Harari P M, Contreras L, Pickart M A, Ritter M A, Kinsella T J
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison.
Arch Otolaryngol Head Neck Surg. 1993 Jul;119(7):738-42. doi: 10.1001/archotol.1993.01880190034007.
Proliferation of tumor clonogens during a course of conventional head and neck radiotherapy serves to compromise ultimate tumor control. Biologic strategies that attempt to alter tumor proliferation kinetics using cytostatic or antiproliferative agents may therefore prove valuable by limiting tumor cell repopulation during therapy.
Three human squamous cell carcinoma (SCC) cell lines, derived from primary head and neck cancers, have been characterized in vitro via flow cytometric analysis of proliferation kinetics, and in vivo via tumor xenograft growth evaluation in athymic mice.
The antiproliferative agent alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, induced growth inhibition of these SCCs in culture and when administered orally to athymic mice harboring SCC tumor xenografts. Cell cycle kinetic analysis via flow cytometry revealed that DFMO induced a lengthening of in vitro tumor cell potential doubling times. Similarly, DFMO administered continuously via the drinking water to athymic mice harboring human SCC xenografts induced a prolongation of in vivo tumor volume doubling.
These data indicate that biologic agents, such as DFMO, can alter SCC growth kinetics and may prove useful in designing new therapeutic strategies for rapidly proliferating tumors such as those that occur in the head and neck.
在传统的头颈部放射治疗过程中，肿瘤克隆原的增殖会影响最终的肿瘤控制效果。因此，尝试使用细胞生长抑制剂或抗增殖药物来改变肿瘤增殖动力学的生物学策略，可能通过限制治疗期间肿瘤细胞的再增殖而具有重要价值。
通过对增殖动力学进行流式细胞术分析，在体外对源自原发性头颈部癌的三种人鳞状细胞癌（SCC）细胞系进行了表征，并通过无胸腺小鼠体内肿瘤异种移植生长评估在体内进行了表征。
抗增殖药物α-二氟甲基鸟氨酸（DFMO）是一种多胺生物合成抑制剂，在培养中以及口服给予携带SCC肿瘤异种移植的无胸腺小鼠时，均可诱导这些SCC的生长抑制。通过流式细胞术进行的细胞周期动力学分析表明，DFMO可诱导体外肿瘤细胞潜在倍增时间延长。同样，通过饮用水连续给予携带人SCC异种移植的无胸腺小鼠DFMO，可诱导体内肿瘤体积倍增时间延长。
这些数据表明，诸如DFMO之类的生物制剂可改变SCC的生长动力学，并可能在设计针对快速增殖肿瘤（如头颈部肿瘤）的新治疗策略中发挥作用。
