Evidence map›Paper›PMID 28942004›Full record

ArticleToxicology and applied pharmacology2017

Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells.

Zhongwei Liu, Weimin Gao

Open access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

17 citing papers in PubMed, 18 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

2 authors at 1 institution in 1 country.

Zhongwei LiuDepartment of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, United States.
Weimin GaoDepartment of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX, United States. Electronic address: weimin.gao@ttu.edu.
Texas Tech University · US

Funding

Carcinogen-specific Twist1 regulation in lung epithial cellsR15ES026789 · NIEHS · WEST VIRGINIA UNIVERSITY · PI GAO, WEIMIN · 2016 to 2016
$435k
NIEHS NIH HHS R15 ES026789
6 · The paper itself

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has demonstrated dramatic clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of acquired drug resistance. The aim of this study was to explore the potential utility of chromosome region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) in combination with gefitinib to overcome primary and acquired gefitinib resistance in NSCLC cells. The combinative effects of gefitinib and LMB were evaluated by MTT and its underlining mechanism was assessed by flow cytometry and Western blot. LMB displayed a synergistic effect on gefitinib-induced cytotoxicity in A549 (IC50: 25.0±2.1μM of gefitinib+LMB vs. 32.0±2.5μM of gefitinib alone, p<0.05). Gefitinib+LMB caused a significantly different cell cycle distribution and signaling pathways involved in EGFR/survivin/p21 compared with gefitinib. A549 cells then were treated with progressively increased concentrations of gefitinib (A549GR) or in combination with LMB (A549GLR) over 10months to generate gefitinib resistance. IC50 of gefitinib in A549GLR (37.0±2.8μM) was significantly lower than that in A549GR (53.0±3.0μM, p<0.05), which indicates that LMB could reverse gefitinib-induced resistance in A549. Further mechanism investigation revealed that the expression patterns of EGFR pathway and epithelial-mesenchymal transition (EMT) markers in A549, A549GR, and A549GLR were significantly different. In conclusion, LMB at a very low concentration (0.5nM) combined with gefitinib showed synergistic therapeutic effects and ameliorated the development of gefitinib-induced resistance in lung cancer cells.

Indexed as

A549 CellsAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternCell Cycle CheckpointsCell SurvivalCyclin-Dependent Kinase Inhibitor p21Dose-Response Relationship, DrugDrug Resistance, NeoplasmDrug SynergismEpithelial-Mesenchymal TransitionErbB ReceptorsFatty Acids, UnsaturatedFlow CytometryGefitinibGene Expression Regulation, NeoplasticHumansBIRC5 protein, humanCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21EGFR protein, humanErbB ReceptorsFatty Acids, UnsaturatedGefitinibInhibitor of Apoptosis Proteinsleptomycin BProtein Kinase InhibitorsQuinazolinesSurvivinAcquired resistanceCRM1EGFREMTKRAS mutationNSCLC

Identifiers

PMID28942004
PMCPMC5643250
OpenAlexW2760440513

What OpenQuestion holds

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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.