Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model
Abstract The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 gliob...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79465-x |
| _version_ | 1818716586303815680 |
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| author | Masahiro Maeyama Kazuhiro Tanaka Masamitsu Nishihara Yasuhiro Irino Masakazu Shinohara Hiroaki Nagashima Hirotomo Tanaka Satoshi Nakamizo Mitsuru Hashiguchi Yuichi Fujita Masaaki Kohta Eiji Kohmura Takashi Sasayama |
| author_facet | Masahiro Maeyama Kazuhiro Tanaka Masamitsu Nishihara Yasuhiro Irino Masakazu Shinohara Hiroaki Nagashima Hirotomo Tanaka Satoshi Nakamizo Mitsuru Hashiguchi Yuichi Fujita Masaaki Kohta Eiji Kohmura Takashi Sasayama |
| author_sort | Masahiro Maeyama |
| collection | DOAJ |
| description | Abstract The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM. |
| first_indexed | 2024-12-17T19:21:37Z |
| format | Article |
| id | doaj.art-942f1c84e6974655a4b6ecb648c82d2a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T19:21:37Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-942f1c84e6974655a4b6ecb648c82d2a2022-12-21T21:35:30ZengNature PortfolioScientific Reports2045-23222021-01-0111111110.1038/s41598-020-79465-xMetabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse modelMasahiro Maeyama0Kazuhiro Tanaka1Masamitsu Nishihara2Yasuhiro Irino3Masakazu Shinohara4Hiroaki Nagashima5Hirotomo Tanaka6Satoshi Nakamizo7Mitsuru Hashiguchi8Yuichi Fujita9Masaaki Kohta10Eiji Kohmura11Takashi Sasayama12Department of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Nishi-Kobe Medical CenterDivision of Evidence-Based Laboratory Medicine, Kobe University Graduate School of MedicineIntegrated Center for Mass Spectrometry, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Massachusetts General Hospital Research InstituteDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineAbstract The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.https://doi.org/10.1038/s41598-020-79465-x |
| spellingShingle | Masahiro Maeyama Kazuhiro Tanaka Masamitsu Nishihara Yasuhiro Irino Masakazu Shinohara Hiroaki Nagashima Hirotomo Tanaka Satoshi Nakamizo Mitsuru Hashiguchi Yuichi Fujita Masaaki Kohta Eiji Kohmura Takashi Sasayama Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model Scientific Reports |
| title | Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model |
| title_full | Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model |
| title_fullStr | Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model |
| title_full_unstemmed | Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model |
| title_short | Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model |
| title_sort | metabolic changes and anti tumor effects of a ketogenic diet combined with anti angiogenic therapy in a glioblastoma mouse model |
| url | https://doi.org/10.1038/s41598-020-79465-x |
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