Evidence map›Paper›PMID 30967582›Full record

ArticleScientific reports2019

p38 MAPK activation through B7-H3-mediated DUSP10 repression promotes chemoresistance.

Karine Flem-Karlsen, Christina Tekle, Tove Øyjord, Vivi A Flørenes, Gunhild M Mælandsmo, Øystein Fodstad, Caroline E Nunes-Xavier

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

31 citing papers in PubMed, 40 citations in OpenAlex.

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  18. An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
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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 1 institution in 1 country.

Karine Flem-KarlsenDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.ORCID http://orcid.org/0000-0001-8405-3406
Christina TekleDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Tove ØyjordDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Vivi A FlørenesDepartment of Pathology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Gunhild M MælandsmoDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Øystein FodstadDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Caroline E Nunes-XavierDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. carnun@rr-research.no.
Oslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunoregulatory protein B7-H3 is involved in the oncogenic and metastatic potential of cancer cells, as well as in drug resistance. Resistance to conventional chemotherapy is an important aspect of melanoma treatment, and a better understanding of how B7-H3 enhances drug resistance may lead to the development of more effective therapies. We investigated the in vitro and in vivo sensitivity of chemotherapeutic agents dacarbazine (DTIC) and cisplatin in sensitive and drug resistant melanoma cells with knockdown expression of B7-H3. We found that knockdown of B7-H3 increased in vitro and in vivo sensitivity of melanoma cells to the chemotherapeutic agents dacarbazine (DTIC) and cisplatin, in parallel with a decrease in p38 MAPK phosphorylation. Importantly, in B7-H3 knockdown cells we observed an increase in the expression of dual-specific MAP kinase phosphatase (MKP) DUSP10, a MKP known to dephosphorylate and inactivate p38 MAPK. DUSP10 knockdown by siRNA resulted in a reversion of the increased DTIC-sensitivity seen in B7-H3 knockdown cells. Our findings highlight the potential therapeutic benefit of combining chemotherapy with B7-H3 inhibition, and indicate that B7-H3 mediated chemoresistance in melanoma cells is driven through a mechanism involving DUSP10-mediated inactivation of p38 MAPK.

Indexed as

AnimalsAntineoplastic AgentsB7 AntigensCell Line, TumorCisplatinDacarbazineDrug Resistance, NeoplasmDual-Specificity PhosphatasesHumansMelanomaMiceMitogen-Activated Protein Kinase Phosphatasesp38 Mitogen-Activated Protein KinasesPhosphorylationSignal TransductionAntineoplastic AgentsB7 AntigensCD276 protein, humanCisplatinDacarbazineDual-Specificity PhosphatasesDUSP10 protein, humanMitogen-Activated Protein Kinase Phosphatasesp38 Mitogen-Activated Protein Kinases

Identifiers

PMID30967582
PMCPMC6456585
OpenAlexW2939719554

What OpenQuestion holds

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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.