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Human-in-mouse modeling of primary head and neck squamous cell carcinoma.

机译:原发性头颈部鳞状细胞癌的小鼠模型研究。

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OBJECTIVES/HYPOTHESIS: To develop a reliable modeling system for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Laboratory-based translational study. METHODS: HNSCC tissue was obtained from patients at biopsy/resection, cultured, and implanted into mice. In vivo, tumor growth, and survival was monitored by bioluminescence imaging. Histology and immunohistochemistry (IHC) were used to confirm HNSCC and human origin. RESULTS: Short-term culture techniques were optimized allowing survival of primary HNSCC cells more than 7 days in 76% of tumors. The size of the tumor biopsy collected did not correlate with the success of short-term culture or xenograft establishment. Xenograft modeling was attempted in primary HNSCCs from 12 patients with a success rate of 92%. Immunostaining confirmed human origin of epithelial tumor cells within the modeled tumor. Bioluminescence and Ki67 IHC suggested tumor proliferation within the model. Luciferase expression was maintained for as long as 100 days in modeled tumors. CONCLUSIONS: The techniques developed for short-term primary tumor culture followed by xenograft modeling provide a low-cost and tractable model for evaluation of HNSCC response to standard and novel therapies. The high success rate of human-in-mouse tumor formation from primary HNSCC suggests that selection pressures for tumor growth in this model may be less than those observed for establishment of cell lines. Bioluminescent imaging provides a useful tool for evaluating tumor growth and could be expanded to measure response of the modeled tumor to therapy. This model could be adapted for xenograft modeled growth of other primary tumor types.
机译:目的/假设:为头颈部鳞状细胞癌(HNSCC)开发可靠的建模系统。研究设计:基于实验室的翻译研究。方法:从活检/切除患者中获得HNSCC组织,进行培养并植入小鼠。在体内,通过生物发光成像监测肿瘤的生长和存活。组织学和免疫组化(IHC)用于确认HNSCC和人类起源。结果:优化了短期培养技术,可使原代HNSCC细胞在76%的肿瘤中存活超过7天。收集的肿瘤活检的大小与短期培养或异种移植成功与否无关。尝试对来自12例患者的原发性HNSCC进行异种移植建模,成功率为92%。免疫染色证实了人类在模型肿瘤中上皮肿瘤细胞的起源。生物发光和Ki67 IHC提示该模型内肿瘤扩散。在建模的肿瘤中,荧光素酶的表达可以维持长达100天。结论:为短期原发性肿瘤培养和异种移植建模开发的技术为评估HNSCC对标准疗法和新疗法的反应提供了一种低成本且易于处理的模型。从原发性HNSCC形成人体内肿瘤的成功率很高,表明该模型中肿瘤生长的选择压力可能小于建立细胞系时观察到的压力。生物发光成像为评估肿瘤的生长提供了有用的工具,可以扩展以测量建模肿瘤对治疗的反应。该模型可以适合于其他原发性肿瘤类型的异种移植模型生长。

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