Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 459-470 |
| Number of pages | 12 |
| Journal | Neuro-Oncology |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2012 |
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Keywords
- bioluminescence
- dissemination
- measles virus
- medulloblastoma
- oncolytic virus
ASJC Scopus subject areas
- Cancer Research
- Oncology
- Clinical Neurology
Cite this
Oncolytic measles virus prolongs survival in a murine model of cerebral spinal fluiddisseminated medulloblastoma. / Studebaker, Adam W.; Hutzen, Brian; Pierson, Christopher R.; Russell, Stephen J; Galanis, Evanthia; Raffel, Corey.
In: Neuro-Oncology, Vol. 14, No. 4, 04.2012, p. 459-470.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oncolytic measles virus prolongs survival in a murine model of cerebral spinal fluiddisseminated medulloblastoma
AU - Studebaker, Adam W.
AU - Hutzen, Brian
AU - Pierson, Christopher R.
AU - Russell, Stephen J
AU - Galanis, Evanthia
AU - Raffel, Corey
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - bioluminescence
KW - dissemination
KW - measles virus
KW - medulloblastoma
KW - oncolytic virus
UR - http://www.scopus.com/inward/record.url?scp=84859521436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859521436&partnerID=8YFLogxK
U2 - 10.1093/neuonc/nor231
DO - 10.1093/neuonc/nor231
M3 - Article
C2 - 22307474
AN - SCOPUS:84859521436
VL - 14
SP - 459
EP - 470
JO - Neuro-Oncology
JF - Neuro-Oncology
SN - 1522-8517
IS - 4
ER -