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Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid: Case report

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Wagner S, Csatary CM, Gosztonyi G, Koch HC, Hartmann C, Peters O, Hernáiz-Driever P, Théallier-Janko A, Zintl F, Längler A, Wolff JEA, Csatary LK. Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid. APMIS 2006;114:731–43.

The case of a 12-year-old boy with anaplastic astrocytoma of the left thalamus is reported. Postoperative irradiation and chemotherapy could not repress tumor progression; therefore, treatment was undertaken with an oncolytic virus, MTH-68/H, an attenuated strain of Newcastle disease virus (NDV), and valproic acid (VPA), an antiepileptic drug, which also has antineoplastic properties. This treatment resulted in a far-reaching regression of the thalamic glioma, but 4 months later a new tumor manifestation, an extension of the thalamic tumor, appeared in the wall of the IVth ventricle, which required a second neurosurgical intervention. Under continuous MTH-68/H – VPA administration the thalamic tumor remained under control, but the rhombencephalic one progressed relentlessly and led to the fatal outcome. In the final stage, a third tumor manifestation appeared in the left temporal lobe. The possible reasons for the antagonistic behavior of the three manifestations of the same type of glioma to the initially most successful therapy are discussed. The comparative histological study of the thalamic and rhombencephalic tumor manifestations revealed that MTH-68/H treatment induces, similar to in vitro observations, a massive apoptotic tumor cell decline. In the rhombencephalic tumor, in and around the declining tumor cells, NDV antigen could be demonstrated immunohistochemically, and virus particles have been found in the cytoplasm of tumor cells at electron microscopic investigation. These findings document that the oncolytic effect of MTH-68/H treatment is the direct consequence of virus presence and replication in the neoplastic cells. This is the first demonstration of NDV constituents in an MTH-68/H -treated glioma.

Keywords: High-grade glioma; MTH-68/H; Newcastle disease virus (NDV); blood-brain barrier (BBB); oncolytic viruses; valproic acid (VPA)

Document Type: Research Article


Affiliations: 1: Dept. of Pediatric Oncology, Krankenhaus der Barmherzigen Brüder, Klinik St. Hedwig, University of Regensburg, 2: United Cancer Research Institute (UCRI), Alexandria, USA, 3: Dept. of Radiology, 4: Institute of Neuropathology, 5: Dept. of Pediatric Oncology, Charité, Universitätsmedizin Berlin, 6: Dept. of Pathology, Sankt Gertrauden-Krankenhaus, Berlin, 7: Dept. of Pediatric Oncology, Friedrich-Schiller-Universität Jena, 8: Dept. of Pediatrics, Gemeinschaftskrankenhaus Herdecke, Germany, 9: Anderson Cancer Center, University of Texas, Dept. of Pediatrics, Section Pediatric Neurooncology, Houston, USA

Publication date: October 1, 2006


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