Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles
Medulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1129533/full |
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| author | Bohdan J. Soltys Katie B. Grausam Shanta M. Messerli Carleton J. C. Hsia Haotian Zhao Haotian Zhao Haotian Zhao |
| author_facet | Bohdan J. Soltys Katie B. Grausam Shanta M. Messerli Carleton J. C. Hsia Haotian Zhao Haotian Zhao Haotian Zhao |
| author_sort | Bohdan J. Soltys |
| collection | DOAJ |
| description | Medulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic tumor growth was studied in a Sonic Hedgehog transgenic mouse model. PNA treated mice showed an increased lifespan with a mean survival of 95 days (n = 6, P<0.05) compared with 71 days in controls. In primary tumors, proliferation was significantly reduced and differentiation was significantly increased (P<0.001) as shown by Ki-67+ and NeuN+ immunohistochemistry, while cells in spinal cord tumors appeared unaffected. Yet, histochemical analysis of metastatic tumor in spinal cord showed that the mean total number of cells in spinal cord was significantly reduced in mice treated with PNA compared to albumin vehicle (P<0.05). Examination of various levels of the spinal cord showed that PNA treated mice had significantly reduced metastatic cell density in the thoracic, lumbar and sacral spinal cord levels (P<0.05), while cell density in the cervical region was not significantly changed. The mechanism by which PNA may exert these effects on CNS tumors is discussed. |
| first_indexed | 2024-04-09T14:15:10Z |
| format | Article |
| id | doaj.art-5d3d6214982f47ee8192d17ac30f8060 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T14:15:10Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-5d3d6214982f47ee8192d17ac30f80602023-05-05T13:11:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11295331129533Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticlesBohdan J. Soltys0Katie B. Grausam1Shanta M. Messerli2Carleton J. C. Hsia3Haotian Zhao4Haotian Zhao5Haotian Zhao6AntiRadical Therapeutics LLC, Sioux Falls, SD, United StatesCancer Biology and Immunotherapies, Sanford Research, Sioux Falls, SD, United StatesCancer Biology and Immunotherapies, Sanford Research, Sioux Falls, SD, United StatesAntiRadical Therapeutics LLC, Sioux Falls, SD, United StatesCancer Biology and Immunotherapies, Sanford Research, Sioux Falls, SD, United StatesDepartment of Pediatrics, University of South Dakota, Vermillion, SD, United StatesDepartment of Biomedical Sciences, New York Institute of Technology, Old Westbury, NY, United StatesMedulloblastoma is a tumor of the cerebellum that metastasizes to the leptomeninges of the central nervous system (CNS), including to forebrain and to spinal cord. The inhibitory effect of polynitroxylated albumin (PNA), a caged nitroxide nanoparticle, on leptomeningeal dissemination and metastatic tumor growth was studied in a Sonic Hedgehog transgenic mouse model. PNA treated mice showed an increased lifespan with a mean survival of 95 days (n = 6, P<0.05) compared with 71 days in controls. In primary tumors, proliferation was significantly reduced and differentiation was significantly increased (P<0.001) as shown by Ki-67+ and NeuN+ immunohistochemistry, while cells in spinal cord tumors appeared unaffected. Yet, histochemical analysis of metastatic tumor in spinal cord showed that the mean total number of cells in spinal cord was significantly reduced in mice treated with PNA compared to albumin vehicle (P<0.05). Examination of various levels of the spinal cord showed that PNA treated mice had significantly reduced metastatic cell density in the thoracic, lumbar and sacral spinal cord levels (P<0.05), while cell density in the cervical region was not significantly changed. The mechanism by which PNA may exert these effects on CNS tumors is discussed.https://www.frontiersin.org/articles/10.3389/fonc.2023.1129533/fullSonic Hedgehogmedulloblastomametastasisleptomeningeal disseminationhematogenous disseminationnitroxide |
| spellingShingle | Bohdan J. Soltys Katie B. Grausam Shanta M. Messerli Carleton J. C. Hsia Haotian Zhao Haotian Zhao Haotian Zhao Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles Frontiers in Oncology Sonic Hedgehog medulloblastoma metastasis leptomeningeal dissemination hematogenous dissemination nitroxide |
| title | Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| title_full | Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| title_fullStr | Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| title_full_unstemmed | Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| title_short | Inhibition of metastatic brain cancer in Sonic Hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| title_sort | inhibition of metastatic brain cancer in sonic hedgehog medulloblastoma using caged nitric oxide albumin nanoparticles |
| topic | Sonic Hedgehog medulloblastoma metastasis leptomeningeal dissemination hematogenous dissemination nitroxide |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1129533/full |
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