Evidence map›Paper›PMID 26801902›Full record

ArticleBMC cancer2016

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines.

Haatisha Jandu, Kristina Aluzaite, Louise Fogh, Sebastian Wingaard Thrane, Julie B Noer, Joanna Proszek, Khoa Nguyen Do, Stine Ninel Hansen, Britt Damsgaard, Signe Lykke Nielsen and 12 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

29 citing papers in PubMed, 46 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 7 institutions in 3 countries.

Haatisha JanduFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. jxm436@alumni.ku.dk.
Kristina AluzaiteFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. ljg630@alumni.ku.dk.
Louise FoghFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. louisefogh82@gmail.com.
Sebastian Wingaard ThraneFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. sebthr@gmail.com.
Julie B NoerFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. julienoer@gmail.com.
Joanna ProszekDepartment of Pathology, Aarhus University Hospital, Noerrebrogade 44, building 18B, 8000, Aarhus C, Denmark. joanna.proszek@gmail.com.
Khoa Nguyen DoDTU Multiassay Core (DMAC), Technical University of Denmark, Kemitorvet Building 208, DK-2800, Lyngby, Denmark. khoanguyendo@gmail.com.
Stine Ninel HansenFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. stih@sund.ku.dk.
Britt DamsgaardFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. brittdamsgaard@hotmail.com.
Signe Lykke NielsenFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. siln@sund.ku.dk.
Magnus StougaardDepartment of Pathology, Aarhus University Hospital, Noerrebrogade 44, building 18B, 8000, Aarhus C, Denmark. magnstou@rm.dk.
Birgitta R KnudsenDepartment of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé 3, 8000, Aarhus C, Denmark. brk@mb.au.dk.
José MoreiraFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. jomo@sund.ku.dk.
Petra HamerlikBrain Tumor Biology, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. pkn@CANCER.DK.
Madhavsai GajjarBrain Tumor Biology, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. makiga@cancer.dk.
Marcel SmidErasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC, Rotterdam, The Netherlands. m.smid@erasmusmc.nl.
John MartensErasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC, Rotterdam, The Netherlands. j.martens@erasmusmc.nl.
John FoekensErasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC, Rotterdam, The Netherlands. j.foekens@erasmusmc.nl.
Yves PommierNational Institutes of Health, National Cancer Institute, Center for Cancer Research, Developmental Therapeutics Branch and Laboratory of Molecular, Pharmacology, 37 Convent Drive, Building 37, Room 5068, Bethesda, MD, 20892-4255, USA. PommierY@mail.nih.gov.
Nils BrünnerFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. nbr@sund.ku.dk.
Anne-Sofie SchrohlFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. sofie.rasmussen@gmail.com.
Jan StenvangFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Centre, University of Copenhagen, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. stenvang@sund.ku.dk.
University of Copenhagen · DKErasmus MC Cancer Institute · NLAarhus University Hospital · DKDanish Cancer Society · DKAarhus University · DKNational Institutes of Health · USTechnical University of Denmark · DK

Funding

DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer DrugsZIABC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$23.0M
DNA Topoisomerases as Target of Action of Anticancer DrugsZIABC006161 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$16.8M
6 · The paper itself

Abstract

backgroundStudies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC.

methodsWe established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6 months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump.

resultsWe found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance.

conclusionsBased on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan.

Indexed as

Antigens, NeoplasmATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Breast NeoplasmsCamptothecinDNA-Binding ProteinsDNA Topoisomerases, Type IDNA Topoisomerases, Type IIDocetaxelDrug Resistance, NeoplasmFemaleGene DosageGene Expression Regulation, NeoplasticHumansIrinotecanMCF-7 CellsABCG2 protein, humanAntigens, NeoplasmATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CamptothecinDNA-Binding ProteinsDNA Topoisomerases, Type IDNA Topoisomerases, Type IIDocetaxelIrinotecanNeoplasm ProteinsPoly-ADP-Ribose Binding ProteinsTaxoidsTOP1 protein, humanTOP2A protein, human

Identifiers

PMID26801902
PMCPMC4722663
OpenAlexW2268285310

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.