Evidence map›Paper›PMID 26076896›Full record

ArticleInternational journal of cancer2015

Areca nut exposure increases secretion of tumor-promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes.

Rasika P Illeperuma, Do Kyeong Kim, Young Jin Park, Hwa Kyung Son, Jue Young Kim, Jinmi Kim, Doo Young Lee, Ki-Yeol Kim, Da-Woon Jung, Wanninayake M Tilakaratne and 1 more

Open access · hybridAbstract read
In one paragraph

Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

28 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
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  6. Detection of Oral Submucous Fibrosis at the Crossroads of Altering Nucleogeometry, Nuclear Spatial Distribution and Nuclear Molecular Abundance.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2025
    Article
  7. Oral submucous fibrosis: pathogenesis and therapeutic approaches.International journal of oral science · 2025
    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

11 authors at 2 institutions in 3 countries.

Rasika P IlleperumaOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Do Kyeong KimOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Young Jin ParkOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Hwa Kyung SonOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Jue Young KimOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Jinmi KimOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Doo Young LeeOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Ki-Yeol KimOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Da-Woon JungDepartment of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
Wanninayake M TilakaratneFaculty of Dental Sciences, Department of Oral Pathology, University of Peradeniya, Sri Lanka.
Jin KimOral Cancer Research Institute, Department of Oral Pathology, Yonsei University College of Dentistry, Seoul, Korea.
Yonsei University · KRUniversity of Peradeniya · LK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)-exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT-hNOF) was used. We found that the levels of GRO-α, IL-6 and IL-8 increased in AN-exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN-exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8-oxoG FITC-conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN-exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine-triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF.

Indexed as

AntioxidantsArecaCarcinogenesisCells, CulturedDNA Breaks, Double-StrandedDNA DamageFibroblastsGingivaHEK293 CellsHumansInterleukin-6Interleukin-8KeratinocytesMouth MucosaNADPH Oxidase 1NADPH Oxidase 4AntioxidantsInterleukin-6Interleukin-8NADPH Oxidase 1NADPH Oxidase 4NADPH OxidasesNOX1 protein, humanNOX4 protein, humanReactive Oxygen SpeciescarcinogenesiscytokinesDNA damagefibroblastsoral submucous fibrosis

Identifiers

PMID26076896
PMCPMC4744697
OpenAlexW1520881062

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.