黑色素瘤抗原MAGE-A10基因克隆、表达和分布的研究
|
摘要
黑色素瘤抗原(melanoma antigen，MAGE)基因是首先从恶性黑色素瘤中分离、鉴定出的一族肿瘤抗原基因，这类抗原在正常组织中除了睾丸和胎盘组织外均不表达，但在某些肿瘤组织中呈高度特异性表达，部分家族成员可以诱导机体产生特异性的CTL细胞，因而在肿瘤的免疫学治疗方面具有潜在的应用价值。
MAGE-A10属于MAGE-A亚家族，其cDNA全长2.5kb，含有4个外显子，编码蛋白约72kDa。MAGE-A10在肿瘤细胞有较高水平表达，其具有提高肿瘤免疫原性的特点已受到广泛关注。新近采用四聚体(Tetramer)技术发现其编码的HLA-A2限制的九肽GLYDGMEHL(254-262位)可以诱导特异性的CTL应答。基于亚洲人多表达HLA—A2的特点，进一步研究MAGE-A10的表达、功能和潜在的肿瘤治疗作用显得尤为重要。为了研究MAGE-A10蛋白在肿瘤组织的表达规律，进一步了解其功能，探讨其在肿瘤免疫治疗中可能的作用，我们开展了如下工作：
1、人黑色素瘤抗原MAGE-A10的基因克隆与原核表达
目的：克隆人黑色素瘤抗原MAGE-A10(melanoma antigen A10)cDNA，构建原核表达载体，获得大肠杆菌表达的融合蛋白以用于单克隆抗体的制备。方法：从人黑色素瘤细胞系LiBr中提取总RNA，用RT-PCR从中扩增出MAGE-A10 cDNA，插入载体pMD18-T中。测序正确后，克隆至原核表达载体pGEX-4T-3中， 构建重组表达载体DGEX-4T-3-MAGE-A10，转化大肠杆菌BL21株进行表达。经IPTG诱
第四军医大学博士学位论文
导表达、谷耽甘肤亲和层析获得重组目的蛋白。结果:成功获得MAGE一A10
编码基因并构建原核表达载体，测序结果与GenBank收录序列相一致。
可以获得部分可溶性的原核重组蛋白，经亲和层析分析，证实融合蛋白占
总量的58.9%。SDS一PAGE分析其相对分子质量(阿r)为67KD，Western
BI0t证实为目的蛋白，为制备MAGE一A10单抗及研究MAGE一A10可能
参与肿瘤发生发展的机制奠定了基础。
2、人黑色素瘤抗原MAGE一A10特异性单抗的制备与鉴定
目的:制备MAGE一A10特异性单抗并进行鉴定。方法:大量制备
MAGE一AIO一GST融合蛋白，纯化后免疫BALB/c小鼠，应用杂交瘤技术
制备了抗MAGE一A10的单克隆抗体。在此基础上，用正常翠丸组织的免
疫组化染色进行了筛选和鉴定，采用硫酸按盐析、SepharoseG一25柱除
盐和FpLC Q Fast Flow阴离子交换柱连续梯度洗脱的方法纯化抗体，重
复免疫组化染色确定下一步试验用的抗体。结果:制备获得了19株抗
MAGE一A10的单克隆抗体，遴选出一株高效、特异的单抗
以一MAGE一AIO.6。采用上述纯化方法，获得了90%以上纯度的单克隆抗
体。重复试验表明，经该种方法纯化后可以得到高纯度和高活性的单克隆
抗体，为开展MAGE一A10表达分布的研究及探索其参与肿瘤发生发展的
可能机制提供了工具。
3、MAGE一A10蛋白在多种肿瘤组织中的表达分布研究
目的:以制备的抗MAGE一A10单抗LX一MAGE一A10.6开展的免疫
组化S一p染色(Immunohistoehemistry，IHC)，结合组织芯片分析
(TISSue Array，TA)，观测MAGE一A10蛋白在肺癌和四种不同消化系
统肿瘤的表达水平;重点分析了其与肺癌病理类型、病理分级的关系。结
果:①MAGE一A10蛋白在小细胞肺癌、肺鳞癌和肺腺癌中表达的阳性率分
别为36.4%、76.5%和40.0%，在大细胞肺癌和支气管肺泡癌中未见阳
性表达。MAGE一A10蛋白在小细胞肺癌与非小细胞肺癌的表达率未见差
异，其与肺鳞癌、肺腺癌的病理分级也无明显相关。②MAGE一A10蛋白在
食管鳞癌、肝细胞癌、胃癌和结肠癌均有表达，其中在食管癌中表达比例
最高(73.3%)，主要在核内表达，而在肝细胞癌、胃癌和结肠癌中表达
水平较低，比例分别为38.1%、15.4%和10.6%。结论:州AGE一A10
蛋白在肺鳞癌中表达率最高，肺腺癌和小细胞肺癌次之，大细胞肺癌和支
第四军医大学博士学位论文
气管肺泡癌中未见表达，此研究结果对不同病理类型肺癌的鉴别诊断可能
有一定的辅助诊断意义，并可能成为某些肺癌如肺鳞癌生物治疗的潜在靶
点。MAGE一A10蛋白在四种消化系统恶性肿瘤中均有表达，以鳞癌多见，
呈异质性表达特点。
4、PEGFP·Cl一MAGE一A10真核表达载体和PLNCX一MAGE
一A10逆转录病毒表达载体的构建与初步应用
目的:构建MAGE一AIO功能研究的必要的工具载体，并观察
MAGE一A10的细胞内定位。方法:利用基因克隆技术，在前期获得
MAGE一A10开放读框的基础上，构建pEG「p一Cl一MAGE一AIO真核表达
载体和pLNCX一MAGE一AIO逆转录病毒表达载体。将
pEGFp一Cl一MAGE一A10转入293丁细胞，观察MAGE一A10的亚细胞定
位情况。结果:成功构建pEGFp一Cl一MAGE一A10真核表达载体和
pLNCX一MAG一A10逆转录病毒表达载体，发现MAGE一AIO蛋白主要
定位细胞核内。
Melanoma antigen genes (MAGEs) were a number of gene families cloned from Melanoma, which expressed specifically on some types of cancers but not on normal tissue except for testis and placenta. Most members of MAGE families can induce specific CTL response in host, so they have potential value in the immunotherapy of tumors.
MAGE-A10 belongs to MAGE-A subfamily. The full length of cDNA was 2.5kb contained 4 exons, coding a protein with Mr of 72kDa. MAGE-A 10 was highly expressed on tumor cells with a high immunogenesity. A HLA-A2 restricted nona-peptide 254GLYDGMEHL262 coded by MAGE-A10 could elicit specific CTL response which was found by tetramer technology recently. Based on highly frequency of HLA-A2 in Asians, it is important to investigate the expression, function and potential immunotherapy value of this molecule. To explore the expression of MAGE-A 10 and distribution of that in cancers, the following works have been done in our department:
1. Cloning and prokaryotic expression of human MAGE-A10 cDNA
Aims: To clone human MAGE-A10 cDNA, construct the recombination expression vector, and express its recombinant protein in E. coli. Methods: The cDNA encoding human MAGE-A 10 gene was amplified by RT-PCR from human melanoma cell line LiBr. Then the MAGE-A 10 gene was inserted into plasmids pMD18-T. After sequencing, the MAGE-A 10 was cloned into the prokaryotic expression vector pGEX-4T-3 to construct the recombinant
expression vector pGEX-4T-3-MAGE-A10 and were transformed into E. coli BL21.The recombinant GST-MAGE-A10 fusion protein was expressed under induction of IPTG. GST-MAGE-A10 fusion protein was purified through glutathione agarose column. Results: The sequence of MAGE-AIO was identical to that from GenBank. Affinity column purified-GST-MAGE-A10 fusion protein appeared a band of Mr. 70KD on SDS-PAGE, and the antigenic specificity of the fusion protein was confirmed by Western blot. Conclusions: The MAGE-A10 gene was cloned and expressed successfully, which not only provided the immunogen for preparation of anti-MAGE-A10 antibody but also were useful in research work on the mechanism of tumor pathogenesis and cellular immunological response to MAGE molecules.
2. Preparation and identification of monoclonal antibodies against human MAGE-AIO
Aims: To prepare and identify the monoclonal antibody to MAGE-A10 Methods: GST-MAGE-A10 fusion protein was largely prepared and purified. Then BALB/c mice were immunized with purified-GST-MAGE-A10 fusion protein to get anti-MAGE-A10 antibody. Normal testis tissue was used to identify specific mAbs. The anti-MAGE-A10 antibody was purified as follows:Firstly, mAbs from ascites fluid were sedimentated with ammonium sulfate,then desalted by Sepharose G-25 column and purified by anion exchange chromatography on Sepharose Q Fast Flow column using FPLC (Phamarcia Amercia). Results: 19 hybridoma cell lines secreting mAbs against MAGE-A10 have been established. One of them named LX-MAGE-A10.6 was employed in immunohistochemical staining with highly specific and sensitivity. Conclusions: We got one hybridoma cell which could be useful for investigation of its expression and distribution.
3. The expression patterns of MAGE-A10 in tumors
Aims: To explore the expression and the clinical significance of MAGE-A10 in human lung cancer and other four types of digestive system cancers. Methods: By using tissue array and S-P immunohistochemical methods, the expression of MAGE-A10 protein in lung cancer and four types of digestive system cancers was investigated and the correlation of MAGE-A10 expression with histological types and pathological grades was also evaluated. Results: (1)The positive expression rates of MAGE-A10 were 36.4% in small cell lung carcinoma(SCLC), 76.5% in squamous cell lung carcinoma and 40.0%
in lung adenocarcinoma, respectively, whereas no positive case can be found in large cell lung carcinoma and bronchioloalveolar carcinoma. There was no statistical significance between the expression of MAGE-A10 protein in SCLC and that in NSCLC. The
MAGE-A10属于MAGE-A亚家族，其cDNA全长2.5kb，含有4个外显子，编码蛋白约72kDa。MAGE-A10在肿瘤细胞有较高水平表达，其具有提高肿瘤免疫原性的特点已受到广泛关注。新近采用四聚体(Tetramer)技术发现其编码的HLA-A2限制的九肽GLYDGMEHL(254-262位)可以诱导特异性的CTL应答。基于亚洲人多表达HLA—A2的特点，进一步研究MAGE-A10的表达、功能和潜在的肿瘤治疗作用显得尤为重要。为了研究MAGE-A10蛋白在肿瘤组织的表达规律，进一步了解其功能，探讨其在肿瘤免疫治疗中可能的作用，我们开展了如下工作：
1、人黑色素瘤抗原MAGE-A10的基因克隆与原核表达
目的：克隆人黑色素瘤抗原MAGE-A10(melanoma antigen A10)cDNA，构建原核表达载体，获得大肠杆菌表达的融合蛋白以用于单克隆抗体的制备。方法：从人黑色素瘤细胞系LiBr中提取总RNA，用RT-PCR从中扩增出MAGE-A10 cDNA，插入载体pMD18-T中。测序正确后，克隆至原核表达载体pGEX-4T-3中， 构建重组表达载体DGEX-4T-3-MAGE-A10，转化大肠杆菌BL21株进行表达。经IPTG诱
第四军医大学博士学位论文
导表达、谷耽甘肤亲和层析获得重组目的蛋白。结果:成功获得MAGE一A10
编码基因并构建原核表达载体，测序结果与GenBank收录序列相一致。
可以获得部分可溶性的原核重组蛋白，经亲和层析分析，证实融合蛋白占
总量的58.9%。SDS一PAGE分析其相对分子质量(阿r)为67KD，Western
BI0t证实为目的蛋白，为制备MAGE一A10单抗及研究MAGE一A10可能
参与肿瘤发生发展的机制奠定了基础。
2、人黑色素瘤抗原MAGE一A10特异性单抗的制备与鉴定
目的:制备MAGE一A10特异性单抗并进行鉴定。方法:大量制备
MAGE一AIO一GST融合蛋白，纯化后免疫BALB/c小鼠，应用杂交瘤技术
制备了抗MAGE一A10的单克隆抗体。在此基础上，用正常翠丸组织的免
疫组化染色进行了筛选和鉴定，采用硫酸按盐析、SepharoseG一25柱除
盐和FpLC Q Fast Flow阴离子交换柱连续梯度洗脱的方法纯化抗体，重
复免疫组化染色确定下一步试验用的抗体。结果:制备获得了19株抗
MAGE一A10的单克隆抗体，遴选出一株高效、特异的单抗
以一MAGE一AIO.6。采用上述纯化方法，获得了90%以上纯度的单克隆抗
体。重复试验表明，经该种方法纯化后可以得到高纯度和高活性的单克隆
抗体，为开展MAGE一A10表达分布的研究及探索其参与肿瘤发生发展的
可能机制提供了工具。
3、MAGE一A10蛋白在多种肿瘤组织中的表达分布研究
目的:以制备的抗MAGE一A10单抗LX一MAGE一A10.6开展的免疫
组化S一p染色(Immunohistoehemistry，IHC)，结合组织芯片分析
(TISSue Array，TA)，观测MAGE一A10蛋白在肺癌和四种不同消化系
统肿瘤的表达水平;重点分析了其与肺癌病理类型、病理分级的关系。结
果:①MAGE一A10蛋白在小细胞肺癌、肺鳞癌和肺腺癌中表达的阳性率分
别为36.4%、76.5%和40.0%，在大细胞肺癌和支气管肺泡癌中未见阳
性表达。MAGE一A10蛋白在小细胞肺癌与非小细胞肺癌的表达率未见差
异，其与肺鳞癌、肺腺癌的病理分级也无明显相关。②MAGE一A10蛋白在
食管鳞癌、肝细胞癌、胃癌和结肠癌均有表达，其中在食管癌中表达比例
最高(73.3%)，主要在核内表达，而在肝细胞癌、胃癌和结肠癌中表达
水平较低，比例分别为38.1%、15.4%和10.6%。结论:州AGE一A10
蛋白在肺鳞癌中表达率最高，肺腺癌和小细胞肺癌次之，大细胞肺癌和支
第四军医大学博士学位论文
气管肺泡癌中未见表达，此研究结果对不同病理类型肺癌的鉴别诊断可能
有一定的辅助诊断意义，并可能成为某些肺癌如肺鳞癌生物治疗的潜在靶
点。MAGE一A10蛋白在四种消化系统恶性肿瘤中均有表达，以鳞癌多见，
呈异质性表达特点。
4、PEGFP·Cl一MAGE一A10真核表达载体和PLNCX一MAGE
一A10逆转录病毒表达载体的构建与初步应用
目的:构建MAGE一AIO功能研究的必要的工具载体，并观察
MAGE一A10的细胞内定位。方法:利用基因克隆技术，在前期获得
MAGE一A10开放读框的基础上，构建pEG「p一Cl一MAGE一AIO真核表达
载体和pLNCX一MAGE一AIO逆转录病毒表达载体。将
pEGFp一Cl一MAGE一A10转入293丁细胞，观察MAGE一A10的亚细胞定
位情况。结果:成功构建pEGFp一Cl一MAGE一A10真核表达载体和
pLNCX一MAG一A10逆转录病毒表达载体，发现MAGE一AIO蛋白主要
定位细胞核内。
Melanoma antigen genes (MAGEs) were a number of gene families cloned from Melanoma, which expressed specifically on some types of cancers but not on normal tissue except for testis and placenta. Most members of MAGE families can induce specific CTL response in host, so they have potential value in the immunotherapy of tumors.
MAGE-A10 belongs to MAGE-A subfamily. The full length of cDNA was 2.5kb contained 4 exons, coding a protein with Mr of 72kDa. MAGE-A 10 was highly expressed on tumor cells with a high immunogenesity. A HLA-A2 restricted nona-peptide 254GLYDGMEHL262 coded by MAGE-A10 could elicit specific CTL response which was found by tetramer technology recently. Based on highly frequency of HLA-A2 in Asians, it is important to investigate the expression, function and potential immunotherapy value of this molecule. To explore the expression of MAGE-A 10 and distribution of that in cancers, the following works have been done in our department:
1. Cloning and prokaryotic expression of human MAGE-A10 cDNA
Aims: To clone human MAGE-A10 cDNA, construct the recombination expression vector, and express its recombinant protein in E. coli. Methods: The cDNA encoding human MAGE-A 10 gene was amplified by RT-PCR from human melanoma cell line LiBr. Then the MAGE-A 10 gene was inserted into plasmids pMD18-T. After sequencing, the MAGE-A 10 was cloned into the prokaryotic expression vector pGEX-4T-3 to construct the recombinant
expression vector pGEX-4T-3-MAGE-A10 and were transformed into E. coli BL21.The recombinant GST-MAGE-A10 fusion protein was expressed under induction of IPTG. GST-MAGE-A10 fusion protein was purified through glutathione agarose column. Results: The sequence of MAGE-AIO was identical to that from GenBank. Affinity column purified-GST-MAGE-A10 fusion protein appeared a band of Mr. 70KD on SDS-PAGE, and the antigenic specificity of the fusion protein was confirmed by Western blot. Conclusions: The MAGE-A10 gene was cloned and expressed successfully, which not only provided the immunogen for preparation of anti-MAGE-A10 antibody but also were useful in research work on the mechanism of tumor pathogenesis and cellular immunological response to MAGE molecules.
2. Preparation and identification of monoclonal antibodies against human MAGE-AIO
Aims: To prepare and identify the monoclonal antibody to MAGE-A10 Methods: GST-MAGE-A10 fusion protein was largely prepared and purified. Then BALB/c mice were immunized with purified-GST-MAGE-A10 fusion protein to get anti-MAGE-A10 antibody. Normal testis tissue was used to identify specific mAbs. The anti-MAGE-A10 antibody was purified as follows:Firstly, mAbs from ascites fluid were sedimentated with ammonium sulfate,then desalted by Sepharose G-25 column and purified by anion exchange chromatography on Sepharose Q Fast Flow column using FPLC (Phamarcia Amercia). Results: 19 hybridoma cell lines secreting mAbs against MAGE-A10 have been established. One of them named LX-MAGE-A10.6 was employed in immunohistochemical staining with highly specific and sensitivity. Conclusions: We got one hybridoma cell which could be useful for investigation of its expression and distribution.
3. The expression patterns of MAGE-A10 in tumors
Aims: To explore the expression and the clinical significance of MAGE-A10 in human lung cancer and other four types of digestive system cancers. Methods: By using tissue array and S-P immunohistochemical methods, the expression of MAGE-A10 protein in lung cancer and four types of digestive system cancers was investigated and the correlation of MAGE-A10 expression with histological types and pathological grades was also evaluated. Results: (1)The positive expression rates of MAGE-A10 were 36.4% in small cell lung carcinoma(SCLC), 76.5% in squamous cell lung carcinoma and 40.0%
in lung adenocarcinoma, respectively, whereas no positive case can be found in large cell lung carcinoma and bronchioloalveolar carcinoma. There was no statistical significance between the expression of MAGE-A10 protein in SCLC and that in NSCLC. The
引文
1. Old LJ. Cancer immunology: the search for specificity--G. H. A. Clowes Memorial lecture. Cancer Res 1981; 41: 361-75. (PMID: 7004632)
2. Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L, Boon T. Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. Immunogenetics 1992; 35: 145-52.
3. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254: 1643-7.
4. Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 1995; 92: 11810-13.
5. Van den Eynde B, Lethe B, Van Pel A, De Plaen E, Boon T. The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med 1991; 173: 1373-84.
6. Boel P, Wildmann C, Sensi ML, Brasseur R, Renauld JC, Coulie P, Boon T, van der Bruggen P. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 1995; 2: 167-75.
7. Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995; 182: 689-98.
8. Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 1997; 94: 1914-18.
9. Tureci O, Sahin U, Zwick C, Koslowski M, Seitz G, Pfreundschuh M. Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens. Proc Natl Acad Sci USA 1998; 95:5211-16
10. Coulie PG, Karanikas V, Lurquin C, Colau D, Connerotte T, Hanagiri T, Van Pel A, Lucas S, Godelaine D, Lonchay C, Marchand M, Van Baren N, Boon T. Cytolytic T-cell responses of cancer patients vaccinated with a MAGE antigen. Immunol Rev 2002; 188: 33-42.
11. Lethe B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, De Plaen E, Boon T. LAGE-1, a new gene with tumor specificity. Int J Cancer 1998; 76: 903-8.
12. Güre AO, Stockert E, Arden KC, Boyer AD, Viars CS, Scanlan MJ, Old LJ, Chen YT. CT10: A new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational-difference analysis. Int J Cancer 2000; 85: 726-32.
13. Martelange V, De Smet C, De Plaen E, Lurquin C, Boon T. Identification on a human sarcoma of two new genes with tumor-specific expression. Cancer Res 2000; 60: 3848-55.
14. Zendman AJ, Cornelissen IM, Weidle UH, Ruiter DJ, van Muijen GN. CTp11, a novel member of the family of human cancer/testis antigens. Cancer Res 1999; 59: 6223-9.
15. de Wit N, Weidle UH, Ruitter DJ, van Muijen GN. Expression profiling of MMA-1 and splice variant MMA-1B: new cancer/testis antigens identified in human melanoma. Int J Cancer 2002; 98: 547-553.
16. Scanlan MJ, Altorki NK, Güre AO, Williamson B, Jungbluth A, Chen YT, Old LJ. Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9. Cancer Lett 2000; 150: 155-64.
17. Scanlan MJ, Gordon CM, Williamson B, Lee SY, Chen YT, Stockert E, Jungbluth A,
Ritter G, Jager D, Jager E, Knuth A, Old LJ. Identification of cancer/testis genes by database mining and mRNA expression analysis. Int J Cancer 2002; 98: 485-92. (PMID: 11920606)
18. Koslowski M, Tureci O, Bell C, Krause P, Lehr HA, Brunner J, Seitz G, Nestle FO, Huber C, Sahin U. Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Cancer Res 2002; 62: 6750-5.
19. Dong XY, Su YR, Qian XP, Yang XA, Pang XW, Wu HY, Chen WF. Identification of two novel CT antigens and their capacity to elicit antibody response in hepatocellular carcinoma patients. Br J Cancer 2003; 89: 291-7.
20. Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ. Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA 1998; 95: 6919-23.
21. Chomez P, De Backer O, Bertrand M. An overview of the MAGE gene family with the identification of all human members of the family.Cancer Res. 2001 15;61:5544-51.
22. Kirkin AF, Dzhandzhugazyan KN, Zeuthen J.Cancer/testis antigens: structural and immunobiological properties.Cancer Invest. 2002;20222-36.
23. CT Gene database. URL: http://www.cancerimmunity.org/CTdatabase/
24. EST search engine. URL:http://www.ncbi.nlm.nih.gov/BLAST/
25. SAGEmap database. URL:http://www.ncbi.nlm.nih.gov/SAGE/
26. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 2002; 188: 22-32.
27. Tajima K, Obata Y, Tamaki H, Yoshida M, Chen YT, Scanlan MJ, Old LJ, Kuwano H, Takahashi T, Takahashi T, Mitsudomi T. Expression of cancer/testis (CT) antigens in lung cancer. Lung Cancer 2003; 42: 23-33.
28. Jungbluth AA, Chen YT, Stockert E, Busam KJ, Kolb D, Iversen K, Coplan K, Williamson B, Altorki N, Old LJ. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer 2001; 92: 856-60.
29. Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J. PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? Int J Cancer 2002; 101: 581-8.
30. Jungbluth AA, Stockert E, Chen YT, Kolb D, Iversen K, Coplan K, Williamson B, Altorki N, Busam KJ, Old LJ. Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1 antigen in formalin-fixed paraffin embedded lung turnouts. Br J Cancer 2000; 83: 493-7.
31. Stockert E, Jager E, Chen YT, Scanlan MJ, Gout I, Karbach J, Arand M, Knuth A, Old LJ. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med 1998; 187: 1349-54.
32. Chen YT, Stockert E, Chen Y, Garin-Chesa P, Rettig WJ, van der Bruggen P, Boon T, Old LJ. Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. Proc Natl Acad Sci USA 1994; 91: 1004-8.
33. Jungbluth AA, Antonescu CR, Busam KJ, Iversen K, Kolb D, Coplan K, Chen YT, Stockert E, Ladanyi M, Old LJ. Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer 2001; 94:252-6
34. Kocher T, Schultz-Thater E, Gudat F, Schaefer C, Casorati G, Juretic A, Willimann T, Harder F, Heberer M, Spagnoli GC. Identification and intracellular location of MAGE-3 gene product. Cancer Res 1995; 55: 2236-9.
35. Dos Santos NR, Torensma R, de Vries TJ, Schreurs MW, de Bruijn DR, Kater-Baats E, Ruiter DJ, Adema GJ, van Muijen GN, van Kessel AG. Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. Cancer Res 2000; 60: 1654-62.
36. Jungbluth AA, Busam KJ, Kolb D, Iversen K, Coplan K, Chen YT, Spagnoli GC, Old LJ. Expression of MAGE-antigens in normal tissues and cancer. Int J Cancer 2000; 85: 460-5.
37. Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, Aoe M, Nakamura S, Higashi T, Hiraki A, Wada H, Kumon H, Old LJ, Nakayama E.Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.Proc Natl Acad Sci USA. 2001;98(6):3282-7.
38. Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, Mannan P, Larsson E, Kanduri C, Vostrov AA, Cui H, Niemitz EL, Rasko JE, Docquier FM, Kistler M, Breen JJ, Zhuang Z, Quitschke WW, Renkawitz R, Klenova EM, Feinberg AP, Ohlsson R, Morse HC 3rd, Lobanenkov W. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma.Proc Natl Acad Sci U S A. 2002;99(10):6806-11.
39. Shan J, Yuan L, Xiao Q, Chiorazzi N, Budman D, Teichberg S, Xu HP. TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells.Cancer Res.2002;62(1):290-4.
40. Wang Y, Han KJ, Pang XW, Vaughan HA, Qu w, Dong XY, Peng JR, Zhao HT, Rui JA, Leng XS, Cebon J, Burgess AW, Chen WF. Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.J Immunol. 2002; 169(2): 1102-9.
41. Tureci O, Sahin U, Koslowski M, Buss B, Bell C, Ballweber P, Zwick C, Eberle T, Zuber M, Villena-Heinsen C, Seitz G, Pfreundschuh M. A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing.Oncogene. 2002;21(24):3879-88.
42. Ohman Forslund K, Nordqvist K. The melanoma antigen genes--any clues to their functions in normal tissues?Exp Cell Res. 2001 May 1;265(2):185-94. Review.
43. Saburi S, Nadano D, Akama TO, Hirama K, Yamanouchi K, Naito K, Tojo H, Tachi C, Fukuda MN. The trophinin gene encodes a novel group of MAGE proteins, magphinins, and regulates cell proliferation during gaametogenesis in the mouse. J Biol Chem. 2001 Dec 28; 276(52):49378-89.
44. Shiras A, Sengupta A, Shepal V.Cloning and tissue-specific gene expression studies with Dlxin-1, a newly identified transcriptional activator.Mol Cell Biol Res Commun. 2001 Sep;4(5):313-9.
45. Barker PA, Salehi A.The MAGE proteins: emerging roles in cell cycle progression, apoptosis,and neurogenetic disease. J Neurosci Res. 2002 Mar 15;67(6):705-12. Review.
46. Gure AO, Tureci O, Sahin U, Tsang S, Scanlan MJ, Jager E, Knuth A, Pfreundschuh M, Old LJ, Chen YT. SSX: a multigene family with several members transcribed in normal testis and human cancer..Int J Cancer. 1997 Sep 17;72(6):965-71.
47. Lim FL, Soulez M, Koczan D, Thiesen HJ, Knight JC. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas.Oncogene. 1998 Oct 15; 17(15):2013-8.
48. dos Santos NR, de Bruijn DR, Balemans M, Janssen B, Gartner F, Lopes JM, de Leeuw B, Geurts van Kessel A. Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins.Hum Mol Genet. 1997 Sep;6(9):1549-58.
49. dos Santos NR, de Bruijn DR, van Kessel AG. Molecular mechanisms underlying human synovial sarcoma development.Genes Chromosomes Cancer. 2001 Jan;30(1): 1-14.
50. Sa(?)ez M, Sau(?) AJ, Freemont PS, Kright. JCSSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex. Oncogene. 1999 Apr 29; 18(17): 2739-46.
51. dos Santos NR, de Bruijn DR, Kater-Baats E, Otte AP, van Kessel AG. Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization. Exp Cell Res. 2000 Apr 10;256(1):192-202.
52. Zendman AJ, Van Kraats AA, Weidle UH, Ruiter DJ, Van Muijen GNThe XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma.Int J Cancer. 2002 May 20;99(3):361-9.
53. Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28; 245(4916): 371-8.
54. Rimoldi D, Salvi S, Schultz-Thater E, Spagnoli GC, Cerottini JC. Anti-MAGE-3 antibody 57B and anti-MAGE-1 antibody 6C1 can be used to study different proteins of the MAGE-A family.Int J Cancer. 2000 Jun 1;86(5):749-51.
55. Jungbluth AA, Chen YT, Busam KJ, Coplan K, Kolb D, Iversen K, Williamson B, Van Landeghem FK, Stockert E, Old LJ. CT7 (MAGE-C1) antigen expression in normal and neoplastic tissues.Int J Cancer. 2002 Jun 20;99(6):839-45.
56. Cheville JC, Roche PC. MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors.Nod Pathol. 1999 Oct;12(10):974-8.
57. Aubry F, Satie AP, Rioux-Leclercq N, Rajpert-De Meyts E, Spagnoli GC, Chomez P, De Backer O, Jegou B, Samson M. MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors.Cancer. 2001 Dec 1;92(11): 2778-85.
58. Jungbluth AA, Chen YT, Stockert E, Busam KJ, Koib D, Iversen K, Coplan K, Williamson B, Aitorki N, Old LJ. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues.Int J Cancer. 2001 Jun 15;92(6):856-60. Erratum in: Int J Cancer 2002 Feb 20;97(6):878.
59. Satie AP, Rajpert-De Meyts E, Spagnoli GC, Henno S, Olivo L, Jacobsen GK, Rioux-Leclercq N, Jegou B, Samson M. The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma in situ.Lab Invest. 2002 Jun;82(6):775-80.
60. Westbrook VA, Diekman AB, Klotz KL, Khole VV, yon Kap-Herr C, Golden WL, Eddy RL, Shows TB, Stoler MH, Lee CY, Flickinger CJ, Herr JC. Spermatid-specific expression of the novel X-linked gene product SPAN-X localized to the nucleus of human spermatozoa.Biol Reprod. 2000 Aug;63(2):469-81.
61. Hendriksen PJ.Do X and Y spermatozoa differ in proteinsTrheriogenology. 1999 Dec; 52(8): 1295-30771.
62. Lurdy DK, Tai LQ, Nguyen J, Wang Z, Yang HM, Udar N, Naiem F, Concannon P, Gatti RA. MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera. Mol Genet Metab 1998; 63: 3-13.
63. Lea IA, Adoyo P, O'Rand MG. Autoimmunogenicity of the human sperm protein 5p17 in vasectomized men and identification of linear B cell epitopes. Fertil Steril 1997; 67: 355-61.
64. Ayyoub M, Stevanovic S, Sahin U, Guillaume P, Servis C, Rimoldi D, Valmori D, Romero P, Cerottini JC, Rammensee HG, Pfreundschuh M, Speiser D, Levy F. Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor-reactive CTL infiltrating metastatic melanoma. J Immunol 2002; 168: 1717-22
65. Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A. Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA 2000; 97: 4760-5.
66. Peptide database of T-cell defined tumor antigens. URL: http://www.cancerimmunity.org/peptidedatabase/Tcellepitopes.htm
67. Denkberg G, Cohen CJ, Lev A, Chames P, Hoogenboom HR, Reiter Y.Direct visualization of distinct T cell epitopes derived from a melanoma tumor-associated antigen by using human recombinant antibodies with MHC-restricted T cell
receptor-like specificity. Proc Natl Acad Sci USA 2002; 99: 9421-6.76.
68. De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MACE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 1996; 93: 7149-53.
69. Weiser TS, Guo ZS, Ohnmacht CA, Parkhurst ML, Tong-On P, Marincola FM, Fischette MR, Yu X, Chen CA, Hong JA, Stewart JH, Nguyen DM, Rosenberg SA, Schrump DS. Sequential 5-Aza-2 deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. J Immunother 2001; 24: 151-61.
70. Old LJ. Cacer/Testis (CT) antigens-a new link between gametogenesis and cancer. Cancer Immun 2001;1: 1.
71. Zendman AJ, Ruiter DJ, Van Muijen GN. Cancer/Testis-Associated Genes: Identification, Expression Profile, and Putative Function. [J]. J Cell Physiol,2003;194(3):272-288
72. Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MACE gene family with the identification of all human members of the family. Cancer Res., 2001;61: 5544-5551.
73. De Smet C, Courtois SJ, Faraoni I, Lurquin C, Szikora JP, De Backer O, Boon T. Involvement of two Ets binding sites in the transcriptional activation of the MACE1 gene. Immnogenetics, 1995;42:282-290.
74. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. 2004;4:1-21
75. Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, Kim SU, Ikenaka K.MAGE-E1, a new member of the melanomaassociated antigen gene family and its expression in human glioma. Cancer Res., 2001;61:4809-4814.
76. Juretic A, Spagnoli GC, Schultz-Thater E. et al. Cancer/testis tumour-associated antigens: immunohistochemical detection with monoclonal antibodies. Lancet Oncol. 2003:4(2):104-9.
77. Clotman F, De Backer O, De Plaen E, Boon T, Picard J. Cell-andstage-specific expression of mage genes during mouse spermatogenesis. Mamm Genome, 2000; 11: 696-699.
78. Kocher T, Schultz-Thater E, Juretic A, Dellabona P, Luscher U, Siegrist W, Harder F, heberer M, Zuber M, Spagnoli GC. Identification and intracellular location of MACE-3 gene product. Cancer Res.,1995;55:2236-2239.
79. Arnar-Costesec A, Godelaine D, Stockert E, Van der Bruggen P, Beaufay H, Chen YT. The tumor protein MACE-1 is located in the cytosol of human melanoma cells. Biochem. Biophys. Res. Commun. 1994;204:710-715.
80. Rimoldi D, Salvi S, Reed D, Coulie P, Jongeneel VC, De Plaen E, Brasseur F, Rodriguze AM, Boon T, Cerottini JC. cDNA and protein characterization of human MACE-10. Int.J. Cancer, 1999;82:901-907.
81. Jurk M, Kremmer E, Schwarz U, Forster R, Winnacker EL. MACE-11 protein is highly conserverd in higher organisms and located predomainantly in the nucleus. Int.J.Cancer,1998;75: 762-766.
82. Schultz-Thater E, Juretic A, Dellabona P, Luscher U, Siegrist W, Harder F, Heberer M, Zuber M, Spagnoli GC. MACE-1 products is a cytoplasmic protein. Int.J. Cancer, 1994; 59:435-439.
83. Brasseur F, Rimoldi D, Lienard D, Lethe B, Carrel S, Arienti F, Suter L, Vanwijck R, Bourlond A, Humbler Y. Expression of MACE genes in primary and metastatic cutaneous melanoma. Int.J.Cancer, 1995;63:375-380.
84. Kocher T, Zheng M, Bolli M, Simon R, Forster T, Schultz-Thater E, Remmel E, Noppen C, Schmid U, Ackermann D, Mihatsch MJ, Gasser T, Heberer M, Sauter G, Spagnoli GC.Prognostic relevance of MACE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study. Int J Cancer 2002; 100:702-705.
85. Bolli M, Kocher T, Adamina M, Culler U, Dalquen P, Haas P, Mirlacher M, Gambazzi
F, Harder F, Heberer M, Sauter G, Spagnoli GC. Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma. Ann Surg 2002;236:785-93.
86. Brasseur F, et al. Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer 1995;63:375-380.
87. Goydos JS, Patel M, Shih W. NY-ESO-1 and CT-p11 expression may correlate with stage of lineprogression in melanoma. J Surg Res 2001;98:76-80.
88. Patard JJ, et al. Expression of MAGE genes in transitional-cell carcinomas of the urinarybladder. Int J Cancer 1995;64:60-64.
89. Kurashige T, et al. NY-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tupression mor grade. Cancer Res 2001;61:4671-4674.
90. van Baren N, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood 1999;94:1156-1164.
91. Busam KJ, Iversen K, Berwick M, Spagnoli GC, Old LJ, Jungbluth AA. Immunoreactivity with the anti-MAGE antibody 57B in malignant melanoma. frequency of expression and correlation with prognostic parameters. Mod Pathol 2000; 13:459-465.
92. Takahash K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermatocytes of testis. Cancer Res. 1995;55:3478-3482.
93. Osterlund C, Tohomem V, Forstund KO, Nordqvist K.Mage-b4, a novel melanoma antigen(MAGE)gene specifially expressed during germ cell differentiation. Cancer Res. 2000;60:1054-1061.
94. Takahash, K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermatocytes of testis. Cancer Res. 1995; 55: 3478-3482.
95. Aizawa, T, Maruyama K, Kondo H, Yoshikawa K. Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain. Dev. Brain Res. 1992; 68: 265-274.
96. Maruyama K, Usami M, Aizawa T, Yoshikawa K. A novel brainspecific mRNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cells. Biochem Biophys Res Commun. 1991; 178:291-296.
97. Maruyama, K et al. Biocemical characterization of mouse brain necdin. Biochem. 3.1996;314:895-901.
98. Taniura H, Taniguchi N, Hara M, Yoshikawa K. Necdin, a postmiotic neron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J.Bio.Chem. 1998; 273:720-728.
99. Taniura H, Matsumoto K, Yoshikawa K. Physical and functional interactions of neuronal growth suppressor necdin with p53. J Biol chem. 1999;274(23):16242-16248.
100. Tsai TF, Armstrong D, Beaudet AL. Necdin-deficient mice do not show lethality or the obesity and infertility of Prader-Willi syndrome. Nat Genet 1999a;22:15-16.
101. Gerard M, Hernandez L, Wevrick R, Stewart CL. Disruption of the mouse necdin gene results in early post-natal lethality. Nat Genet 1999;23:199-202.
102. Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H. Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 2000;9:3101-3110.
103. Itoh K, Hayashi A, Nakao M, Human tumor rejection antigens MAGE. J Biochem (Tokyo). 1996; 119(3):385-90.
104. Marchand M, van Baren N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer,1999;80:219-30.
105. Tahara K, Mori M, Sadanaga N,et al.Expression of the MAGE gene family in human hepatocellular carcinoma.Cancer,1999;85:1234-40.
106. Reynolds SR, Oratz R, Shapiro RL,et al.Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.Int J Cancer. 1997;72:972-6.
107. Van Pel A, De Plaen E, Duffour MT, Warnier G, Uyttenhove C, Perricaudet M, Boon T. Induction of cytolytic T lymphocytes by immunization of mice with an adenovirus containing a mouse homolog of the human MAGE-A genes. Cancer Immunol Immunother. 2001;49(11):593-602.
108. Andersen MH, Keikavoussi P, Brocker EB, Schuler-Thurner B, Jonassen M, Sondergaard I, Straten PT, Becker JC, Kampgen E. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: cessation of CTL responses is associated with disease progression. Int J Cancer. 2001 15;94(6):820-824.
109. Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells.Nat Med, 1998;4:328-32.
110. Sakurai T, Itoh K, Higashitsuji H, Nagao T, Nonoguchi K, Chiba T, Fujita J. A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. J Biol Chem. 2004 9;279(:15):15505-14
111. Atanackovic D, Altorki NK, Stockert E, Williamson B, Jungbluth AA, Ritter E, Santiago D, Ferrara CA, Matsuo M, Selvakumar A, Dupont B, Chen YT, Hoffman EW, Ritter G, Old LJ, Gnjatic S. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients. J Immunol. 2004,172(5):3289-96.
112. Vantomme V, Dantinne C, Amrani N, Permanne P, Gheysen D, Bruck C, Stoter G, Britten CM, Keilholz U, Lamers CH, Marchand M, Delire M, Gueguen M. Immunologic analysis of a phase Ⅰ/Ⅱ study of vaccination with NAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors. J Immunother. 2004; 27(2): 124-35
113. Albert J.W. Zendman, Dirk JR, et al. Cancer/Testis-Associated Genes: Identification, Expression Profile, and Putative Function. [J]. J Cell Physiol,2003; 194(3):272-288
114. Rimoldi D, Salvi S, Reed D et al., cDNA and protein characterization of human MAGE-A10. [J]. Int J Cancer 1999;82(6):901-907
115. Gillespie AM, Coleman RE.The potential of melanoma antigen expression in cancer therapy. [J].Cancer Treat Rev. 1999;25(4):219-227
116. van Pel A, De Plaen E, Duffour MT. et al., Induction of cytolytic T lymphocytes by immunization of mice with an adenovirus containing a mouse homolog of the human MAGE-A genes. [J]. Cancer Immunol Immunother. 2001;49(11):593-602
117. Brossart P. Dendritic cells in vaccination therapies of malignant diseases. [J]. Transfus Apheresis Sci. 2002;27(2):183-186
118. Marchand. M, Weynants P, Rankin E, et al. Tumor regression responses in melanoma patients meated with a peptide encoded by gene MAGE-3 and presented by HLA-A1. [J]. Int J Cancer. 1995(6); 63:883-885
119. Marchand. M, van Baren N, Weynants P, et al. Tumor regression observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. [J]. Int J Cancer. 1999;80(2):219-230
120. Duffour MT, Chaux P, Lurquin C, et al. A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes.[J].Eur J Immunol, 1999,299(10):33
121. Zendman AJ, Dirk JR, et al. Cancer/testis-associated genes: identification, expression profile, and putative function [J]. J Cell Physio, 2003; 194:272-288
122. Rimoldi D, Salvi S, Reed D et al., cDNA and protein characterization of human MAGE-A10 [J]. Int J Cancer 1999;82(6):901-907.
123. Mathew JS, Ali OG, Achim AJ, et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy [J]. Immunological Reviews. 2002(188): 22-32
124. Duffour MT, Chaux P, Lurquin C, et al. MAGE A peptide presented by HLA A2 is recognized by cytolytic T lymphocytes [J]. Eur J Immunol,, 1999,29:3329 3337.
125. Huang LQ, Brasseur F, Serrrano A, et al. Cytolytic T lymphocytes recognize an antigen coded by MAGE A10 on a human melanoma [J]. J Immunol,1999, 162:6849 6854.
126. Sugta M, Geraci M, Gao B, et al. Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma[J]. Cancer Res. 2002 15; 62(14): 3971-3979.
127. Zambon A, Mandruzzato S, Parenti A, Macino B, Dalerba P, Ruol A, Merigliano S, Zaninotto G, Zanovello P. MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell carcinoma and adenocarcinoma of the gastric cardia. Cancer. 2001;91(10):1882-8
128. Kavalar R, Sarcevic B, Spagnoli GC,et al.Expression of MAGE tumour-associated antigens is inversely correlated with tumour differentiation in invasive ductal breast cancers: an immunohistochemical study.Virchows Arch. 2001;439(2):127-31.
129. Sadanaga N, Nagashima H, Tahara K, et al, The heterogeneous expression of MAGE-3 protein: difference between primary lesions and metastatic lymph nodes in gastric carcinoma.Oncol Rep. 1999;6(5):975-7.
130. Kim YM, Lee YH, Shin SH, et al. Expression of MAGE-1, -2, and -3 genes in gastric carcinomas and cancer cell lines derived from Korean patients.J Korean Ned Sci. 2001; 16(1):62-8.
131. Fischer C, Gudat F, Stulz P, et al. High expression of MAGE-3 protein in squamous-cell lung carcinoma. Int J Cancer. 1997;71(6):1119-21.
132. Serrano A, Lethe B, Delroisse JM, Lurquin C, De Plaen E, Brasseur F, Rimoldi D, Boon T. Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries. Int J Cancer. 1999 Nov 26;83(5):664-9.
133. Marshall A, Hodgson J. DNA chips: an array of possibilities [J]. Natl Biotechnol, 1998,16(1):27-31.
134. Gillett CE, Springall RJ, Barnes DM, et al. Multiple tissue core arrays in histopathology research: a validation study[J]. J Pathol, 2000,192 (2): 549-553.
135. Bubendorf L, Nocito A, Moch H, et al. Tissue microarray(TMA) technology: miniaturized pathology archives for high2throughput in situ studies[J]. J Pathol, 2001, 195 (1): 72-79.
136. Duffour MT, Chaux P, Lurquin C, et al. A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes.[J].Eur J Immunol, 1999,299(10): 3329-3337
137．蔡胜利，陈红松，王瑜，等．黑色素瘤抗原-1基因在肝细胞癌中的表达．中华医学杂志．1999，79：668-671．
138．何勇，周峻，窦科峰，等．原代培养大鼠肝细胞的基因转染．世界华人消化杂志．2004，12(3)：642-645
139．成党校，黄桂君，钱桂生．新型基因转染阳离子脂质体研究进展[J]．国外医学药学分册2000，27(5)：257-260
140. Robbins PD, Ghivizzani SC. Viral vector for gene therapy. Pharmacal Ther, 1998;80:35-47
2. Traversari C, van der Bruggen P, Van den Eynde B, Hainaut P, Lemoine C, Ohta N, Old L, Boon T. Transfection and expression of a gene coding for a human melanoma antigen recognized by autologous cytolytic T lymphocytes. Immunogenetics 1992; 35: 145-52.
3. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991; 254: 1643-7.
4. Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci USA 1995; 92: 11810-13.
5. Van den Eynde B, Lethe B, Van Pel A, De Plaen E, Boon T. The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med 1991; 173: 1373-84.
6. Boel P, Wildmann C, Sensi ML, Brasseur R, Renauld JC, Coulie P, Boon T, van der Bruggen P. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 1995; 2: 167-75.
7. Van den Eynde B, Peeters O, De Backer O, Gaugler B, Lucas S, Boon T. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995; 182: 689-98.
8. Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 1997; 94: 1914-18.
9. Tureci O, Sahin U, Zwick C, Koslowski M, Seitz G, Pfreundschuh M. Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens. Proc Natl Acad Sci USA 1998; 95:5211-16
10. Coulie PG, Karanikas V, Lurquin C, Colau D, Connerotte T, Hanagiri T, Van Pel A, Lucas S, Godelaine D, Lonchay C, Marchand M, Van Baren N, Boon T. Cytolytic T-cell responses of cancer patients vaccinated with a MAGE antigen. Immunol Rev 2002; 188: 33-42.
11. Lethe B, Lucas S, Michaux L, De Smet C, Godelaine D, Serrano A, De Plaen E, Boon T. LAGE-1, a new gene with tumor specificity. Int J Cancer 1998; 76: 903-8.
12. Güre AO, Stockert E, Arden KC, Boyer AD, Viars CS, Scanlan MJ, Old LJ, Chen YT. CT10: A new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational-difference analysis. Int J Cancer 2000; 85: 726-32.
13. Martelange V, De Smet C, De Plaen E, Lurquin C, Boon T. Identification on a human sarcoma of two new genes with tumor-specific expression. Cancer Res 2000; 60: 3848-55.
14. Zendman AJ, Cornelissen IM, Weidle UH, Ruiter DJ, van Muijen GN. CTp11, a novel member of the family of human cancer/testis antigens. Cancer Res 1999; 59: 6223-9.
15. de Wit N, Weidle UH, Ruitter DJ, van Muijen GN. Expression profiling of MMA-1 and splice variant MMA-1B: new cancer/testis antigens identified in human melanoma. Int J Cancer 2002; 98: 547-553.
16. Scanlan MJ, Altorki NK, Güre AO, Williamson B, Jungbluth A, Chen YT, Old LJ. Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9. Cancer Lett 2000; 150: 155-64.
17. Scanlan MJ, Gordon CM, Williamson B, Lee SY, Chen YT, Stockert E, Jungbluth A,
Ritter G, Jager D, Jager E, Knuth A, Old LJ. Identification of cancer/testis genes by database mining and mRNA expression analysis. Int J Cancer 2002; 98: 485-92. (PMID: 11920606)
18. Koslowski M, Tureci O, Bell C, Krause P, Lehr HA, Brunner J, Seitz G, Nestle FO, Huber C, Sahin U. Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer. Cancer Res 2002; 62: 6750-5.
19. Dong XY, Su YR, Qian XP, Yang XA, Pang XW, Wu HY, Chen WF. Identification of two novel CT antigens and their capacity to elicit antibody response in hepatocellular carcinoma patients. Br J Cancer 2003; 89: 291-7.
20. Chen YT, Gure AO, Tsang S, Stockert E, Jager E, Knuth A, Old LJ. Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci USA 1998; 95: 6919-23.
21. Chomez P, De Backer O, Bertrand M. An overview of the MAGE gene family with the identification of all human members of the family.Cancer Res. 2001 15;61:5544-51.
22. Kirkin AF, Dzhandzhugazyan KN, Zeuthen J.Cancer/testis antigens: structural and immunobiological properties.Cancer Invest. 2002;20222-36.
23. CT Gene database. URL: http://www.cancerimmunity.org/CTdatabase/
24. EST search engine. URL:http://www.ncbi.nlm.nih.gov/BLAST/
25. SAGEmap database. URL:http://www.ncbi.nlm.nih.gov/SAGE/
26. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 2002; 188: 22-32.
27. Tajima K, Obata Y, Tamaki H, Yoshida M, Chen YT, Scanlan MJ, Old LJ, Kuwano H, Takahashi T, Takahashi T, Mitsudomi T. Expression of cancer/testis (CT) antigens in lung cancer. Lung Cancer 2003; 42: 23-33.
28. Jungbluth AA, Chen YT, Stockert E, Busam KJ, Kolb D, Iversen K, Coplan K, Williamson B, Altorki N, Old LJ. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer 2001; 92: 856-60.
29. Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J. PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? Int J Cancer 2002; 101: 581-8.
30. Jungbluth AA, Stockert E, Chen YT, Kolb D, Iversen K, Coplan K, Williamson B, Altorki N, Busam KJ, Old LJ. Monoclonal antibody MA454 reveals a heterogeneous expression pattern of MAGE-1 antigen in formalin-fixed paraffin embedded lung turnouts. Br J Cancer 2000; 83: 493-7.
31. Stockert E, Jager E, Chen YT, Scanlan MJ, Gout I, Karbach J, Arand M, Knuth A, Old LJ. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med 1998; 187: 1349-54.
32. Chen YT, Stockert E, Chen Y, Garin-Chesa P, Rettig WJ, van der Bruggen P, Boon T, Old LJ. Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. Proc Natl Acad Sci USA 1994; 91: 1004-8.
33. Jungbluth AA, Antonescu CR, Busam KJ, Iversen K, Kolb D, Coplan K, Chen YT, Stockert E, Ladanyi M, Old LJ. Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7. Int J Cancer 2001; 94:252-6
34. Kocher T, Schultz-Thater E, Gudat F, Schaefer C, Casorati G, Juretic A, Willimann T, Harder F, Heberer M, Spagnoli GC. Identification and intracellular location of MAGE-3 gene product. Cancer Res 1995; 55: 2236-9.
35. Dos Santos NR, Torensma R, de Vries TJ, Schreurs MW, de Bruijn DR, Kater-Baats E, Ruiter DJ, Adema GJ, van Muijen GN, van Kessel AG. Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. Cancer Res 2000; 60: 1654-62.
36. Jungbluth AA, Busam KJ, Kolb D, Iversen K, Coplan K, Chen YT, Spagnoli GC, Old LJ. Expression of MAGE-antigens in normal tissues and cancer. Int J Cancer 2000; 85: 460-5.
37. Ono T, Kurashige T, Harada N, Noguchi Y, Saika T, Niikawa N, Aoe M, Nakamura S, Higashi T, Hiraki A, Wada H, Kumon H, Old LJ, Nakayama E.Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.Proc Natl Acad Sci USA. 2001;98(6):3282-7.
38. Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, Mannan P, Larsson E, Kanduri C, Vostrov AA, Cui H, Niemitz EL, Rasko JE, Docquier FM, Kistler M, Breen JJ, Zhuang Z, Quitschke WW, Renkawitz R, Klenova EM, Feinberg AP, Ohlsson R, Morse HC 3rd, Lobanenkov W. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma.Proc Natl Acad Sci U S A. 2002;99(10):6806-11.
39. Shan J, Yuan L, Xiao Q, Chiorazzi N, Budman D, Teichberg S, Xu HP. TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells.Cancer Res.2002;62(1):290-4.
40. Wang Y, Han KJ, Pang XW, Vaughan HA, Qu w, Dong XY, Peng JR, Zhao HT, Rui JA, Leng XS, Cebon J, Burgess AW, Chen WF. Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.J Immunol. 2002; 169(2): 1102-9.
41. Tureci O, Sahin U, Koslowski M, Buss B, Bell C, Ballweber P, Zwick C, Eberle T, Zuber M, Villena-Heinsen C, Seitz G, Pfreundschuh M. A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing.Oncogene. 2002;21(24):3879-88.
42. Ohman Forslund K, Nordqvist K. The melanoma antigen genes--any clues to their functions in normal tissues?Exp Cell Res. 2001 May 1;265(2):185-94. Review.
43. Saburi S, Nadano D, Akama TO, Hirama K, Yamanouchi K, Naito K, Tojo H, Tachi C, Fukuda MN. The trophinin gene encodes a novel group of MAGE proteins, magphinins, and regulates cell proliferation during gaametogenesis in the mouse. J Biol Chem. 2001 Dec 28; 276(52):49378-89.
44. Shiras A, Sengupta A, Shepal V.Cloning and tissue-specific gene expression studies with Dlxin-1, a newly identified transcriptional activator.Mol Cell Biol Res Commun. 2001 Sep;4(5):313-9.
45. Barker PA, Salehi A.The MAGE proteins: emerging roles in cell cycle progression, apoptosis,and neurogenetic disease. J Neurosci Res. 2002 Mar 15;67(6):705-12. Review.
46. Gure AO, Tureci O, Sahin U, Tsang S, Scanlan MJ, Jager E, Knuth A, Pfreundschuh M, Old LJ, Chen YT. SSX: a multigene family with several members transcribed in normal testis and human cancer..Int J Cancer. 1997 Sep 17;72(6):965-71.
47. Lim FL, Soulez M, Koczan D, Thiesen HJ, Knight JC. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas.Oncogene. 1998 Oct 15; 17(15):2013-8.
48. dos Santos NR, de Bruijn DR, Balemans M, Janssen B, Gartner F, Lopes JM, de Leeuw B, Geurts van Kessel A. Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins.Hum Mol Genet. 1997 Sep;6(9):1549-58.
49. dos Santos NR, de Bruijn DR, van Kessel AG. Molecular mechanisms underlying human synovial sarcoma development.Genes Chromosomes Cancer. 2001 Jan;30(1): 1-14.
50. Sa(?)ez M, Sau(?) AJ, Freemont PS, Kright. JCSSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex. Oncogene. 1999 Apr 29; 18(17): 2739-46.
51. dos Santos NR, de Bruijn DR, Kater-Baats E, Otte AP, van Kessel AG. Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization. Exp Cell Res. 2000 Apr 10;256(1):192-202.
52. Zendman AJ, Van Kraats AA, Weidle UH, Ruiter DJ, Van Muijen GNThe XAGE family of cancer/testis-associated genes: alignment and expression profile in normal tissues, melanoma lesions and Ewing's sarcoma.Int J Cancer. 2002 May 20;99(3):361-9.
53. Mitchell PJ, Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28; 245(4916): 371-8.
54. Rimoldi D, Salvi S, Schultz-Thater E, Spagnoli GC, Cerottini JC. Anti-MAGE-3 antibody 57B and anti-MAGE-1 antibody 6C1 can be used to study different proteins of the MAGE-A family.Int J Cancer. 2000 Jun 1;86(5):749-51.
55. Jungbluth AA, Chen YT, Busam KJ, Coplan K, Kolb D, Iversen K, Williamson B, Van Landeghem FK, Stockert E, Old LJ. CT7 (MAGE-C1) antigen expression in normal and neoplastic tissues.Int J Cancer. 2002 Jun 20;99(6):839-45.
56. Cheville JC, Roche PC. MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors.Nod Pathol. 1999 Oct;12(10):974-8.
57. Aubry F, Satie AP, Rioux-Leclercq N, Rajpert-De Meyts E, Spagnoli GC, Chomez P, De Backer O, Jegou B, Samson M. MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors.Cancer. 2001 Dec 1;92(11): 2778-85.
58. Jungbluth AA, Chen YT, Stockert E, Busam KJ, Koib D, Iversen K, Coplan K, Williamson B, Aitorki N, Old LJ. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues.Int J Cancer. 2001 Jun 15;92(6):856-60. Erratum in: Int J Cancer 2002 Feb 20;97(6):878.
59. Satie AP, Rajpert-De Meyts E, Spagnoli GC, Henno S, Olivo L, Jacobsen GK, Rioux-Leclercq N, Jegou B, Samson M. The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma in situ.Lab Invest. 2002 Jun;82(6):775-80.
60. Westbrook VA, Diekman AB, Klotz KL, Khole VV, yon Kap-Herr C, Golden WL, Eddy RL, Shows TB, Stoler MH, Lee CY, Flickinger CJ, Herr JC. Spermatid-specific expression of the novel X-linked gene product SPAN-X localized to the nucleus of human spermatozoa.Biol Reprod. 2000 Aug;63(2):469-81.
61. Hendriksen PJ.Do X and Y spermatozoa differ in proteinsTrheriogenology. 1999 Dec; 52(8): 1295-30771.
62. Lurdy DK, Tai LQ, Nguyen J, Wang Z, Yang HM, Udar N, Naiem F, Concannon P, Gatti RA. MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera. Mol Genet Metab 1998; 63: 3-13.
63. Lea IA, Adoyo P, O'Rand MG. Autoimmunogenicity of the human sperm protein 5p17 in vasectomized men and identification of linear B cell epitopes. Fertil Steril 1997; 67: 355-61.
64. Ayyoub M, Stevanovic S, Sahin U, Guillaume P, Servis C, Rimoldi D, Valmori D, Romero P, Cerottini JC, Rammensee HG, Pfreundschuh M, Speiser D, Levy F. Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor-reactive CTL infiltrating metastatic melanoma. J Immunol 2002; 168: 1717-22
65. Jager E, Nagata Y, Gnjatic S, Wada H, Stockert E, Karbach J, Dunbar PR, Lee SY, Jungbluth A, Jager D, Arand M, Ritter G, Cerundolo V, Dupont B, Chen YT, Old LJ, Knuth A. Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc Natl Acad Sci USA 2000; 97: 4760-5.
66. Peptide database of T-cell defined tumor antigens. URL: http://www.cancerimmunity.org/peptidedatabase/Tcellepitopes.htm
67. Denkberg G, Cohen CJ, Lev A, Chames P, Hoogenboom HR, Reiter Y.Direct visualization of distinct T cell epitopes derived from a melanoma tumor-associated antigen by using human recombinant antibodies with MHC-restricted T cell
receptor-like specificity. Proc Natl Acad Sci USA 2002; 99: 9421-6.76.
68. De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MACE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA 1996; 93: 7149-53.
69. Weiser TS, Guo ZS, Ohnmacht CA, Parkhurst ML, Tong-On P, Marincola FM, Fischette MR, Yu X, Chen CA, Hong JA, Stewart JH, Nguyen DM, Rosenberg SA, Schrump DS. Sequential 5-Aza-2 deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1. J Immunother 2001; 24: 151-61.
70. Old LJ. Cacer/Testis (CT) antigens-a new link between gametogenesis and cancer. Cancer Immun 2001;1: 1.
71. Zendman AJ, Ruiter DJ, Van Muijen GN. Cancer/Testis-Associated Genes: Identification, Expression Profile, and Putative Function. [J]. J Cell Physiol,2003;194(3):272-288
72. Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MACE gene family with the identification of all human members of the family. Cancer Res., 2001;61: 5544-5551.
73. De Smet C, Courtois SJ, Faraoni I, Lurquin C, Szikora JP, De Backer O, Boon T. Involvement of two Ets binding sites in the transcriptional activation of the MACE1 gene. Immnogenetics, 1995;42:282-290.
74. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: review, standardization, and commentary. 2004;4:1-21
75. Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, Kim SU, Ikenaka K.MAGE-E1, a new member of the melanomaassociated antigen gene family and its expression in human glioma. Cancer Res., 2001;61:4809-4814.
76. Juretic A, Spagnoli GC, Schultz-Thater E. et al. Cancer/testis tumour-associated antigens: immunohistochemical detection with monoclonal antibodies. Lancet Oncol. 2003:4(2):104-9.
77. Clotman F, De Backer O, De Plaen E, Boon T, Picard J. Cell-andstage-specific expression of mage genes during mouse spermatogenesis. Mamm Genome, 2000; 11: 696-699.
78. Kocher T, Schultz-Thater E, Juretic A, Dellabona P, Luscher U, Siegrist W, Harder F, heberer M, Zuber M, Spagnoli GC. Identification and intracellular location of MACE-3 gene product. Cancer Res.,1995;55:2236-2239.
79. Arnar-Costesec A, Godelaine D, Stockert E, Van der Bruggen P, Beaufay H, Chen YT. The tumor protein MACE-1 is located in the cytosol of human melanoma cells. Biochem. Biophys. Res. Commun. 1994;204:710-715.
80. Rimoldi D, Salvi S, Reed D, Coulie P, Jongeneel VC, De Plaen E, Brasseur F, Rodriguze AM, Boon T, Cerottini JC. cDNA and protein characterization of human MACE-10. Int.J. Cancer, 1999;82:901-907.
81. Jurk M, Kremmer E, Schwarz U, Forster R, Winnacker EL. MACE-11 protein is highly conserverd in higher organisms and located predomainantly in the nucleus. Int.J.Cancer,1998;75: 762-766.
82. Schultz-Thater E, Juretic A, Dellabona P, Luscher U, Siegrist W, Harder F, Heberer M, Zuber M, Spagnoli GC. MACE-1 products is a cytoplasmic protein. Int.J. Cancer, 1994; 59:435-439.
83. Brasseur F, Rimoldi D, Lienard D, Lethe B, Carrel S, Arienti F, Suter L, Vanwijck R, Bourlond A, Humbler Y. Expression of MACE genes in primary and metastatic cutaneous melanoma. Int.J.Cancer, 1995;63:375-380.
84. Kocher T, Zheng M, Bolli M, Simon R, Forster T, Schultz-Thater E, Remmel E, Noppen C, Schmid U, Ackermann D, Mihatsch MJ, Gasser T, Heberer M, Sauter G, Spagnoli GC.Prognostic relevance of MACE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study. Int J Cancer 2002; 100:702-705.
85. Bolli M, Kocher T, Adamina M, Culler U, Dalquen P, Haas P, Mirlacher M, Gambazzi
F, Harder F, Heberer M, Sauter G, Spagnoli GC. Tissue microarray evaluation of Melanoma antigen E (MAGE) tumor-associated antigen expression: potential indications for specific immunotherapy and prognostic relevance in squamous cell lung carcinoma. Ann Surg 2002;236:785-93.
86. Brasseur F, et al. Expression of MAGE genes in primary and metastatic cutaneous melanoma. Int J Cancer 1995;63:375-380.
87. Goydos JS, Patel M, Shih W. NY-ESO-1 and CT-p11 expression may correlate with stage of lineprogression in melanoma. J Surg Res 2001;98:76-80.
88. Patard JJ, et al. Expression of MAGE genes in transitional-cell carcinomas of the urinarybladder. Int J Cancer 1995;64:60-64.
89. Kurashige T, et al. NY-ESO-1 expression and immunogenicity associated with transitional cell carcinoma: correlation with tupression mor grade. Cancer Res 2001;61:4671-4674.
90. van Baren N, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood 1999;94:1156-1164.
91. Busam KJ, Iversen K, Berwick M, Spagnoli GC, Old LJ, Jungbluth AA. Immunoreactivity with the anti-MAGE antibody 57B in malignant melanoma. frequency of expression and correlation with prognostic parameters. Mod Pathol 2000; 13:459-465.
92. Takahash K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermatocytes of testis. Cancer Res. 1995;55:3478-3482.
93. Osterlund C, Tohomem V, Forstund KO, Nordqvist K.Mage-b4, a novel melanoma antigen(MAGE)gene specifially expressed during germ cell differentiation. Cancer Res. 2000;60:1054-1061.
94. Takahash, K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermatocytes of testis. Cancer Res. 1995; 55: 3478-3482.
95. Aizawa, T, Maruyama K, Kondo H, Yoshikawa K. Expression of necdin, an embryonal carcinoma-derived nuclear protein, in developing mouse brain. Dev. Brain Res. 1992; 68: 265-274.
96. Maruyama K, Usami M, Aizawa T, Yoshikawa K. A novel brainspecific mRNA encoding nuclear protein (necdin) expressed in neurally differentiated embryonal carcinoma cells. Biochem Biophys Res Commun. 1991; 178:291-296.
97. Maruyama, K et al. Biocemical characterization of mouse brain necdin. Biochem. 3.1996;314:895-901.
98. Taniura H, Taniguchi N, Hara M, Yoshikawa K. Necdin, a postmiotic neron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J.Bio.Chem. 1998; 273:720-728.
99. Taniura H, Matsumoto K, Yoshikawa K. Physical and functional interactions of neuronal growth suppressor necdin with p53. J Biol chem. 1999;274(23):16242-16248.
100. Tsai TF, Armstrong D, Beaudet AL. Necdin-deficient mice do not show lethality or the obesity and infertility of Prader-Willi syndrome. Nat Genet 1999a;22:15-16.
101. Gerard M, Hernandez L, Wevrick R, Stewart CL. Disruption of the mouse necdin gene results in early post-natal lethality. Nat Genet 1999;23:199-202.
102. Muscatelli F, Abrous DN, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H. Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 2000;9:3101-3110.
103. Itoh K, Hayashi A, Nakao M, Human tumor rejection antigens MAGE. J Biochem (Tokyo). 1996; 119(3):385-90.
104. Marchand M, van Baren N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer,1999;80:219-30.
105. Tahara K, Mori M, Sadanaga N,et al.Expression of the MAGE gene family in human hepatocellular carcinoma.Cancer,1999;85:1234-40.
106. Reynolds SR, Oratz R, Shapiro RL,et al.Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine.Int J Cancer. 1997;72:972-6.
107. Van Pel A, De Plaen E, Duffour MT, Warnier G, Uyttenhove C, Perricaudet M, Boon T. Induction of cytolytic T lymphocytes by immunization of mice with an adenovirus containing a mouse homolog of the human MAGE-A genes. Cancer Immunol Immunother. 2001;49(11):593-602.
108. Andersen MH, Keikavoussi P, Brocker EB, Schuler-Thurner B, Jonassen M, Sondergaard I, Straten PT, Becker JC, Kampgen E. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: cessation of CTL responses is associated with disease progression. Int J Cancer. 2001 15;94(6):820-824.
109. Nestle FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells.Nat Med, 1998;4:328-32.
110. Sakurai T, Itoh K, Higashitsuji H, Nagao T, Nonoguchi K, Chiba T, Fujita J. A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. J Biol Chem. 2004 9;279(:15):15505-14
111. Atanackovic D, Altorki NK, Stockert E, Williamson B, Jungbluth AA, Ritter E, Santiago D, Ferrara CA, Matsuo M, Selvakumar A, Dupont B, Chen YT, Hoffman EW, Ritter G, Old LJ, Gnjatic S. Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients. J Immunol. 2004,172(5):3289-96.
112. Vantomme V, Dantinne C, Amrani N, Permanne P, Gheysen D, Bruck C, Stoter G, Britten CM, Keilholz U, Lamers CH, Marchand M, Delire M, Gueguen M. Immunologic analysis of a phase Ⅰ/Ⅱ study of vaccination with NAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors. J Immunother. 2004; 27(2): 124-35
113. Albert J.W. Zendman, Dirk JR, et al. Cancer/Testis-Associated Genes: Identification, Expression Profile, and Putative Function. [J]. J Cell Physiol,2003; 194(3):272-288
114. Rimoldi D, Salvi S, Reed D et al., cDNA and protein characterization of human MAGE-A10. [J]. Int J Cancer 1999;82(6):901-907
115. Gillespie AM, Coleman RE.The potential of melanoma antigen expression in cancer therapy. [J].Cancer Treat Rev. 1999;25(4):219-227
116. van Pel A, De Plaen E, Duffour MT. et al., Induction of cytolytic T lymphocytes by immunization of mice with an adenovirus containing a mouse homolog of the human MAGE-A genes. [J]. Cancer Immunol Immunother. 2001;49(11):593-602
117. Brossart P. Dendritic cells in vaccination therapies of malignant diseases. [J]. Transfus Apheresis Sci. 2002;27(2):183-186
118. Marchand. M, Weynants P, Rankin E, et al. Tumor regression responses in melanoma patients meated with a peptide encoded by gene MAGE-3 and presented by HLA-A1. [J]. Int J Cancer. 1995(6); 63:883-885
119. Marchand. M, van Baren N, Weynants P, et al. Tumor regression observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. [J]. Int J Cancer. 1999;80(2):219-230
120. Duffour MT, Chaux P, Lurquin C, et al. A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes.[J].Eur J Immunol, 1999,299(10):33
121. Zendman AJ, Dirk JR, et al. Cancer/testis-associated genes: identification, expression profile, and putative function [J]. J Cell Physio, 2003; 194:272-288
122. Rimoldi D, Salvi S, Reed D et al., cDNA and protein characterization of human MAGE-A10 [J]. Int J Cancer 1999;82(6):901-907.
123. Mathew JS, Ali OG, Achim AJ, et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy [J]. Immunological Reviews. 2002(188): 22-32
124. Duffour MT, Chaux P, Lurquin C, et al. MAGE A peptide presented by HLA A2 is recognized by cytolytic T lymphocytes [J]. Eur J Immunol,, 1999,29:3329 3337.
125. Huang LQ, Brasseur F, Serrrano A, et al. Cytolytic T lymphocytes recognize an antigen coded by MAGE A10 on a human melanoma [J]. J Immunol,1999, 162:6849 6854.
126. Sugta M, Geraci M, Gao B, et al. Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma[J]. Cancer Res. 2002 15; 62(14): 3971-3979.
127. Zambon A, Mandruzzato S, Parenti A, Macino B, Dalerba P, Ruol A, Merigliano S, Zaninotto G, Zanovello P. MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell carcinoma and adenocarcinoma of the gastric cardia. Cancer. 2001;91(10):1882-8
128. Kavalar R, Sarcevic B, Spagnoli GC,et al.Expression of MAGE tumour-associated antigens is inversely correlated with tumour differentiation in invasive ductal breast cancers: an immunohistochemical study.Virchows Arch. 2001;439(2):127-31.
129. Sadanaga N, Nagashima H, Tahara K, et al, The heterogeneous expression of MAGE-3 protein: difference between primary lesions and metastatic lymph nodes in gastric carcinoma.Oncol Rep. 1999;6(5):975-7.
130. Kim YM, Lee YH, Shin SH, et al. Expression of MAGE-1, -2, and -3 genes in gastric carcinomas and cancer cell lines derived from Korean patients.J Korean Ned Sci. 2001; 16(1):62-8.
131. Fischer C, Gudat F, Stulz P, et al. High expression of MAGE-3 protein in squamous-cell lung carcinoma. Int J Cancer. 1997;71(6):1119-21.
132. Serrano A, Lethe B, Delroisse JM, Lurquin C, De Plaen E, Brasseur F, Rimoldi D, Boon T. Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries. Int J Cancer. 1999 Nov 26;83(5):664-9.
133. Marshall A, Hodgson J. DNA chips: an array of possibilities [J]. Natl Biotechnol, 1998,16(1):27-31.
134. Gillett CE, Springall RJ, Barnes DM, et al. Multiple tissue core arrays in histopathology research: a validation study[J]. J Pathol, 2000,192 (2): 549-553.
135. Bubendorf L, Nocito A, Moch H, et al. Tissue microarray(TMA) technology: miniaturized pathology archives for high2throughput in situ studies[J]. J Pathol, 2001, 195 (1): 72-79.
136. Duffour MT, Chaux P, Lurquin C, et al. A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes.[J].Eur J Immunol, 1999,299(10): 3329-3337
137．蔡胜利，陈红松，王瑜，等．黑色素瘤抗原-1基因在肝细胞癌中的表达．中华医学杂志．1999，79：668-671．
138．何勇，周峻，窦科峰，等．原代培养大鼠肝细胞的基因转染．世界华人消化杂志．2004，12(3)：642-645
139．成党校，黄桂君，钱桂生．新型基因转染阳离子脂质体研究进展[J]．国外医学药学分册2000，27(5)：257-260
140. Robbins PD, Ghivizzani SC. Viral vector for gene therapy. Pharmacal Ther, 1998;80:35-47