Evidence map›Paper›PMID 35284625›Full record

ArticleMolecular therapy oncolytics2022

NAD+ depletion enhances reovirus-induced oncolysis in multiple myeloma.

Barry E Kennedy, Michael Giacomantonio, J Patrick Murphy, Samuel Cutler, Maryanne Sadek, Prathyusha Konda, Joao A Paulo, Gopal P Pathak, Saskia H J Renkens, Stacy Grieve and 8 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy oncolytics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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 4 institutions in 5 countries.

Barry E KennedyDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Michael GiacomantonioDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
J Patrick MurphyDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Samuel CutlerDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Maryanne SadekDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Prathyusha KondaDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Gopal P PathakDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Saskia H J RenkensDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Stacy GrieveDepartment of Biology, University of New Brunswick, Saint John E2L 4L2, Canada.
Jonathan PolGustave Roussy Comprehensive Cancer Institute, Villejuif 94800, France.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Christopher RichardsonDepartment of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada.
Daniel GastonDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Anthony ReimanDepartment of Biology, University of New Brunswick, Saint John E2L 4L2, Canada.
Guido KroemerDepartment of Pathology and Laboratory Medicine, Nova Scotia Health Authority (NSHA), Halifax, NS B3H 1V8, Canada.
Manal O ElnenaeiDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Shashi A GujarDepartment of Pathology, Dalhousie University, Rm. 11J Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS B3H 1X5, Canada.
Dalhousie University · CAHarvard University · USUniversity of New Brunswick · CAInserm · FR

Funding

Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
NIGMS NIH HHS R01 GM132129
6 · The paper itself

Abstract

Cancer cell energy metabolism plays an important role in dictating the efficacy of oncolysis by oncolytic viruses. To understand the role of multiple myeloma metabolism in reovirus oncolysis, we performed semi-targeted mass spectrometry-based metabolomics on 12 multiple myeloma cell lines and revealed a negative correlation between NAD+ levels and susceptibility to oncolysis. Likewise, a negative correlation was observed between the activity of the rate-limiting NAD+ synthesis enzyme NAMPT and oncolysis. Indeed, depletion of NAD+ levels by pharmacological inhibition of NAMPT using FK866 sensitized several myeloma cell lines to reovirus-induced killing. The myelomas that were most sensitive to this combination therapy expressed a functional p53 and had a metabolic and transcriptomic profile favoring mitochondrial metabolism over glycolysis, with the highest synergistic effect in KMS12 cells. Mechanistically, U-

Indexed as

aerobic glycolysisautophagycancer metabolismFK866mitochondrial metabolismNAD+NAMPToncolytic virusp53reovirus

Identifiers

PMID35284625
PMCPMC8904403
OpenAlexW4212894372

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.