Evidence map›Paper›PMID 25940338›Full record

ArticleThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society2015

Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue Microarrays as a Medium-Throughput, Quantitative Method for Measuring the Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition in an In Vivo Model of Cancer.

Jessica Kalra, Weislawa H Dragowska, Marcel B Bally

Open access · bronzeAbstract read
In one paragraph

Article in The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Unlocking the Therapeutic Potential of Integrin-Linked Kinase Inhibitors in Bioengineered 3D Breast Tumor Stroma Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  6. CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019
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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

3 authors at 3 institutions in 2 countries.

Jessica KalraExperimental Therapeutics BC Cancer Agency, British Columbia, Canada (JK,WHD,MBB)
Weislawa H DragowskaExperimental Therapeutics BC Cancer Agency, British Columbia, Canada (JK,WHD,MBB)
Marcel B BallyExperimental Therapeutics BC Cancer Agency, British Columbia, Canada (JK,WHD,MBB)
BC Cancer Agency · CACentre for Drug Research and Development · CALangara College · CA

Funding

Medical Research Council MOP 106638
6 · The paper itself

Abstract

A small molecule inhibitor (QLT0267) targeting integrin-linked kinase is able to slow breast tumor growth in vivo; however, the mechanism of action remains unknown. Understanding how targeting molecules involved in intersecting signaling pathways impact disease is challenging. To facilitate this understanding, we used tumor tissue microarrays (TMA) and digital image analysis for quantification of immunohistochemistry (IHC) in order to investigate how QLT0267 affects signaling pathways in an orthotopic model of breast cancer over time. Female NCR nude mice were inoculated with luciferase-positive human breast tumor cells (LCC6(Luc)) and tumor growth was assessed by bioluminescent imaging (BLI). The plasma levels of QLT0267 were determined by LC-MS/MS methods following oral dosing of QLT0267 (200 mg/kg). A TMA was constructed using tumor tissue collected at 2, 4, 6, 24, 78 and 168 hr after treatment. IHC methods were used to assess changes in ILK-related signaling. The TMA was digitized, and Aperio ScanScope and ImageScope software were used to provide semi-quantitative assessments of staining levels. Using medium-throughput IHC quantitation, we show that ILK targeting by QLT0267 in vivo influences tumor physiology through transient changes in pathways involving AKT, GSK-3 and TWIST accompanied by the translocation of the pro-apoptotic protein BAD and an increase in Caspase-3 activity.

Indexed as

AnimalsAzo Compoundsbcl-Associated Death ProteinCaspase 3Cell Line, TumorDrug Screening Assays, AntitumorFemaleGene Expression Regulation, NeoplasticGlycogen Synthase Kinase 3HumansImage Processing, Computer-AssistedImmunohistochemistryKineticsMammary Neoplasms, ExperimentalMiceMice, NudeAzo Compoundsbcl-Associated Death ProteinCaspase 3Glycogen Synthase Kinase 3PhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyrazolesQLT 0267Scaffold Protein ILKSerineTwist-Related Protein 1AperioapoptosisBADbreast cancer modelCaspase-3 pharmacokineticsimmunohistochemistryintegrin-linked kinasepAKTQLT0267tissue microarrayTWIST

Identifiers

PMID25940338
PMCPMC4804727
OpenAlexW2145220115

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.