Evidence map›Paper›PMID 37060903›Full record

ArticleCell reports. Medicine2023

PPRX-1701, a nanoparticle formulation of 6'-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models.

Mykola Zdioruk, Jorge-Luis Jimenez-Macias, Michal Oskar Nowicki, Katherine E Manz, Kurt D Pennell, Marilin S Koch, Tomer Finkelberg, Bin Wu, Paul Boucher, Yuji Takeda and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

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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

15 authors at 3 institutions in 1 country.

Mykola ZdiorukHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jorge-Luis Jimenez-MaciasHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology and Laboratory Medicine, Department of Neurosurgery, Legorreta Cancer Center, Brown University, Providence, RI 02903, USA.
Michal Oskar NowickiHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Katherine E ManzSchool of Engineering, Brown University, Providence, RI 02912, USA.
Kurt D PennellSchool of Engineering, Brown University, Providence, RI 02912, USA.
Marilin S KochHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tomer FinkelbergHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Bin WuPhosphorex, Inc, Hopkinton, MA 01748, USA; Cytodigm, Inc., Hopkinton, MA 01748, USA.
Paul BoucherPhosphorex, Inc, Hopkinton, MA 01748, USA.
Yuji TakedaPhosphorex, Inc, Hopkinton, MA 01748, USA.
Weiyi LiPhosphorex, Inc, Hopkinton, MA 01748, USA.
Raziye PiranliogluHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Alexander L LingHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
E Antonio ChioccaHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Sean E LawlerHarvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology and Laboratory Medicine, Department of Neurosurgery, Legorreta Cancer Center, Brown University, Providence, RI 02903, USA. Electronic address: sean_lawler@brown.edu.
Brigham and Women's Hospital · USPhosphorTech (United States) · USBrown University · US

Funding

TRAINING IN ENVIRONMENTAL PATHOLOGYT32ES007272 · NIEHS · BROWN UNIVERSITY · PI ZHITKOVICH, ANATOLY · 1992 to 2021
$7.5M
Indirubins: novel anti-invasive and anti-angiogenic drugs for malignant gliomasR01CA166172 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHIOCCA, E. ANTONIO · 2013 to 2017
$1.8M
Innovative approaches for the advancement of glioblastoma therapiesR50CA243706 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI NOWICKI, MICHAL OSKAR · 2019 to 2023
$662k
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 CA166172NCI NIH HHS R21 CA259734NCI NIH HHS R50 CA243706NIEHS NIH HHS T32 ES007272
6 · The paper itself

Abstract

Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6'-bromoindirubin-3'-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells. BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression in vitro and enhances T cell-mediated tumor cell killing in GBM stem-like cell co-culture models. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in immunocompetent GBM models in vivo. Our results indicate that BiA improves survival in murine GBM models via effects on important immunotherapeutic targets in GBM and that it can be delivered efficiently via PPRX-1701, a nanoparticle injectable formulation of BiA.

Indexed as

GlioblastomaAnimalsKynurenineMiceOximesTryptophanacetoximeKynurenineOximesTryptophan6-bromoindirubin-3′-acetoximeglioblastomaIDO1indoleamine-pyrrole 2,3-dioxygenasetumor microenvironment

Identifiers

PMID37060903
PMCPMC10213750
OpenAlexW4365998152

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.