Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model
Abstract Neuroblastoma accounts for 15% of pediatric cancer deaths, despite multimodal therapy including surgical resection. Current neuroblastoma rodent models are insufficient for studying the impact of surgery and combination treatments, largely due to the small size of mouse models. Human neurob...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47537-3 |
| _version_ | 1797559942924730368 |
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| author | ReidAnn E. Sever Lauren Taylor Rosenblum Miguel Reyes-Múgica W. Barry Edwards Marcus M. Malek Gary Kohanbash |
| author_facet | ReidAnn E. Sever Lauren Taylor Rosenblum Miguel Reyes-Múgica W. Barry Edwards Marcus M. Malek Gary Kohanbash |
| author_sort | ReidAnn E. Sever |
| collection | DOAJ |
| description | Abstract Neuroblastoma accounts for 15% of pediatric cancer deaths, despite multimodal therapy including surgical resection. Current neuroblastoma rodent models are insufficient for studying the impact of surgery and combination treatments, largely due to the small size of mouse models. Human neuroblastoma SK-N-BE(2) cells were injected into the left adrenal gland of 5–6-week-old RNU homozygous nude rats. Rats were either monitored by MRI until humane endpoint was reached or after 5 weeks underwent operative tumor resection, followed by monitoring for recurrence and survival. Following neuroblastoma cell implantation, the majority of tumors grew to greater than 5000 mm3 within 5.5–6.5 weeks, meeting the humane endpoint. Surgical resection was successfully done in 8 out of 9 rats, extending survival following tumor implantation from a median of 42 days to 78 days (p < 0.005). Pathology was consistent with human neuroblastoma, showing small round blue cell tumors with Homer-Wright rosettes, high mitoses and karyorrhectic index, and strong PHOX2B staining. Thus, we have established a novel orthotopic xenograft rat model of neuroblastoma and demonstrated increased survival of rats after surgical tumor resection. This model can be used for the development of surgical techniques, such as the use of intraoperative molecular imaging or assessment of combination therapies that include surgery. |
| first_indexed | 2024-03-10T17:53:23Z |
| format | Article |
| id | doaj.art-f665f394d9b240ff931ce6f30c56f2e1 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:53:23Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f665f394d9b240ff931ce6f30c56f2e12023-11-20T09:18:34ZengNature PortfolioScientific Reports2045-23222023-11-011311910.1038/s41598-023-47537-3Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft modelReidAnn E. Sever0Lauren Taylor Rosenblum1Miguel Reyes-Múgica2W. Barry Edwards3Marcus M. Malek4Gary Kohanbash5Department of Neurological Surgery, University of PittsburghDepartment of Surgery, University of PittsburghDepartment of Pathology, UPMC Children’s Hospital of PittsburghDepartment of Biochemistry, University of MissouriDepartment of Surgery, University of PittsburghDepartment of Neurological Surgery, University of PittsburghAbstract Neuroblastoma accounts for 15% of pediatric cancer deaths, despite multimodal therapy including surgical resection. Current neuroblastoma rodent models are insufficient for studying the impact of surgery and combination treatments, largely due to the small size of mouse models. Human neuroblastoma SK-N-BE(2) cells were injected into the left adrenal gland of 5–6-week-old RNU homozygous nude rats. Rats were either monitored by MRI until humane endpoint was reached or after 5 weeks underwent operative tumor resection, followed by monitoring for recurrence and survival. Following neuroblastoma cell implantation, the majority of tumors grew to greater than 5000 mm3 within 5.5–6.5 weeks, meeting the humane endpoint. Surgical resection was successfully done in 8 out of 9 rats, extending survival following tumor implantation from a median of 42 days to 78 days (p < 0.005). Pathology was consistent with human neuroblastoma, showing small round blue cell tumors with Homer-Wright rosettes, high mitoses and karyorrhectic index, and strong PHOX2B staining. Thus, we have established a novel orthotopic xenograft rat model of neuroblastoma and demonstrated increased survival of rats after surgical tumor resection. This model can be used for the development of surgical techniques, such as the use of intraoperative molecular imaging or assessment of combination therapies that include surgery.https://doi.org/10.1038/s41598-023-47537-3 |
| spellingShingle | ReidAnn E. Sever Lauren Taylor Rosenblum Miguel Reyes-Múgica W. Barry Edwards Marcus M. Malek Gary Kohanbash Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model Scientific Reports |
| title | Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| title_full | Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| title_fullStr | Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| title_full_unstemmed | Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| title_short | Survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| title_sort | survival following complete resection of neuroblastoma in novel orthotopic rat xenograft model |
| url | https://doi.org/10.1038/s41598-023-47537-3 |
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