Evidence map›Paper›PMID 26298202›Full record

ArticleRedox biology2015

Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

Charlotta Ryk, Lotta Renström Koskela, Tomas Thiel, N Peter Wiklund, Gunnar Steineck, Martin C Schumacher, Petra J de Verdier

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

Article in Redox biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.5field-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, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
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  7. Review
  8. Immune escape mechanisms and immunotherapy of urothelial bladder cancer.Journal of clinical and translational research · 2021
    Review
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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 1 country.

Charlotta RykUrology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden. Electronic address: charlotta.ryk@ki.se.
Lotta Renström KoskelaUrology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Tomas ThielUrology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
N Peter WiklundUrology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Gunnar SteineckClinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden; Division of Clinical Cancer Epidemiology, Department of Oncology, Onkologiskt centrum, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden.
Martin C SchumacherDepartment of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Petra J de VerdierUrology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Department of Urology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Karolinska University Hospital · SESahlgrenska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeBacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. MATERIALS AND

methodsAll NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests.

resultsBCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment.

conclusionsOur results suggest that the investigated polymorphisms influence patient response to BCG-treatment and thus may serve as possible markers for identification of BCG-failures.

Indexed as

AgedAllelesAntineoplastic AgentsCarcinoma in SituCarcinoma, Transitional CellFemaleGene ExpressionHumansMaleMiddle AgedMycobacterium bovisNeoplasm Recurrence, LocalNeoplasm StagingNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIPolymorphism, GeneticAntineoplastic AgentsNitric Oxide Synthase Type IINitric Oxide Synthase Type IIINOS2 protein, humanNOS3 protein, humanBCG vaccineCancer survivalGenetic polymorphismNitric oxide synthaseUrinary bladder neoplasms

Identifiers

PMID26298202
PMCPMC4556773
OpenAlexW1563092890

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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.