Evidence map›Paper›PMID 42291750›Full record

ArticleNeuro-oncology advances

Pharmacologic inhibition of RBBP4/p300-mediated homologous recombination activity enhances glioblastoma sensitivity to temozolomide.

Josephine A Mapunda, Daniel J Laverty, Faisal Aziz, An Le, Junita Sangare, Lin Zhang, Zachary D Nagel, Jarrod B French, Jann N Sarkaria, Gaspar J Kitange

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Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

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

10 authors.

Josephine A MapundaThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Daniel J LavertyDepartment of Environmental Health, Harvard T.H. School of Public Health, Boston, Massachusetts, USA.
Faisal AzizThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
An LeThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Junita SangareThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Lin ZhangDivision of Biostatistics & Health Data Science, University of Minnesota, Minneapolis, Minnesota, USA.
Zachary D NagelDepartment of Environmental Health, Harvard T.H. School of Public Health, Boston, Massachusetts, USA.
Jarrod B FrenchThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Gaspar J KitangeThe Hormel Institute, University of Minnesota, Austin, Minnesota, USA.ORCID https://orcid.org/0000-0002-0548-1312

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Upstream regulators of the homologous recombination (HR) repair pathway are promising targets for overcoming temozolomide (TMZ) resistance. We investigated whether pharmacologic inhibition of Retinoblastoma Binding Protein 4 (RBBP4)/p300-mediated HR activity by CCS1477 or NEO2734 sensitizes glioblastoma (GBM) to TMZ. Methods: Lentiviral-mediated shRNA was used to silence RBBP4 and EP300 (p300). A fluorescence-based multiplex flow-cytometric host cell reactivation assay was used to measure DNA repair activity, while TMZ-induced double-strand breaks (DSBs) were assessed using a comet assay and γ-H2AX foci formation. Cytotoxicity was monitored using an Incucyte device, and survival analysis was performed to evaluate efficacy in orthotopic tumor models. Drug distribution was assessed using liquid chromatography-mass spectrometry (LC-MS/MS) and acetylation of lysine 27 of histone H3 (H3K27Ac) immunofluorescence for target inhibition. Promoter occupancy was determined using chromatin immunoprecipitation. Results: GBM patient-derived xenograft tumors with high Conclusion: These findings suggest that the RBBP4/p300-axis is a key regulator of HR-mediated repair of TMZ-induced DSBs, and inhibition by either CCS1477 or NEO2734 may be beneficial as monotherapy, but further studies are needed to determine the benefit of combining these agents with TMZ.

Indexed as

DNA damage repairglioblastomahomologous recombinationp300RBBP4temozolomide

Identifiers

PMID42291750
PMCPMC13264390

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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.