Evers B M, Hurlbut S C, Tyring S K, Townsend C M, Uchida T, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550.
Ann Surg. 1991 May;213(5):411-6. doi: 10.1097/00000658-199105000-00005.
Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS.(ABSTRACT TRUNCATED AT 250 WORDS)
由于缺乏实验模型,类癌患者有效治疗方法的研发受到了阻碍。作者建立了唯一能在裸鼠体内产生肿瘤的功能性人胰腺类癌长期细胞系(BON)。在本研究中,作者检测了三种药物,即α-干扰素(IFN)、生长抑素类似物SMS 201-995(SMS)和多胺生物合成抑制剂α-二氟甲基鸟氨酸(DFMO)对BON肿瘤生长的影响。将BON切成3平方毫米大小的碎片,双侧皮下植入雄性BALB/c裸鼠体内。在第一项研究中,23只小鼠被随机分为四组:对照组、IFN组(1×10⁶单位,皮下注射,每天4次)、IFN + SMS组(300微克/千克,腹腔注射,每天3次)和饮用水中含3% DFMO的IFN组。在肿瘤植入当天开始治疗。在第二项研究中,小鼠被随机分为六组:对照组、IFN组、SMS组、DFMO组、IFN + SMS组、IFN + DFMO组和IFN + SMS + DFMO组。在肿瘤植入后第15天开始治疗。每周测量肿瘤面积和体重。在两项研究中,BON植入后第28天处死小鼠,取出肿瘤,称重,并分析其DNA和RNA含量。在第一项研究中,IFN单独使用或与SMS或DFMO联合使用均能抑制BON肿瘤生长。然而,当在肿瘤生长确立后开始治疗(研究2)时,抑制BON生长的唯一有效治疗方法是IFN + DFMO和IFN + DFMO + SMS。(摘要截短至250字)