Evidence map›Paper›PMID 25884597›Full record

ArticleJournal of experimental & clinical cancer research : CR2015

Combined enzyme/prodrug treatment by genetically engineered AT-MSC exerts synergy and inhibits growth of MDA-MB-231 induced lung metastases.

Miroslava Matuskova, Zuzana Kozovska, Lenka Toro, Erika Durinikova, Silvia Tyciakova, Zuzana Cierna, Roman Bohovic, Lucia Kucerova

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 3% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 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

8 authors at 3 institutions in 1 country.

Miroslava MatuskovaLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. miroslava.matuskova@savba.sk.
Zuzana KozovskaLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. zuzana.kozovska@savba.sk.
Lenka ToroLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. lenka.baranovicova@savba.sk.
Erika DurinikovaLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. erika.durinikova@savba.sk.
Silvia TyciakovaLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. silvia.tyciakova@savba.sk.
Zuzana CiernaInstitute of Pathological Anatomy, Faculty of Medicine, Comenius University, Sasinkova 4, Bratislava, 813 72, Slovakia. ciernaz@gmail.com.
Roman BohovicLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. roman.bohovic@savba.sk.
Lucia KucerovaLaboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, Bratislava, 833 91, Slovakia. lucia.kucerova@savba.sk.
Cancer Research Institute of the Slovak Academy of Sciences · SKSlovak Academy of Sciences · SKComenius University Bratislava · SK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetastatic spread of tumor cells remains a serious problem in cancer treatment. Gene-directed enzyme/prodrug therapy mediated by tumor-homing genetically engineered mesenchymal stromal cells (MSC) represents a promising therapeutic modality for elimination of disseminated cells. Efficacy of gene-directed enzyme/prodrug therapy can be improved by combination of individual systems. We aimed to define the combination effect of two systems of gene therapy mediated by MSC, and evaluate the ability of systemically administered genetically engineered mesenchymal stromal cells to inhibit the growth of experimental metastases derived from human breast adenocarcinoma cells MDA-MB-231/EGFP.

methodsHuman adipose tissue-derived mesenchymal stromal cells (AT-MSC) were retrovirally transduced with fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD::UPRT) or with Herpes simplex virus thymidine kinase (HSVtk). Engineered MSC were cocultured with tumor cells in the presence of prodrugs 5-fluorocytosin (5-FC) and ganciclovir (GCV). Combination effect of these enzyme/prodrug approaches was calculated. SCID/bg mice bearing experimental lung metastases were treated with CD::UPRT-MSC, HSVtk-MSC or both in combination in the presence of respective prodrug(s). Treatment efficiency was evaluated by EGFP-positive cell detection by flow cytometry combined with real-time PCR quantification of human cells in mouse organs. Results were confirmed by histological and immunohistochemical examination.

resultsWe demonstrated various extent of synergy depending on tested cell line and experimental setup. The strongest synergism was observed on breast cancer-derived cell line MDA-MB-231/EGFP. Systemic administration of CD::UPRT-MSC and HSVtk-MSC in combination with 5-FC and GCV inhibited growth of MDA-MB-231 induced lung metastases.

conclusionsCombined gene-directed enzyme/prodrug therapy mediated by MSC exerted synergic cytotoxic effect and resulted in high therapeutic efficacy in vivo.

Indexed as

Genetic TherapyTransduction, GeneticAnimalsCell Line, TumorDisease Models, AnimalGanciclovirHumansLung NeoplasmsMesenchymal Stem CellsMesenchymal Stem Cell TransplantationMiceMoloney murine leukemia virusThymidine KinaseXenograft Model Antitumor AssaysGanciclovirThymidine Kinase

Identifiers

PMID25884597
PMCPMC4431639
OpenAlexW2145163108

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.