由于癌症研究的最新进展,大多数接受癌症治疗的儿童都能存活到成年。然而,抗癌药物的长期后果研究不足,尤其是在儿科人群中。我们和其他人已经表明,常规使用化疗药物会导致肌肉骨骼改变,这有助于增加治疗相关的毒性和长期发病率。然而,抗癌治疗后这些持久的肌肉骨骼缺陷的性质和范围,以及它们是否可能影响年轻人的生长和生活质量,还有待阐明。这里,我们的目的是调查化疗对年轻(儿科)小鼠的持续肌肉骨骼后果。四周大的雄性小鼠给予5-FU的组合,亚叶酸,伊立替康(又名,Folfiri)或车辆长达5周。在牺牲的时候,骨骼肌,骨头,收集了其他组织,已处理,并存储用于进一步分析。在另一组实验中,停止治疗后,对接受化疗的小鼠进行长达4周的监测.总的来说,在接受化疗的动物中,生长速度明显较慢,导致瘦肉和脂肪量减少,以及显著较小的骨骼肌。有趣的是,停止治疗后4周,接受化疗的动物表现出持续性的肌肉骨骼缺陷,包括肌肉神经支配缺陷和线粒体稳态异常。总之,我们的数据支持抗癌治疗可能导致活跃生长的儿科小鼠长期持续的肌肉骨骼并发症,并支持需要进一步研究以确定导致这些并发症的机制。因此,可以确定预防或减少化疗相关毒性的新疗法。
Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity. Yet, the nature and scope of these enduring musculoskeletal defects following anticancer treatments and whether they can potentially impact growth and quality of life in young individuals remain to be elucidated. Here, we aimed at investigating the persistent musculoskeletal consequences of chemotherapy in young (pediatric) mice. Four-week-old male mice were administered a combination of 5-FU, leucovorin, irinotecan (a.k.a., Folfiri) or the vehicle for up to 5 wk. At time of sacrifice, skeletal muscle, bones, and other tissues were collected, processed, and stored for further analyses. In another set of experiments, chemotherapy-treated mice were monitored for up to 4 wk after cessation of treatment. Overall, the growth rate was significantly slower in the chemotherapy-treated animals, resulting in diminished lean and fat mass, as well as significantly smaller skeletal muscles. Interestingly, 4 wk after cessation of the treatment, the animals exposed to chemotherapy showed persistent musculoskeletal defects, including muscle innervation deficits and abnormal mitochondrial homeostasis. Altogether, our data support that anticancer treatments may lead to long-lasting musculoskeletal complications in actively growing pediatric mice and support the need for further studies to determine the mechanisms responsible for these complications, so that new therapies to prevent or diminish chemotherapy-related toxicities can be identified.