Evidence map›Paper›PMID 33888065›Full record

ArticleBMC cancer2021

Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.

Helena de Castro E Gloria, Laura Jesuíno Nogueira, Patrícia Bencke Grudzinski, Paola Victória da Costa Ghignatti, Temenouga Nikolova Guecheva, Natalia Motta Leguisamo, Jenifer Saffi

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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  6. PARP Inhibitors in Colorectal Malignancies: A 2023 Update.Reviews on recent clinical trials · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Helena de Castro E GloriaLaboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Sarmento Leite st 245, Porto Alegre, RS, Brazil.
Laura Jesuíno NogueiraCardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (ICFUC), Porto Alegre, RS, Brazil.
Patrícia Bencke GrudzinskiCardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (ICFUC), Porto Alegre, RS, Brazil.
Paola Victória da Costa GhignattiCardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (ICFUC), Porto Alegre, RS, Brazil.
Temenouga Nikolova GuechevaCardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (ICFUC), Porto Alegre, RS, Brazil.
Natalia Motta Leguisamo *Cardiology Institute of Rio Grande do Sul/ University Foundation of Cardiology (ICFUC), Porto Alegre, RS, Brazil.
Jenifer Saffi *Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Sarmento Leite st 245, Porto Alegre, RS, Brazil. jenifers@ufcspa.edu.br.
Universidade Federal de Ciências da Saúde de Porto Alegre · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe advances in colorectal cancer (CRC) treatment include the identification of deficiencies in Mismatch Repair (MMR) pathway to predict the benefit of adjuvant 5-fluorouracil (5-FU) and oxaliplatin for stage II CRC and immunotherapy. Defective MMR contributes to chemoresistance in CRC. A growing body of evidence supports the role of Poly-(ADP-ribose) polymerase (PARP) inhibitors, such as Olaparib, in the treatment of different subsets of cancer beyond the tumors with homologous recombination deficiencies. In this work we evaluated the effect of Olaparib on 5-FU cytotoxicity in MMR-deficient and proficient CRC cells and the mechanisms involved.

methodsHuman colon cancer cell lines, proficient (HT29) and deficient (HCT116) in MMR, were treated with 5-FU and Olaparib. Cytotoxicity was assessed by MTT and clonogenic assays, apoptosis induction and cell cycle progression by flow cytometry, DNA damage by comet assay. Adhesion and transwell migration assays were also performed.

resultsOur results showed enhancement of the 5-FU citotoxicity by Olaparib in MMR-deficient HCT116 colon cancer cells. Moreover, the combined treatment with Olaparib and 5-FU induced G2/M arrest, apoptosis and polyploidy in these cells. In MMR proficient HT29 cells, the Olaparib alone reduced clonogenic survival, induced DNA damage accumulation and decreased the adhesion and migration capacities.

conclusionOur results suggest benefits of Olaparib inclusion in CRC treatment, as combination with 5-FU for MMR deficient CRC and as monotherapy for MMR proficient CRC. Thus, combined therapy with Olaparib could be a strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.

Indexed as

Antineoplastic AgentsApoptosisCell AdhesionCell CycleCell Line, TumorCell SurvivalColonic NeoplasmsDNA DamageDNA Mismatch RepairDNA RepairDrug SynergismFluorouracilHCT116 CellsHumansPhthalazinesPiperazinesAntineoplastic AgentsFluorouracilolaparibPhthalazinesPiperazines5-fluorouracilColorectal cancerMismatch repairOlaparibPARP

Identifiers

PMID33888065
PMCPMC8063290
OpenAlexW3156345623

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.