OBJECTIVES: To evaluate and compare the profile of expression of genes related to drug resistance in brain tumors and to analyze the impact of the increased expression of these genes on overall survival. METHODS: Eighty microdissected brain tumor samples from 79 patients were analyzed by RQ-PCR for the genes MDR1, MRP1, MRP3, LRP and BCRP. Protein expression was assessed by immunohistochemistry for MRP1 and LRP genes. Pediatric cases (0 to 20 years): 46 (17F:29M, median age 7.3 +/- 5.9 years); adult tumors: 33 (17F:16M, median age 46.6 +/- 14.5 years). Histological diagnoses: 21 astrocytomas I and II, 28 astrocytomas III and glioblastomas, 17 medulloblastomas, 8 ependymomas, and 6 oligodendrogliomas. RESULTS: glial tumors expressed higher MDR1 (P = 0.003) and BCRP (P = 0.03) levels than embryonic tumors. Low-grade astrocytomas expressed high MDR1 (P = 0.001), MRP3 (P = 0.01) and LRP (P = 0.02) levels. The MRP1 gene was preferentially expressed by medulloblastomas (P = 0.04) and ependymomas (P = 0.04); ependymomas also presented an increase of LRP (P = 0.02). The mRNA levels of MRP1 and LRP genes were associated to protein expression. The profile of gene expression of primary pilocytic astrocytomas of the hypothalamus and of the other locations was similar. Increased expression of resistance genes, separately or jointly, was not correlated with shorter overall survival in patients with medulloblastomas/PNET and malignant gliomas. CONCLUSIONS: Drug resistance genes do not explain the higher sensitivity of gliomas of the hypothalamus/pituitary/optic pathways to chemotherapy. The increased expression of resistance genes had no impact on the overall survival of patients with medulloblastomas/PNET and high grade gliomas. High MDR1, MRP3 and LRP levels may be implicated in the primary resistance of pilocytic astrocytomas to chemotherapy.
OBJECTIVES: To evaluate and compare the profile of expression of genes related to drug resistance in brain tumors and to analyze the impact of the increased expression of these genes on overall survival. METHODS: Eighty microdissected brain tumor samples from 79 patients were analyzed by RQ-PCR for the genes MDR1, MRP1, MRP3, LRP and BCRP. Protein expression was assessed by immunohistochemistry for MRP1 and LRP genes. Pediatric cases (0 to 20 years): 46 (17F:29M, median age 7.3 +/- 5.9 years); adult tumors: 33 (17F:16M, median age 46.6 +/- 14.5 years). Histological diagnoses: 21 astrocytomas I and II, 28 astrocytomas III and glioblastomas, 17 medulloblastomas, 8 ependymomas, and 6 oligodendrogliomas. RESULTS: glial tumors expressed higher MDR1 (P = 0.003) and BCRP (P = 0.03) levels than embryonic tumors. Low-grade astrocytomas expressed high MDR1 (P = 0.001), MRP3 (P = 0.01) and LRP (P = 0.02) levels. The MRP1 gene was preferentially expressed by medulloblastomas (P = 0.04) and ependymomas (P = 0.04); ependymomas also presented an increase of LRP (P = 0.02). The mRNA levels of MRP1 and LRP genes were associated to protein expression. The profile of gene expression of primary pilocytic astrocytomas of the hypothalamus and of the other locations was similar. Increased expression of resistance genes, separately or jointly, was not correlated with shorter overall survival in patients with medulloblastomas/PNET and malignant gliomas. CONCLUSIONS: Drug resistance genes do not explain the higher sensitivity of gliomas of the hypothalamus/pituitary/optic pathways to chemotherapy. The increased expression of resistance genes had no impact on the overall survival of patients with medulloblastomas/PNET and high grade gliomas. High MDR1, MRP3 and LRP levels may be implicated in the primary resistance of pilocytic astrocytomas to chemotherapy.
Authors: C Calatozzolo; M Gelati; E Ciusani; F L Sciacca; B Pollo; L Cajola; C Marras; A Silvani; L Vitellaro-Zuccarello; D Croci; A Boiardi; A Salmaggi Journal: J Neurooncol Date: 2005-09 Impact factor: 4.130
Authors: Holger Bronger; Jörg König; Kathrin Kopplow; Hans-Herbert Steiner; Rezvan Ahmadi; Christel Herold-Mende; Dietrich Keppler; Anne T Nies Journal: Cancer Res Date: 2005-12-15 Impact factor: 12.701
Authors: Y Tanaka; Y Abe; A Tsugu; Y Takamiya; A Akatsuka; T Tsuruo; H Yamazaki; Y Ueyama; O Sato; N Tamaoki Journal: Virchows Arch Date: 1994 Impact factor: 4.064
Authors: Marie Morfouace; Satish Cheepala; Sadhana Jackson; Yu Fukuda; Yogesh T Patel; Soghra Fatima; Daisuke Kawauchi; Anang A Shelat; Clinton F Stewart; Brian P Sorrentino; John D Schuetz; Martine F Roussel Journal: Cancer Res Date: 2015-07-21 Impact factor: 12.701
Authors: Elvis Terci Valera; Maria Angélica Abdalla de Freitas Cortez; Rosane Gomes de Paula Queiroz; Fabio Morato de Oliveira; María Sol Brassesco; Nada Jabado; Damien Faury; Michael S Bobola; Hélio Rubens Machado; Carlos Alberto Scrideli; Luiz Gonzaga Tone Journal: Childs Nerv Syst Date: 2008-10-23 Impact factor: 1.475