Evidence map›Paper›PMID 32562798›Full record

ArticleMetabolism: clinical and experimental2020

Targeting pheochromocytoma/paraganglioma with polyamine inhibitors.

Sudhir Kumar Rai, Fernando Bril, Heather M Hatch, Yiling Xu, Laura Shelton, Srilaxmi Kalavalapalli, Arielle Click, Douglas Lee, Chris Beecher, Austin Kirby and 29 more

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

Article in Metabolism: clinical and experimental, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Pheochromocytomas and Paragangliomas.Endocrinology and metabolism clinics of North America · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. New Biology of Pheochromocytoma and Paraganglioma.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Review
  9. Article
  10. Article
  11. Review
  12. Review
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

39 authors at 16 institutions in 6 countries.

Sudhir Kumar RaiDepartment of Medicine, Division of Endocrinology, University of Florida, Gainesville, FL, USA.
Fernando BrilDepartment of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, USA.
Heather M HatchDepartment of Physiological Sciences, University of Florida, Gainesville, FL, USA.
Yiling XuDepartment of Medicine, Division of Endocrinology, University of Florida, Gainesville, FL, USA.
Laura SheltonScientific Project Development, Human Metabolome Technologies, Boston, MA, USA.
Srilaxmi KalavalapalliDepartment of Medicine, Division of Endocrinology, University of Florida, Gainesville, FL, USA.
Arielle ClickDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Douglas LeeOmic Insight, LLC, Durham, NC, USA.
Chris BeecherIROA Technologies, Chapel Hill, NC, USA.
Austin KirbyDepartment of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Kimi KongDepartment of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Jose TrevinoDepartment of Surgery, University of Florida, Gainesville, FL, USA.
Abhishek JhaElucidata, Cambridge, MA, USA.
Shashank JatavElucidata, Cambridge, MA, USA.
Kriti KritiElucidata, Cambridge, MA, USA.
Soumya LuthraElucidata, Cambridge, MA, USA.
Timothy J GarrettDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Joy Guingab-CagmatDepartment of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Daniel PlantDepartment of Physiological Sciences, University of Florida, Malcom Randall VA Medical Center, Gainesville, FL, USA.
Prodip BoseDepartment of Physiological Sciences, University of Florida, Malcom Randall VA Medical Center, Gainesville, FL, USA.
Kenneth CusiDepartment of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, USA.
Robert A HromasDepartment of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Arthur S TischlerDepartment of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA.
James F PowersDepartment of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA.
Priyanka GuptaDepartment of Surgery, University of Alabama, Birmingham, AL, USA.
James BibbDepartment of Surgery, University of Alabama, Birmingham, AL, USA.
Felix BeuschleinKlinik für Endokrinologie, Diabetologie und Klinische Ernährung, UniversitätsSpital Zurich, Zurich, Switzerland.
Mercedes RobledoHereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Bruna CalsinaHereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Henri TimmersDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
David TaiebDepartment of Nuclear Medicine, La Timone University Hospital, European Center for Research in Medical Imaging, Aix Marseille Université, Marseille, France.
Matthias KroissDepartment of Internal Medicine, Division of Endocrinology and Diabetology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Susan RichterInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Katharina LangtonDepartment of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Graeme EisenhoferInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, and Department of Medicine, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Raymond BergeronDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL, USA.
Karel PacakEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Sergei G TevosianDepartment of Physiological Sciences, University of Florida, Gainesville, FL, USA. Electronic address: stevosian@ufl.edu.
Hans K GhayeeDepartment of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, USA. Electronic address: hans.ghayee@medicine.ufl.edu.
University of Florida · USMalcom Randall VA Medical Center · USThe University of Texas Health Science Center at San Antonio · USTufts Medical Center · USUniversity Hospital Carl Gustav Carus · DEUniversity of Alabama at Birmingham · USAix-Marseille Université · FRCentre for Biomedical Network Research on Rare Diseases · ESEunice Kennedy Shriver National Institute of Child Health and Human Development · USRadboud University Medical Center · NLSpanish National Cancer Research Centre · ESStrategic Insight (United States) · USThe University of Texas Southwestern Medical Center · USTU Dresden · DEUniversitätsklinik für Diabetologie, Endokrinologie, Ernährungsmedizin & Metabolismus · CHUniversity of Würzburg · DE

Funding

Diagnosis, Pathophysiology And Molecular Biology of Pheochromocytoma and ParagangliomaZIAHD008735 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PACAK, KAREL · 2009 to 2024
$28.4M
EEPD1 Repair of Stressed Replication ForksR01CA205224 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robert A Hromas · 2016 to 2026
$3.3M
Biomarkers For BRCA1-Deficient CancersR01CA279971 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Kimi Y Kong · 2024 to 2026
$1.3M
Intramural NIH HHS Z99 HD999999Intramural NIH HHS ZIA HD008735NCI NIH HHS R01 CA205224NCI NIH HHS R01 CA279971RRD VA I01 RX003123
6 · The paper itself

Abstract

backgroundPheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors that are mostly benign. Metastatic disease does occur in about 10% of cases of PCC and up to 25% of PGL, and for these patients no effective therapies are available. Patients with mutations in the succinate dehydrogenase subunit B (SDHB) gene tend to have metastatic disease. We hypothesized that a down-regulation in the active succinate dehydrogenase B subunit should result in notable changes in cellular metabolic profile and could present a vulnerability point for successful pharmacological targeting.

methodsMetabolomic analysis was performed on human hPheo1 cells and shRNA SDHB knockdown hPheo1 (hPheo1 SDHB KD) cells. Additional analysis of 115 human fresh frozen samples was conducted. In vitro studies using N

resultsComponents of the polyamine pathway were elevated in hPheo1 SDHB KD cells compared to wild-type cells. A similar observation was noted in SDHx PCC/PGLs tissues compared to their non-mutated counterparts. Specifically, spermidine, and spermine were significantly elevated in SDHx-mutated PCC/PGLs, with a similar trend in hPheo1 SDHB KD cells. Polyamine pathway inhibitors DENSPM and DESPM effectively inhibited growth of hPheo1 cells in vitro as well in mouse xenografts.

conclusionsThis study demonstrates overactive polyamine pathway in PCC/PGL with SDHB mutations. Treatment with polyamine pathway inhibitors significantly inhibited hPheo1 cell growth and led to growth suppression in xenograft mice treated with DENSPM. These studies strongly implicate the polyamine pathway in PCC/PGL pathophysiology and provide new foundation for exploring the role for polyamine analogue inhibitors in treating metastatic PCC/PGL. PRéCIS: Cell line metabolomics on hPheo1 cells and PCC/PGL tumor tissue indicate that the polyamine pathway is activated. Polyamine inhibitors in vitro and in vivo demonstrate that polyamine inhibitors are promising for malignant PCC/PGL treatment. However, further research is warranted.

Indexed as

Adrenal Gland NeoplasmsAnimalsBiogenic PolyaminesCell Line, TumorHumansMaleMetabolomicsMiceMutationParagangliomaPheochromocytomaSuccinate DehydrogenaseXenograft Model Antitumor AssaysBiogenic PolyaminesSDHB protein, humanSuccinate DehydrogenaseDENSPMDESPMParaganglioma (PGL)Pheochromocytoma (PCC)PolyamineSDHB

Identifiers

PMID32562798
PMCPMC7482423
OpenAlexW3036713531

What Socratic 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 Socratic graph.