Evidence map›Paper›PMID 25647012›Full record

ArticleBritish journal of cancer2015

Effect of pantoprazole to enhance activity of docetaxel against human tumour xenografts by inhibiting autophagy.

Q Tan, A M Joshua, J K Saggar, M Yu, M Wang, N Kanga, J Y Zhang, X Chen, B G Wouters, I F Tannock

RetractedOpen access · hybridAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 54 citations in OpenAlex.

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  6. Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Q TanDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
A M Joshua1] Division of Medical Oncology and Hematology, Princess Margaret Cancer Center and University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9 [2] Institute of Medical Science, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
J K SaggarDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
M YuDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
M WangDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
N KangaDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
J Y ZhangDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
X ChenDivision of Medical Oncology and Hematology, Princess Margaret Cancer Center and University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
B G WoutersDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
I F Tannock1] Department of Medical Biophysics, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9 [2] Division of Medical Oncology and Hematology, Princess Margaret Cancer Center and University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9 [3] Institute of Medical Science, University Health Network, University of Toronto, Toronto, ON, Canada M5G2M9.
University of Toronto · CAUniversity Health Network · CAPrincess Margaret Cancer Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutophagy allows recycling of cellular components and may facilitate cell survival after chemotherapy. Pantoprazole inhibits proton pumps and is reported to inhibit autophagy. Here we evaluate the effects of pantoprazole to modify cytotoxicity of the anticancer drug docetaxel, and underlying mechanisms.

methodsEffects of docetaxel±pantoprazole were studied against wild-type and autophagy-deficient PC3 cells and against four human xenografts. Effects of pantoprazole on autophagy were evaluated by quantifying LC3-I, LC3-II and p62 proteins in western blots, and by fluorescent microscopy of cells transfected with RFP-GFP-LC3. The distribution of drug effects and of autophagy was quantified in tumour sections in relation to blood vessels and hypoxia by immunohistochemistry using γH2AX, cleaved caspase-3, Ki67 and LC3/ p62.

resultsPantoprazole increased the toxicity of docetaxel in vitro, increased docetaxel-induced expression of γH2AX and cleaved caspase-3, and decreased Ki67 in tumour sections. Pantoprazole increased growth delay of four human xenografts of low, moderate and high sensitivity to docetaxel, with minimal increase in toxicity. Docetaxel led to increased autophagy throughout tumour sections. Pantoprazole inhibited autophagy, and effects of pantoprazole were reduced against genetically modified cells with decreased ability to undergo autophagy.

conclusionsAutophagy is a mechanism of resistance to docetaxel chemotherapy that may be modified by pantoprazole to improve therapeutic index.

Indexed as

2-PyridinylmethylsulfinylbenzimidazolesAnimalsAntineoplastic AgentsAutophagyBiomarkers, TumorCell Line, TumorDocetaxelDrug SynergismGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiceNeoplasmsNeoplasm TransplantationPantoprazoleSingle-Cell Analysis2-PyridinylmethylsulfinylbenzimidazolesAntineoplastic AgentsBiomarkers, TumorDocetaxelPantoprazoleTaxoids

Identifiers

PMID25647012
PMCPMC4453951
OpenAlexW2061547059

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.