Evidence map›Paper›PMID 32264844›Full record

Trial reportBMC cancer2020

Intranasal perillyl alcohol therapy improves survival of patients with recurrent glioblastoma harboring mutant variant for MTHFR rs1801133 polymorphism.

Giselle M Faria, Igor D P Soares, Marcela D'Alincourt Salazar, Marcia R Amorim, Bruno L Pessoa, Clovis O da Fonseca, Thereza Quirico-Santos

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-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

13 citing papers in PubMed, 22 citations in OpenAlex.

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  11. Genes · 2021
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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

7 authors at 2 institutions in 2 countries.

Giselle M FariaInstituto de Biologia, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, ZC, 24020-141, Brazil.ORCID https://orcid.org/0000-0002-4287-1651
Igor D P SoaresInstituto de Biologia, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, ZC, 24020-141, Brazil.
Marcela D'Alincourt SalazarDepartment of Hematology and HCT, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.
Marcia R AmorimInstituto de Biologia, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, ZC, 24020-141, Brazil.
Bruno L PessoaPrograma de Pós-graduação em Neurologia, Faculdade de Medicina, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, 24020-141, Brazil.
Clovis O da FonsecaDepartamento de Medicina Especializada, Unidade de Pesquisa Clínica (UPC-HUAP), Universidade Federal Fluminense, Niteroi, RJ, Brazil.
Thereza Quirico-SantosInstituto de Biologia, Universidade Federal Fluminense, Niteroi, Rio de Janeiro, ZC, 24020-141, Brazil. tquirico@id.uff.br.ORCID https://orcid.org/0000-0003-0501-8720
Universidade Federal Fluminense · BRCity of Hope · US

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico MCT/CNPq/CT-Saude 401943/2010-0; CNPq/Universal 481059/2011-3Coordenação de Aperfeiçoamento de Pessoal de Nível Superior FellowshipEuclides da Cunha Foundation - UFF 3662
6 · The paper itself

Abstract

backgroundPolymorphisms in MTHFR gene influence risk and overall survival of patients with brain tumor. Global genomic DNA (gDNA) methylation profile from tumor tissues is replicated in peripheral leukocytes. This study aimed to draw a correlation between rs1801133 MTHFR variants, gDNA methylation and overall survival of patients with recurrent glioblastoma (rGBM) under perillyl alcohol (POH) treatment.

methodsgDNA from whole blood was extracted using a commercially available kit (Axygen) and quantified by spectrophotometry. Global gDNA methylation was determined by ELISA and rs1801133 polymorphism by PCR-RFLP. Statistical analysis of gDNA methylation profile and rs1801133 variants included Mann-Whitney, Kruskal-Wallis, Spearman point-biserial correlation tests (SPSS and Graphpad Prism packages; significant results for effect size higher than 0.4). Prognostic value of gDNA methylation and rs1801133 variants considered survival profiles at 25 weeks of POH treatment, having the date of protocol adhesion as starting count and death as the final event.

resultsMost rGBM patients showed global gDNA hypomethylation (median = 31.7%) and a significant, moderate and negative correlation between TT genotype and gDNA hypomethylation (median = 13.35%; rho = - 0.520; p = 0.003) compared to CC variant (median = 32.10%), which was not observed for CT variant (median = 33.34%; rho = - 0.289; p = 0.06). gDNA hypermethylated phenotype (median = 131.90%) exhibited significant, moderate and negative correlations between TT genotype (median = 112.02%) and gDNA hypermethylation levels when compared to CC (median = 132.45%; rho = - 0,450; p = 0.04) or CT (median = 137.80%; rho = - 0.518; p = 0.023) variants. TT variant of rs1801133 significantly decreased gDNA methylation levels for both patient groups, when compared to CC (d values: hypomethylated = 1.189; hypermethylated = 0.979) or CT (d values: hypomethylated = 0.597; hypermethylated = 1.167) variants. Positive prognostic for rGBM patients may be assigned to gDNA hypermethylation for survivors above 25 weeks of treatment (median = 88 weeks); and TT variant of rs1801133 regardless POH treatment length.

conclusionrGBM patients under POH-based therapy harboring hypermethylated phenotype and TT variant for rs1801133 had longer survival. Intranasal POH therapy mitigates detrimental effects of gDNA hypomethylation and improved survival of patients with rGBM harboring TT mutant variant for MTHFR rs1801133 polymorphism.

trial registrationCONEP -9681- 25,000.009267 / 2004. Registered 12th July, 2004.

Indexed as

DNA MethylationNeoplasm Recurrence, LocalAdministration, IntranasalAdolescentAdultAgedAntineoplastic AgentsBiomarkers, TumorBrain NeoplasmsFemaleGlioblastomaHumansLeukocytesMaleMethylenetetrahydrofolate Reductase (NADPH2)Middle AgedAntineoplastic AgentsBiomarkers, TumorMethylenetetrahydrofolate Reductase (NADPH2)MonoterpenesMTHFR protein, humanperillyl alcoholEpigeneticsGlioblastomaMethylationMTHFRPerillyl alcoholPolymorphism

Identifiers

PMID32264844
PMCPMC7137265
OpenAlexW3014581333

What OpenQuestion holds

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LicenceCC BY
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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.