Evidence map›Paper›PMID 28453190›Full record

ArticleMolecular oncology2017

Synergistic activity of everolimus and 5-aza-2'-deoxycytidine in medullary thyroid carcinoma cell lines.

Giovanni Vitale, Alessandra Dicitore, Daniele Pepe, Davide Gentilini, Elisa S Grassi, Maria O Borghi, Giulia Gelmini, Maria C Cantone, Germano Gaudenzi, Gabriella Misso and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-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

17 citing papers in PubMed, 31 citations in OpenAlex.

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  12. New Therapies for Advanced Thyroid Cancer.Frontiers in endocrinology · 2020
    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

14 authors at 7 institutions in 3 countries.

Giovanni VitaleDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
Alessandra DicitoreLaboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Daniele PepeI-BioStat, Hasselt University, Belgium.
Davide GentiliniMolecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy.
Elisa S GrassiDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
Maria O BorghiDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
Giulia GelminiLaboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Maria C CantoneDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
Germano GaudenziDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
Gabriella MissoDepartment of Biochemistry, Biophysics and General Pathology, Second University of Naples, Italy.
Anna M Di BlasioMolecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy.
Leo J HoflandSection Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Michele CaragliaDepartment of Biochemistry, Biophysics and General Pathology, Second University of Naples, Italy.
Luca PersaniDepartment of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy.
IRCCS Istituto Auxologico Italiano · ITUniversity of Milan · ITUniversity of Milano-Bicocca · ITErasmus MC · NLHasselt University · BEUniversity of Campania "Luigi Vanvitelli" · ITUniversity of Naples Federico II · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Medullary thyroid cancer (MTC) is a tumor highly resistant to chemo- and radiotherapy. Drug resistance can be induced by epigenetic changes such as aberrant DNA methylation. To overcome drug resistance, we explored a promising approach based on the use of 5-aza-2'-deoxycytidine (AZA), a demethylating agent, in combination with the mTOR inhibitor everolimus in MTC cells (MZ-CRC-1 and TT). This combined treatment showed a strong synergistic antiproliferative activity through the induction of apoptosis. The effect of everolimus and/or AZA on genome-wide expression profiling was evaluated by Illumina BeadChip in MZ-CRC-1 cells. An innovative bioinformatic pipeline identified four potential molecular pathways implicated in the synergy between AZA and everolimus: PI3K-Akt signaling, the neurotrophin pathway, ECM/receptor interaction, and focal adhesion. Among these, the neurotrophin signaling pathway was most directly involved in apoptosis, through the overexpression of NGFR and Bax genes. The increased expression of genes involved in the NGFR-MAPK10-TP53-Bax/Bcl2 pathway during incubation with AZA plus everolimus was validated by western blotting in MZ-CRC-1 cells. Interestingly, addition of a neutralizing anti-NGFR antibody inhibited the synergistic cytotoxic activity between AZA and everolimus. These results open a new therapeutic scenario for MTC and potentially other neuroendocrine tumors, where therapy with mTOR inhibitors is currently approved.

Indexed as

Carcinoma, NeuroendocrineThyroid NeoplasmsAzacitidineDecitabineDrug SynergismEverolimusGene Expression Regulation, NeoplasticGenome-Wide Association StudyHumansNeoplasm ProteinsAzacitidineDecitabineEverolimusNeoplasm Proteins5-aza-2′-deoxycytidineeverolimusmedullary thyroid cancermTORneurotrophin pathwayNGFR

Identifiers

PMID28453190
PMCPMC5537710
OpenAlexW2607886433

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.