Evidence map›Paper›PMID 34085099›Full record

ArticleJournal of cancer research and clinical oncology2021

PARP inhibition in UV-associated angiosarcoma preclinical models.

Marije E Weidema, Ingrid M E Desar, Melissa H S Hillebrandt-Roeffen, Anke E M van Erp, Mikio Masuzawa, PALGA-group, Uta E Flucke, Winette T A van der Graaf, Yvonne M H Versleijen-Jonkers

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In one paragraph

Article in Journal of cancer research and clinical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
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 2 institutions in 2 countries.

Marije E WeidemaDepartment of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Marije.Weidema@radboudumc.nl.ORCID http://orcid.org/0000-0002-5737-7744
Ingrid M E DesarDepartment of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Melissa H S Hillebrandt-RoeffenDepartment of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Anke E M van ErpDepartment of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Mikio MasuzawaDepartment of Regulation Biochemistry, Kitasato University School of Allied Sciences, Sagamihara, Japan.
PALGA-group
Uta E FluckeDepartment of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Winette T A van der GraafDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Yvonne M H Versleijen-JonkersDepartment of Medical Oncology, Radboud University Medical Center, Internal Postal Code 452, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLKitasato University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAngiosarcoma (AS) is a rare vasoformative sarcoma, with poor overall survival and a high need for novel treatment options. Clinically, AS consists of different subtypes, including AS related to previous UV exposure (UV AS) which could indicate susceptibility to DNA damage repair inhibition. We, therefore, investigated the presence of biomarkers PARP1 (poly(ADP-ribose)polymerase-1) and Schlafen-11 (SLFN11) in UV AS. Based on experiences in other sarcomas, we examined (combination) treatment of PARP inhibitor (PARPi) olaparib and temozolomide (TMZ) in UV AS cell lines.

methodsPreviously collected UV AS (n = 47) and non-UV AS (n = 96) patient samples and two UV AS cell lines (MO-LAS and AS-M) were immunohistochemically assessed for PARP1 and SLFN11 expression. Both cell lines were treated with single agents PARPi olaparib and TMZ, and the combination treatment. Next, cell viability and treatment synergy were analyzed. In addition, effects on apoptosis and DNA damage were examined.

resultsIn 46/47 UV AS samples (98%), PARP1 expression was present. SLFN11 was expressed in 80% (37/46) of cases. Olaparib and TMZ combination treatment was synergistic in both cell lines, with significantly increased apoptosis compared to single agent treatment. Furthermore, a significant increase in DNA damage marker γH2AX was present in both cell lines after combination therapy.

conclusionWe showed combination treatment of olaparib with TMZ was synergistic in UV AS cell lines. Expression of PARP1 and SLFN11 was present in the majority of UV AS tumor samples. Together, these results suggest combination treatment of olaparib and TMZ is a potential novel AS subtype-specific treatment option for UV AS patients.

Indexed as

Drug SynergismUltraviolet RaysAntineoplastic Agents, AlkylatingApoptosisCell ProliferationDrug CombinationsDrug Evaluation, PreclinicalHemangiosarcomaHumansNuclear ProteinsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPrognosisTemozolomideTumor Cells, CulturedAntineoplastic Agents, AlkylatingDrug CombinationsNuclear ProteinsPARP1 protein, humanPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSLFN11 protein, humanTemozolomideAngiosarcomaCombination treatmentPARPSLFN11SubtypeTemozolomide

Identifiers

PMID34085099
PMCPMC8310857
OpenAlexW3165424640

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.