ArticleJournal of drug metabolism & toxicology2011
Gemcitabine Cytotoxicity: Interaction of Efflux and Deamination.
Article in Journal of drug metabolism & toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Association between ABCB1 genetic polymorphisms with treatment outcomes in patients with metastatic pancreatic cancer.International journal of clinical oncology · 2026Article
- Tissue- and Temporal-Dependent Dynamics of Myeloablation in Response to Gemcitabine Chemotherapy.Cells · 2024Article
- Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids.Nature materials · 2024Article
- Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.Biomedicines · 2024Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Drug resistance: from bacteria to cancer.Molecular biomedicine · 2021Review
- Decreased drug resistance of bladder cancer using phytochemicals treatment.The Kaohsiung journal of medical sciences · 2021Article
- Gambogic acid potentiates gemcitabine induced anticancer activity in non-small cell lung cancer.European journal of pharmacology · 2020Article
- Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.International journal of molecular sciences · 2020Review
- Attempts to remodel the pathways of gemcitabine metabolism: Recent approaches to overcoming tumours with acquired chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study.International journal of molecular sciences · 2019Article
- Interstitial Flow Recapitulates Gemcitabine Chemoresistance in A 3D Microfluidic Pancreatic Ductal Adenocarcinoma Model by Induction of Multidrug Resistance Proteins.International journal of molecular sciences · 2019Article
- Article
- Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles.International journal of nanomedicine · 2018Review
- In Vitro and In Vivo Comparison of Gemcitabine and the Gemcitabine Analog 1-(2'-deoxy-2'-fluoroarabinofuranosyl) Cytosine (FAC) in Human Orthotopic and Genetically Modified Mouse Pancreatic Cancer Models.Molecular imaging and biology · 2017Article
- Hippo pathway mediates resistance to cytotoxic drugs.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Enhancing Drug Efficacy and Therapeutic Index through Cheminformatics-Based Selection of Small Molecule Binary Weapons That Improve Transporter-Mediated Targeting: A Cytotoxicity System Based on Gemcitabine.Frontiers in pharmacology · 2017Article
- Hypoxia regulates ABCG2 activity through the activivation of ERK1/2/HIF-1α and contributes to chemoresistance in pancreatic cancer cells.Cancer biology & therapy · 2016Article
- Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine-resistant human urothelial carcinoma sublines.The Kaohsiung journal of medical sciences · 2014Article
- ATP-Binding Cassette Genes Genotype and Expression: A Potential Association with Pancreatic Cancer Development and Chemoresistance?Gastroenterology research and practice · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Gemcitabine is a cytidine analogue used in the treatment of various solid tumors. Little is known about how gemcitabine and its metabolites are transported out of cells. We set out to study the efflux of gemcitabine and the possible consequences of that process in cancer cells. We observed the efflux of gemcitabine and its deaminated metabolite, 2',2'-difluorodeoxyuridine (dFdU) using high performance liquid chromatography and tandem mass spectrometry (LC-MS/MS) after gemcitabine treatment. Non-selective ABCC-transport inhibition with probenecid significantly increased intracellular dFdU concentrations, with a similar trend observed with verapamil, a non-selective ABCB1 and ABCG2 transport inhibitor. Neither probenecid nor verapamil altered intracellular gemcitabine levels after the inhibition of deamination with tetrahydrourudine, suggesting that efflux of dFdU, but not gemcitabine, was mediated by ABC transporters. MTS assays showed that probenecid increased sensitivity to gemcitabine. While dFdU displayed little cytotoxicity, intracellular dFdU accumulation inhibited cytidine deaminase, resulting in increased gemcitabine levels and enhanced cytotoxicity. Knockdown of ABCC3, ABCC5 or ABCC10 individually did not significantly increase gemcitabine sensitivity, suggesting the involvement of multiple transporters. In summary, ABCC-mediated efflux may contribute to gemcitabine resistance through increased dFdU efflux that allows for the continuation of gemcitabine deamination. Reversing efflux-mediated gemcitabine resistance may require broad-based efflux inhibition.
Identifiers
What OpenQuestion holds
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.