Evidence map›Paper›PMID 26160429›Full record

ArticleMolecular oncology2015

Guadecitabine (SGI-110) priming sensitizes hepatocellular carcinoma cells to oxaliplatin.

Yuting Kuang, Anthony El-Khoueiry, Pietro Taverna, Mats Ljungman, Nouri Neamati

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

Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

40 citing papers in PubMed, 53 citations in OpenAlex.

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  14. The Role of DNA Methylation and DNA Methyltransferases in Cancer.Advances in experimental medicine and biology · 2022
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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

5 authors at 3 institutions in 1 country.

Yuting KuangDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA; Department of Medicinal Chemistry, College of Pharmacy, Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA.
Anthony El-KhoueiryKeck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Pietro TavernaAstex Pharmaceutical Inc., Pleasanton, CA, USA.
Mats LjungmanDepartment of Radiation Oncology, Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA.
Nouri NeamatiDepartment of Medicinal Chemistry, College of Pharmacy, Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: neamati@umich.edu.
University of Michigan–Ann Arbor · USUniversity of Southern California · USAstex Pharmaceuticals

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Promoter DNA hypermethylation is an important biomarker of hepatocellular carcinoma (HCC), supporting the potential utility of demethylating agents in this disease. Guadecitabine (SGI-110) is a second-generation hypomethylating agent formulated as a dinucleotide of decitabine and deoxyguanosine that yields longer half-life and more extended decitabine exposure than decitabine IV infusion. Here we performed preclinical evaluation of SGI-110 in HCC models to guide the design of a phase I/II clinical trial. HCC cell lines and xenograft models were used to determine the antitumor activity of SGI-110 as a single agent and in combination with oxaliplatin. Pretreatment with low doses of SGI-110 significantly synergized with oxaliplatin yielding enhanced cytotoxicity. The combination of SGI-110 and oxaliplatin was well tolerated and significantly delayed tumor growth in mice compared to oxaliplatin alone. Bromouridine-labeled RNA sequencing (Bru-seq) was employed to elucidate the effects of SGI-110 and/or oxaliplatin on genome-wide transcription. SGI-110 and the combination treatment inhibited the expression of genes involved in WNT/EGF/IGF signaling. DNMT1 and survivin were identified as novel PD markers to monitor the efficacy of the combination treatment. In conclusion, SGI-110 priming sensitizes HCC cells to oxaliplatin by inhibiting distinct signaling pathways. We expect that this combination treatment will show low toxicity and high efficacy in patients. Our study supports the use of the combination of low doses of SGI-110 and oxaliplatin in HCC patients.

Indexed as

AnimalsAntineoplastic AgentsAzacitidineCarcinoma, HepatocellularCell Line, TumorCell ProliferationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDrug SynergismHumansInhibitor of Apoptosis ProteinsLiverLiver NeoplasmsMiceOrganoplatinum CompoundsOxaliplatinAntineoplastic AgentsAzacitidineBIRC5 protein, humanDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanDnmt1 protein, mouseguadecitabineInhibitor of Apoptosis ProteinsOrganoplatinum CompoundsOxaliplatinSurvivinWnt3A ProteinCombination therapyDNMT1Hepatocellular carcinomaOxaliplatinSGI-110

Identifiers

PMID26160429
PMCPMC5528722
OpenAlexW1851020169

What OpenQuestion holds

Textmetadata
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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.