Balducci L, Hardy C L
Department of Medicine, University of Mississippi Medical Center, Jackson.
Cancer Invest. 1988;6(6):681-6. doi: 10.3109/07357908809078035.
Lewis lung carcinoma (LLC) induces a range of hemopoietic alterations in its murine host including progressive anemia, thrombocytopenia, splenomegaly, neutrophilia, and marrow and splenic myeloid hyperplasia. Concentrations of both pluripotent and committed marrow hemopoietic progenitors is increased and the cycling fraction of granulocyte-macrophage progenitors is accelerated. We have developed a way to study whether these hemopoietic effects become long-term consequences of cancer, using LLC-bearing mice with advanced tumor treated with the antineoplastic agent tiazofurin, 2-beta-D-ribofuranosyl-thiazole-4-carboxyamide, NSC 286193 (TZ). LLC mice were treated with a single dose of TZ either 150, 300, or 600 mg/kg, intraperitoneally on day 6 posttumor implant when lung metastases are present and all hemopoietic effects of the tumor are recognizable. Even a single dose of 150 mg/kg of TZ produced a significant survival advantage, and 600 mg/kg resulted in 30% of the animals remaining disease free during a 5-month follow-up. A 6-week treatment schedule was devised, administering TZ intraperitoneally, 600 mg/kg, weekly beginning on day 6. In this group, median survival was not reached after 9 months of follow-up. The only evidence of myelotoxicity produced by intermittent administration of TZ was a mild anemia which was fully reversible 2 weeks after discontinuance of the drug. No difference in white blood cell count, differential count, or platelet count was detected in tumor bearers and controls treated with TZ. Both pluripotent and committed marrow hemopoietic precursors remained unchanged in TZ-LLC, TZ-controls and untreated controls throughout treatment and 2 weeks thereafter. This study demonstrates that TZ-cured LLC mice are suitable to explore late hemopoietic effects of cancer.
刘易斯肺癌（LLC）在其小鼠宿主中会引发一系列造血改变，包括进行性贫血、血小板减少、脾肿大、中性粒细胞增多以及骨髓和脾脏髓样增生。多能和定向骨髓造血祖细胞的浓度均增加，粒细胞 - 巨噬细胞祖细胞的循环分数加快。我们已经开发出一种方法来研究这些造血效应是否会成为癌症的长期后果，即使用携带LLC且患有晚期肿瘤的小鼠，用抗肿瘤药物替唑呋林（2-β-D-呋喃核糖基噻唑-4-甲酰胺，NSC 286193，简称TZ）进行治疗。在肿瘤植入后第6天，当出现肺转移且肿瘤的所有造血效应都可识别时，给LLC小鼠腹腔内注射单次剂量的TZ，剂量分别为150、300或600mg/kg。即使单次剂量150mg/kg的TZ也产生了显著的生存优势，600mg/kg的剂量导致30%的动物在5个月的随访期间无疾病。设计了一个为期6周的治疗方案，从第6天开始每周腹腔内注射600mg/kg的TZ。在这个组中，随访9个月后未达到中位生存期。间歇性给予TZ产生的唯一骨髓毒性证据是轻度贫血，停药2周后完全可逆。在接受TZ治疗的肿瘤携带者和对照组中，未检测到白细胞计数、分类计数或血小板计数的差异。在整个治疗期间及之后2周，多能和定向骨髓造血前体细胞在TZ-LLC组、TZ-对照组和未治疗的对照组中均保持不变。这项研究表明，经TZ治愈的LLC小鼠适合用于探索癌症的晚期造血效应。
