Evidence map›Paper›PMID 19798049›Full record

ArticleGene therapy2010

The HSV-2 mutant DeltaPK induces melanoma oncolysis through nonredundant death programs and associated with autophagy and pyroptosis proteins.

A G Colunga, J M Laing, L Aurelian

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

41 citing papers in PubMed, 53 citations in OpenAlex.

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  12. Non-Apoptotic Cell Death Signaling Pathways in Melanoma.International journal of molecular sciences · 2020
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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

3 authors at 1 institution in 1 country.

A G ColungaDepartment of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore, MD 21201-1559, USA.
J M Laing
L Aurelian
University of Maryland, Baltimore · US

Funding

Training in Molecular and Mechanistic ToxicologyT32ES007263 · NIEHS · UNIVERSITY OF MARYLAND BALTIMORE · PI ALBUQUERQUE, EDSON X · 1990 to 2012
$2.4M
Apoptosis of skin melanoma by the new Hsp H11R01AR053512 · NIAMS · UNIVERSITY OF MARYLAND BALTIMORE · PI AURELIAN, LAURE · 2007 to 2011
$1.6M
NIAMS NIH HHS AR053512NIAMS NIH HHS R01 AR053512NIEHS NIH HHS ES07263NIEHS NIH HHS T32 ES007263
6 · The paper itself

Abstract

Malignant melanoma is a highly aggressive and drug-resistant cancer. Virotherapy is a novel therapeutic strategy based on cancer cell lysis through selective virus replication. However, its clinical efficacy is modest, apparently related to poor virus replication within the tumors. We report that the growth compromised herpes simplex virus type 2 (HSV-2) mutant, DeltaPK, has strong oncolytic activity for melanoma largely caused by a mechanism other than replication-induced cell lysis. The ratio of dead cells (determined by trypan blue or ethidium homodimer staining) to cells that stain with antibody to the major capsid protein VP5 (indicative of productive infection) was 1.8-4.1 for different melanoma cultures at 24-72 h post-infection. Cell death was due to activation of calpain as well as caspases-7 and -3 and it was abolished by the combination of calpain (PD150606) and pancaspase (benzyloxycarbonyl-Val-Ala-Asp-fluormethyl ketone, z-VAD-fmk) inhibitors. Upregulation of the autopahgy protein Beclin-1 and the pro-apoptotic protein H11/HspB8 accompanied DeltaPK-induced melanoma oncolysis. Intratumoral DeltaPK injection (10(6)-10(7) plaque-forming unit (pfu)) significantly reduced melanoma tumor burden associated with calpain and caspases-7 and -3 activation, Beclin-1 and H11/HspB8 upregulation and activation of caspase-1-related inflammation. Complete remission was seen for 87.5% of the LM melanoma xenografts at 5 months after treatment termination. The data indicate that DeltaPK is a promising virotherapy for melanoma that functions through virus-induced programmed cell death pathways.

Indexed as

AnimalsApoptosisAutophagyCalpainCapsid ProteinsCaspase 3Caspase 7Caspase InhibitorsCell Line, TumorGene DeletionHerpesvirus 2, HumanHumansMelanomaMiceMice, NudeOncolytic VirotherapyCalpainCapsid ProteinsCaspase 3Caspase 7Caspase InhibitorsICP10 protein, herpes simplex virus type 2Protein Serine-Threonine KinasesRibonucleotide Reductases

Identifiers

PMID19798049
PMCPMC2904070
OpenAlexW2033442756

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.