Evidence map›Paper›PMID 26188016›Full record

ArticleNeuro-oncology2016

Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses.

Gregory K Friedman, Blake P Moore, Li Nan, Virginia M Kelly, Tina Etminan, Catherine P Langford, Hui Xu, Xiaosi Han, James M Markert, Elizabeth A Beierle and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
–field-weighted citation impact
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

51 citing papers in PubMed.

  1. Review
  2. From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Review
  3. Review
  4. Review
  5. Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Safety and Efficacy of Intraventricular Immunovirotherapy with Oncolytic HSV-1 for CNS Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
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

11 authors.

Gregory K FriedmanDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Blake P MooreDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Li NanDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Virginia M KellyDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Tina EtminanDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Catherine P LangfordDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Hui XuDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Xiaosi HanDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
James M MarkertDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
Elizabeth A BeierleDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).
G Yancey GillespieDivision of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham (UAB), Birmingham, Alabama (G.K.F., B.P.M., L.N., V.M.K.); Science and Technology Honors Program, Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama (T.E.); Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama (C.P.L., J.M.M., G.Y.G.); Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama (H.X.); Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama (X.H.); Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (E.A.B.).

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
Virus Production CoreP01CA071933 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WEICHSELBAUM, RALPH R · 1997 to 2013
$14.5M
Viral and molecular chemotherapy of malignant CNS tumorsP50CA097247 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GILLESPIE, G. YANCEY · 2002 to 2009
$13.5M
ROS Modulation of Innate and Adaptive Immunity in RAP30AR048311 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MOUNTZ, JOHN D · 2001 to 2017
$9.5M
CONTEMPORARY THERAPEUTICS FOR ANAPLASTIC GLIOMASP20CA151129 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GILLESPIE, G. YANCEY · 2011 to 2013
$2.3M
Targeting PRMT5 in Cancer Initiating Cells as a New Therapy for GlioblastomaR01NS095626 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HAN, XIAOSI · 2015 to 2019
$1.6M
NCI NIH HHS CA071933NCI NIH HHS CA097247NCI NIH HHS CA13148-40NCI NIH HHS CA151129NCI NIH HHS P30 CA013148NIAID NIH HHS P30 AI027767NIAMS NIH HHS P30 AR048311NINDS NIH HHS R01 NS095626
6 · The paper itself

Abstract

backgroundChildhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15.

methodsUsing 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies.

resultsWe demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002.

conclusionsPediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted.

Indexed as

Oncolytic VirotherapyAC133 AntigenAnimalsAntigens, CDApoptosisCell ProliferationCerebellar NeoplasmsChildFucosyltransferasesGlycoproteinsHumansImmunoenzyme TechniquesLewis X AntigenMedulloblastomaMiceMice, NudeAC133 AntigenAntigens, CDFucosyltransferasesFUT4 protein, humanGlycoproteinsLewis X AntigenPeptidesPROM1 protein, humanProm1 protein, mouseCD133CD15HSVmedulloblastomavirotherapy

Identifiers

PMID26188016
PMCPMC4724175

What OpenQuestion holds

Textmetadata
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.