Evidence map›Paper›PMID 19755992›Full record

ArticleBritish journal of cancer2009

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells.

D L Roberts, K J Williams, R L Cowen, M Barathova, A J Eustace, S Brittain-Dissont, M J Tilby, D G Pearson, C J Ottley, I J Stratford and 1 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

25 citing papers in PubMed, 50 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

11 authors at 5 institutions in 2 countries.

D L RobertsPaterson Institute for Cancer Research, University of Manchester, Manchester, UK.
K J Williams
R L Cowen
M Barathova
A J Eustace
S Brittain-Dissont
M J Tilby
D G Pearson
C J Ottley
I J Stratford
C Dive
University of Manchester · GBDurham University · GBInstitute of Virology of the Slovak Academy of Sciences · SKManchester Academic Health Science Centre · GBNewcastle University · GB

Funding

Cancer Research UK C147/A6058Cancer Research UK C84/A4394Medical Research Council G0500366
6 · The paper itself

Abstract

backgroundHypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investigate the relative contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and drug penetrance to oxaliplatin resistance using three-dimensional spheroids.

methodsHypoxia-inducible factor-1alpha function was suppressed by the stable expression of a dominant-negative form in HCT116 cells (DN). Cells were drug exposed as monolayer or multicellular spheroid cultures. Cells residing at differing oxygenation status were isolated from Hoechst 33342-treated spheroids using flow cytometry. Sub-populations were subjected to clonogenic survival assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine oxaliplatin uptake.

resultsIn spheroids, a sensitivity gradient (hypoxic<aerobic) was revealed by survival assays and this correlated with levels of platinum-bound DNA. The resistance of hypoxic sub-populations exceeded relative changes in adduct levels, implicating factors other than drug penetrance in cell response. Dominant-negative monolayer cells showed no resistance to oxaliplatin in hypoxia and spheroids; the relative resistance of hypoxic compared with aerobic sub-populations was reduced compared with those from controls.

conclusionOverall, data show that drug penetration, DNA damage levels and HIF-1-dependent processes, all contribute to the resistance of hypoxic cells to oxaliplatin.

Indexed as

Antineoplastic AgentsCell HypoxiaCell SurvivalColorectal NeoplasmsDrug Resistance, NeoplasmHCT116 CellsHumansHypoxia-Inducible Factor 1Organoplatinum CompoundsOxaliplatinSpheroids, CellularAntineoplastic AgentsHypoxia-Inducible Factor 1Organoplatinum CompoundsOxaliplatin

Identifiers

PMID19755992
PMCPMC2768443
OpenAlexW2120805410

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.