TY - JOUR
T1 - Efficacy of vincristine administered via convection-enhanced delivery in a rodent brainstem tumor model documented by bioluminescence imaging
AU - Xi, Guifa
AU - Rajaram, Veena
AU - Mania-Farnell, Babara
AU - Mayanil, Chandra S.
AU - Soares, Marcelo B.
AU - Tomita, Tadanori
AU - Goldman, Stewart
N1 - Funding Information:
Acknowledgments This project was supported by the Rory David Deutsch Foundation, the Neuro-Oncology Research Foundation of Children’s Memorial Hospital, and the Dr. Ralph and Marian C. Falk Medical Research Trust. (All Chicago, IL, USA). We thank practice manager of neurosurgical department Sana Abbed for her kindly organizing for this project and Dr. Jose Hernandez for his help in the animal housing. We also acknowledge the Department of Pathology and Laboratory Medicine, Children’s Memorial Hospital, Chicago, IL, USA and all the members of the Soares Laboratory (Cancer Biology and Epigenomics Program, Children’s Memorial Research Center) for their technical advice.
PY - 2012/4
Y1 - 2012/4
N2 - Purpose: Brain stem gliomas account for 20% of childhood brain tumors. Presently, there is no effective treatment for these tumors, and the prognosis remains poor. One reason for this is that chemotherapeutic drugs cannot cross the blood-brain barrier. In this study, we used a rodent brainstem tumor model, monitored both qualitatively and quantitatively, to examine the effectiveness of vincristine (VCR) administered via convection-enhanced delivery (CED). Methods: C6 rat glioblastoma cells, transduced with an oncoretroviral plasmid containing a luciferase coding sequence, were inoculated into Fischer 344 rat brainstems. Tumor growth was monitored by bioluminescence intensity (BLI), and tumor volume was calculated from serial histopathologic sections. Therapeutic efficacy of VCR delivered via CED was assessed. Intravenous (I.V.) and intraperitoneal (I.P.) drug administration were used as a comparison for CED efficacy. Results: BLI monitoring revealed progressive tumor growth in inoculated rats. Symptoms caused by tumor burden were evident 16-18 days after inoculation. BLI correlated quantitatively with tumor volume (r 2=0.9413), established by histopathological analysis of tumor growth within the pons. VCR administered through CED was more effective than I.V. or I.P. administration in reducing tumor size and increasing survival times. TUNEL assay results suggest that VCR induced glioblastoma cell apoptosis. Conclusions: VCR administered by CED was effective in reducing tumors and prolonging survival time.
AB - Purpose: Brain stem gliomas account for 20% of childhood brain tumors. Presently, there is no effective treatment for these tumors, and the prognosis remains poor. One reason for this is that chemotherapeutic drugs cannot cross the blood-brain barrier. In this study, we used a rodent brainstem tumor model, monitored both qualitatively and quantitatively, to examine the effectiveness of vincristine (VCR) administered via convection-enhanced delivery (CED). Methods: C6 rat glioblastoma cells, transduced with an oncoretroviral plasmid containing a luciferase coding sequence, were inoculated into Fischer 344 rat brainstems. Tumor growth was monitored by bioluminescence intensity (BLI), and tumor volume was calculated from serial histopathologic sections. Therapeutic efficacy of VCR delivered via CED was assessed. Intravenous (I.V.) and intraperitoneal (I.P.) drug administration were used as a comparison for CED efficacy. Results: BLI monitoring revealed progressive tumor growth in inoculated rats. Symptoms caused by tumor burden were evident 16-18 days after inoculation. BLI correlated quantitatively with tumor volume (r 2=0.9413), established by histopathological analysis of tumor growth within the pons. VCR administered through CED was more effective than I.V. or I.P. administration in reducing tumor size and increasing survival times. TUNEL assay results suggest that VCR induced glioblastoma cell apoptosis. Conclusions: VCR administered by CED was effective in reducing tumors and prolonging survival time.
KW - Bioluminescence
KW - Brainstem tumor
KW - Convection-enhanced delivery
KW - Rodent model
KW - Vincristine
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U2 - 10.1007/s00381-012-1690-3
DO - 10.1007/s00381-012-1690-3
M3 - Article
C2 - 22282078
AN - SCOPUS:84859855434
SN - 0256-7040
VL - 28
SP - 565
EP - 574
JO - Child's Nervous System
JF - Child's Nervous System
IS - 4
ER -