Evidence map›Paper›PMID 30253737›Full record

ArticleBMC cancer2018

Combination of lutetium-177 labelled anti-L1CAM antibody chCE7 with the clinically relevant protein kinase inhibitor MK1775: a novel combination against human ovarian carcinoma.

Dennis Lindenblatt, Nastassja Terraneo, Giovanni Pellegrini, Susan Cohrs, Philipp René Spycher, David Vukovic, Martin Béhé, Roger Schibli, Jürgen Grünberg

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

8 citing papers in PubMed, 14 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

9 authors at 3 institutions in 1 country.

Dennis LindenblattCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Nastassja TerraneoCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Giovanni PellegriniInstitut for Veterinary Pathology, University of Zurich, Zurich, Switzerland.
Susan CohrsCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Philipp René SpycherCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
David VukovicCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Martin BéhéCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Roger SchibliCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland.
Jürgen GrünbergCenter for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232, Villigen PSI, Switzerland. juergen.gruenberg@psi.ch.
Paul Scherrer Institute · CHETH Zurich · CHUniversity of Zurich · CH

Funding

Krebsforschung Schweiz KFS-2546-02-2010Krebsforschung Schweiz KFS-3585-02-2015
6 · The paper itself

Abstract

backgroundProtein kinase inhibitors (PKIs) are currently tested in clinical studies (phase I-III) as an alternative strategy against (recurrent) ovarian cancer. Besides their anti-tumour efficacy, several PKIs have also shown radiosensitizing effects when combined with external beam radiation. Based on these results we asked if the addition of PKIs offers a therapeutic opportunity to improve radioimmunotherapy (RIT) against ovarian cancer. Five PKIs (alisertib, MK1775, MK2206, saracatinib, temsirolimus) were chosen for cytotoxicity screenings based on their current clinical trials in the treatment of ovarian cancer and their influence on cell cycle regulation and DNA damage repair pathways. We combined selected PKIs with

methodsPKIs cytotoxicity was determined via cell colony-forming assays. Biomarker of DNA double-strand breaks (DSBs, γH2A.X) was analysed by western blot and fluorescence microscopy. Flow cytometric measurements were performed to evaluate levels of apoptosis based on mono- or combination treatments. The best combination was used for in vivo combination therapy studies in nude mice with SKOV3ip and IGROV1 human ovarian cancer xenografts. Bonferroni correction was used to determine statistical significance for multiple comparisons.

resultsThe highest cytotoxicity against both cell lines was observed for MK1775 and alisertib. Combinations including

conclusionsOur results warrant further evaluation of combination of MK1775 and radioimmunotherapy.

Indexed as

LutetiumRadioisotopesAnimalsAntineoplastic Agents, ImmunologicalApoptosisCell Line, TumorCell SurvivalDisease Models, AnimalDNA Breaks, Double-StrandedFemaleHumansImmunoconjugatesMiceNeural Cell Adhesion Molecule L1Protein Kinase InhibitorsPyrazolesadavosertibAntineoplastic Agents, ImmunologicalImmunoconjugatesLutetiumLutetium-177Neural Cell Adhesion Molecule L1Protein Kinase InhibitorsPyrazolesPyrimidinesPyrimidinonesRadioisotopes177Lu-radioimmunotherapyCombination therapyL1CAMmAb chCE7MK1775 (AZD1775)Ovarian carcinomaProtein kinase inhibitor

Identifiers

PMID30253737
PMCPMC6156869
OpenAlexW2893211377

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.