Evidence map›Paper›PMID 24126464›Full record

ArticleInternational journal of oncology2013

Increased killing of SCCVII squamous cell carcinoma cells after the combination of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3 activity and ceramide synthase 1 upregulation.

Duska Separovic, Paul Breen, Nithin B Boppana, Eric Van Buren, Nicholas Joseph, Jacqueline M Kraveka, Mehrdad Rahmaniyan, Li Li, Tatyana I Gudz, Alicja Bielawska and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of oncology, 2013. 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
1.0field-weighted citation impact, top 23% 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, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2016
    Article
  5. Article
  6. 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

14 authors at 6 institutions in 2 countries.

Duska SeparovicDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Paul Breen
Nithin B Boppana
Eric Van Buren
Nicholas Joseph
Jacqueline M Kraveka
Mehrdad Rahmaniyan
Li Li
Tatyana I Gudz
Alicja Bielawska
Aiping Bai
Jacek Bielawski
Jason S Pierce
Mladen Korbelik
Medical University of South Carolina · USEugene Applebaum College of Pharmacy and Health Sciences · USMUSC Hollings Cancer Center · USWayne State University · USBC Cancer Agency · CAThe Barbara Ann Karmanos Cancer Institute · US

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MAO, CUNGUI · 2002 to 2011
$23.4M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR018823 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2003 to 2003
$2.9M
Sphingolipids in Cell Death after PhotodamageR01CA077475 · NCI · WAYNE STATE UNIVERSITY · PI SEPAROVIC, DUSKA M · 2005 to 2012
$1.6M
NCI NIH HHS IPO1CA097132NCI NIH HHS P01 CA097132NCI NIH HHS P30 CA022453NCI NIH HHS P30 CA 138313NCI NIH HHS P30 CA138313NCI NIH HHS P30 CA22453NCI NIH HHS R01 CA077475NCI NIH HHS R01 CA77475NCRR NIH HHS C06 RR018823NCRR NIH HHS P20 RR017677NCRR NIH HHS P20-RR17677
6 · The paper itself

Abstract

Photodynamic therapy (PDT) is not always effective as an anticancer treatment, therefore, PDT is combined with other anticancer agents for improved efficacy. The combination of dasatinib and PDT with the silicone phthalocyanine photosensitizer Pc 4 was assessed for increased killing of SCCVII mouse squamous cell carcinoma cells, a preclinical model of head and neck squamous cell carcinoma, using apoptotic markers and colony formation as experimental end-points. Because each of these treatments regulates the metabolism of the sphingolipid ceramide, their effects on mRNA levels of ceramide synthase, a ceramide-producing enzyme, and the sphingolipid profile were determined. PDT + dasatinib induced an additive loss of clonogenicity. Unlike PDT alone or PDT + dasatinib, dasatinib induced zVAD-fmk-dependent cell killing. PDT or dasatinib-induced caspase-3 activation was potentiated after the combination. PDT alone induced mitochondrial depolarization, and the effect was inhibited after the combination. Annexin V+ and propidium iodide+ cells remained at control levels after treatments. In contrast to PDT alone, dasatinib induced upregulation of ceramide synthase 1 mRNA, and the effect was enhanced after the combination. Dasatinib induced a modest increase in C20:1- and C22-ceramide but had no effect on total ceramide levels. PDT increased the levels of 12 individual ceramides and total ceramides, and the addition of dasatinib did not affect these increases. PDT alone decreased substantially sphingosine levels and inhibited the activity of acid ceramidase, an enzyme that converts ceramide to sphingosine. The data suggest that PDT-induced increases in ceramide levels do not correlate with ceramide synthase mRNA levels but rather with inhibition of ceramidase. Cell killing was zVAD-fmk-sensitive after dasatinib but not after either PDT or the combination and enhanced cell killing after the combination correlated with potentiated caspase-3 activation and upregulation of ceramide synthase 1 mRNA but not the production of ceramide. The data imply potential significance of the combination for cancer treatment.

Indexed as

Abdominal NeoplasmsAcid CeramidaseAmino Acid Chloromethyl KetonesAnimalsAnnexin A5ApoptosisCarcinoma, Squamous CellCaspase 3Caspase 9Cell Line, TumorCeramidesDasatinibEnzyme ActivationHead and Neck NeoplasmsIndolesMiceAcid CeramidaseAmino Acid Chloromethyl KetonesAnnexin A5benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketoneCaspase 3Caspase 9CeramidesDasatinibdihydroceramide desaturaseIndolesOxidoreductasesphthalocyanine Pc 4PropidiumProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrimidinesRNA, MessengerSphingosineThiazoles

Identifiers

PMID24126464
PMCPMC3834346
OpenAlexW2139723436

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.