Evidence map›Paper›PMID 25600708›Full record

ArticleCancer letters2015

Defective hCNT1 transport contributes to gemcitabine chemoresistance in ovarian cancer subtypes: overcoming transport defects using a nanoparticle approach.

Sau Wai Hung, Sean Marrache, Shannon Cummins, Yangzom D Bhutia, Hardik Mody, Shelley B Hooks, Shanta Dhar, Rajgopal Govindarajan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.1field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  7. Nanoparticle-Based Combination Therapy for Ovarian Cancer.International journal of nanomedicine · 2023
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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

8 authors at 1 institution in 1 country.

Sau Wai HungDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.
Sean MarracheDepartment of Chemistry, University of Georgia, Athens, GA, USA.
Shannon CumminsDepartment of Biological Sciences, University of Georgia, Athens, GA, USA.
Yangzom D BhutiaDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.
Hardik ModyDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.
Shelley B HooksDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.
Shanta DharDepartment of Chemistry, University of Georgia, Athens, GA, USA.
Rajgopal GovindarajanDepartment of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA. Electronic address: rgovinda@rx.uga.edu.
University of Georgia · US

Funding

Epigenetic priming in pancreatic cancer chemotherapyR01CA188464 · NCI · UNIVERSITY OF GEORGIA · PI GOVINDARAJAN, RAJGOPAL · 2014 to 2018
$1.6M
Recruitment of a Bioinorganic Chemistry Faculty MemberP30GM092378 · NIGMS · UNIVERSITY OF GEORGIA · PI JOHNSON, MICHAEL K. · 2009 to 2010
$684k
Nucleoside Transporter-Connexin Interplay in Pancreatic Cancer ChemotherapyR15CA176528 · NCI · UNIVERSITY OF GEORGIA · PI GOVINDARAJAN, RAJGOPAL · 2014 to 2014
$454k
NCI NIH HHS 1R15CA176528-01A1NCI NIH HHS R01 CA188464NCI NIH HHS R15 CA176528NIGMS NIH HHS P30 GM 092378NIGMS NIH HHS P30 GM092378
6 · The paper itself

Abstract

Nucleoside analogs are used as chemotherapeutic options for the treatment of platinum-resistant ovarian cancers. Human concentrative nucleoside transporter 1 (hCNT1) is implicated in sensitizing solid tumors to nucleoside analogs although its role in determining drug efficacy in ovarian cancers remains unclear. Here we examined the functional expression of hCNT1 and compared its contributions toward gemcitabine efficacy in histological subtypes of ovarian cancer. Radioactivity analysis identified hCNT1-mediated (3)H-gemcitabine transport in ovarian cancer cells to be significantly reduced compared with that of normal ovarian surface epithelial cells. Biochemical and immunocytochemical analysis identified that unlike normal ovarian cells which expressed high levels of hCNT1 at the apical cell surface, the transporter was either diminished in expression and/or mislocalized in cell lines of various subtypes of ovarian cancer. Retroviral expression of hCNT1 selectively rescued gemcitabine transport in cell lines representing serous, teratocarcinoma, and endometrioid subtypes, but not clear cell carcinoma (CCC). In addition, exogenous hCNT1 predominantly accumulated in intracytoplasmic vesicles in CCC suggesting defective cellular trafficking of hCNT1 as a contributing factor to transport deficiency. Despite diminution of hCNT1 transport in the majority of ovarian cancers and apparent trafficking defects with CCC, the chemotherapeutic efficacy of gemcitabine was broadly enhanced in all subtypes when delivered via engineered nanoparticles (NPs). Additionally, by bypassing the transport requirement, the delivery of a gemcitabine-cisplatin combination in NP formulation increased their synergistic interactions. These findings uncover hCNT1 as a putative determinant for nucleoside analog chemoresistance in ovarian cancer and may help rationalize drug selection and delivery strategies for various histological subtypes of ovarian cancer.

Indexed as

Drug Resistance, NeoplasmAntimetabolites, AntineoplasticBiological TransportCell Line, TumorCisplatinDeoxycytidineDrug SynergismFemaleGemcitabineHumansInhibitory Concentration 50Membrane Transport ProteinsNanocapsulesOvarian NeoplasmsAntimetabolites, Antineoplasticcif nucleoside transporterCisplatinDeoxycytidineGemcitabineMembrane Transport ProteinsNanocapsulesChemoresistanceGemcitabinehCNT1NanoparticlesNucleoside transporterOvarian cancer

Identifiers

PMID25600708
PMCPMC4433543
OpenAlexW1976986479

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.