Evidence map›Paper›PMID 24062988›Full record

ArticleFrontiers in oncology2013

Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines.

Sandeep R Bhave, David Y A Dadey, Rowan M Karvas, Daniel J Ferraro, Rama P Kotipatruni, Jerry J Jaboin, Andrew N Hallahan, Todd A Dewees, Amanda G Linkous, Dennis E Hallahan and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

30 citing papers in PubMed, 56 citations in OpenAlex.

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  11. World journal of gastrointestinal oncology · 2022
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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 3 institutions in 1 country.

Sandeep R BhaveDepartment of Radiation Oncology, Washington University in Saint Louis , St. Louis, MO , USA ; School of Medicine, Washington University in Saint Louis , St. Louis, MO , USA.
David Y A Dadey
Rowan M Karvas
Daniel J Ferraro
Rama P Kotipatruni
Jerry J Jaboin
Andrew N Hallahan
Todd A Dewees
Amanda G Linkous
Dennis E Hallahan
Dinesh Thotala
Washington University in St. Louis · USNew York University · USUniversity of Washington · US

Funding

X-ray Targeted Therapeutic Genes within NanoparticlesR01CA125757 · NCI · WASHINGTON UNIVERSITY · PI HALLAHAN, DENNIS E · 2007 to 2011
$1.7M
Lysophospholipids in Radiation Induced Signal Transduction in Malignant GliomasR01CA140220 · NCI · WASHINGTON UNIVERSITY · PI HALLAHAN, DENNIS E · 2010 to 2014
$1.7M
Pharmacodynamic Assessment of RTK Inhibitors in CancerR01CA112385 · NCI · WASHINGTON UNIVERSITY · PI HALLAHAN, DENNIS E · 2005 to 2009
$1.3M
NCI NIH HHS R01 CA112385NCI NIH HHS R01 CA125757NCI NIH HHS R01 CA140220
6 · The paper itself

Abstract

purposeGlioblastoma multiforme (GBM) is an aggressive primary brain tumor that is radio-resistant and recurs despite aggressive surgery, chemo, and radiotherapy. Autotaxin (ATX) is over expressed in various cancers including GBM and is implicated in tumor progression, invasion, and angiogenesis. Using the ATX specific inhibitor, PF-8380, we studied ATX as a potential target to enhance radiosensitivity in GBM. METHODS AND MATERIALS: Mouse GL261 and Human U87-MG cells were used as GBM cell models. Clonogenic survival assays and tumor transwell invasion assays were performed using PF-8380 to evaluate role of ATX in survival and invasion. Radiation dependent activation of Akt was analyzed by immunoblotting. Tumor induced angiogenesis was studied using the dorsal skin fold model in GL261. Heterotopic mouse GL261 tumors were used to evaluate the efficacy of PF-8380 as a radiosensitizer.

resultsPre-treatment of GL261 and U87-MG cells with 1 μM PF-8380 followed by 4 Gy irradiation resulted in decreased clonogenic survival, decreased migration (33% in GL261; P = 0.002 and 17.9% in U87-MG; P = 0.012), decreased invasion (35.6% in GL261; P = 0.0037 and 31.8% in U87-MG; P = 0.002), and attenuated radiation-induced Akt phosphorylation. In the tumor window model, inhibition of ATX abrogated radiation induced tumor neovascularization (65%; P = 0.011). In a heterotopic mouse GL261 tumors untreated mice took 11.2 days to reach a tumor volume of 7000 mm(3), however combination of PF-8380 (10 mg/kg) with irradiation (five fractions of 2 Gy) took more than 32 days to reach a tumor volume of 7000 mm(3).

conclusionInhibition of ATX by PF-8380 led to decreased invasion and enhanced radiosensitization of GBM cells. Radiation-induced activation of Akt was abrogated by inhibition of ATX. Furthermore, inhibition of ATX led to diminished tumor vascularity and delayed tumor growth. These results suggest that inhibition of ATX may ameliorate GBM response to radiotherapy.

Indexed as

autotaxinglioblastomalysophosphatidic acidPF-8380radiosensitizer

Identifiers

PMID24062988
PMCPMC3775313
OpenAlexW2136778780

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.