Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA.
Toxicol Pathol. 2022 Jun;50(4):507-511. doi: 10.1177/01926233221095445. Epub 2022 May 5.
Malignant neuroendocrine tumors were diagnosed in the stomach of two out of sixty female Sprague-Dawley rats treated for 89 weeks with a high dose of a novel, small molecule, cannabinoid-1 antagonist. The tumors were associated with parietal cell atrophy accompanied by foveolar hyperplasia of the glandular stomach mucosa. Parietal cell atrophy/foveolar hyperplasia was considered test article related at the high dose, given the higher incidence and severity relative to untreated controls, although the precise mechanism of the parietal cell atrophy was undetermined. Spontaneous gastric neuroendocrine tumors are very rare in rats, and the current cases were considered secondary to parietal cell atrophy causing reduced gastric acid secretion and subsequent overstimulation of gastrin release through a feedback loop.
在 89 周的高剂量新型小分子大麻素 1 型拮抗剂治疗后，两只雌性 Sprague-Dawley 大鼠的胃中诊断出恶性神经内分泌肿瘤。肿瘤与壁细胞萎缩伴胃腺黏膜的滤泡增生有关。鉴于相对于未处理的对照组，高剂量时的发生率和严重程度更高，因此认为壁细胞萎缩/滤泡增生与受试物有关，尽管壁细胞萎缩的确切机制尚不清楚。大鼠的自发性胃神经内分泌肿瘤非常罕见，目前的病例被认为继发于壁细胞萎缩导致胃酸分泌减少，随后通过反馈回路过度刺激胃泌素释放。
