Evidence map›Paper›PMID 24440048›Full record

ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2014

CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells.

Amar Desai, Bryan Webb, Stanton L Gerson

Abstract read
In one paragraph

Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

63 citing papers in PubMed, 123 citations in OpenAlex.

  1. Article
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  7. DNA repair in tumor radioresistance: insights from fruit flies genetics.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
  8. Article
  9. DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 2024
    Review
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3 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

3 authors at 2 institutions in 1 country.

Amar DesaiDepartment of Pharmacology, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States; Division of Hematology/Oncology, National Center for Regenerative Medicine, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States.
Bryan WebbDivision of Hematology/Oncology, National Center for Regenerative Medicine, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States.
Stanton L GersonDepartment of Pharmacology, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States; Division of Hematology/Oncology, National Center for Regenerative Medicine, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States; Case Comprehensive Cancer Center, Seidman Cancer Center, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, United States. Electronic address: slg5@case.edu.
Case Western Reserve University · USUniversity Hospitals Seidman Cancer Center · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
PREDOCTORAL TRAINING PROGRAM IN MOLECULAR THERAPEUTICST32GM008803 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MIEYAL, JOHN J, NIEMAN, MARVIN THOMAS · 2001 to 2023
$4.2M
Declining DNA repair in Aging Hematopoietic Stem CellR01AG024916 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI GERSON, STANTON L. · 2004 to 2008
$1.6M
TRANSGENIC APPROACH TO ONCOGENE AND DNA REPAIR IMBALANCER01CA063193 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI GERSON, STANTON L · 1994 to 2005
$1.3M
NCI NIH HHS P30 CA043703NCI NIH HHS P30 CA43703NCI NIH HHS P30CA43703NCI NIH HHS R01 CA063193NIA NIH HHS R01 AG024916NIA NIH HHS R01AG024916NIGMS NIH HHS 5T32GM008803-10NIGMS NIH HHS T32 GM008803
6 · The paper itself

Abstract

backgroundRadioresistance in human tumors has been linked in part to a subset of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface protein is proposed to be a marker enriching for CSCs. We explore the importance of DNA repair in contributing to radioresistance in CD133+ lung cancer cells. MATERIALS AND

methodsA549 and H1299 lung cancer cell lines were used. Sorted CD133+ cells were exposed to either single 4 Gy or 8 Gy doses and clonogenic survival measured. ϒ-H2AX immunofluorescence and quantitative real time PCR was performed on sorted CD133+ cells both in the absence of IR and after two single 4 Gy doses. Lentiviral shRNA was used to silence repair genes.

resultsA549 but not H1299 cells expand their CD133+ population after single 4 Gy exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This resistance corresponded with enhanced repair of DNA double strand breaks (DSBs) and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure of two single 4 Gy doses resulted in acquired DNA repair upregulation and improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51 silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced IR sensitivity in sorted CD133+ cells.

conclusionsCD133 identifies a population of cells within specific tumor types containing altered expression of DNA repair genes that are inducible upon exposure to chemotherapy. This altered gene expression contributes to enhanced DSB resolution and the radioresistance phenotype of these cells. We also identify DNA repair genes which may serve as promising therapeutic targets to confer radiosensitivity to CSCs.

Indexed as

Radiation ToleranceAC133 AntigenAntigens, CDCell Line, TumorDNA Breaks, Double-StrandedDNA RepairGlycoproteinsHumansLung NeoplasmsNeoplastic Stem CellsPeptidesRad51 RecombinaseAC133 AntigenAntigens, CDGlycoproteinsPeptidesPROM1 protein, humanRAD51 protein, humanRad51 RecombinaseCancer stem cellsCD133Radiation resistance

Identifiers

PMID24440048
PMCPMC4004669
OpenAlexW2072696652

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.