Kozacko M F, Mang T S, Schally A V, Priore R L, Liebow C
Department of Oral and Maxillofacial Surgery, School of Dental Medicine,State University of New York at Buffalo, 14214, USA.
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2953-7. doi: 10.1073/pnas.93.7.2953.
We previously reported that CO2 laser incisions in carcinogen-initiated fields promoted cancer development and caused release of growth factors. Here we examined the quantitative and additive properties of this tumor-promoting event and examined whether this promotion could be nullified by treatment with a bombesin antagonist, which down-regulates epidermal growth factor receptors. The model used for cancer promotion was the hamster buccal cheek pouch that had been treated with a carcinogen (9,10-dimethyl-1,2-benzanthracene) for 6 weeks, producing premalignant lesions. These lesions would evolve into a cancer eventually without further treatment. Promotion was measured both by increased fluorescence in response to systemically administered Photofrin, measured noninvasively using an in vivo fluorescence photometer, and by the timing of appearance of clinical tumors. Laser incisions (0-3) were made into the hamster cheek 1 week apart, or three incisions were done 1 day apart. Another group of animals received bombesin antagonist RC-3095 for 4 weeks during the time incisions were made, again measuring promotion. Laser incisions 1 week apart produced additive promotion, whereas three incisions 1 day apart were not statistically different from the group receiving only one incision. RC-3095 treatment completely eliminated the promoting effects of incision and totally stopped promotion for the 4-week period of treatment. After discontinuing treatment with RC-3095, lesion progression resumed at the untreated control rate. This work confirms that the promoting event of a laser incision follows a comparable time course to release of growth factors after such an incision and that it can be eliminated by treatment with bombesin antagonists.
我们之前报道过，在致癌物引发的区域进行二氧化碳激光切割会促进癌症发展并导致生长因子释放。在此，我们研究了这一肿瘤促进事件的定量和累加特性，并探究这种促进作用是否可以通过用蛙皮素拮抗剂治疗来消除，该拮抗剂可下调表皮生长因子受体。用于癌症促进研究的模型是仓鼠颊囊，其已用致癌物（9,10 - 二甲基 - 1,2 - 苯并蒽）处理6周，产生癌前病变。这些病变在不进行进一步治疗的情况下最终会演变成癌症。通过对全身注射光敏剂后的荧光增强来测量促进作用，使用体内荧光光度计进行无创测量，同时也通过临床肿瘤出现的时间来衡量。激光切割（0 - 3次）在仓鼠颊部分别间隔1周进行，或者3次切割在1天内完成。另一组动物在进行切割的时间段内接受蛙皮素拮抗剂RC - 3095治疗4周，同样测量促进作用。间隔1周进行的激光切割产生累加促进作用，而1天内进行3次切割与仅接受1次切割的组相比无统计学差异。RC - 3095治疗完全消除了切割的促进作用，并在4周的治疗期间完全停止了促进作用。停止使用RC - 3095治疗后，病变进展恢复到未治疗对照组的速率。这项工作证实，激光切割的促进事件与切割后生长因子释放的时间进程相似，并且可以通过用蛙皮素拮抗剂治疗来消除。
