Evidence map›Paper›PMID 28801914›Full record

ArticleInternational journal of cancer2017

Blockade of transforming growth factor-β signaling enhances oncolytic herpes simplex virus efficacy in patient-derived recurrent glioblastoma models.

Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  8. The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024
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  14. Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Article
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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

12 authors at 2 institutions in 2 countries.

Shinichi EsakiDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Fares NigimDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Esther MoonDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Samantha LukDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Juri KiyokawaDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
William CurryDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Andrew S ChiLaura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY.
A John IafrateDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Robert L MartuzaDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Samuel D RabkinDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Hiroaki WakimotoDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-8225-241X
Harvard University · USNYU Langone Health · US

Funding

GENETICALLY ENGINEERED VIRUSES FOR BRAIN TUMOR THERAPYR01NS032677 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MARTUZA, ROBERT L · 1994 to 2022
$9.0M
Targeting Tumorigenic Pathways in Glioblastoma with Oncolytic HSVR01CA160762 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI RABKIN, SAMUEL DAVID · 2012 to 2023
$3.7M
Novel oncolytic virotherapy for brain tumorsR21NS103187 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI WAKIMOTO, HIROAKI · 2017 to 2018
$464k
NCI NIH HHS R01 CA160762NINDS NIH HHS R01 NS032677NINDS NIH HHS R21 NS103187
6 · The paper itself

Abstract

Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis. We hypothesized that oHSV and TGF-β inhibitors would synergistically exert antitumor effects for recurrent GBM. Here we established a panel of patient-derived recurrent tumor models from GBMs that relapsed after postsurgical radiation and chemotherapy, based on GSC-enriched tumor sphere cultures. These GSCs are resistant to the standard-of-care temozolomide but susceptible to oHSVs G47Δ and MG18L. Inhibition of TGF-β receptor kinase with selective targeted small molecules reduced clonogenic sphere formation in all tested recurrent GSCs. The combination of oHSV and TGF-βR inhibitor was synergistic in killing recurrent GSCs through, in part, an inhibitor-induced JNK-MAPK blockade and increase in oHSV replication. In vivo, systemic treatment with TGF-βR inhibitor greatly enhanced the antitumor effects of single intratumoral oHSV injections, resulting in cures in 60% of mice bearing orthotopic recurrent GBM. These results reveal a novel synergistic interaction of oHSV therapy and TGF-β signaling blockade, and warrant further investigations aimed at clinical translation of this combination strategy for GBM patients.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsBlotting, WesternBrain NeoplasmsGlioblastomaHumansImmunohistochemistryMiceMice, SCIDNeoplastic Stem CellsOncolytic VirotherapyReal-Time Polymerase Chain ReactionSignal TransductionSimplexvirusTransforming Growth Factor betaXenograft Model Antitumor AssaysTransforming Growth Factor betaJNKoncolytic HSVrecurrent glioblastomaTGF-β

Identifiers

PMID28801914
PMCPMC5765440
OpenAlexW2745132180

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.