Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.
Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which req...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4398547?pdf=render |
| _version_ | 1828236392977661952 |
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| author | Joseph F Georges Xiaowei Liu Jennifer Eschbacher Joshua Nichols Michael A Mooney Anna Joy Robert F Spetzler Burt G Feuerstein Mark C Preul Trent Anderson Hao Yan Peter Nakaji |
| author_facet | Joseph F Georges Xiaowei Liu Jennifer Eschbacher Joshua Nichols Michael A Mooney Anna Joy Robert F Spetzler Burt G Feuerstein Mark C Preul Trent Anderson Hao Yan Peter Nakaji |
| author_sort | Joseph F Georges |
| collection | DOAJ |
| description | Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making. |
| first_indexed | 2024-04-12T20:31:23Z |
| format | Article |
| id | doaj.art-513417a8b4e74bbfab5675f09163d2c7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T20:31:23Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-513417a8b4e74bbfab5675f09163d2c72022-12-22T03:17:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012360710.1371/journal.pone.0123607Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.Joseph F GeorgesXiaowei LiuJennifer EschbacherJoshua NicholsMichael A MooneyAnna JoyRobert F SpetzlerBurt G FeuersteinMark C PreulTrent AndersonHao YanPeter NakajiImproved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.http://europepmc.org/articles/PMC4398547?pdf=render |
| spellingShingle | Joseph F Georges Xiaowei Liu Jennifer Eschbacher Joshua Nichols Michael A Mooney Anna Joy Robert F Spetzler Burt G Feuerstein Mark C Preul Trent Anderson Hao Yan Peter Nakaji Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. PLoS ONE |
| title | Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. |
| title_full | Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. |
| title_fullStr | Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. |
| title_full_unstemmed | Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. |
| title_short | Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model. |
| title_sort | use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model |
| url | http://europepmc.org/articles/PMC4398547?pdf=render |
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