Evidence map›Paper›PMID 24948741›Full record

ArticleJournal of the National Cancer Institute2014

DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer.

Stephan Woditschka, Lynda Evans, Renata Duchnowska, L Tiffany Reed, Diane Palmieri, Yongzhen Qian, Sunil Badve, George Sledge, Brunilde Gril, Mirit I Aladjem and 12 more

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

Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

47 citing papers in PubMed, 67 citations in OpenAlex.

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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

22 authors at 5 institutions in 2 countries.

Stephan WoditschkaAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA. woditschkas@mail.nih.gov steegp@mail.nih.gov.
Lynda EvansAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Renata DuchnowskaAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
L Tiffany ReedAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Diane PalmieriAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Yongzhen QianAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Sunil BadveAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
George SledgeAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Brunilde GrilAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Mirit I AladjemAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Haiqing FuAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Natasha M FloresAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Yesim Gökmen-PolarAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Wojciech BiernatAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Ewa Szutowicz-ZielińskaAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Tomasz MandatAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Tomasz TrojanowskiAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Waldemar OchAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Bogumiła Czartoryska-ArlukowiczAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Jacek JassemAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
James B MitchellAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA.
Patricia S SteegAffiliations of authors: Women's Malignancies Branch (SW, LE, TR, DP, BG, NMF, PSS), DNA Replication Group, Laboratory of Molecular Pharmacology (MIA, HF), and Tumor Biology Section, Radiation Biology Branch (JBM), Center for Cancer Research, National Cancer Institute, Bethesda, MD; Department of Oncology, Military Institute of Medicine, Warsaw, Poland (RD); Laboratory Animal Sciences Program, Frederick National Laboratory, Frederick MD (YQ); Departments of Pathology and Laboratory Medicine (SB), and Departments of Medicine (GS, YG-P), Indiana University School of Medicine, Indianapolis, IN; Department of Pathology (WB), and Department of Oncology and Radiotherapy (ES-Z, JJ), Medical University of Gdańsk, Gdańsk, Poland; Department of Neurosurgery, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland (TM); Department of Neurosurgery and Children's Neurosurgery Clinic, Medical University of Lublin, Lublin, Poland (TT); Department of Neurosurgery, Interior Affairs Hospital, Olsztyn, Poland (WO); Department of Clinical Oncology, Białystok Oncology Center, Białystok, Poland (BC-A); Present addresses: Teach for America, Baltimore, MD (LE); National Heart, Lung, and Blood Institute, Bethesda, MD (DP); Cancer Biology Program (NMF), and Department of Oncology (GS), Stanford University, Stanford, CA. woditschkas@mail.nih.gov steegp@mail.nih.gov.
Indiana University – Purdue University Indianapolis · USFrederick National Laboratory for Cancer Research · USNational Cancer Institute · USNational Institutes of Health · USLaboratory of Molecular Genetics · PL

Funding

Molecular Analysis of Breast Cancer Metastasis to the BrainZIABC010538 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STEEG, PATRICIA SCHRIVER · 2009 to 2025
$17.1M
Intramural NIH HHS
6 · The paper itself

Abstract

backgroundBreast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood.

methodsExpression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group).

resultsHuman brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression.

conclusionsBARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain.

Indexed as

DNA Breaks, Double-StrandedOxidative StressAnimalsAntioxidantsBrain NeoplasmsBreast NeoplasmsCell Line, TumorCyclic N-OxidesDNA RepairFemaleGene Expression Regulation, NeoplasticHumansMiceNeuroprotective AgentsRad51 RecombinaseReactive Oxygen SpeciesAntioxidantsBARD1 protein, humanBard1 protein, mouseCyclic N-OxidesNeuroprotective AgentsRAD51 protein, humanRad51 protein, mouseRad51 RecombinaseReactive Oxygen SpeciesSpin LabelstempolTumor Suppressor ProteinsUbiquitin-Protein Ligases

Identifiers

PMID24948741
PMCPMC4073622
OpenAlexW2119569174

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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.