Impact of limb amputation and cisplatin chemotherapy on metastatic progression in mouse models of osteosarcoma.

Impact of limb amputation and cisplatin chemotherapy on metastatic progression in mouse models of osteosarcoma.
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DOI:
10.1038/s41598-021-04018-9
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发表时间:
2021-12-24
期刊:
影响因子:
4.6
通讯作者:
LeBlanc AK
LeBlanc AK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ren L;Huang S;Beck J;LeBlanc AK

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开发准确再现人类癌症的动物模型是一个持续的挑战。这与骨肉瘤(OS)的研究尤其相关,骨肉瘤是一种高度恶性的骨肿瘤,每年有大约1000名儿童/青少年患者被诊断出。转移是患者死亡的主要原因,强调需要相关的动物模型的转移性OS。在这项研究中,我们描述了如何现有的OS小鼠模型可以在一个时间过程的背景下询问,以确定自发转移的动力学从原位植入的原发性肿瘤。我们评估了四种高转移性OS细胞系(3种人,1种小鼠),以建立免疫缺陷NSG小鼠中转移进展的时间轴。为了辨别治疗对这些模型中肿瘤发展和转移的影响,我们研究了顺铂治疗和早期和晚期时间点的手术截肢。这些数据有助于确定OS转移进展研究的适当观察期,并进一步加深我们对现有小鼠模型的理解。努力推进转移性OS的研究对于促进新疗法的鉴定和提高患者生存率至关重要。
Development of animal models that accurately recapitulate human cancer is an ongoing challenge. This is particularly relevant in the study of osteosarcoma (OS), a highly malignant bone tumor diagnosed in approximately 1000 pediatric/adolescent patients each year. Metastasis is the leading cause of patient death underscoring the need for relevant animal models of metastatic OS. In this study, we describe how existing OS mouse models can be interrogated in a time-course context to determine the kinetics of spontaneous metastasis from an orthotopically implanted primary tumor. We evaluated four highly metastatic OS cell lines (3 human, 1 mouse) to establish a timeline for metastatic progression in immune deficient NSG mice. To discern the effects of therapy on tumor development and metastasis in these models, we investigated cisplatin therapy and surgical limb amputation at early and late timepoints. These data help define the appropriate observational periods for studies of metastatic progression in OS and further our understanding of existing mouse models. Efforts to advance the study of metastatic OS are critical for facilitating the identification of novel therapeutics and for improving patient survival.
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