A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease.
A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease.
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DOI：
10.3389/fonc.2023.1105395
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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弥漫性中线胶质瘤是一种侵袭性强、转移性强的小儿中枢神经系统肿瘤。随着原发性肿瘤的局部治疗的改善，转移性疾病正在成为治疗中更重要的因素。我们假设我们可以通过DMG患者来源的异种移植物（PDX）模型来模拟颅脊髓照射（CSI），并且CSI将限制转移性肿瘤。我们使用BT245鼠原位DMG PDX模型进行这项工作。我们开发了一种方案和专门的平台，以提供颅脊髓照射（CSI）（4戈伊x2天）和脑桥加强（4戈伊x2天），并通过病理学、生物发光和MRI将转移性疾病与仅接受局灶性辐射（4戈伊x4天）或无辐射治疗的小鼠进行比较。与仅接受脑桥辐射或不接受辐射的小鼠相比，接受CSI加加强的小鼠通过生物发光、MRI和病理学显示出最小的脊髓和脑软脑膜转移性疾病。在DMG PDX模型中，与局灶性辐射相比，CSI+加强使肿瘤扩散最小化。通过将有效的DMG治疗扩展到整个轴突，CSI有潜力作为DMG联合多模式治疗的关键组成部分，一旦新疗法明确证明改善了局部控制，则可实现长期生存。
Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor. We used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation. Mice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation. In a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control.
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DOI：
10.1158/1078-0432.ccr-18-1345
发表时间：
2018-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Panditharatna E;Kilburn LB;Aboian MS;Kambhampati M;Gordish-Dressman H;Magge SN;Gupta N;Myseros JS;Hwang EI;Kline C;Crawford JR;Warren KE;Cha S;Liang WS;Berens ME;Packer RJ;Resnick AC;Prados M;Mueller S;Nazarian J
通讯作者：
Nazarian J
影响因子：
3.9
作者：
Sethi, Rajni;Allen, Jeffrey;Narayana, Ashwatha
通讯作者：
Narayana, Ashwatha
影响因子：
4.7
作者：
Green, Adam L.;Kieran, Mark W.
通讯作者：
Kieran, Mark W.
影响因子：
16.6
作者：
Harutyunyan, Ashot S.;Krug, Brian;Majewski, Jacek
通讯作者：
Majewski, Jacek
影响因子：
15.9
作者：
Pierce, Angela M.;Witt, Davis A.;Griesinger, Andrea M.
通讯作者：
Griesinger, Andrea M.