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用于治疗猫口腔鳞状细胞癌的多胺抑制剂:一项概念验证研究。

Polyamine inhibitors for treatment of feline oral squamous cell carcinoma: a proof-of-concept study.

作者信息

Lewis John R, O'Brien Thomas G, Skorupski Katherine A, Krick Erika L, Reiter Alexander M, Jennings Michael W, Jurney Carrie H, Shofer F S

机构信息

Mari Lowe Center for Comparative Oncology, Ryan Veterinary Hospital, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104-6010, USA.

Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA.

出版信息

J Vet Dent. 2013 Fall;30(3):140-5. doi: 10.1177/089875641303000301.

Abstract

This study assessed proof-of-concept for use of polyamine inhibitor 2-diluoromethylornithine (DFMO) as a treatment for oral squamous cell carcinoma (SCC) in client-owned cats. Polyamine levels in tumor tissue and normal oral mucosa were quantified before and after treatment. DFMO was administered orally to 14 client-owned cats with histologically confirmed oral SCC. Patients were monitored for gastrointestinal, dermatologic, auditory, hematological, and biochemical abnormalities. Total polyamine levels in tumor tissue decreased after treatment, as did the specific polyamine putrescine in both tumor tissue and normal mucosa. Ototoxicity was observed in 5 of 6 cats receiving pre- and post-treatment brainstem auditory evoked potential tests. Subclinical thrombocytopenia was observed in 6 of 14 cats. One cat showed mild post-anesthetic tremors that resolved without treatment. Oral administration of DFMO at doses used in this study resulted in significantly decreased tumor polyamine levels without life-threatening clinical or hematological toxicities. Further studies are warranted to explore pathophysiology of polyamine biochemistry and use of polyamine inhibitors in treatment of cats with oral SCC.

摘要

本研究评估了多胺抑制剂2-二氟甲基鸟氨酸(DFMO)作为治疗客户拥有的猫口腔鳞状细胞癌(SCC)的概念验证。在治疗前后对肿瘤组织和正常口腔黏膜中的多胺水平进行了定量。对14只经组织学确诊为口腔SCC的客户拥有的猫口服DFMO。对患者进行胃肠道、皮肤、听觉、血液学和生化异常监测。治疗后肿瘤组织中的总多胺水平下降,肿瘤组织和正常黏膜中的特定多胺腐胺水平也下降。在6只接受治疗前和治疗后脑干听觉诱发电位测试的猫中,有5只观察到耳毒性。14只猫中有6只观察到亚临床血小板减少症。1只猫出现轻度麻醉后震颤,未经治疗自行缓解。以本研究中使用的剂量口服DFMO可显著降低肿瘤多胺水平,且无危及生命的临床或血液学毒性。有必要进一步研究多胺生物化学的病理生理学以及多胺抑制剂在治疗猫口腔SCC中的应用。

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