Evidence map›Paper›PMID 27626308›Full record

ArticleOncotarget2016

The pathophysiological significance of PPM1D and therapeutic targeting of PPM1D-mediated signaling by GSK2830371 in mantle cell lymphoma.

Kensuke Kojima, Aya Maeda, Mariko Yoshimura, Yuki Nishida, Shinya Kimura

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 25% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020
    Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. WIP1 phosphatase as pharmacological target in cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2017
    Review
  9. Article
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 1 institution in 1 country.

Kensuke KojimaDepartment of Hematology, Respiratory Medicine and Oncology, Division of Medicine, Saga University, Saga, Japan.
Aya MaedaDepartment of Hematology, Respiratory Medicine and Oncology, Division of Medicine, Saga University, Saga, Japan.
Mariko YoshimuraDepartment of Hematology, Respiratory Medicine and Oncology, Division of Medicine, Saga University, Saga, Japan.
Yuki NishidaDepartment of Hematology, Respiratory Medicine and Oncology, Division of Medicine, Saga University, Saga, Japan.
Shinya KimuraDepartment of Hematology, Respiratory Medicine and Oncology, Division of Medicine, Saga University, Saga, Japan.
Saga University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PPM1D is a serine/threonine phosphatase that negatively regulates key DNA damage response proteins, such as p53, p38 MAPK, histone H2A.X, and ATM. We investigated the pathophysiological significance of PPM1D and its therapeutic targeting by the novel PPM1D inhibitor GSK2830371 in mantle cell lymphoma (MCL). Oncomine-based analyses indicated increased PPM1D mRNA levels in MCL cells compared with their normal counterpart cells. Higher PPM1D expression was associated with higher expression of the proliferation gene signature and poorer prognosis in patients. Eight MCL (three p53 wild-type and five mutant) cell lines were exposed to GSK2830371. GSK2830371 inhibited the cell growth, being prominent in p53 wild-type cells. GSK2830371 induced apoptosis in sensitive cells, as evidenced by induction of phosphatidylserine externalization and loss of mitochondrial membrane potential. p53 knockdown de-sensitized cell sensitivity. GSK2830371 increased the levels of total and Ser15-phosphorylated p53, and p53 targets p21 and PUMA. GSK2830371 and the MDM2 inhibitor Nutlin-3a acted synergistically in p53 wild-type cells. Interestingly, GSK2830371 sensitized MCL cells to bortezomib and doxorubicin in p53 wild-type and mutant cells; p38 signaling appeared to be involved in the GSK2830371/bortezomib lethality. PPM1D inhibition may represent a novel therapeutic strategy for MCL, which can be exploited in combination therapeutic strategies for MCL.

Indexed as

AminopyridinesApoptosisBortezomibCell Line, TumorDipeptidesDoxorubicinGenes, p53HumansImidazolesLymphoma, Mantle-CellPhosphorylationPiperazinesPrognosisProtein Phosphatase 2CSignal TransductionAminopyridinesBortezomibDipeptidesDoxorubicinGSK2830371Imidazolesnutlin 3PiperazinesPPM1D protein, humanProtein Phosphatase 2Cmantle cell lymphomaMDM2p38 MAPKp53PPM1D

Identifiers

PMID27626308
PMCPMC5342503
OpenAlexW2516976438

What OpenQuestion holds

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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.