Watson S A, Michaeli D, Grimes S, Morris T M, Robinson G, Varro A, Justin T A, Hardcastle J D
Department of Surgery, Queen's Medical Centre, University of Nottingham, United Kingdom.
Cancer Res. 1996 Feb 15;56(4):880-5.
The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced degree of necrosis, with the area of viable tumor in the Gastrimmune-immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.
评估了胃泌素中和对大鼠结肠细胞系DHDK12体内生长的影响，该细胞系表达胆囊收缩素B/胃泌素受体并分泌甘氨酸延伸型胃泌素-17（G17）。通过给予免疫原Gastrimmune实现胃泌素中和，Gastrimmune由与白喉类毒素连接的G17氨基末端部分组成。使用大鼠特异性版本的Gastrimmune对大鼠进行预免疫，对照动物仅接受白喉类毒素。产生的抗体可中和羧基酰胺化和甘氨酸延伸型G17。将肿瘤植入腹壁肌肉层，与对照大鼠相比，用Gastrimmune免疫的大鼠的肿瘤中位横截面积显著减小（减少70.2%；P = 0.005），重量也显著减轻（减少56.5%；P = 0.0078）。组织学分析显示，肿瘤坏死程度增强，Gastrimmune免疫大鼠的存活肿瘤面积降至40.3%，而对照大鼠为58.6%（P = 0.003）。用Gastrimmune免疫可产生抑制大鼠结肠肿瘤生长的抗体。这可能是通过中和血清G17和细胞相关的前体胃泌素分子介导的。
