torque B, Rey I, et al. Short modified antisense-directed against Ha-ras point mutation induce selective cleavage of the mRNA and T24 cells proliferation. EMBO J, 1991,10:1111.
[25] Indolfi C, Chiarello M, Arredimento EV. Selective gene therapy for proliferation disorders: sense and antisense[ J].Nature Medicine, 1996,2:634-635.
[26] Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nautre Medicine, 1997;3:887-893.
[27] Tanaka K, Iwakuma T, Harimaya K, et al. EWS-Fli Antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neurectodermal tumor cells. Journal of c linical Investigation, 1997;99:239-247.
[28] Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res, 2002, 107:99-118.
[29]黄培堂译．分子克隆实验指南[M]．第3版,北京：科学技术出版社．2003,1001-1002．
[30] Jaenisch R, Transgenic animals[J]. Science, 1998,240(4858): 1468-1474.
[31]黄培堂译．分子克隆实验指南[M]．第3版,北京：科学技术出版社．2003,786-787．
[32] Andreason GL, Evans GA. Introduction and expression of DNA molecules in eukaryotic cells by electroporation[J]. Biotechniques, 1998,6(7):650-660.
[33] 卢圣栋主编．现代分子生物学实验技术[M]】．第2版,北京：中国协和医科大学出版社．2004, 354-365．
[34] Weinstein JN, Steller MA, Covell DG, et al. Monoclonal antitumor antibodies in the lymphatics[J]. Cancer Treat Rep, 1994,68(1): 257-264.
[35] Mannino RJ, Gould-Fogerite S. Liposome mediated gene transfer[J]. Biotechniques, 1998,6(7):682-690.
[36]成国祥,左嘉客．生产转基因动物的技术现状[J]．细胞生物学杂志,2002,21(3)：107-110．
[33]李华,刘维全,王太一,等．基因导入的脂质体转染法和磷酸钙转染法之比较[J]．中国实验动物学杂志,2000,10(2)：65-68．
[38] Lee MJ, Cho SS, You JR, et al .Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer mode.[J]. Gene Ther,2029 (13):859-866.
[39] Stewart MJ, Plautz GE, Del Buono L, et al. Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice[J]. Hum Gene Ther, 1999, 3(3):267-275.
[40] Gershon H, Ghirlando R, Guttman SB, et al. Mode of formation and structural features of DNA-cationic liposome complexes used for transfection.[J]. Biochemistry, 2003,32(28): 7143-7151.
[41] Shen M, FengY, Ge B, et al. Li posome-C-erbB2 antisense oligodoxynucleotides inhuman ovarian
cancer cells[J].Chin Med J (Engl),2001,114(7):735-737.
[42] Ross PC, Hui SW. Lipoplex size is a major determinant of in virtro lipofection efficiency [J]. Gene
Ther, 2004,6(4):651-659.
[43] 边杰芳，张柏根，陈诗书.反义c-myc、增殖细胞核抗原基因片段抑制血管平滑肌相关基因表达.中华医学杂志,1999,79(1):242-245.
[44] Crawford Retal. Gynecologic Oncology: Current Diagnosis and treatment. London: WB
saunders,1996;203-212.
[45] Skilling JS, Squatrito RC, Connor JP, et al. P53 gene mutation analysic and antisense-mediated
growth inhibition of human ovarian carcinoma cell lines. Gynecol Oncol 1996;60:72-80
[46] Wu S, Meeker WA, Wiener JR, et al. Transfection of ovarian cancer cells with tumor nerosis factor-
α (TNF- α ) antisense mRNA abolishes the Proliferative response to interleukin-1 but not TNF-
α . Gyncol Oncol 1994;53(1):59-63.
[47] Wang S, Lee RJ, Cauchon G, et al. Delivery of antisense oligodeoxynucleotides against the human
epidermal growth factor receptor in cultured KB cells with lipsomes conjugates to folate via
polyethylenglycol. Proc Natl Acad Sci USA 1995;92:3318-3322.
[48] Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging
implications in tissue kinetics. Br J Cancer, 1972,26(2):239-257.
[49] Cook PD. Antisensere search and applications. Boca Ra ton ,CRC press; 1993
[50] Girard PM, Foray N, Stumnn M, et al. Radiosensitivity in nijmegen breakage synaroma cells is
attributable to repair defect and not cell cycle. Cancer Res,2000,60(15):4881-4888.
[51] Darzynkiewicz Z, Li X, Gong J. Assays of cell viability: discrimination of cells dying by apoptosis.
Methods Cell Biol, 1994;41:15-38.
[52] O'Connor L, Strasser A, O'Reilly LA, et al .Bim: a novel member of the bal-z family that promotes
apoptosis. EMBO J,1998,2(3):384-386.
[53] Khodarev NN, Sokolova LA, Vaughan ATM, et al. Mechanism of reduction of apoptotic DNA
fragmentation. Int Radiat Biol,1998,73(3):455-459.
[54] Funato T, Kozawa K, Fujimaki S, et al. Increased sensitivity to cisplatin in gastric cancer by
antisense inhibition of the HER-2/neu(C-erbB-2) Gene. Chemotherapy, 2001,47(4):297-303.
[55] Peethambaram PP, Long HJ. Second-line and subsequent therapy for ovarian carcinoma. Curr
Oncol Rep,2002,4(2):159-164.
[56] Patmasiriwat P, Fraizer GC, Claxton D, et al. Expression pattern of WT1 and GATA-1 in AML
with chromosome 16q22 abnormalities. Leukemia, 1996 10(7):1127-1033.
[57] Deuel TF, Guan IS, Wang ZY. Wilms' tumor gene product WT1 arrests macrophage differentiation of HL60 cells through its zinc finger domain. Bioch Bioph Res Com, 1999 254:192-196.
[58] Oji Y, Oqawa H, Tamaki H, et al. Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res. 1999 Feb;90(2): 194-204.
[1]李文锦，钱和年，吕文英.人卵巢上皮性癌裸鼠皮下移植瘤模型和腹小瘤模型的建立[J].中华妇产科杂志，1993, 28(1):38.
[2] Herr I,Ucur E,Herzer K,et al. Glucocorticoid corteatment induces apoptosis resistance toward cancer therapy in carcinomas[J]. Cancer Res,2003,63 (12) :112-20.
[3] Zhu X, Sui M, Fan W. Invitro and in vivo characterizations of tetrandrine on the reversal of P-glycoprotein-mediated drug resistance to paclitaxel[J].Anticancer Res,2005,25 (3B) : 1953-62
[4] Islan A, Handley SL, Thompson KS, et al. Studies on uptake, sub-celluar trafficking and efflux of antisense oligonucleiotides in glioma cells using self-assembing cationic lipoplexes as delivery systems.J Drug Target,2000,7(5):373-382.
[5] Londono-Vallejo JA, DerSarkissian H, Cazes L, et al. Differences in telomere length between homologous chromosomes in humans. Nucleic Acids Res,2001,29(15):3164-3171.
[6] Taillandier L, Antunes L, Angioi-Duprez KS. Models for neuro-oncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci. Methods,2003,125(1-2): 147-157.
[7] Euhus DM, Cler L , Shivapurkar N, et al. Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk. J Natl Cancer Inst,2002,94(11):858-860.
[8] Marwick C. First antisense drug will treat CMV retinitis. JAMA, 1998, 280(10):871.
[9] Yoo BH, Bochkareva E, Bochkarcv A, et al. 2'-0-methyl-modified phosphorothioate antisense oligonucleotides have reduced non-specific effects in vitro. Nucleic Acids Res,2004,32(6):2008-2016.
[10] Madry H, Reszka R, Bohlender J, et al. Efficacy of cationic liposome mediated gene transfer to mesangial cells in vitro and in vivo. J Mol Med,2001,79(4): 184-189.
[11] Kaiser S, Toborek M. Liposome-mediated high-efficiency transfection of human endothelial cells. J Vasc Res,2001,38(2):133-143.
[12] Stein C, Tonkinson J, Zhang I, et al. Dynamics of the internalization of phosphodiester oligodeoxynucleotides in HL60 cells. Biochemistry,1993,32(14):4855-63.
[13] Krieg A, Gmelig-Meyling F, Gourley M, et al. Uptake of oligodeoxyribonucleotides by lymphoid cells is heterogeneous and inducible. Antisense Res Deve 1,1991,1 (2): 161-9.
[14] Krieg A, Tonkinson J, Matson S, et al. Modification of antisense phosphodiester oligodeoxynucleotides by 5'-cholesteryl moiety increases cellular association and improves efficacy.Proc Natl Acad Sci USA,1993,90(6):1048-53.
[15] Sen L, Hong YS. Lao H, et al. Efficiency, efficacy and adverse effects of adenovirus vs liposome -mediated gene therapy in cardiac allografts. Am J Physiol Heart Circ Physiol, 2001,281(3): 1433-1441.
[16] Silberstein GB, Van Horn K, Strickland P, Roberts CT Jr, Daniel CW. Altered expression of the WT1 wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA. 1997 Jul 22;94(15):8132-8137.
[17] Ezzel C. Beyond the human genome. Sci Am, 2000, 283(1): 64-69.
[18] May M, Hecbner G. The Power of Proteomics. Science, 2001, 292(5515): 317-328.
[1]Kronenwett R,Haas R.Antisense strategies for the treatment of hematological malignancies and solid tumors[J].Annals of Hematology,1998;77,1-12.
[2]Wang ZY,Gaggero A,Rubartelli A,et al.Expression of interleukin-18 in human ovarian carcinoma and normal ovarian epithelium:evidence for defective processing in tumor cells[J].Int J Cancer,200298(6):873-878.
[3]Lechanteur C,Princen F,Lo Bue S,et a 1.HSV-1 thymidine kinase gene therapy for peritoneal carcinomatosis[J].Adv Exp Med biol,1998,451:115-119.
[4]Qian HN,Liu GZ,Cao SJ,et al.The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-gamma genes.Int J Gynecol Cancer[J],2002 12(1):80 -85.
[5]Guha C,Guha U,Tribius S,et al.Antisense ATM gene therapy:a strategy to increase the radiosensitivity of human tumors.Gene Ther,2000;7(10):852-858.
[6]Raizada MK,Francis SC,Wang HW,et al.Targeting of the renin-angiotensin system by antisense gene therapy:a possible strategy for the long-term control of hypertension.J Hypertens.2000;19(4):353-62.
[7]Kristian P,Arne O,Mats S,et al.Inhibition of platelet-deried Growth Factor Receptor reduces interstitial hypertension and increase transcapillary transport in tumor.Cancer Res,2001;61:2929-2934.
[8]Skimisdotir I,Sorbe B,Scidal T.The growth factor receptors HER-2/neu and EGFR,their relationship,and their effects on the prognosis in early stage(FIGO Ⅰ -Ⅱ) epithelial ovarian carcinoma.Int J Gynecol Cancer,2001 11(2):119-29.
[9]Institute of Experimental Dermatology,University of Munster,Munster,Germany.Growth inhibition of human mammary carcinoma by liposomal hexadecyl-phocholine:participation of activated macrophages in the antitumor mechanism[J].Int J Cancer,2001,92:426-433.
[10]Fletcher JC.Evolution of ethical debate about human gene therapy.Human Gene Therapy,1990,1(1):55-68.
[11] Stixg. Shutting down a gene. Antisense drug wings approval.Sci Am. 1998, 279 (5):46-50.
[12] Galderisi U, Bernard G. Antisense inhibitory effects: a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides. J cell Biochem, 1997,74:31-37.
[13]董凡,金由辛．寡聚脱氧核苷酸的结构和抗降解特性的研究．中国生物化学和分子生物学报,1998,14(1)：62-64．
[14] Oberbauer R. Not nonsense but antisense- applications of antisense oligonucleotides in diferent fields of medicine [J]. Wiener klinische wochenschrift,1997,109(2):40-46.
[15] Marcusson EG, Yacyshyn BR, Shanahan WJ, et al. Preclinical and clinical pharmacology of antisense oligonucleotides [J].Molecular Biothechnology, 1999,12 (1);1-11.
[16] Blay J. Technology evaluation: gEM-231, Hybridon Inc [J]. Current Opinion in molecular therapeutics,2000,2(4):468-472.
[17] Ferkol T, Perales JC, Eckman E, et al. Gene transfer into airway epithelium of animals by targeting the polymeric immunoglobulin recepto[J].Journal of Clinical Investigation, 1995,95:493-502.
[18] Agrawal S, Zhang X, Lit Z, et al. Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleolide following orala dministration [J]. Biochemical Pharmacology, 1995;50:571-576.
[19] Jaenisch R, Transgenic animals[J]. Science, 1998,240(4858): 1468-1474.
[20]成国祥,左嘉客．生产转基因动物的技术现状[J]．细胞生物学杂志,2002,21(3)：107-110．
[21] Lee MJ, Cho SS, You JR, et al .Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer mode.[J]. Gene Ther,2029 (13):859-866.
[22] Weinstein JN, Steller MA, Covell DG, et al. Monoclonal antitumor antibodies in the lymphatics[J]. Cancer Treat Rep, 1994,68(1): 257-264.
[23] Mannino RJ, Gould-Fogerite S. Liposome mediated gene transfer[J]. Biotechniques, 1998,6(7):682-690.
[24] Stewart MJ, Plautz GE, Del Buono L, et al. Gene transfer in vivo with DNA-liposome complexes:safety and acute toxicity in mice[J]. Hum Gene Ther, 1999, 3(3):267-275.
[25] Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nautre Medicine, 1997;3:887-93.
[26] Shen M, FengY, Ge B, et al. Li posome-C-erbB2 antisense oligodoxynucleotides inhuman ovarian cancer cells[J].Chin Med J (Engl),2001,l 14(7):735-7.
[27] Ross PC, Hui SW. Lipoplex size is a major determinant of in virtro lipofection efficiency[J]. Gene Ther, 2004,6(4):651-659.
[28] 边杰芳，张柏银，陈诗书.反义c-myc、增殖细胞核抗原基因片段抑制血管平滑肌相关基因表达.
中华医学杂志，1999,79(1):242-245.
[29] 黄培堂译.分子克隆实验指南[M].第3版，北京：科学技术出版社.2003,786-787.
[30] Andreason GL, Evans GA. Introduction and expression of DNA molecules in eukaryotic cells by electroporation[J]. Biotechniques, 1998,6(7):650-660.
[31] 曹泽毅主编.北京.人民卫生出版社.1999
[32] Wadler S. New developments in treatment of ovarian cancer. Expert Opin Investig Drugs,2001,10(6):1167-72.
[33] Werness BA, Eltabbkh GH. et al. Familial ovarian cancer and early ovarian cancer: biologic and clinical features. Int J Gynecol Pathol,2001,20(1):48-63
[34] Markman M, Kennedy A, Webster K, et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol. 2001;19(7): 1901-5.
[35] Gerenlee RT. et al. Cancer statistics. CA Cancer J. Clin, 2001,51(1):15-36
[36] Saison-BT, Torque B, Rey I, et al. Short modified antisense-directed against Ha-ras point mutation induce selective cleavage of the mRNA and T24 cells proliferation. EMBO J, 1991,10:1111.
[37] Cuningham CC, Holmulund JT, Schiller JH, et al. A phase I trial of c-raf-1 kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer[J]. Clin Cancer Res,2000,6(5):1626-31.
[38] Cagnoli M, Barbieri F, Bruzzo C, et al. Control of cyclinDl expression by antisense olignonudeotldes in three ovarian cancer cell lines. Gynecol oncol.1998, 70(3):372-377.
[39] Helm CW, shrestha K, Thomas S, et al. A unique c-myc-Targeted Triplex-forming oligonucleotide inhibits the growth of ovarian and cervical carcinomas in vitro. Gynecol oncol ,1993,4 9(3):339-343.
[40] Masanek U, Stammler G, Volm M. Modulation of multidrug resistance in human ovarian cancer cell lines by inhibition of P-glycoprotein 170 and PKC isoenzymes with antisense oligonucleotides. J Exp Ther Oncol,2002,2(1):37-41.
[41] Annab LA, Hawkins RE, Solomon G, et al. Increased cell survial by inhibition of BRCA1 using anantisense approach in estrogen responsive ovarian carcinoma cell line. Breast Cancer Res,2000,2(2):139-148.
[42] Skilling JS, Squatrito RC, Connor JP, et al. P53 gene mutation analysis and antisense-mediated growth inhibition of human ovarian carcinoma cell lines. Gynecol oncol, 1996,60(1) :72-80.
[43] Casamallimi A, De-Luca, Agrawal S, et al. EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells. Ann oncol,2000,l 1 (3):319-325.
[44] Coppola D, Saunders B, Fu L, et al .The insulin-like growth factor 1 receptor induces transformation and tumorigenicity of ovarian mesothelial cells and down-regulates their Fas-receptor expression. Cancer Res, 1999,59 (13):3264-3270.
[45] Morrison BH, Baucer JA, Kalvakolanu DJ, et al. Inositol Hexakisphosphate kinase2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. J- Biol-chem,2001,276(27):24965-24970.
[46] Pirollo KF, Hao Z, Rait A, et al. Evidence supporting a singal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem-Biophys-Res-Commun. 1997,230(1): 196-201.
[47] Indolfi C, Chiarello M, Arredimento EV. Selective gene therapy for proliferation disorders: sense and antisense[J].Nature Medicine, 1996,2:634-635.
[48] Fei R, Shaoyang L. Combination antigene therapy targeting c-myc and c-erbB2 in the ovarian cancer COC1 cell line [J]. Gynecol Oncol.2002,85 (1):40-44.
[49] Tanaka K, Iwakuma T, Harimaya K, et al. EWS-Fli Antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neurectodermal tumor cells. Journal of c linical Investigation, 1997;99:239-47.
[50] Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res, 2002,107:99-118.
[51] Islan A, Handley SL, Thompson KS, et al. Studies on uptake, sub-celluar trafficking and efflux of antisense oligonucleiotides in glioma cells using self-assembing cationic lipoplexes as delivery systems.J Drug Target,2000,7(5):373-382.
[52] Londono-Vallejo JA, DerSarkissian H, Cazes L, et al. Differences in telomere length between homologous chromosomes in humans. Nucleic A.
[2] Gessler, M. Poustka A, Covenee W, et al. Homozygous deletion in Wilms' tumors of a zinc-finger gene identified by Chromosome jumping. Nature. 1990, 343:774-778.
[3] Pritehard jones K, Fleming S, Davidson D, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature, 1990,346 (6280): 194-197.
[4] Miwa H, Beran M, Saunders GF, et al. Expression of the tumor gene (WT1) in human leukemia.Leukmia, 1992;6:405-408.
[5] Sugiyama H. Wilms' tumor gene WT1: its oncogenic function and clinical application [J]. Int J Hematol, 2001, 73 (2): 177-187.
[6]曹泽毅主编．北京．人民卫生出版社．1999年．
[7] Wadler S. New developments in treatment of ovarian cancer. Expert Opin Investig Drugs,2001,10(6):1167-1172.
[8] Werness BA, Eltabbkh GH. et al. Familial ovarian cancer and early ovarian cancer: biologic and clinical features. Int J Gynecol Pathol,2001,20(1):48-63.
[9] Markman M, Kennedy A, Webster K, et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol. 2001;19(7): 1901-1905.
[10] Gerenlee RT. et al. Cancer statistics. CA Cancer J. Clin, 2001,51(1):15 -36.
[11] Rubina S. Ismail, Rae Lynn Balduin, Junguo Fang, et al. Differential Gene Expression between Normal and Tumor-derived Ovarian Epithelial Cells. Cancer Research, 2000(23):6744-6749.
[12] Harber A, Bukler J, Glaser T, et al. An internal deletion within an 11p13 zinc finger gene contributes to the development of wilm's tumor. Cell, 1990, 6(7):1257-1269.
[13] Lee TH, Lwu S, Kim J, et al. Inhibition of Wilms Tumor 1 Transactivation by B one Morrow ZincFinger2 ,a NPvel Transcripitional Repressor. J Biol Chem, 2002,277: 44826-44837.
[14] Larsson SH, Charlien JP, Miyayawa K, et al. Subnuclear localization of WT1 in splicing localization of domains is regulated by alternative splicing. Cell, 1995;81:391- 401.
[15] Inoue K, Sugiyama H, Ogawa H, et al. WT1 as a new prognostic factor and new maker for the detection of minimal residual disease in acute leukemica. Blood, 1994;84:3071 - 3079.
[16] Frainer GC, Patmasiriwat P, Zhong XH, et al. Expression of the tumor suppressor geneWT1 in both human and mouse bone marrow. Blood, 1995; 86: 4704-4706.
[17] Siberstein GB, Van Horn K, Strickland P, et al. Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA. 1997, 94(15):8132-8137.
[18] David M, Ella E, Chirag B, et al. Wilms tumor suppression gene WT1 is expressed in primary breast tumors despite tumor-specifit promoter methylation. Cancer Res, 2001,61, 921-925.
[19] Sekiya M, Adachi M, Hinoda Y, et al. Down regulation of Wilms' tumor gene (WT1) during myelomoonocytic diferentiation in HL-60 cells. Blood, 1994,83(7): 1876-1882.
[20] Phelan SA, Lindberg C, Call KM, et al. Wilms' tumor gene WT1 mRNA is down regulated during induction of erythroid and megakaryocytic diferentiation of K562 cells. Cell Growth Differ, 1994,5 (6) :677-686.
[21] Miyagi T, Ahuja H, Kubota T, et al. Expression of the candidate Wilm's tumor gene, WT1, in human leukemia cells. Leukemia, 1993,7(7):970-977.
[22] Wang ZY, Qiu QQ, Deuel TF. The Wilms' tumor gene product WT1 activates or supresses transcription through separate functional domains. J Biol Chem, 1993, 268(13):9172-9175
[23] Hylander B, Repasky E, Shrikant P, et al. Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol. 2006 Apr; 101(1): 12-17
[24] Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol 2001;116(2):246-252.
[25] Al-Hussaini M, Stockman A, Foster H, McCluggage WG. WT-1 assist in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid carcinoma. Histopathology 2004; 44(2): 109-115.
[26] Acs G, Pasha T, Zhang PJ. WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary and endometrium. Int J Gynecol Pathol 2004; 23(2): 110-118.
[27] Shimizu M, Toki T, Takagi Y, et al. Immunohistochemical detection of the Wilms tumor gene (WT1) in epithelial ovarian tumors. Int J Gynecol Pathol 2000; 19(2): 158-163.
[28] Wirote N, Jitti H, Chavaboon D, et al. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. BMC Cancer. 2006,6: 90
[26] Laux DE. Hypermethylation of the Wilms tumor suppressor gene CpG island in human breast carcinomas. Breast cancer Res Treat. 1999,56:35-43.
[27] Huang TH. Identification of DNA methylation markers for human breast carcinomas using the methylation-sensitive restriction fingerprinting technique. Cancer Res. 1997,57:1030-1034.
[28] Evron E. Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet, 2001,357:1335-1336.
[29] Tornos C, Soslow R, Chen S, et al. Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.Am J Surg Pathol, 2005 Nov;29(11): 1482-1489.
[30] Goldstein NS, Uzieblo A. WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas. Am J Clin Pathol, 2002 Apr;l 17(4):541-545.
[31] Oka Y. Human cytotoxic T-lymphocyte responaes specific for peptides of the wild-type Wilms tumor gene (WT1) product. Immunogenetics,2000,51:99-107.
[32] Ohminami H. HLA class I- restricted lysis of leukemia cells by a CD8 cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood, 2000,95:286-293.
[33] Oka Y. Cancer immunotherapy targeting Wilms tumor gene WTI product. J immunol,2000,164:1873-1880.
[34] GAO L. Selective elimination of leukemac CD34 progenitor cells by cytotoxic T-lymphocyte specific for WTI. Bllod,2000,95:2198-2203.
[1]Zhou H,Kuang J,Zhong L,et al.Tumor amplified kinase STK15/BTAK induces centrosome amplification,aneuploidy and transformation.NatGenet,1998,20:189-193.
[2]McGuire WP,Rowinsky EK,Rosenshein NB,et al.Taxol:a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms.Ann Intern Med,1989,111:273-277.
[3]李文锦,钱和年,吕文英.人卵巢上皮性癌裸鼠皮下移植瘤模型和腹水瘤模型的建立[J].中 华妇产科杂志,1993, 28(1): 38.
[4] Meihua Sui, Feng Chen, Zhi Chen, Weimin Fan. Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors .Int.J.Cancer 2006,119:712-717.
[5] Herr I,Ucur E,Herzer K,et al. Glucocorticoid corteatment induces apoptosis resistance toward cancer therapy in carcinomas[J]. Cancer Res,2003,63 (12) :112-120.
[6] Zhu X, Sui M, Fan W. Invitro and in vivo characterizations of tetrandrine on the reversal of P-glycoprotein-mediated drug resistance to paclitaxel[J].Anticancer Res,2005,25 (38) : 1953-1962.
[7] 江希明，郑数，丁仁瑞主编.肿瘤生物学.浙江科学技术出版社1990.231-250.
[8] Sui L, Tokuda M, Ohno M, et al. The concurrent expression of p27kip1 and cyclin D1 in epithelial ovarian tumors. Gynecol Oncol 1999,73:202-209.
[9] Davy M, Mossige J, Johannessen JV. Heterologous growth of human ovarian cancer. Acta Obstet Gynecol Scand, 1977,56:55-59.
[10] Fu X, Hofman RM. Human ovarian carcinoma metastatic models constructed in nude mice by orthotopic transplantation of histologically-intact patient specimens. Anti-cancer Res ,1993,13:283-288.
[11] Astoul P, Colt HG, Wang X, et al. Metastatic human pleural ovarian cancer model constructed by orthotopic implantation of fresh histologically intact patient carcinoma in nude mice. Anticancer Res,1993,13(6A):1999-2006.
[12] Fidler IJ, Yano S, Zhang RD, et al. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol,2002,3(1):53-57.
[13] Qiu C, Wu H, He H, Qiu W. A cervical lymph node metastatic model of human tongue carcinoma: Serial and orthotopic transplantation of histologically intact patient specimens in nude mice. J Oral Maxillofac Surg,2003, 61(6):696-700.
[14] Tang ZY, Sun FX, Tian J, et al. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential. World J Gastroenterol,2001,7(5): 597-601.
[15] Adelman DC, Erickson KL, Gershwin ME. Macrophage-mediated inhibition of melanoma cell growth in nude mice. Exp Cell Biol.l983,51(3):165-171.
[16] Taillandier L, Antunes L, Angioi-Duprez KS. Models for neuro-oncological preclinical studies:solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci. Methods,2003.125(1-2):147-157.
[17] Euhus DM, Cler L , Shivapurkar N, et al. Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk. J Natl Cancer Inst,2002,94(11):858-860.
[19] Haldar S, Chintapalli J, Croce CM. Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res, 1996,Mar 15:56(6): 1253 -1255.
[20] Scatena CD, Stewart ZA, Mays D, Tang LJ, Keefer CJ, Leach SD, Pietenpol JA . Mitotic phosphorylation of Bcl-2 during normal cell cycle progression and Taxol-induced growth arrest. J B iol Chem,1998,Nov 13; 273(46) :30777-30784.
[21] Haldar S, Basu A, Croce CM. Serine-70 is one of the critical sites for drug-induced Bcl-2 phosphorylation in cancer cells. Cancer Res.l998,Apr 15;58(8): 1609-1615.
[22] Haldar S, Jena N, Croce CM. Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA.1995,May9;92(10):4507-4511.
[23] Manthey CL, Perera PY, Vogel SN. Taxol provides a second signal for murine macrophage tumoricidal activity. J Immunol, 1994; 152(2):825-831.
[24] 梅兴国，鲁明波。紫杉醇的抗癌作用及治疗其它疾病的潜力。国外医学药学分册,1996,2 3(3): 136-140.
[25] Mei ZZ, Sun ZX. Inhibitor of apoptosis proteins and the regulation of apoptosis. Foreign M edical Science of Genetics, 1999,22(6):281.
[1]Kronenwett R,Haas R.Antisense strategies for the treatment of hematological malignancies and solid tumors[J].Annals of Hematology,1998;77,1-12.
[2]Rosenberg SA,Aebersold P,Cornetta K,et al.Gene transfer into humans-immunotherapy of patients with advanced melanoma using tumor-infiltrating lymphocytes modified by retroviral gene transduction.N Engl J Med,1990,323:570.
[3]Hung WC,Huang JS,Chuang LY.Antisense oligodeoxynucleotides targeted against different reigions of cyclin D mRNA may exert different inhibitory effects on cell growth and gene expression.Biochem Biophys Res Commun 1996;220:719-723.
[4]Piroll KF,Hao Z,Rait A,et al.Evidence supporting a signal transduction pathway leading to the radio-resistant phenotype in human tumor cells.Biochem Biophys Res Commun 1997;230(1):196-201.
[5]Gautschio O,Tschopp S,Olie RA,et al.Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins.J Natl Cancer Inst,2001,93(6):463-471.
[6]Hung MC,Hortobagyi GN,Ueno NT.Development of clinical trial of EIA gene therapy targeting HER-2/neu-overexpressing breast and ovarian cancer.Adv Exp Med Bio,2000,465:171-180.
[7]Kim CK,Haider KhH,Choi SH.Nonviral vector for efficient gene transfer to human ovarian adenocarcinoma cells.Gynecol Oncol,2002,84(1):85-93.
[8]Wang ZY,Gaggero A,Rubartelli A,et al.Expression of interleukin- 18 in human ovarian carcinoma and normal ovarian epithelium:evidence for defective processing in tumor cells[J].Int J Cancer,200298(6):873-878.
[9]Lechanteur C,Princen F,Lo Bue S,et a 1.HSV-1 thymidine kinase gene therapy for peritoneal carcinomatosis[J].Adv Exp Med bio1,1998,451:115-119.
[10]Qian HN,Liu GZ,Cao SJ,et al.The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-gamma genes.Int J Gynecol Cancer[J],2002 12(1):80 -85.
[11]Guha C,Guha U,Tribius S,et al.Antisense ATM gene therapy:a strategy to increase the radiosensitivity of human tumors.Gene Ther,2000;7(10):852-858.
[12]Raizada MK,Francis SC,Wang HW,et al.Targeting of the renin-angiotensin system by antisense gene therapy:a possible strategy for the long-term control of hypertension.J Hypertens.2000;19(4):353-362.
[13]Kristian P,Ame O,Mats S,et al.Inhibition of platelet-deried Growth Factor Receptor reduces interstitial hypertension and increase transcapillary transport in tumor.Cancer Res,2001;61:2929-2934.
[14]Skimisdotir I,Sorbe B,Scidal T.The growth factor receptors HER-2/neu and EGFR,their relationship,and their effects on the prognosis in early stage(FIGO Ⅰ -Ⅱ) epithelial ovarian carcinoma.Int J Gynecol Cancer,2001 11(2):119-129.
[15]Institute of Experimental Dermatology,University of Munster,Munster,Germany.Growth inhibition of human mammary carcinoma by liposomal hexadecyl-phocholine:participation of activated macrophages in the antitumor mechanism[J].Int J Cancer,2001,92:426-433.
[16]Fletcher JC.Evolution of ethical debate about human gene therapy.Human Gene Therapy,1990,1(1):55-68.
[17]Galderisi U,Bernard G.Antisense inhibitory effects:a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides.J cell Biochem,1997,74:31-37.
[18]董凡,金由辛.寡聚脱氧核苷酸的结构和抗降解特性的研究.中国生物化学和分子生物学报,1998,14(1):62 64.
[19]Oberbauer R.Not nonsense but antisense- applications of antisense oligonucleotides in diferent fields of medicine[J].Wiener klinische wochenschrift,1997,109(2):40-46.
[20]Marcusson EG,Yacyshyn BR,Shanahan WJ,et al.Preclinical and clinical pharmacology of antisense oligonucleotides[J].Molecular Biothechnology,1999,12(1);1-11.
[21]Blay J.Technology evaluation:gEM-231,Hybridon Inc[J].Current Opinion in molecular therapeutics,2000,2(4):468-472.
[22]Ferkol T,Perales JC,Eckman E,et al.Gene transfer into airway epithelium of animals by targeting the polymeric immunoglobulin receptor[J].Journal of Clinical Investigation,1995,95:493-502.
[23]Agrawal S,Zhang X,Lit Z,et al.Absorption,tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleolide following orala dministration[J].Biochemical Pharmacology, 1995;50:571-576.
[24] Saison-BT, Torque B, Rey I, et al. Short modified antisense-directed against Ha-ras point mutation induce selective cleavage of the mRNA and T24 cells proliferation. EMBO J, 1991,10:1111.
[25] Indolfi C, Chiarello M, Arredimento EV. Selective gene therapy for proliferation disorders: sense and antisense[ J].Nature Medicine, 1996,2:634-635.
[26] Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nautre Medicine, 1997;3:887-893.
[27] Tanaka K, Iwakuma T, Harimaya K, et al. EWS-Fli Antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neurectodermal tumor cells. Journal of c linical Investigation, 1997;99:239-247.
[28] Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res, 2002, 107:99-118.
[29]黄培堂译．分子克隆实验指南[M]．第3版,北京：科学技术出版社．2003,1001-1002．
[30] Jaenisch R, Transgenic animals[J]. Science, 1998,240(4858): 1468-1474.
[31]黄培堂译．分子克隆实验指南[M]．第3版,北京：科学技术出版社．2003,786-787．
[32] Andreason GL, Evans GA. Introduction and expression of DNA molecules in eukaryotic cells by electroporation[J]. Biotechniques, 1998,6(7):650-660.
[33] 卢圣栋主编．现代分子生物学实验技术[M]】．第2版,北京：中国协和医科大学出版社．2004, 354-365．
[34] Weinstein JN, Steller MA, Covell DG, et al. Monoclonal antitumor antibodies in the lymphatics[J]. Cancer Treat Rep, 1994,68(1): 257-264.
[35] Mannino RJ, Gould-Fogerite S. Liposome mediated gene transfer[J]. Biotechniques, 1998,6(7):682-690.
[36]成国祥,左嘉客．生产转基因动物的技术现状[J]．细胞生物学杂志,2002,21(3)：107-110．
[33]李华,刘维全,王太一,等．基因导入的脂质体转染法和磷酸钙转染法之比较[J]．中国实验动物学杂志,2000,10(2)：65-68．
[38] Lee MJ, Cho SS, You JR, et al .Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer mode.[J]. Gene Ther,2029 (13):859-866.
[39] Stewart MJ, Plautz GE, Del Buono L, et al. Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice[J]. Hum Gene Ther, 1999, 3(3):267-275.
[40] Gershon H, Ghirlando R, Guttman SB, et al. Mode of formation and structural features of DNA-cationic liposome complexes used for transfection.[J]. Biochemistry, 2003,32(28): 7143-7151.
[41] Shen M, FengY, Ge B, et al. Li posome-C-erbB2 antisense oligodoxynucleotides inhuman ovarian
cancer cells[J].Chin Med J (Engl),2001,114(7):735-737.
[42] Ross PC, Hui SW. Lipoplex size is a major determinant of in virtro lipofection efficiency [J]. Gene
Ther, 2004,6(4):651-659.
[43] 边杰芳，张柏根，陈诗书.反义c-myc、增殖细胞核抗原基因片段抑制血管平滑肌相关基因表达.中华医学杂志,1999,79(1):242-245.
[44] Crawford Retal. Gynecologic Oncology: Current Diagnosis and treatment. London: WB
saunders,1996;203-212.
[45] Skilling JS, Squatrito RC, Connor JP, et al. P53 gene mutation analysic and antisense-mediated
growth inhibition of human ovarian carcinoma cell lines. Gynecol Oncol 1996;60:72-80
[46] Wu S, Meeker WA, Wiener JR, et al. Transfection of ovarian cancer cells with tumor nerosis factor-
α (TNF- α ) antisense mRNA abolishes the Proliferative response to interleukin-1 but not TNF-
α . Gyncol Oncol 1994;53(1):59-63.
[47] Wang S, Lee RJ, Cauchon G, et al. Delivery of antisense oligodeoxynucleotides against the human
epidermal growth factor receptor in cultured KB cells with lipsomes conjugates to folate via
polyethylenglycol. Proc Natl Acad Sci USA 1995;92:3318-3322.
[48] Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging
implications in tissue kinetics. Br J Cancer, 1972,26(2):239-257.
[49] Cook PD. Antisensere search and applications. Boca Ra ton ,CRC press; 1993
[50] Girard PM, Foray N, Stumnn M, et al. Radiosensitivity in nijmegen breakage synaroma cells is
attributable to repair defect and not cell cycle. Cancer Res,2000,60(15):4881-4888.
[51] Darzynkiewicz Z, Li X, Gong J. Assays of cell viability: discrimination of cells dying by apoptosis.
Methods Cell Biol, 1994;41:15-38.
[52] O'Connor L, Strasser A, O'Reilly LA, et al .Bim: a novel member of the bal-z family that promotes
apoptosis. EMBO J,1998,2(3):384-386.
[53] Khodarev NN, Sokolova LA, Vaughan ATM, et al. Mechanism of reduction of apoptotic DNA
fragmentation. Int Radiat Biol,1998,73(3):455-459.
[54] Funato T, Kozawa K, Fujimaki S, et al. Increased sensitivity to cisplatin in gastric cancer by
antisense inhibition of the HER-2/neu(C-erbB-2) Gene. Chemotherapy, 2001,47(4):297-303.
[55] Peethambaram PP, Long HJ. Second-line and subsequent therapy for ovarian carcinoma. Curr
Oncol Rep,2002,4(2):159-164.
[56] Patmasiriwat P, Fraizer GC, Claxton D, et al. Expression pattern of WT1 and GATA-1 in AML
with chromosome 16q22 abnormalities. Leukemia, 1996 10(7):1127-1033.
[57] Deuel TF, Guan IS, Wang ZY. Wilms' tumor gene product WT1 arrests macrophage differentiation of HL60 cells through its zinc finger domain. Bioch Bioph Res Com, 1999 254:192-196.
[58] Oji Y, Oqawa H, Tamaki H, et al. Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth. Jpn J Cancer Res. 1999 Feb;90(2): 194-204.
[1]李文锦，钱和年，吕文英.人卵巢上皮性癌裸鼠皮下移植瘤模型和腹小瘤模型的建立[J].中华妇产科杂志，1993, 28(1):38.
[2] Herr I,Ucur E,Herzer K,et al. Glucocorticoid corteatment induces apoptosis resistance toward cancer therapy in carcinomas[J]. Cancer Res,2003,63 (12) :112-20.
[3] Zhu X, Sui M, Fan W. Invitro and in vivo characterizations of tetrandrine on the reversal of P-glycoprotein-mediated drug resistance to paclitaxel[J].Anticancer Res,2005,25 (3B) : 1953-62
[4] Islan A, Handley SL, Thompson KS, et al. Studies on uptake, sub-celluar trafficking and efflux of antisense oligonucleiotides in glioma cells using self-assembing cationic lipoplexes as delivery systems.J Drug Target,2000,7(5):373-382.
[5] Londono-Vallejo JA, DerSarkissian H, Cazes L, et al. Differences in telomere length between homologous chromosomes in humans. Nucleic Acids Res,2001,29(15):3164-3171.
[6] Taillandier L, Antunes L, Angioi-Duprez KS. Models for neuro-oncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci. Methods,2003,125(1-2): 147-157.
[7] Euhus DM, Cler L , Shivapurkar N, et al. Loss of heterozygosity in benign breast epithelium in relation to breast cancer risk. J Natl Cancer Inst,2002,94(11):858-860.
[8] Marwick C. First antisense drug will treat CMV retinitis. JAMA, 1998, 280(10):871.
[9] Yoo BH, Bochkareva E, Bochkarcv A, et al. 2'-0-methyl-modified phosphorothioate antisense oligonucleotides have reduced non-specific effects in vitro. Nucleic Acids Res,2004,32(6):2008-2016.
[10] Madry H, Reszka R, Bohlender J, et al. Efficacy of cationic liposome mediated gene transfer to mesangial cells in vitro and in vivo. J Mol Med,2001,79(4): 184-189.
[11] Kaiser S, Toborek M. Liposome-mediated high-efficiency transfection of human endothelial cells. J Vasc Res,2001,38(2):133-143.
[12] Stein C, Tonkinson J, Zhang I, et al. Dynamics of the internalization of phosphodiester oligodeoxynucleotides in HL60 cells. Biochemistry,1993,32(14):4855-63.
[13] Krieg A, Gmelig-Meyling F, Gourley M, et al. Uptake of oligodeoxyribonucleotides by lymphoid cells is heterogeneous and inducible. Antisense Res Deve 1,1991,1 (2): 161-9.
[14] Krieg A, Tonkinson J, Matson S, et al. Modification of antisense phosphodiester oligodeoxynucleotides by 5'-cholesteryl moiety increases cellular association and improves efficacy.Proc Natl Acad Sci USA,1993,90(6):1048-53.
[15] Sen L, Hong YS. Lao H, et al. Efficiency, efficacy and adverse effects of adenovirus vs liposome -mediated gene therapy in cardiac allografts. Am J Physiol Heart Circ Physiol, 2001,281(3): 1433-1441.
[16] Silberstein GB, Van Horn K, Strickland P, Roberts CT Jr, Daniel CW. Altered expression of the WT1 wilms tumor suppressor gene in human breast cancer. Proc Natl Acad Sci USA. 1997 Jul 22;94(15):8132-8137.
[17] Ezzel C. Beyond the human genome. Sci Am, 2000, 283(1): 64-69.
[18] May M, Hecbner G. The Power of Proteomics. Science, 2001, 292(5515): 317-328.
[1]Kronenwett R,Haas R.Antisense strategies for the treatment of hematological malignancies and solid tumors[J].Annals of Hematology,1998;77,1-12.
[2]Wang ZY,Gaggero A,Rubartelli A,et al.Expression of interleukin-18 in human ovarian carcinoma and normal ovarian epithelium:evidence for defective processing in tumor cells[J].Int J Cancer,200298(6):873-878.
[3]Lechanteur C,Princen F,Lo Bue S,et a 1.HSV-1 thymidine kinase gene therapy for peritoneal carcinomatosis[J].Adv Exp Med biol,1998,451:115-119.
[4]Qian HN,Liu GZ,Cao SJ,et al.The experimental study of ovarian carcinoma vaccine modified by human B7-1 and IFN-gamma genes.Int J Gynecol Cancer[J],2002 12(1):80 -85.
[5]Guha C,Guha U,Tribius S,et al.Antisense ATM gene therapy:a strategy to increase the radiosensitivity of human tumors.Gene Ther,2000;7(10):852-858.
[6]Raizada MK,Francis SC,Wang HW,et al.Targeting of the renin-angiotensin system by antisense gene therapy:a possible strategy for the long-term control of hypertension.J Hypertens.2000;19(4):353-62.
[7]Kristian P,Arne O,Mats S,et al.Inhibition of platelet-deried Growth Factor Receptor reduces interstitial hypertension and increase transcapillary transport in tumor.Cancer Res,2001;61:2929-2934.
[8]Skimisdotir I,Sorbe B,Scidal T.The growth factor receptors HER-2/neu and EGFR,their relationship,and their effects on the prognosis in early stage(FIGO Ⅰ -Ⅱ) epithelial ovarian carcinoma.Int J Gynecol Cancer,2001 11(2):119-29.
[9]Institute of Experimental Dermatology,University of Munster,Munster,Germany.Growth inhibition of human mammary carcinoma by liposomal hexadecyl-phocholine:participation of activated macrophages in the antitumor mechanism[J].Int J Cancer,2001,92:426-433.
[10]Fletcher JC.Evolution of ethical debate about human gene therapy.Human Gene Therapy,1990,1(1):55-68.
[11] Stixg. Shutting down a gene. Antisense drug wings approval.Sci Am. 1998, 279 (5):46-50.
[12] Galderisi U, Bernard G. Antisense inhibitory effects: a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides. J cell Biochem, 1997,74:31-37.
[13]董凡,金由辛．寡聚脱氧核苷酸的结构和抗降解特性的研究．中国生物化学和分子生物学报,1998,14(1)：62-64．
[14] Oberbauer R. Not nonsense but antisense- applications of antisense oligonucleotides in diferent fields of medicine [J]. Wiener klinische wochenschrift,1997,109(2):40-46.
[15] Marcusson EG, Yacyshyn BR, Shanahan WJ, et al. Preclinical and clinical pharmacology of antisense oligonucleotides [J].Molecular Biothechnology, 1999,12 (1);1-11.
[16] Blay J. Technology evaluation: gEM-231, Hybridon Inc [J]. Current Opinion in molecular therapeutics,2000,2(4):468-472.
[17] Ferkol T, Perales JC, Eckman E, et al. Gene transfer into airway epithelium of animals by targeting the polymeric immunoglobulin recepto[J].Journal of Clinical Investigation, 1995,95:493-502.
[18] Agrawal S, Zhang X, Lit Z, et al. Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleolide following orala dministration [J]. Biochemical Pharmacology, 1995;50:571-576.
[19] Jaenisch R, Transgenic animals[J]. Science, 1998,240(4858): 1468-1474.
[20]成国祥,左嘉客．生产转基因动物的技术现状[J]．细胞生物学杂志,2002,21(3)：107-110．
[21] Lee MJ, Cho SS, You JR, et al .Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer mode.[J]. Gene Ther,2029 (13):859-866.
[22] Weinstein JN, Steller MA, Covell DG, et al. Monoclonal antitumor antibodies in the lymphatics[J]. Cancer Treat Rep, 1994,68(1): 257-264.
[23] Mannino RJ, Gould-Fogerite S. Liposome mediated gene transfer[J]. Biotechniques, 1998,6(7):682-690.
[24] Stewart MJ, Plautz GE, Del Buono L, et al. Gene transfer in vivo with DNA-liposome complexes:safety and acute toxicity in mice[J]. Hum Gene Ther, 1999, 3(3):267-275.
[25] Wang Y, Becker D. Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nautre Medicine, 1997;3:887-93.
[26] Shen M, FengY, Ge B, et al. Li posome-C-erbB2 antisense oligodoxynucleotides inhuman ovarian cancer cells[J].Chin Med J (Engl),2001,l 14(7):735-7.
[27] Ross PC, Hui SW. Lipoplex size is a major determinant of in virtro lipofection efficiency[J]. Gene Ther, 2004,6(4):651-659.
[28] 边杰芳，张柏银，陈诗书.反义c-myc、增殖细胞核抗原基因片段抑制血管平滑肌相关基因表达.
中华医学杂志，1999,79(1):242-245.
[29] 黄培堂译.分子克隆实验指南[M].第3版，北京：科学技术出版社.2003,786-787.
[30] Andreason GL, Evans GA. Introduction and expression of DNA molecules in eukaryotic cells by electroporation[J]. Biotechniques, 1998,6(7):650-660.
[31] 曹泽毅主编.北京.人民卫生出版社.1999
[32] Wadler S. New developments in treatment of ovarian cancer. Expert Opin Investig Drugs,2001,10(6):1167-72.
[33] Werness BA, Eltabbkh GH. et al. Familial ovarian cancer and early ovarian cancer: biologic and clinical features. Int J Gynecol Pathol,2001,20(1):48-63
[34] Markman M, Kennedy A, Webster K, et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol. 2001;19(7): 1901-5.
[35] Gerenlee RT. et al. Cancer statistics. CA Cancer J. Clin, 2001,51(1):15-36
[36] Saison-BT, Torque B, Rey I, et al. Short modified antisense-directed against Ha-ras point mutation induce selective cleavage of the mRNA and T24 cells proliferation. EMBO J, 1991,10:1111.
[37] Cuningham CC, Holmulund JT, Schiller JH, et al. A phase I trial of c-raf-1 kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer[J]. Clin Cancer Res,2000,6(5):1626-31.
[38] Cagnoli M, Barbieri F, Bruzzo C, et al. Control of cyclinDl expression by antisense olignonudeotldes in three ovarian cancer cell lines. Gynecol oncol.1998, 70(3):372-377.
[39] Helm CW, shrestha K, Thomas S, et al. A unique c-myc-Targeted Triplex-forming oligonucleotide inhibits the growth of ovarian and cervical carcinomas in vitro. Gynecol oncol ,1993,4 9(3):339-343.
[40] Masanek U, Stammler G, Volm M. Modulation of multidrug resistance in human ovarian cancer cell lines by inhibition of P-glycoprotein 170 and PKC isoenzymes with antisense oligonucleotides. J Exp Ther Oncol,2002,2(1):37-41.
[41] Annab LA, Hawkins RE, Solomon G, et al. Increased cell survial by inhibition of BRCA1 using anantisense approach in estrogen responsive ovarian carcinoma cell line. Breast Cancer Res,2000,2(2):139-148.
[42] Skilling JS, Squatrito RC, Connor JP, et al. P53 gene mutation analysis and antisense-mediated growth inhibition of human ovarian carcinoma cell lines. Gynecol oncol, 1996,60(1) :72-80.
[43] Casamallimi A, De-Luca, Agrawal S, et al. EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells. Ann oncol,2000,l 1 (3):319-325.
[44] Coppola D, Saunders B, Fu L, et al .The insulin-like growth factor 1 receptor induces transformation and tumorigenicity of ovarian mesothelial cells and down-regulates their Fas-receptor expression. Cancer Res, 1999,59 (13):3264-3270.
[45] Morrison BH, Baucer JA, Kalvakolanu DJ, et al. Inositol Hexakisphosphate kinase2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. J- Biol-chem,2001,276(27):24965-24970.
[46] Pirollo KF, Hao Z, Rait A, et al. Evidence supporting a singal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem-Biophys-Res-Commun. 1997,230(1): 196-201.
[47] Indolfi C, Chiarello M, Arredimento EV. Selective gene therapy for proliferation disorders: sense and antisense[J].Nature Medicine, 1996,2:634-635.
[48] Fei R, Shaoyang L. Combination antigene therapy targeting c-myc and c-erbB2 in the ovarian cancer COC1 cell line [J]. Gynecol Oncol.2002,85 (1):40-44.
[49] Tanaka K, Iwakuma T, Harimaya K, et al. EWS-Fli Antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neurectodermal tumor cells. Journal of c linical Investigation, 1997;99:239-47.
[50] Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res, 2002,107:99-118.
[51] Islan A, Handley SL, Thompson KS, et al. Studies on uptake, sub-celluar trafficking and efflux of antisense oligonucleiotides in glioma cells using self-assembing cationic lipoplexes as delivery systems.J Drug Target,2000,7(5):373-382.
[52] Londono-Vallejo JA, DerSarkissian H, Cazes L, et al. Differences in telomere length between homologous chromosomes in humans. Nucleic A.