OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera
Current therapies for high-grade gliomas, particularly glioblastomas (GBM), do not extend patient survival beyond 16–22 months. OKN-007 (OKlahoma Nitrone 007), which is currently in phase II (multi-institutional) clinical trials for GBM patients, and has demonstrated efficacy in several rodent and h...
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MDPI AG
2022-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/12/1/100 |
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| author | Rheal A. Towner James Hocker Nataliya Smith Debra Saunders James Battiste Jay Hanas |
| author_facet | Rheal A. Towner James Hocker Nataliya Smith Debra Saunders James Battiste Jay Hanas |
| author_sort | Rheal A. Towner |
| collection | DOAJ |
| description | Current therapies for high-grade gliomas, particularly glioblastomas (GBM), do not extend patient survival beyond 16–22 months. OKN-007 (OKlahoma Nitrone 007), which is currently in phase II (multi-institutional) clinical trials for GBM patients, and has demonstrated efficacy in several rodent and human xenograft glioma models, shows some promise as an anti-glioma therapeutic, as it affects most aspects of tumorigenesis (tumor cell proliferation, angiogenesis, migration, and apoptosis). Combined with the chemotherapeutic agent temozolomide (TMZ), OKN-007 is even more effective by affecting chemo-resistant tumor cells. In this study, mass spectrometry (MS) methodology ESI-MS, mass peak analysis (Leave One Out Cross Validation (LOOCV) and tandem MS peptide sequence analyses), and bioinformatics analyses (Ingenuity<sup>®</sup> Pathway Analysis (IPA<sup>®</sup>)), were used to identify up- or down-regulated proteins in the blood sera of F98 glioma-bearing rats, that were either untreated or treated with OKN-007. Proteins of interest identified by tandem MS-MS that were decreased in sera from tumor-bearing rats that were either OKN-007-treated or untreated included ABCA2, ATP5B, CNTN2, ITGA3, KMT2D, MYCBP2, NOTCH3, and VCAN. Conversely, proteins of interest in tumor-bearing rats that were elevated following OKN-007 treatment included ABCA6, ADAMTS18, VWA8, MACF1, and LAMA5. These findings, in general, support our previous gene analysis, indicating that OKN-007 may be effective against the ECM. These findings also surmise that OKN-007 may be more effective against oligodendrogliomas, other brain tumors such as medulloblastoma, and possibly other types of cancers. |
| first_indexed | 2024-03-10T01:48:13Z |
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| language | English |
| last_indexed | 2024-03-10T01:48:13Z |
| publishDate | 2022-01-01 |
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| series | Brain Sciences |
| spelling | doaj.art-75237a60d85e4d78984516f9ea8655742023-11-23T13:10:09ZengMDPI AGBrain Sciences2076-34252022-01-0112110010.3390/brainsci12010100OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood SeraRheal A. Towner0James Hocker1Nataliya Smith2Debra Saunders3James Battiste4Jay Hanas5Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAAdvanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USAAdvanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USADepartment of Neurosurgery, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USACurrent therapies for high-grade gliomas, particularly glioblastomas (GBM), do not extend patient survival beyond 16–22 months. OKN-007 (OKlahoma Nitrone 007), which is currently in phase II (multi-institutional) clinical trials for GBM patients, and has demonstrated efficacy in several rodent and human xenograft glioma models, shows some promise as an anti-glioma therapeutic, as it affects most aspects of tumorigenesis (tumor cell proliferation, angiogenesis, migration, and apoptosis). Combined with the chemotherapeutic agent temozolomide (TMZ), OKN-007 is even more effective by affecting chemo-resistant tumor cells. In this study, mass spectrometry (MS) methodology ESI-MS, mass peak analysis (Leave One Out Cross Validation (LOOCV) and tandem MS peptide sequence analyses), and bioinformatics analyses (Ingenuity<sup>®</sup> Pathway Analysis (IPA<sup>®</sup>)), were used to identify up- or down-regulated proteins in the blood sera of F98 glioma-bearing rats, that were either untreated or treated with OKN-007. Proteins of interest identified by tandem MS-MS that were decreased in sera from tumor-bearing rats that were either OKN-007-treated or untreated included ABCA2, ATP5B, CNTN2, ITGA3, KMT2D, MYCBP2, NOTCH3, and VCAN. Conversely, proteins of interest in tumor-bearing rats that were elevated following OKN-007 treatment included ABCA6, ADAMTS18, VWA8, MACF1, and LAMA5. These findings, in general, support our previous gene analysis, indicating that OKN-007 may be effective against the ECM. These findings also surmise that OKN-007 may be more effective against oligodendrogliomas, other brain tumors such as medulloblastoma, and possibly other types of cancers.https://www.mdpi.com/2076-3425/12/1/100OKN-007high-grade-gliomaratblood seramass spectrometry (MS)protein profiles |
| spellingShingle | Rheal A. Towner James Hocker Nataliya Smith Debra Saunders James Battiste Jay Hanas OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera Brain Sciences OKN-007 high-grade-glioma rat blood sera mass spectrometry (MS) protein profiles |
| title | OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera |
| title_full | OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera |
| title_fullStr | OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera |
| title_full_unstemmed | OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera |
| title_short | OKN-007 Alters Protein Expression Profiles in High-Grade Gliomas: Mass Spectral Analysis of Blood Sera |
| title_sort | okn 007 alters protein expression profiles in high grade gliomas mass spectral analysis of blood sera |
| topic | OKN-007 high-grade-glioma rat blood sera mass spectrometry (MS) protein profiles |
| url | https://www.mdpi.com/2076-3425/12/1/100 |
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