The Center for Childhood Cancer, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA.
Neuro Oncol. 2012 Apr;14(4):459-70. doi: 10.1093/neuonc/nor231. Epub 2012 Feb 3.
Medulloblastoma is the most common malignant brain tumor of childhood. Although the survival rate of afflicted children has improved considerably over the past several years, a subset of these patients will present with disseminated disease and face a much bleaker prognosis. In addition, patients may present with disseminated disease at recurrence. We previously demonstrated the efficacy of a recombinant oncolytic measles virus (MV) to treat localized medulloblastoma in a mouse xenograft model. In the present study, we sought to extend our findings to the treatment of disseminated disease. To this end, we developed and characterized a mouse xenograft model of disseminated medulloblastoma using serial bioluminescent imaging techniques in combination with histopathological examination. Mice injected with medulloblastoma cells into their right lateral ventricle showed tumor growth in their ventricles and in both intracranial and spinal subarachnoid spaces, closely recapitulating the human disease. Subsequent intraventricular administration of MV resulted in stabilization and shrinkage of the tumor, significantly prolonging the survival of the treated animals, compared with those treated with an inactivated virus. These data demonstrate that oncolytic MV may be of use in treating disseminated medulloblastoma. In addition, our protocol of intraventricular tumor cell injection, followed by bioluminescent imaging coupled with histopathological examination, provides a model for use in evaluating future recombinant oncolytic viruses and other preclinical therapeutic approaches for disseminated medulloblastoma.
髓母细胞瘤是儿童中最常见的恶性脑肿瘤。尽管近年来患病儿童的生存率有了显著提高，但仍有一部分患者会出现弥散性疾病，预后更为严峻。此外，患者在复发时可能也会出现弥散性疾病。我们之前证明了重组溶瘤麻疹病毒（MV）在治疗局部髓母细胞瘤的小鼠异种移植模型中的疗效。在本研究中，我们试图将我们的发现扩展到弥散性疾病的治疗中。为此，我们开发并鉴定了一种使用连续生物发光成像技术结合组织病理学检查的弥散性髓母细胞瘤小鼠异种移植模型。将髓母细胞瘤细胞注射到右侧侧脑室的小鼠表现出脑室以及颅内和脊髓蛛网膜下腔的肿瘤生长，非常类似于人类疾病。随后，脑室内给予 MV 治疗可使肿瘤稳定和缩小，与接受灭活病毒治疗的动物相比，显著延长了治疗动物的存活时间。这些数据表明溶瘤 MV 可能对治疗弥散性髓母细胞瘤有用。此外，我们的脑室肿瘤细胞注射方案，随后进行生物发光成像结合组织病理学检查，为评估未来的重组溶瘤病毒和其他弥散性髓母细胞瘤的临床前治疗方法提供了一个模型。
