Evidence map›Paper›PMID 25053853›Full record

ArticleNeuro-oncology2015

Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma.

Robert T Wicks, Javad Azadi, Antonella Mangraviti, Irma Zhang, Lee Hwang, Avadhut Joshi, Hansen Bow, Marianne Hutt-Cabezas, Kristin L Martin, Michelle A Rudek and 3 more

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

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

33 citing papers in PubMed, 57 citations in OpenAlex.

  1. Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025
    Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  8. Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023
    Review
  9. Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Perampanel Add-on to Standard RadiochemotherapyFrontiers in neuroscience · 2020
    Article
  18. Review
  19. Review
  20. Review
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 3 institutions in 1 country.

Robert T WicksDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Javad AzadiDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Antonella MangravitiDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Irma ZhangDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Lee HwangDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Avadhut JoshiDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Hansen BowDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Marianne Hutt-CabezasDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Kristin L MartinDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Michelle A RudekDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Ming ZhaoDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Henry BremDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Betty M TylerDepartment of Neurosurgery (R.T.W., J.A., A.M., I.Z., L.H., A.J., H.B., M.H.-C., K.L.M., H.B., B.M.T.); Departments of Oncology, Ophthalmology, and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland (H.B.); Division of Chemical Therapeutics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland (M.A.R., M.Z.).
Sidney Kimmel Comprehensive Cancer Center · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
UPLC with Tandem MS for Sensitive Quantitative Analysis of Small MoleculesS10RR026824 · NCRR · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2010 to 2010
$429k
NCRR NIH HHS 1S10RR026824-01NCRR NIH HHS UL1 RR 025005NCRR NIH HHS UL1 RR025005
6 · The paper itself

Abstract

background3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed.

methodsCytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT).

results3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%.

conclusionIntracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect.

Indexed as

Absorbable ImplantsAnimalsAntineoplastic AgentsAntineoplastic Agents, AlkylatingBrain NeoplasmsCell Line, TumorCell ProliferationCombined Modality TherapyDacarbazineDichloroacetic AcidDrug Administration RoutesDrug CombinationsDrug Delivery SystemsFemaleGlioblastomaGlycolysisAntineoplastic AgentsAntineoplastic Agents, AlkylatingbromopyruvateDacarbazineDichloroacetic AcidDrug CombinationsPolymersPyruvatesTemozolomide3-bromopyruvatedichloroacetategliomaglycolytic inhibitorpCPP:SA

Identifiers

PMID25053853
PMCPMC4483048
OpenAlexW1968612951

What OpenQuestion holds

Textmetadata
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.