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dc.contributor.authorCapper, D
dc.contributor.authorvon Deimling, A
dc.contributor.authorBrandes, AA
dc.contributor.authorCarpentier, AF
dc.contributor.authorKesari, S
dc.contributor.authorSepulveda-Sanchez, JM
dc.contributor.authorWheeler, HR
dc.contributor.authorChinot, O
dc.contributor.authorCher, L
dc.contributor.authorSteinbach, JP
dc.contributor.authorSpecenier, P
dc.contributor.authorRodon, J
dc.contributor.authorCleverly, A
dc.contributor.authorSmith, C
dc.contributor.authorGueorguieva, I
dc.contributor.authorMiles, C
dc.contributor.authorGuba, SC
dc.contributor.authorDesaiah, D
dc.contributor.authorEstrem, ST
dc.contributor.authorLahn, MM
dc.contributor.authorWick, W
dc.date.accessioned2020-12-21T04:24:04Z
dc.date.available2020-12-21T04:24:04Z
dc.date.issued2017-05-01
dc.identifierpii: ijms18050995
dc.identifier.citationCapper, D., von Deimling, A., Brandes, A. A., Carpentier, A. F., Kesari, S., Sepulveda-Sanchez, J. M., Wheeler, H. R., Chinot, O., Cher, L., Steinbach, J. P., Specenier, P., Rodon, J., Cleverly, A., Smith, C., Gueorguieva, I., Miles, C., Guba, S. C., Desaiah, D., Estrem, S. T. ,... Wick, W. (2017). Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 18 (5), https://doi.org/10.3390/ijms18050995.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11343/257608
dc.description.abstractGalunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations. 158 patients were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39) and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate for central pathology review and biomarker work. Isocitrate dehydrogenase (IDH1) negative glioblastoma patients with baseline pSMAD2⁺ in cytoplasm had median overall survival (OS) 9.5 months vs. 6.9 months for patients with no tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H⁺ and had a median OS of 10.4 months compared to 6.9 months for patients with negative IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and reduced tumor CD3⁺ T cell counts. Compared to the baseline, treatment with galunisertib monotherapy preserved CD4⁺ T cell counts, eosinophils, lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was associated with better OS with MDC/CCL22 as a prominent prognostic marker.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleBiomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine
dc.typeJournal Article
dc.identifier.doi10.3390/ijms18050995
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleInternational Journal of Molecular Sciences
melbourne.source.volume18
melbourne.source.issue5
dc.rights.licenseCC BY
melbourne.elementsid1281512
melbourne.contributor.authorCher, Lawrence
dc.identifier.eissn1422-0067
melbourne.accessrightsOpen Access


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