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对胃肠道肿瘤具有特异性的单克隆抗体的免疫组织化学抗原表达及体内肿瘤摄取情况。

Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract.

作者信息

Douillard J Y, Lehur P A, Aillet G, Kremer M, Bianco-Arco A, Peltier P, Chatal J F

出版信息

Cancer Res. 1986 Aug;46(8):4221-4.

PMID:3524803
Abstract

Two monoclonal antibodies with specificity for carcinoembryonic antigen and Ca 19-9 gastrointestinal tract tumor associated antigens were infused after iodination with 125I and 131I, respectively, in six patients 3 days and in one patient 4 days before radical surgery for colon or rectal carcinoma. Biopsy specimens from tumor, normal colon, fat, muscle, and skin along with a blood sample were excised at surgery and counting was performed for gamma emission. Fragments were then studied by two independent pathologists for immunohistochemical expression of corresponding antigens using the avidin-biotin peroxidase complex. A correlation study was thereafter performed between the amount of antibody bound in vivo, expressed as the percentage of injected dose per gram of tissue and the quantitative expression of tumor associated antigens, taking into account both the percentage of cells expressing the antigen and intensity of staining. For this limited number of patients a good correlation was found between amount of targeted antibodies and amount of expressed antigens. For carcinoembryonic antigen, r values were 0.69 and 0.90 for each pathologist (with an r value of interobserver correlation of 0.74); for Ca 19-9, values of 0.78 and 0.84 were obtained for each observer, with an interobserver r value of 0.97. Based on this limited study, it may be assumed that the possibility of imaging a given tumor is in part correlated to intensity of antigenic expression at the tumor site; other parameters, like tumor vascularization and blood flow for instance, are, however, to be considered for accessibility of antibodies to corresponding antigens.

摘要

分别用¹²⁵I和¹³¹I碘化后,针对癌胚抗原和Ca 19-9这两种胃肠道肿瘤相关抗原的两种单克隆抗体,在6例患者结肠癌或直肠癌根治手术前3天注入,1例患者在术前4天注入。手术时切除肿瘤、正常结肠、脂肪、肌肉和皮肤的活检标本以及一份血样,进行γ射线发射计数。然后由两位独立的病理学家使用抗生物素蛋白-生物素过氧化物酶复合物研究切片中相应抗原的免疫组织化学表达。此后进行了一项相关性研究,以每克组织中结合抗体的量(以注射剂量的百分比表示)与肿瘤相关抗原的定量表达之间的相关性为研究对象,同时考虑表达抗原的细胞百分比和染色强度。对于这有限数量的患者,发现靶向抗体的量与表达抗原的量之间存在良好的相关性。对于癌胚抗原,每位病理学家的r值分别为0.69和0.90(观察者间相关性的r值为0.74);对于Ca 19-9,每位观察者得到的值为0.78和0.84,观察者间r值为0.97。基于这项有限的研究,可以假定对特定肿瘤进行成像的可能性部分与肿瘤部位的抗原表达强度相关;然而,对于抗体与相应抗原的可及性,还需要考虑其他参数,例如肿瘤血管形成和血流量等。

相似文献

1
Immunohistochemical antigenic expression and in vivo tumor uptake of monoclonal antibodies with specificity for tumors of the gastrointestinal tract.对胃肠道肿瘤具有特异性的单克隆抗体的免疫组织化学抗原表达及体内肿瘤摄取情况。
Cancer Res. 1986 Aug;46(8):4221-4.
2
Generation of tumor cell-reactive human monoclonal antibodies using peripheral blood lymphocytes from actively immunized colorectal carcinoma patients.利用主动免疫的结直肠癌患者外周血淋巴细胞产生肿瘤细胞反应性人单克隆抗体。
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Comparison of portal and peripheral blood levels of carcinoembryonic antigen, CA 19-9, and CA 125 tumor-associated antigens in patients with colorectal and pancreatic cancer.结直肠癌和胰腺癌患者门静脉血与外周血中癌胚抗原、CA 19-9和CA 125肿瘤相关抗原水平的比较。
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Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids.放射性标记的抗癌胚抗原单克隆抗体及其抗原结合片段在人结肠多细胞肿瘤球体中的穿透与结合
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引用本文的文献

1
Bystander killing of tumour cells by antibody-targeted enzymatic activation of a glucuronide prodrug.通过抗体靶向的葡糖醛酸苷前药酶促激活实现旁观者杀伤肿瘤细胞
Br J Cancer. 1999 Mar;79(9-10):1378-85. doi: 10.1038/sj.bjc.6690221.
2
Influence of cocktails of labeled monoclonal antibodies on the localization of antibodies in human tumor xenografts.标记单克隆抗体鸡尾酒对人肿瘤异种移植物中抗体定位的影响。
Jpn J Cancer Res. 1990 Mar;81(3):266-71. doi: 10.1111/j.1349-7006.1990.tb02560.x.
3
Multi-centre immunoscintigraphic study using indium-111-labelled CEA-specific and/or 19-9 monoclonal antibody F(ab')2 fragments.
使用铟-111标记的癌胚抗原特异性和/或19-9单克隆抗体F(ab')2片段的多中心免疫闪烁显像研究。
Eur J Nucl Med. 1990;17(5):223-9. doi: 10.1007/BF00812361.