Evidence map›Paper›PMID 31534222›Full record

ArticleNature2019

Electrical and synaptic integration of glioma into neural circuits.

Humsa S Venkatesh, Wade Morishita, Anna C Geraghty, Dana Silverbush, Shawn M Gillespie, Marlene Arzt, Lydia T Tam, Cedric Espenel, Anitha Ponnuswami, Lijun Ni and 11 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04224441 (Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme), which is not on this map. Cited by 834 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
834citing papers in PubMed, 2 pooled it
56.4field-weighted citation impact, top 1% 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.

NCT04224441 phase2unknown statusnot on this map

Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme

TypeinterventionalSponsorMarco G Paggi, MD, PhDRan2019 to 2022Enrolled41ConditionsGlioblastoma Multiforme, MGMT-Unmethylated GlioblastomaArmsChlorpromazine Pill
3 · Its place in the literature

Who cites it

834 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,260 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  17. Review
  18. Article
  19. Review
  20. Article

774 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Humsa S VenkateshDepartment of Neurology, Stanford University, Stanford, CA, USA.
Wade MorishitaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Anna C GeraghtyDepartment of Neurology, Stanford University, Stanford, CA, USA.
Dana SilverbushDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shawn M GillespieDepartment of Neurology, Stanford University, Stanford, CA, USA.
Marlene ArztDepartment of Neurology, Stanford University, Stanford, CA, USA.
Lydia T TamDepartment of Neurology, Stanford University, Stanford, CA, USA.
Cedric EspenelCell Sciences Imaging Facility, Stanford University School of Medicine, Stanford, CA, USA.
Anitha PonnuswamiDepartment of Neurology, Stanford University, Stanford, CA, USA.
Lijun NiDepartment of Neurology, Stanford University, Stanford, CA, USA.
Pamelyn J WooDepartment of Neurology, Stanford University, Stanford, CA, USA.
Kathryn R TaylorDepartment of Neurology, Stanford University, Stanford, CA, USA.
Amit AgarwalDepartment of Neuroscience, Johns Hopkins University, Baltimore, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
David BrangDepartment of Psychology, University of Michigan, Ann Arbor, MI, USA.
Hannes VogelDepartment of Neurology, Stanford University, Stanford, CA, USA.
Shawn Hervey-JumperDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Dwight E BerglesDepartment of Neuroscience, Johns Hopkins University, Baltimore, MA, USA.
Mario L SuvàDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Robert C MalenkaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Michelle MonjeDepartment of Neurology, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
Stanford University · USBroad Institute · USChica and Heinz Schaller Foundation · DEJohns Hopkins University · USUniversity of California, San Francisco · USUniversity of Michigan–Ann Arbor · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Role of synaptotagmins and neurexin ligands in homeostatic synaptic plasticityP50MH086403 · NIMH · STANFORD UNIVERSITY · PI DEISSEROTH, KARL A. · 2009 to 2019
$18.4M
VECTOR COREP30NS069375 · NINDS · STANFORD UNIVERSITY · PI SHAMLOO, MEHRDAD · 2011 to 2019
$6.3M
Glioma Circuitry: Bridging Systems Neuroscience and CancerDP1NS111132 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2018 to 2022
$5.7M
Neuronal activity-regulated mechanisms of glioma growthR01NS092597 · NINDS · STANFORD UNIVERSITY · PI MONJE-DEISSEROTH, MICHELLE · 2016 to 2021
$2.1M
Intratumoral functional connectivity with implications on synaptogenesis and aphasia recovery in adult astrocytic WHO II-III gliomaK08NS110919 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERVEY-JUMPER, SHAWN L. · 2019 to 2023
$1.0M
A Mechanistic Understanding of Neuronal Activity Promotion of High-Grade Glioma Growth through Activity-Regulated Secretion of Neuroligin-3F31CA200273 · NCI · STANFORD UNIVERSITY · PI VENKATESH, HUMSA · 2015 to 2017
$125k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA200273NCI NIH HHS T32 CA009302NIMH NIH HHS P50 MH086403NINDS NIH HHS DP1 NS111132NINDS NIH HHS K08 NS110919NINDS NIH HHS P30 NS069375NINDS NIH HHS R01 NS092597
6 · The paper itself

Abstract

High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron-glioma synapses. Neuronal activity also evokes non-synaptic activity-dependent potassium currents that are amplified by gap junction-mediated tumour interconnections, forming an electrically coupled network. Depolarization of glioma membranes assessed by in vivo optogenetics promotes proliferation, whereas pharmacologically or genetically blocking electrochemical signalling inhibits the growth of glioma xenografts and extends mouse survival. Emphasizing the positive feedback mechanisms by which gliomas increase neuronal excitability and thus activity-regulated glioma growth, human intraoperative electrocorticography demonstrates increased cortical excitability in the glioma-infiltrated brain. Together, these findings indicate that synaptic and electrical integration into neural circuits promotes glioma progression.

Indexed as

Electrophysiological PhenomenaAnimalsBrainCell MembraneCell ProliferationElectrical SynapsesGap JunctionsGene Expression ProfilingGene Expression Regulation, NeoplasticGliomaHeterograftsHumansMiceMice, Inbred NODNeuronsOptogeneticsPotassium

Identifiers

PMID31534222
PMCPMC7038898
OpenAlexW2974724557

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.