Evidence map›Paper›PMID 26459178›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

Mithramycin Depletes Specificity Protein 1 and Activates p53 to Mediate Senescence and Apoptosis of Malignant Pleural Mesothelioma Cells.

Mahadev Rao, Scott M Atay, Vivek Shukla, Young Hong, Trevor Upham, R Taylor Ripley, Julie A Hong, Mary Zhang, Emily Reardon, Patricia Fetsch and 8 more

Open access · greenAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-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

22 citing papers in PubMed, 31 citations in OpenAlex.

  1. Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Observational
  11. UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021
    Article
  12. Article
  13. Genomics and Functional Genomics of Malignant Pleural Mesothelioma.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Article
  16. Mithramycin A Enhances Tumor Sensitivity to Mitotic Catastrophe Resulting From DNA Damage.International journal of radiation oncology, biology, physics · 2018
    Article
  17. Article
  18. Targeting the epigenome in malignant pleural mesothelioma.Translational lung cancer research · 2017
    Review
  19. Article
  20. 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

18 authors at 3 institutions in 1 country.

Mahadev RaoThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Scott M AtayThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Vivek ShuklaThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Young HongThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Trevor UphamThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
R Taylor RipleyThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Julie A HongThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Mary ZhangThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Emily ReardonThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland.
Patricia FetschLaboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
Markku MiettinenLaboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
Xinmin LiClinical Micro-array Core, University of California, Los Angeles, California.
Cody J PeerMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Tristan SissungMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
William D FiggMolecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Assunta De RienzoDivision of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Raphael BuenoDivision of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
David S SchrumpThoracic Epigenetics Section, Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, Maryland. david.schrump@nih.gov.
National Cancer Institute · USBrigham and Women's Hospital · USBioClinica (United States) · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Modulating Cancer Stem Cell Signaling in Thoracic MalignanciesZIABC011418 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHRUMP, DAVID · 2011 to 2025
$17.4M
Epigenetic Mechanisms of Gene Expression in Thoracic MalignanciesZIABC011115 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHRUMP, DAVID · 2009 to 2025
$15.1M
Epigenetic Alterations Induced by Tobacco SmokeZIABC011122 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHRUMP, DAVID · 2009 to 2013
$3.3M
Intramural NIH HHS ZIA BC011122Intramural NIH HHS ZIA BC011418NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

purposeSpecificity protein 1 (SP1) is an oncogenic transcription factor overexpressed in various human malignancies. This study sought to examine SP1 expression in malignant pleural mesotheliomas (MPM) and ascertain the potential efficacy of targeting SP1 in these neoplasms. EXPERIMENTAL

designqRT-PCR, immunoblotting, and immunohistochemical techniques were used to evaluate SP1 expression in cultured MPM cells and MPM specimens and normal mesothelial cells/pleura. MTS, chemotaxis, soft agar, β-galactosidase, and Apo-BrdUrd techniques were used to assess proliferation, migration, clonogenicity, senescence, and apoptosis in MPM cells following SP1 knockdown, p53 overexpression, or mithramycin treatment. Murine subcutaneous and intraperitoneal xenograft models were used to examine effects of mithramycin on MPM growth in vivo. Microarray, qRT-PCR, immunoblotting, and chromatin immunoprecipitation techniques were used to examine gene expression profiles mediated by mithramycin and combined SP1 knockdown/p53 overexpression and correlate these changes with SP1 and p53 levels within target gene promoters.

resultsMPM cells and tumors exhibited higher SP1 mRNA and protein levels relative to control cells/tissues. SP1 knockdown significantly inhibited proliferation, migration, and clonogenicity of MPM cells. Mithramycin depleted SP1 and activated p53, dramatically inhibiting proliferation and clonogenicity of MPM cells. Intraperitoneal mithramycin significantly inhibited growth of subcutaneous MPM xenografts and completely eradicated mesothelioma carcinomatosis in 75% of mice. Mithramycin modulated genes mediating oncogene signaling, cell-cycle regulation, senescence, and apoptosis in vitro and in vivo. The growth-inhibitory effects of mithramycin in MPM cells were recapitulated by combined SP1 knockdown/p53 overexpression.

conclusionsThese findings provide preclinical rationale for phase II evaluation of mithramycin in patients with mesothelioma.

Indexed as

AnimalsApoptosisBiomarkers, TumorCell ProliferationCellular SenescenceFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMesotheliomaMesothelioma, MalignantMiceMiddle AgedPleural NeoplasmsPlicamycinRNA, MessengerBiomarkers, TumorPlicamycinRNA, MessengerSP1 protein, humanSp1 Transcription FactorTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26459178
PMCPMC4775437
OpenAlexW2213319405

What OpenQuestion holds

Textmetadata
LicenceTDM
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.