Khanna Chand, Prehn Jennifer, Hayden David, Cassaday Ryan D, Caylor Jana, Jacob Shevin, Bose Seuli M, Hong Sung-Hyeok, Hewitt Stephen M, Helman Lee J
Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2002 Jul;8(7):2406-12.
The purpose of this research was to determine whether insulin-like growth factor (IGF) suppression, using a long-acting analogue of somatostatin (OncoLAR, octreotide pamoate long-acting release), will decrease chemotherapy resistance by eliminating an important survival signal to osteosarcoma (OSA) cells in a relevant naturally occurring cancer model. EXPERIMNETAL DESIGN: We conducted a randomized, blinded, placebo-controlled preclinical study in pet dogs with naturally occurring OSA. The study compared primary tumor necrosis and apoptosis, and survival of pet dogs receiving OncoLAR and carboplatin chemotherapy compared with dogs receiving placebo and carboplatin.
Dogs receiving OncoLAR had suppression of serum IGF levels by approximately 43% without toxicity. No differences in primary tumor necrosis, apoptosis, tumor IGF mRNA expression, or survival were seen between the dogs receiving OncoLAR plus chemotherapy compared with OncoLAR alone.
The suppression of IGF levels by the extent and/or duration achieved in the trial was not sufficient to improve chemotherapy-related antitumor effects in pet dogs with OSA.
本研究的目的是在一个相关的自然发生的癌症模型中,确定使用长效生长抑素类似物(OncoLAR,长效帕莫酸奥曲肽)抑制胰岛素样生长因子(IGF)是否会通过消除骨肉瘤(OSA)细胞的重要生存信号来降低化疗耐药性。实验设计:我们在患有自然发生的OSA的宠物狗中进行了一项随机、双盲、安慰剂对照的临床前研究。该研究比较了接受OncoLAR和卡铂化疗的宠物狗与接受安慰剂和卡铂的宠物狗的原发性肿瘤坏死、凋亡及生存率。
接受OncoLAR的狗血清IGF水平被抑制约43%,且无毒性。与单独接受OncoLAR相比,接受OncoLAR加化疗的狗在原发性肿瘤坏死、凋亡、肿瘤IGF mRNA表达或生存率方面没有差异。
在试验中所达到的IGF水平抑制程度和/或持续时间不足以改善患有OSA的宠物狗的化疗相关抗肿瘤效果。