PURPOSE: Drug resistance in malignant gliomas contributes to poor clinical outcomes. We determined the in vitro drug response profiles for 478 biopsy specimens from patients with the following malignant glial histologies: astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n = 259), oligodendroglioma (n = 40), and glioma (n = 69). EXPERIMENTAL DESIGN: Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan. Biomarkers associated with drug resistance were detected by immunohistochemistry, including multidrug resistance gene-1, glutathione S-transferase pi (GSTP1), O(6)-methylguanine-DNA methyltransferase (MGMT), and mutant p53. RESULTS: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance. CONCLUSIONS: Assessment of in vitro drug response and profiles of relevant tumor-associated biomarkers may assist the clinician in stratifying patient treatment regimens.
PURPOSE: Drug resistance in malignant gliomas contributes to poor clinical outcomes. We determined the in vitro drug response profiles for 478 biopsy specimens from patients with the following malignant glial histologies: astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n = 259), oligodendroglioma (n = 40), and glioma (n = 69). EXPERIMENTAL DESIGN: Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan. Biomarkers associated with drug resistance were detected by immunohistochemistry, including multidrug resistance gene-1, glutathione S-transferase pi (GSTP1), O(6)-methylguanine-DNA methyltransferase (MGMT), and mutant p53. RESULTS: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance. CONCLUSIONS: Assessment of in vitro drug response and profiles of relevant tumor-associated biomarkers may assist the clinician in stratifying patient treatment regimens.
Authors: A Lo Dico; C Martelli; S Valtorta; I Raccagni; C Diceglie; S Belloli; U Gianelli; V Vaira; L S Politi; S Bosari; G Lucignani; R M Moresco; L Ottobrini Journal: Eur J Nucl Med Mol Imaging Date: 2015-03-27 Impact factor: 9.236
Authors: Susan Searles Nielsen; Beth A Mueller; Susan Preston-Martin; Federico M Farin; Elizabeth A Holly; Roberta McKean-Cowdin Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-09-13 Impact factor: 4.254
Authors: Ute Gesche Tallen; Matthias Truss; Frank Kunitz; Sven Wellmann; Brad Unryn; Brigitte Sinn; Ulrike Lass; Sonja Krabbe; Nikola Holtkamp; Christian Hagemeier; Reinhard Wurm; Guenter Henze; Karl T Riabowol; Andreas von Deimling Journal: J Neurooncol Date: 2007-09-01 Impact factor: 4.130
Authors: Antonio Silvani; Paola Gaviani; Elena A Lamperti; Marica Eoli; Chiara Falcone; Francesco Dimeco; Ida M Milanesi; Alessandra Erbetta; Amerigo Boiardi; Laura Fariselli; Andrea Salmaggi Journal: J Neurooncol Date: 2009-02-11 Impact factor: 4.130
Authors: Hasan Caglar Ugur; Mehmet Taspinar; Seda Ilgaz; Fatma Sert; Hande Canpinar; Juan A Rey; Javier S Castresana; Asuman Sunguroglu Journal: Mol Biol Rep Date: 2013-12-25 Impact factor: 2.316