Evidence map›Paper›PMID 34634662›Full record

ArticleBiomaterials2021

Polymeric nanomedicine for overcoming resistance mechanisms in hedgehog and Myc-amplified medulloblastoma.

Virender Kumar, Qiyue Wang, Bharti Sethi, Feng Lin, Vinod Kumar, Donald W Coulter, Yuxiang Dong, Ram I Mahato

Open access · bronzeAbstract read
In one paragraph

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Lipid nanomedicine simultaneously inhibits BRD4/PI3K and MDM2/XIAP signaling pathways for effective treatment of Medulloblastoma.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  4. COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Targeting BRD4 and PI3K signaling pathways for the treatment of medulloblastoma.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  13. Article
  14. Review
  15. Recent advances in drug delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Review
  16. pH-sensitive nanomedicine of novel tubulin polymerization inhibitor for lung metastatic melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2022
    Article
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

8 authors at 2 institutions in 1 country.

Virender KumarDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Qiyue WangDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Bharti SethiDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Feng LinDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Vinod KumarDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Donald W CoulterDepartment of Pediatrics, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Yuxiang DongDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Ram I MahatoDepartment of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: ram.mahato@unmc.edu.
University of Nebraska Medical Center · USNebraska Medical Center · US

Funding

Overcoming Resistance Mechanisms in Hedgehog and Myc-amplified MedulloblastomaR01NS116037 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI COULTER, DONALD, MAHATO, RAM I. · 2021 to 2025
$1.9M
NINDS NIH HHS R01 NS116037
6 · The paper itself

Abstract

Chemoresistance and inadequate therapeutics transport across the blood brain barrier (BBB) remain the major barriers to treating medulloblastoma (MB). Hedgehog (Hh) and IGF/PI3K pathways regulate tumor cell proliferation and resistance in MB. Current Hh inhibitors are effective initially to treat SHH-MB but acquire resistance. Herein, we showed that Hh inhibitor MDB5 and BRD4/PI3K dual inhibitor SF2523 synergistically inhibited the proliferation of DAOY and HD-MB03 cells when used in combination. Treatment of these MB cells with the combination of MDB5 and SF2523 significantly decreased colony formation and expression of MYCN, p-AKT, and cyclin D1 but significantly increased in Bax expression, compared to individual drugs. We used our previously reported copolymer mPEG-b-PCC-g-DC copolymer, which showed 8.7 ± 1.0 and 6.5 ± 0.1% loading for MDB5 and SF2523 when formulated into nanoparticles (NPs). There was sustained drug release from NPs, wherein 100% of MDB5 was released in 50 h, but only 60% of SF2523 was released in 80 h. Targeted NPs prepared by mixing 30:70 ratio of COG-133-PEG-b-PBC and mPEG-b-PCC-g-DC copolymer delivered a significantly higher drug concentration in the cerebellum at 6 and 24h after intravenous injection into orthotopic SHH-MB tumor-bearing NSG mice. Moreover, systemic administration of COG-133-NPs loaded with MDB5 and SF2523 resulted in decreased tumor burden compared to non-targeted drug-loaded NPs, without any hepatic toxicity. In conclusion, our nanomedicine of MDB5 and SF2523 offers a novel therapeutic strategy to treat chemoresistant MB.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCerebellar NeoplasmsMedulloblastomaAnimalsBenzene DerivativesCell Line, TumorDrug SynergismHedgehog ProteinsMiceMorpholinesNanomedicineNuclear ProteinsPhosphatidylinositol 3-KinasesPyransPyridinesTranscription FactorsBenzene DerivativesHedgehog ProteinsMDB5MorpholinesNuclear ProteinsPhosphatidylinositol 3-KinasesPyransPyridinesSF2523Transcription FactorsBlood-brain barrierBromodomain-containing protein 4Hedgehog inhibitorMedulloblastomaMimetic peptideMYC proto-oncogene

Identifiers

PMID34634662
PMCPMC8573532
OpenAlexW3202507092

What OpenQuestion holds

Textmetadata
LicenceTDM
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.