Sweeney Kieron J, Jarzabek Monika A, Dicker Patrick, O'Brien Donncha F, Callanan John J, Byrne Annette T, Prehn Jochen H M
National Centre for Neurosurgery, Beaumont Hospital, Dublin, Ireland; Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Centre for Systems Medicine, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
J Neurosci Methods. 2014 Aug 15;233:99-104. doi: 10.1016/j.jneumeth.2014.05.006. Epub 2014 Jun 18.
Glioblastoma (GBM) is the most common and malignant primary brain tumour having a median survival of just 12-18 months following standard therapy protocols. Local recurrence, post-resection and adjuvant therapy occurs in most cases.
U87MG-luc2-bearing GBM xenografts underwent 4.5mm craniectomy and tumour resection using microsurgical techniques. The cranial defect was repaired using a novel modified cranial window technique consisting of a circular microscope coverslip held in place with glue.
Immediate post-operative bioluminescence imaging (BLI) revealed a gross total resection rate of 75%. At censor point 4 weeks post-resection, Kaplan-Meier survival analysis revealed 100% survival in the surgical group compared to 0% in the non-surgical cohort (p=0.01). No neurological defects or infections in the surgical group were observed. GBM recurrence was reliably imaged using facile non-invasive optical bioluminescence (BLI) imaging with recurrence observed at week 4.
COMPARISON WITH EXISTING METHOD(S): For the first time, we have used a novel cranial defect repair method to extend and improve intracranial surgical resection methods for application in translational GBM rodent disease models. Combining BLI and the cranial window technique described herein facilitates non-invasive serial imaging follow-up.
Within the current context we have developed a robust methodology for establishing a clinically relevant imageable GBM surgical resection model that appropriately mimics GBM recurrence post resection in patients.
胶质母细胞瘤(GBM)是最常见且恶性程度最高的原发性脑肿瘤,按照标准治疗方案,其平均生存期仅为12 - 18个月。大多数病例会出现局部复发、切除术后复发以及辅助治疗后复发的情况。
对携带U87MG - luc2的GBM异种移植瘤进行4.5毫米颅骨切除术,并使用显微外科技术切除肿瘤。颅骨缺损采用一种新型改良颅窗技术进行修复,该技术由用胶水固定到位的圆形显微镜盖玻片组成。
术后即刻进行的生物发光成像(BLI)显示,肿瘤全切除率为75%。在切除术后4周的审查点,Kaplan - Meier生存分析显示,手术组的生存率为100%,而非手术组为0%(p = 0.01)。手术组未观察到神经功能缺损或感染情况。使用简便的非侵入性光学生物发光(BLI)成像能够可靠地对GBM复发进行成像,在第4周观察到了复发情况。
我们首次使用了一种新型颅骨缺损修复方法来扩展和改进颅内手术切除方法,并将其应用于转化性GBM啮齿动物疾病模型。将BLI与本文所述的颅窗技术相结合,便于进行非侵入性的连续成像随访。
在当前背景下,我们开发了一种强大的方法,用于建立一个与临床相关的、可成像的GBM手术切除模型,该模型能恰当地模拟患者切除术后GBM的复发情况。