Characterization of plasma-derived protoporphyrin-IX-positive extracellular vesicles following 5-ALA use in patients with malignant glioma
| Autor: | Anudeep Yekula, Elizabeth Lansbury, Scott Mordecai, Fred H. Hochberg, Leonora Balaj, Bethany Delcuze, Julia L. Small, Pamela S. Jones, John Tigges, Alain Charest, Caroline M. Ayinon, Bob S. Carter, Ionita Ghiran |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Imaging flow cytometry Male Fluorescence guided surgery Research paper PpIX protoporphyrin IX EV extracellular vesicle Protoporphyrins lcsh:Medicine 5-ALA 5-aminolevulinic acid Tumor Status chemistry.chemical_compound Mice 0302 clinical medicine Malignant gliomas lcsh:R5-920 Photosensitizing Agents Protoporphyrin IX Chemistry Optical Imaging IFC Image flow cytometry General Medicine Glioma Middle Aged Magnetic Resonance Imaging 3. Good health Surgery Computer-Assisted 030220 oncology & carcinogenesis Female lcsh:Medicine (General) Adult Cell Survival Mice Transgenic Extracellular vesicles General Biochemistry Genetics and Molecular Biology sEVs single EVs 03 medical and health sciences Extracellular Vesicles In vivo Cell Line Tumor medicine Animals Humans Liquid biopsy 5-ALA Aged Fluorescent Dyes lcsh:R GBM glioblastoma multiforme medicine.disease In vitro Levulinic Acids FGS fluorescence guided surgery Disease Models Animal 030104 developmental biology Cancer research ISX Image Streamx HBMVEC human brain microvascular endothelial cells |
| Zdroj: | EBioMedicine, Vol 48, Iss, Pp 23-35 (2019) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Summary: Background: Malignant gliomas are rapidly progressive brain tumors with high mortality. Fluorescence guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) provides fluorescent delineation of malignant tissue, which helps achieve maximum safe resection. 5-ALA-based fluorescence is due to preferential accumulation of the fluorophore protoporphyrin-IX (PpIX) in malignant glioma tissue. Additionally, gliomas cells release extracellular vesicles (EVs) which carry biomarkers of disease. Herein, we performed animal and human studies to investigate whether 5-ALA dosed glioma cells, in vitro and in vivo, release PpIX positive EVs in circulation which can be captured and analyzed. Methods: We used imaging flow cytometry (IFC) to characterize PpIX-positive EVs released from 5-ALA-dosed glioma cells, glioma-bearing xenograft models, as well as patients with malignant glioma undergoing FGS. Findings: We first show that glioma cells dosed with 5-ALA release 247-fold higher PpIX positive EVs compared to mock dosed glioma cells. Second, we demonstrate that the plasma of glioma-bearing mice (n = 2) dosed with 5-ALA contain significantly higher levels of circulating PpIX-positive EVs than their pre-dosing background (p = 0.004). Lastly, we also show that the plasma of patients with avidly fluorescent tumors (n = 4) undergoing FGS contain circulating PpIX-positive EVs at levels significantly higher than their pre-dosing background (p = 0.00009) and this rise in signal correlates with enhancing tumor volumes (r 2 = 0.888). Interpretation: Our findings highlight the potential of plasma-derived PpIX-positive EV-based diagnostics for malignant gliomas, offering a novel liquid biopsy platform for confirming and monitoring tumor status. Keywords: Extracellular vesicles, Malignant gliomas, Liquid biopsy, Imaging flow cytometry, 5-ALA, Fluorescence guided surgery |
| Databáze: | OpenAIRE |
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