ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia.
Malignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5536352?pdf=render |
| _version_ | 1819010431150194688 |
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| author | Carl J Fisher Carolyn Niu Warren Foltz Yonghong Chen Elena Sidorova-Darmos James H Eubanks Lothar Lilge |
| author_facet | Carl J Fisher Carolyn Niu Warren Foltz Yonghong Chen Elena Sidorova-Darmos James H Eubanks Lothar Lilge |
| author_sort | Carl J Fisher |
| collection | DOAJ |
| description | Malignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild hypothermia leads to increased glioma cell kill while protecting normal neuronal structures.Photosensitizer accumulation and PDT efficacy in vitro were quantified in various glioma cell lines, primary rat neurons, and astrocytes. In vivo studies were carried out in healthy brain and RG2 glioma of naïve Fischer rats. Hypothermia was induced at 1 hour pre- to 2 hours post-PDT, with ALA-PpIX accumulation and PDT treatments effects on tumor and normal brain PDT quantified using optical spectroscopy, histology, immunohistochemistry, MRI, and survival studies, respectively.In vitro studies demonstrated significantly improved post-PDT survival in primary rat neuronal cells. Rat in vivo studies confirmed a neuroprotective effect to hypothermia following PpIX mediated PDT by T2 mapping at day 10, reflecting edema/inflammation volume reduction. Mild hypothermia increased PpIX fluorescence in tumors five-fold, and the median post-PDT rat survival time (8.5 days normothermia; 14 days hypothermia). Histology and immunohistochemistry show close to complete cellular protection in normal brain structures under hypothermia.The benefits of hypothermia on both normal neuronal tissue as well as increased PpIX fluorescence and RG2 induced rat survival strongly suggest a role for hypothermia in photonics-based surgical techniques, and that a hypothermic intervention could lead to considerable patient outcome improvements. |
| first_indexed | 2024-12-21T01:12:09Z |
| format | Article |
| id | doaj.art-577786159afc4c8dba1873a8f93c8969 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:12:09Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-577786159afc4c8dba1873a8f93c89692022-12-21T19:20:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018165410.1371/journal.pone.0181654ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia.Carl J FisherCarolyn NiuWarren FoltzYonghong ChenElena Sidorova-DarmosJames H EubanksLothar LilgeMalignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild hypothermia leads to increased glioma cell kill while protecting normal neuronal structures.Photosensitizer accumulation and PDT efficacy in vitro were quantified in various glioma cell lines, primary rat neurons, and astrocytes. In vivo studies were carried out in healthy brain and RG2 glioma of naïve Fischer rats. Hypothermia was induced at 1 hour pre- to 2 hours post-PDT, with ALA-PpIX accumulation and PDT treatments effects on tumor and normal brain PDT quantified using optical spectroscopy, histology, immunohistochemistry, MRI, and survival studies, respectively.In vitro studies demonstrated significantly improved post-PDT survival in primary rat neuronal cells. Rat in vivo studies confirmed a neuroprotective effect to hypothermia following PpIX mediated PDT by T2 mapping at day 10, reflecting edema/inflammation volume reduction. Mild hypothermia increased PpIX fluorescence in tumors five-fold, and the median post-PDT rat survival time (8.5 days normothermia; 14 days hypothermia). Histology and immunohistochemistry show close to complete cellular protection in normal brain structures under hypothermia.The benefits of hypothermia on both normal neuronal tissue as well as increased PpIX fluorescence and RG2 induced rat survival strongly suggest a role for hypothermia in photonics-based surgical techniques, and that a hypothermic intervention could lead to considerable patient outcome improvements.http://europepmc.org/articles/PMC5536352?pdf=render |
| spellingShingle | Carl J Fisher Carolyn Niu Warren Foltz Yonghong Chen Elena Sidorova-Darmos James H Eubanks Lothar Lilge ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. PLoS ONE |
| title | ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. |
| title_full | ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. |
| title_fullStr | ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. |
| title_full_unstemmed | ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. |
| title_short | ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. |
| title_sort | ala ppix mediated photodynamic therapy of malignant gliomas augmented by hypothermia |
| url | http://europepmc.org/articles/PMC5536352?pdf=render |
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