Evidence map›Paper›PMID 39253453›Full record

ArticlebioRxiv : the preprint server for biology2024

Modulation of blood-tumor barrier transcriptional programs improves intra-tumoral drug delivery and potentiates chemotherapy in GBM.

Jorge L Jimenez-Macias, Philippa Vaughn-Beaucaire, Ayush Bharati, Zheyun Xu, Megan Forrest, Jason Hong, Michael Sun, Andrea Schmidt, Jasmine Clark, William Hawkins and 14 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Jorge L Jimenez-MaciasLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Philippa Vaughn-BeaucaireLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Ayush BharatiLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Zheyun XuLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Megan ForrestLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Jason HongLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Michael SunLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Andrea SchmidtLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Jasmine ClarkLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
William HawkinsLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Noe MercadoLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Jacqueline RealLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Kelsey HuntingtonLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Mykola ZdiorukHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Michal O NowickiHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Choi-Fong ChoHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Bin WuCytodigm, Inc, Natick, MA 01760, USA.
Weiyi LiPhosphorex, Inc, Hopkinton, MA 01748, USA.
Theresa LoganPhosphorex, Inc, Hopkinton, MA 01748, USA.
Katherine E ManzSchool of Engineering, Brown University, Providence, RI 02912, USA.
Kurt D PennellSchool of Engineering, Brown University, Providence, RI 02912, USA.
Bogdan I FedelesCenter for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alexander S BrodskyLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
Sean E LawlerLegorreta Cancer Center, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.

Funding

TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NILES, JACQUIN C · 1985 to 2020
$25.6M
TRAINING IN ENVIRONMENTAL PATHOLOGYT32ES007272 · NIEHS · BROWN UNIVERSITY · PI ZHITKOVICH, ANATOLY · 1992 to 2021
$7.5M
Intra and Extra-Chromosomal Probes for Mutagenesis by CarcinogensR01CA080024 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1998 to 2025
$5.9M
Fluorinated macrocyclic peptides as BBB penetrating agent for improved GBM treatmentR01CA237063 · NCI · BROWN UNIVERSITY · PI LAWLER, SEAN EDWARD, PENTELUTE, BRADLEY LETHER · 2019 to 2023
$3.0M
Targeting platinum(IV) prodrug to GBM tumors using a brevican-binding peptideR01CA272573 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, CHOI-FONG · 2022 to 2025
$2.7M
Preclinical assessment of efficacy and tumor microenvironment alterations by PPRX-1701 in glioblastomaR21CA259734 · NCI · BROWN UNIVERSITY · PI LAWLER, SEAN EDWARD · 2023 to 2024
$411k
NCI NIH HHS R01 CA080024NCI NIH HHS R01 CA237063NCI NIH HHS R01 CA272573NCI NIH HHS R21 CA259734NIEHS NIH HHS P30 ES002109NIEHS NIH HHS T32 ES007272
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor. GBM has an extremely poor prognosis and new treatments are badly needed. Efficient drug delivery to GBM is a major obstacle as the blood-brain barrier (BBB) prevents passage of the majority of cancer drugs into the brain. It is also recognized that the blood-brain tumor barrier (BTB) in the growing tumor represents a challenge. The BTB is heterogeneous and poorly characterized, but similar to the BBB it can prevent therapeutics from reaching effective intra-tumoral doses, dramatically hindering their potential. Here, we identified a 12-gene signature associated with the BTB, with functions related to vasculature development, morphogenesis and cell migration. We identified CDH5 as a core molecule in this set and confirmed its over-expression in GBM vasculature using spatial transcriptomics of GBM patient specimens. We found that the indirubin-derivative, 6-bromoindirubin acetoxime (BIA), could downregulate CDH5 and other BTB signature genes, causing endothelial barrier disruption in endothelial monolayers and BBB 3D spheroids

Identifiers

PMID39253453
PMCPMC11382996

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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.