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01.02.2013 | Laboratory Investigation

B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma

verfasst von: Zhiping Zhou, Neal Luther, George M. Ibrahim, Cynthia Hawkins, Rajeev Vibhakar, Michael H. Handler, Mark M. Souweidane

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2013

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Abstract

Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.

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Titel: B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma
verfasst von: Zhiping Zhou
Neal Luther
George M. Ibrahim
Cynthia Hawkins
Rajeev Vibhakar
Michael H. Handler
Mark M. Souweidane
Publikationsdatum: 01.02.2013
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2013
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-012-1021-2

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