Evidence map›Paper›PMID 18472964›Full record

ArticleNeoplasia (New York, N.Y.)2008

Decitabine-induced demethylation of 5' CpG island in GADD45A leads to apoptosis in osteosarcoma cells.

Khaldoun Al-Romaih, Bekim Sadikovic, Maisa Yoshimoto, Yuzhuo Wang, Maria Zielenska, Jeremy A Squire

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.2field-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

37 citing papers in PubMed, 59 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

6 authors at 5 institutions in 1 country.

Khaldoun Al-RomaihDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Bekim Sadikovic
Maisa Yoshimoto
Yuzhuo Wang
Maria Zielenska
Jeremy A Squire
Ontario Institute for Cancer Research · CABC Cancer Agency · CAHospital for Sick Children · CAPrincess Margaret Cancer Centre · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GADD45 genes are epigenetically inactivated in various types of cancer and tumor cell lines. To date, defects of the GADD45 gene family have not been implicated in osteosarcoma (OS) oncogenesis, and the role of this pathway in regulating apoptosis in this tumor is unknown. The therapeutic potential of Gadd45 in OS emerged when our previous studies showed that GADD45A was reexpressed by treatment with the demethylation drug decitabine. In this study, we analyze the OS cell lines MG63 and U2OS and show that on treatment with decitabine, a significant loss of DNA methylation of GADD45A was associated with elevated expression and induction of apoptosis. In vivo affects of decitabine treatment in mice showed that untreated control xenografts exhibited low nuclear staining for Gadd45a protein, whereas the nuclei from xenografts in decitabine-treated mice exhibited increased amounts of protein and elevated apoptosis. To show the specificity of this gene for decitabine-induced apoptosis in OS, GADD45A mRNAs were disrupted using short interference RNA, and the ability of the drug to induce apoptosis was reduced. Understanding the role of demethylation of GADD45A in reexpression of this pathway and restoration of apoptotic control is important for understanding OS oncogenesis and for more targeted therapeutic approaches.

Indexed as

AnimalsApoptosisAzacitidineBlotting, WesternBone NeoplasmsCell Cycle ProteinsCpG IslandsDecitabineDNA MethylationDNA Modification MethylasesEnzyme InhibitorsGADD45 ProteinsHumansImmunoenzyme TechniquesMaleMiceAzacitidineCell Cycle ProteinsDecitabineDNA Modification MethylasesEnzyme InhibitorsGADD45A protein, humanGadd45a protein, mouseGADD45 ProteinsNuclear ProteinsRNA, Small Interfering

Identifiers

PMID18472964
PMCPMC2373908
OpenAlexW1518200090

What OpenQuestion holds

Textmetadata
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.