Evidence map›Paper›PMID 31628025›Full record

ArticleEBioMedicine2019

Characterization of plasma-derived protoporphyrin-IX-positive extracellular vesicles following 5-ALA use in patients with malignant glioma.

Pamela S Jones, Anudeep Yekula, Elizabeth Lansbury, Julia L Small, Caroline Ayinon, Scott Mordecai, Fred H Hochberg, John Tigges, Bethany Delcuze, Alain Charest and 3 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 36 citations in OpenAlex.

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  16. Exosome-based liquid biopsies in cancer: opportunities and challenges.Annals of oncology : official journal of the European Society for Medical Oncology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Pamela S JonesDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Anudeep YekulaDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Elizabeth LansburyDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Julia L SmallDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Caroline AyinonDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Scott MordecaiDepartment of Pathology, Flow Cytometry Core, Massachusetts General Hospital, Boston, MA, United States.
Fred H HochbergScintillon Institute, La Jolla, CA, United States.
John TiggesFlow Cytometry Core, Beth Israel Deaconess Medical Center, Boston, MA, United States.
Bethany DelcuzeDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Alain CharestDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Ionita GhiranDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Leonora BalajDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: balaj.leonora@mgh.harvard.edu.
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: bcarter@mgh.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USMassachusetts General Hospital · USScintillon Institute · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KAHN, BARBARA B. · 2000 to 2019
$31.4M
The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, CHIOCCA, E. ANTONIO · 1996 to 2021
$30.9M
Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
Liquid Biopsy for treatment stratification of IDH1.R132H and EGFRvIII mutant gliomasU01CA230697 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CARTER, BOB S, SKOG, JOHAN · 2018 to 2022
$4.0M
Uncovering exRNA and protein determinants of secreted vesicle heterogeneity by flow cytometric purification of vesicle subsets from cells and plasmaUG3CA241685 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CHAREST, ALAIN, COFFEY, ROBERT J. · 2019 to 2020
$1.0M
ImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595k
A Nikon A1R Confocal Microscope SystemS10RR031563 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BROWN, DENNIS · 2011 to 2011
$561k
NCI NIH HHS K12 CA090354NCI NIH HHS P01 CA069246NCI NIH HHS U01 CA230697NCI NIH HHS UG3 CA241685NCRR NIH HHS S10 RR031563NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIH HHS S10 OD012027
6 · The paper itself

Abstract

backgroundMalignant 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.

methodsWe 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.

findingsWe 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

interpretationOur 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.

Indexed as

AdultAgedAminolevulinic AcidAnimalsCell Line, TumorCell SurvivalDisease Models, AnimalExtracellular VesiclesFemaleFluorescent DyesGliomaHumansLevulinic AcidsMagnetic Resonance ImagingMaleMiceAminolevulinic AcidFluorescent DyesLevulinic AcidsPhotosensitizing Agentsprotoporphyrin IXProtoporphyrins5-ALAExtracellular vesiclesFluorescence guided surgeryImaging flow cytometryLiquid biopsyMalignant gliomas

Identifiers

PMID31628025
PMCPMC6838454
OpenAlexW2980742761

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.