Optimized creation of glioblastoma patient derived xenografts for use in preclinical studies.
Optimized creation of glioblastoma patient derived xenografts for use in preclinical studies.
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DOI：
10.1186/s12967-017-1128-5
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发表时间：
2017-02-09
影响因子：
7.4
通讯作者：
Linnebacher M
中科院分区：
文献类型：
--
作者：
William D;Mullins CS;Schneider B;Orthmann A;Lamp N;Krohn M;Hoffmann A;Classen CF;Linnebacher M
多形性胶质母细胞瘤（GBM）是成人中最常见和最致命的脑肿瘤，突出了对新治疗策略的需求。患者来源的异种移植物（PDX）是完成这一任务的有价值的工具。通过皮下植入GBM组织建立PDX。比较了NMRI Foxn 1 nu和NOD/SCID之间以及新鲜和冷冻保存组织之间的植入成功率。对建立的PDX进行组织学和分子学分析。用不同的药物对五种PDX进行实验性处理，以评估其用于临床前药物测试的潜力。在NMRI Foxn 1 nu小鼠中，尝试对36例连续GBM病例建立PDX，总体成功率为22.2%。在直接比较中（n = 10例），未观察到新鲜或冷冻保存（20-1057天）组织之间的差异。此外，NOD/SCID小鼠（38.8%）的移植直接优于NMRI Foxn 1 nu小鼠（27.7%）（n = 18例）。PDX的分子数据和组织学与原发性GBM相当。实验性治疗揭示了对几种临床相关药物敏感性的个体差异。使用有活力的冷冻GBM组织允许更方便的工作流程而不损失效率。与NMRI Foxn 1 nu小鼠相比，NOD/SCID小鼠似乎更适合于肿瘤组织的初始植入。本文的在线版本（doi：10.1186/s12967-017-1128-5）包含补充材料，可供授权用户使用。
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Patient derived xenografts (PDX) represent a valuable tool to accomplish this task. PDX were established by implanting GBM tissue subcutaneously. Engraftment success was compared between NMRI Foxn1nu and NOD/SCID as well as between fresh and cryopreserved tissue. Established PDX were analyzed histologically and molecularly. Five PDX were experimentally treated with different drugs to assess their potential for preclinical drug testing. Establishment of PDX was attempted for 36 consecutive GBM cases with an overall success rate of 22.2% in NMRI Foxn1nu mice. No difference was observed between fresh or cryopreserved (20–1057 days) tissue in direct comparison (n = 10 cases). Additionally, engraftment was better in NOD/SCID mice (38.8%) directly compared to NMRI Foxn1nu mice (27.7%) (n = 18 cases). Molecular data and histology of the PDX compare well to the primary GBM. The experimental treatment revealed individual differences in the sensitivity towards several clinically relevant drugs. The use of vitally frozen GBM tissue allows a more convenient workflow without efficiency loss. NOD/SCID mice appear to be better suited for initial engraftment of tumor tissue compared to NMRI Foxn1nu mice. The online version of this article (doi:10.1186/s12967-017-1128-5) contains supplementary material, which is available to authorized users.