Evidence map›Paper›PMID 15367671›Full record

ArticleMolecular and cellular biology2004

Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells.

Ranjit S Bindra, Paul J Schaffer, Alice Meng, Jennifer Woo, Kårstein Måseide, Matt E Roth, Paul Lizardi, David W Hedley, Robert G Bristow, Peter M Glazer

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

Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03462212 (A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced), which is not on this map. Cited by 201 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% 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.

NCT03462212 phase1 / phase2unknown statusnot on this mapstarted 2021, after this paper: background citation

A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced (Stage III B-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer Preceded by a Phase I Dose Escalation Study on Rucaparib-Bevacizumab Combination

TypeinterventionalSponsorFondazione Policlinico Universitario Agostino Gemelli IRCCSRan2021 to 2025Enrolled290ConditionsAdvanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube CancerArmsCarboplatin, Paclitaxel, Bevacizumab, Rucaparib
3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 2 syntheses or guidelines pooled it, 354 citations in OpenAlex.

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  15. Oligometastatic Prostate Cancer: Clues from an N-of-1.Journal of clinical medicine · 2026
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141 more citing papers are in PubMed but not listed here.

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 at 4 institutions in 2 countries.

Ranjit S BindraDepartment of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040, USA.
Paul J Schaffer
Alice Meng
Jennifer Woo
Kårstein Måseide
Matt E Roth
Paul Lizardi
David W Hedley
Robert G Bristow
Peter M Glazer
Princess Margaret Cancer Centre · CAYale University · USUniversity Health Network · CAUniversity of Toronto · CA

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Oncometabolites, DNA Repair, and CancerR01ES005775 · NIEHS · YALE UNIVERSITY · PI PETER M GLAZER · 1998 to 2026
$8.0M
XRAY INDUCED MUTAGENESIS IN TRANSGENIC MICER29ES005775 · NIEHS · YALE UNIVERSITY · PI GLAZER, PETER M · 1992 to 1997
–
NIEHS NIH HHS ES05775NIEHS NIH HHS R01 ES005775NIGMS NIH HHS GM07205NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

There is an emerging concept that acquired genetic instability in cancer cells can arise from the dysregulation of critical DNA repair pathways due to cell stresses such as inflammation and hypoxia. Here we report that hypoxia specifically down-regulates the expression of RAD51, a key mediator of homologous recombination in mammalian cells. Decreased levels of Rad51 were observed in multiple cancer cell types during hypoxic exposure and were not associated with the cell cycle profile or with expression of hypoxia-inducible factor. Analyses of RAD51 gene promoter activity, as well as mRNA and protein stability, indicate that the hypoxia-mediated regulation of this gene occurs via transcriptional repression. Decreased expression of Rad51 was also observed to persist in posthypoxic cells for as long as 48 h following reoxygenation. Correspondingly, we found reduced levels of homologous recombination in both hypoxic and posthypoxic cells, suggesting that the hypoxia-associated reduction in Rad51 expression has functional consequences for DNA repair. In addition, hypoxia-mediated down-regulation of Rad51 was confirmed in vivo via immunofluorescent image analysis of experimental tumors in mice. Based on these findings, we propose a novel mechanism of genetic instability in the tumor microenvironment mediated by hypoxia-induced suppression of the homologous recombination pathway in cancer cells. The aberrant regulation of Rad51 expression may also create heterogeneity in the DNA damage response among cells within tumors, with implications for the response to cancer therapies.

Indexed as

Cell CycleDNA-Binding ProteinsDNA RepairDown-RegulationFemaleGene Expression RegulationHumansHypoxiaHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitIronMaleNuclear ProteinsProstatic NeoplasmsRecombination, GeneticRNA, MessengerDNA-Binding ProteinsHIF1A protein, humanHypoxia-Inducible Factor 1Hypoxia-Inducible Factor 1, alpha SubunitIronNuclear ProteinsRAD51C protein, humanRNA, MessengerTranscription Factors

Identifiers

PMID15367671
PMCPMC516750
OpenAlexW2136689090

What OpenQuestion holds

Textmetadata
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.