Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library.

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library.
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DOI:
10.1038/sj.bjc.6600439
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发表时间:
2002-07-29
影响因子:
8.8
通讯作者:
Diamandis EP
Diamandis EP
中科院分区:
医学1区
文献类型:
--
作者:
Luo LY;Herrera I;Soosaipillai A;Diamandis EP

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重组cDNA表达文库的血清学筛选已广泛用于鉴定各种癌症类型中的肿瘤抗原。卵巢癌肿瘤抗原的鉴定可能有助于基于疫苗的治疗和疾病生物标志物的发展。本研究的目的是利用重组cDNA表达文库的血清学分析方法,鉴定卵巢癌的肿瘤抗原。从5例卵巢癌患者的腹水中筛选重组卵巢癌cDNA表达文库。分离到12个已知基因编码的肿瘤抗原,包括核糖体蛋白S18、热休克蛋白90、JK重组信号结合蛋白、核糖核蛋白H1、RAN结合蛋白7、TG相互作用因子、真核生物翻译起始因子p40亚基、人淀粉样前体蛋白结合蛋白1、核糖体蛋白L 8、CDC 23、含IQ基序的GT3活化蛋白1、和核糖体蛋白L3。选择热休克蛋白90进行进一步研究。用免疫分析法检测卵巢癌组织中hsp 90自身抗体的阳性率。对22例正常女性、32例卵巢癌(22例III/IV期,10例I/II期)、37例结直肠癌、13例乳腺癌、10例肺癌、20例良性妇科疾病和10例良性乳腺病变的血清进行筛选。7例(32%)III/IV期卵巢癌,1例(10%)I/II期卵巢癌,1例(3%)结直肠癌,1例(8%)乳腺癌和1例(5%)良性妇科疾病血清中发现含有hsp 90自身抗体。这些数据支持这样的观点,热休克蛋白90自身抗体经常发现在晚期卵巢癌。因此,热休克蛋白90可能是卵巢癌的一种新的生物标志物,也是卵巢癌疫苗的候选靶点。英国癌症杂志(2002)87,339-343。www.bjcancer.com © 2002英国癌症研究中心
Serological screening of recombinant cDNA expression libraries has been widely used for the identification of tumour antigens in various cancer types. Identification of tumour antigens in ovarian cancer may facilitate the development of vaccine-based therapies and of disease biomarkers. The purpose of our investigation is to identify tumour antigens in ovarian cancer by using the serological analysis of recombinant cDNA expression libraries method. A recombinant ovarian carcinoma cDNA expression library was screened with ascites fluid, pooled from five ovarian cancer patients. Twelve tumour antigens encoded by known genes were isolated, including ribosomal protein S18, heat shock protein 90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding protein 7, TG-interacting factor, eukaryotic translation initiation factor p40 subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8, CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3. Heat shock protein 90 was chosen for further investigation. The prevalence of hsp90 autoantibodies in ovarian cancer was determined with immunoassay. Sera from 22 normal females, 32 from ovarian cancer (22 stage III/IV, 10 stage I/II), 37 colorectal cancer, 13 breast cancer, 10 lung cancer, 20 benign gynaecologic diseases, and 10 benign breast lesions were screened. Seven (32%) stage III/IV ovarian cancer, 1 (10%) stage I/II ovarian cancer, 1 (3%) colorectal cancer, 1 (8%) breast cancer, and 1 (5%) benign gynaecologic disease sera were found to contain hsp90 autoantibodies. These data support the view that hsp90 autoantibodies are frequently found in late stage ovarian cancer. Hsp90 may, therefore, represent a novel biomarker for ovarian cancer and a candidate ovarian cancer vaccine target. British Journal of Cancer (2002) 87, 339–343. doi:10.1038/sj.bjc.6600439 www.bjcancer.com © 2002 Cancer Research UK
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