Porcine-human glioma xenograft model. Immunosuppression and model reproducibility
Background: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they hav...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cancer Treatment and Research Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294224000017 |
| _version_ | 1797319451855552512 |
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| author | P.Jack Hoopes Armin D. Tavakkoli Karen A. Moodie Kirk J. Maurer Kenneth R. Meehan Diana J. Wallin Ethan Aulwes Kayla E.A. Duval Kristen L. Chen Margaret A.Crary -Burney Chen Li Xiaoyao Fan Linton T. Evans Keith D. Paulsen |
| author_facet | P.Jack Hoopes Armin D. Tavakkoli Karen A. Moodie Kirk J. Maurer Kenneth R. Meehan Diana J. Wallin Ethan Aulwes Kayla E.A. Duval Kristen L. Chen Margaret A.Crary -Burney Chen Li Xiaoyao Fan Linton T. Evans Keith D. Paulsen |
| author_sort | P.Jack Hoopes |
| collection | DOAJ |
| description | Background: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. Methods: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. Results: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. Conclusion: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging. |
| first_indexed | 2024-03-08T04:07:05Z |
| format | Article |
| id | doaj.art-ed4ebadcd68c4ee08c9a65edfba55139 |
| institution | Directory Open Access Journal |
| issn | 2468-2942 |
| language | English |
| last_indexed | 2024-03-08T04:07:05Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj.art-ed4ebadcd68c4ee08c9a65edfba551392024-02-09T04:48:53ZengElsevierCancer Treatment and Research Communications2468-29422024-01-0138100789Porcine-human glioma xenograft model. Immunosuppression and model reproducibilityP.Jack Hoopes0Armin D. Tavakkoli1Karen A. Moodie2Kirk J. Maurer3Kenneth R. Meehan4Diana J. Wallin5Ethan Aulwes6Kayla E.A. Duval7Kristen L. Chen8Margaret A.Crary -Burney9Chen Li10Xiaoyao Fan11Linton T. Evans12Keith D. Paulsen13Geisel School of Medicine, Dartmouth College, Hanover, NH, USA; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA; Center for Comparative Medicine and Research, Dartmouth College, Lebanon, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USA; Corresponding author.Geisel School of Medicine, Dartmouth College, Hanover, NH, USACenter for Comparative Medicine and Research, Dartmouth College, Lebanon, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USACenter for Comparative Medicine and Research, Dartmouth College, Lebanon, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USAGeisel School of Medicine, Dartmouth College, Hanover, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USADartmouth Cancer Center, Lebanon, NH, USAGeisel School of Medicine, Dartmouth College, Hanover, NH, USAThayer School of Engineering, Dartmouth College, Hanover, NH, USAThayer School of Engineering, Dartmouth College, Hanover, NH, USAGeisel School of Medicine, Dartmouth College, Hanover, NH, USA; Center for Comparative Medicine and Research, Dartmouth College, Lebanon, NH, USAThayer School of Engineering, Dartmouth College, Hanover, NH, USAThayer School of Engineering, Dartmouth College, Hanover, NH, USAGeisel School of Medicine, Dartmouth College, Hanover, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USAGeisel School of Medicine, Dartmouth College, Hanover, NH, USA; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA; Dartmouth Cancer Center, Lebanon, NH, USABackground: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. Methods: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. Results: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. Conclusion: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.http://www.sciencedirect.com/science/article/pii/S2468294224000017Porcine Glioma ModelImmunosuppressionImage Guided NeurosurgeryBrain Shift |
| spellingShingle | P.Jack Hoopes Armin D. Tavakkoli Karen A. Moodie Kirk J. Maurer Kenneth R. Meehan Diana J. Wallin Ethan Aulwes Kayla E.A. Duval Kristen L. Chen Margaret A.Crary -Burney Chen Li Xiaoyao Fan Linton T. Evans Keith D. Paulsen Porcine-human glioma xenograft model. Immunosuppression and model reproducibility Cancer Treatment and Research Communications Porcine Glioma Model Immunosuppression Image Guided Neurosurgery Brain Shift |
| title | Porcine-human glioma xenograft model. Immunosuppression and model reproducibility |
| title_full | Porcine-human glioma xenograft model. Immunosuppression and model reproducibility |
| title_fullStr | Porcine-human glioma xenograft model. Immunosuppression and model reproducibility |
| title_full_unstemmed | Porcine-human glioma xenograft model. Immunosuppression and model reproducibility |
| title_short | Porcine-human glioma xenograft model. Immunosuppression and model reproducibility |
| title_sort | porcine human glioma xenograft model immunosuppression and model reproducibility |
| topic | Porcine Glioma Model Immunosuppression Image Guided Neurosurgery Brain Shift |
| url | http://www.sciencedirect.com/science/article/pii/S2468294224000017 |
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