Maddalo Gemma, Spolverato Ylenia, Rugge Massimo, Farinati Fabio
aDepartment of Surgery, Oncology and Gastroenterology, Padua University Hospital bDepartment of Medicine, Padua University, Padova, Italy.
Eur J Cancer Prev. 2014 Jul;23(4):258-63. doi: 10.1097/CEJ.0000000000000008.
Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.
胃泌素已被确定为胃酸分泌的主要效应物，但多项研究表明其作为癌症风险生物标志物以及作为结直肠癌、胃癌、肝癌和胰腺癌生长因子的作用。高胃泌素血症是自身免疫性胃炎的特征，伴有胃体和胃底腺萎缩，患胃腺癌和神经内分泌肿瘤的风险增加。I型胃类癌在自身免疫性胃炎的背景下发生，因为胃泌素对肠嗜铬样细胞施加刺激，并且由于高胃泌素血症的消除导致肿瘤消退，所以长期对胃泌素敏感。胃类癌的治疗仍存在争议，但当疾病频繁复发、多中心或浸润性时，主张手术治疗，或者另一种选择是使用长效生长抑素类似物进行昂贵且持久的治疗。已经开发出一种技术，可制备一种免疫原，引发免疫系统反应并产生针对G17的抗体。这种疫苗已在结直肠癌、胰腺癌或晚期胃癌患者中进行了测试。该疫苗也已用于治疗I型胃类癌，对患有这些病变的患者给予G17DT可导致类癌消退。抗胃泌素疫苗在胃肠道癌治疗中的应用显然需要验证，但这种免疫疗法很可能代表一种简单、廉价且有效的“辅助”治疗方法。
