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PDTM-19. TUMOUR TREATING FIELDS (TTFIELDS) EXHIBIT EFFICACY ON HIGH-GRADE PAEDIATRIC BRAIN TUMOUR CELL LINES

机译:PDTM-19。高等级小儿脑肿瘤细胞系的肿瘤治疗场(TTFIELDS)展示功效

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摘要

INTRODUCTION The EF-14 trial of the Optune system which utilises Tumour Treating Fields (TTFields) has shown positive results in adult Glioblastoma multiforme (GBM) patients. These results have given strength to the feasibility of TTFields being added to existing chemotherapy and radiation therapy for brain tumour patients. Here we present the data showing the efficacy of TTFields on a panel of paediatric GBM, Medulloblastoma and Ependymoma cell lines. METHODS The Inovitro system is the laboratory testing system used to develop the clinically approved Optune system. Inovitro was used to deliver TTFields over a range of clinically relevant frequencies (100-400kHz) to our panel of high grade paediatric cell lines. The effects of TTFields on cell viability was assessed using metabolic viability tests, and cell cycle analysis was performed using flow cytometry. Gene expression analysis was performed via Affymetrix microarray. RESULTS TTFields have significant efficacy on all of our cell lines, and the extent of this is dependent upon frequency. Cells treated with TTFields were re-seeded and growth rates were compared to control cells. The treated cells experienced up to 75% slower growth rates following treatment. Cell cycle analysis revealed that TTFields treated cells have significantly greater levels of G2/M phase accumulation relative to control, and this coincides with previous observations in adult GBM cell lines. The efficacy of TTFields may be significantly increased with the addition of the mitotic inhibitor, paclitaxel. The effects of TTFields treatment on gene expression will be discussed. CONCLUSIONS TTFields treatment has demonstrated efficacy against our panel of paediatric GBM, Medulloblastoma and Ependymoma cell lines - further investigation is warranted so that this may be translated into the clinic.
机译:简介使用肿瘤治疗场(TTFields)的Optune系统的EF-14试验在成年成年胶质母细胞瘤(GBM)患者中显示出积极的结果。这些结果增强了将TTFields添加到现有的针对脑肿瘤患者的化学疗法和放射疗法中的可行性。在这里,我们提供数据显示TTFields在一组小儿GBM,髓母细胞瘤和室管膜瘤细胞系中的功效。方法Inovitro系统是用于开发临床认可的Optune系统的实验室测试系统。 Inovitro被用于将一系列临床相关频率(100-400kHz)的TTFields提供给我们的高级儿科细胞系。使用代谢活力测试评估TTFields对细胞活力的影响,并使用流式细胞仪进行细胞周期分析。通过Affymetrix微阵列进行基因表达分析。结果TTFields在我们所有的细胞系中都具有显着的功效,其程度取决于频率。重新接种TTFields处理的细胞,并将生长速率与对照细胞进行比较。处理后,处理过的细胞的生长速度最多可降低75%。细胞周期分析表明,与对照相比,TTFields处理的细胞具有更高水平的G2 / M相积累,这与成年GBM细胞系中先前的观察结果一致。添加有丝分裂抑制剂紫杉醇可显着提高TTFields的功效。将讨论TTFields处理对基因表达的影响。结论TTFields治疗已证明对我们的小儿GBM,髓母细胞瘤和室管膜瘤细胞系有效-需要进一步研究,以便将其转化为临床药物。

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