Evidence map›Paper›PMID 36790532›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2023

Simultaneous targeting of mitochondrial Kv1.3 and lysosomal acid sphingomyelinase amplifies killing of pancreatic ductal adenocarcinoma cells in vitro and in vivo.

Sameer H Patel, Magdalena Bachmann, Stephanie Kadow, Gregory C Wilson, Mostafa M L Abdel-Salam, Kui Xu, Simone Keitsch, Matthias Soddemann, Barbara Wilker, Katrin Anne Becker and 4 more

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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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 3 institutions in 3 countries.

Sameer H PatelDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Magdalena BachmannDepartment of Biologyand , CNR Institute of Neurosciences, University of Padua, Padua, Italy.
Stephanie KadowInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Gregory C WilsonDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Mostafa M L Abdel-SalamDepartment of Biologyand , CNR Institute of Neurosciences, University of Padua, Padua, Italy.
Kui XuDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Simone KeitschInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Matthias SoddemannInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Barbara WilkerInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Katrin Anne BeckerInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Alexander CarpinteiroInstitute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Syed A AhmadDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Ildiko SzaboDepartment of Biologyand , CNR Institute of Neurosciences, University of Padua, Padua, Italy. ildiko.szabo@unipd.it.
Erich GulbinsDepartment of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA. erich.gulbins@uni-due.de.ORCID 0000-0002-3117-1342
Institute of Molecular Biology · DEUniversity of Cincinnati Medical Center · USUniversity of Padua · IT

Funding

Worldwide Cancer Research 22-0348
6 · The paper itself

Abstract

Pancreas ductal adenocarcinoma (PDAC) remains a malignant tumor with very poor prognosis and low 5-year overall survival. Here, we aimed to simultaneously target mitochondria and lysosomes as a new treatment paradigm of malignant pancreas cancer in vitro and in vivo. We demonstrate that the clinically used sphingosine analog FTY-720 together with PAPTP, an inhibitor of mitochondrial Kv1.3, induce death of pancreas cancer cells in vitro and in vivo. The combination of both drugs results in a marked inhibition of the acid sphingomyelinase and accumulation of cellular sphingomyelin in vitro and in vivo in orthotopic and flank pancreas cancers. Mechanistically, PAPTP and FTY-720 cause a disruption of both mitochondria and lysosomes, an alteration of mitochondrial bioenergetics and accumulation of cytoplasmic Ca

Indexed as

Carcinoma, Pancreatic DuctalPancreatic NeoplasmsCell Line, TumorFingolimod HydrochlorideHumansLysosomesMitochondriaPancreatic DuctsSphingomyelin PhosphodiesteraseSphingomyelinsFingolimod HydrochlorideSphingomyelin PhosphodiesteraseSphingomyelinsAcid sphingomyelinaseKv1.3LysosomesMitochondriaPancreas cancerSphingolipids

Identifiers

PMID36790532
PMCPMC10036429
OpenAlexW4320856339

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read76
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.