Project description:This SuperSeries is composed of the following subset Series: GSE22005: Medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse allografted in nude mice GSE22006: Medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse allografted in nude mice Refer to individual Series
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and treated with vehicle or NVP-LDE225. RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and hybridized on the Affymetrix Mouse Genome 430A 2.0 RNA expression microarray.
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and treated with vehicle or NVP-LDE225.
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and treated with vehicle or NVP-LDE225. RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on the Affymetrix Mouse Genome 430A 2.0 RNA expression microarray.
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and treated with vehicle or NVP-LDE225.
Project description:Mutations in Hedgehog (Hh) pathway genes, leading to constitutive activation of Smoothened (Smo), occur in sporadic medulloblastoma, the most common brain cancer in children. Antagonists of Smo induce tumor regression in mouse models of medulloblastoma and hold great promise for targeted therapy for this tumor. However, acquired resistance has emerged as one of the major challenges of targeted cancer therapy. Here, we describe novel mechanisms of acquired resistance to Smo antagonists in medulloblastoma. NVP-LDE225, a potent and selective Smo antagonist, inhibits Hh signaling and induces tumor regressions in allograft models of medulloblastoma that are driven by mutations of Patched (Ptch), a tumor suppressor in the Hh pathway. However, after long-term treatment, evidence of acquired resistance was observed. Genome-wide profiling of resistant tumors revealed distinct mechanisms to evade the inhibitory effects of Smo antagonists. Chromosomal amplification of Gli2, a downstream effector of Hh signaling, reactivated Hh signaling and restored tumor growth. Analysis of pathway gene-expression signatures selectively deregulated in resistant tumors identified increased phosphoinosite-3-kinase (PI3K) signaling as another potential resistance mechanism. Probing the functional relevance of increased PI3K signaling, we showed that the combination of NVP-LDE225 with the dual PI3K/mTOR inhibitor NVP-BEZ235 markedly delayed the development of resistance. Our findings have important clinical implications for future treatment strategies in medulloblastoma. mRNA profiling: RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on Affymetrix Mouse Genome 430 2.0 RNA expression array. The dosage terminology (BID & QD) reflects the dosing schedule, where BID = twice a day, QD = once a day. aCGH: DNA was prepared from tumors from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on Agilent mouse CGH 244K Array.
Project description:The goals of this study are to compare the different transcriptome signiture between s.c. tumors from nude mouse allografted by R728T1 (non-SMCs derived from Rb/P53 mouse model)with and without Taz knockdown with NGS-derived retinal transcriptome profiling (RNA-seq).
Project description:Analysis of the transcriptome of allografted mouse tumors after treatment with rapamycin and PD0325901. Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+ (NPK mice) were induced and their tumors removed to generate allograft lines by implanting a 1.5 mm3 tumor fragment in the subcutaneous space of athymic nude mice. Allografted NPK tumors were allowed to grow until they reached a volume of 1 cm3, at which moment they were randomly assigned to either vehicle (Veh) or combination therapy using rapamycin and PD0325901 (RAPPD). Allografted mice were administered rapamycin (10 mg/kg) and PD0325901 (10 mg/kg) during five consecutive days (Allo SHORT). Mice were euthanized in the fifth day 6 hours after having received the last treatment and the tumors were harvested and snap frozen for subsequent molecular analysis.
Project description:Analysis of the transcriptome of allografted mouse tumors after treatment with rapamycin and PD0325901. Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+ (NPK mice) were induced and their tumors removed to generate allograft lines by implanting a 1.5 mm3 tumor fragment in the subcutaneous space of athymic nude mice. Allografted NPK tumors were allowed to grow until they reached a volume of 1 cm3, at which moment they were randomly assigned to either vehicle (Veh) or combination therapy using rapamycin and PD0325901 (RAPPD). Allografted mice were administered rapamycin (10 mg/kg) and PD0325901 (10 mg/kg) during five consecutive days (Allo SHORT). Mice were euthanized in the fifth day 6 hours after having received the last treatment and the tumors were harvested and snap frozen for subsequent molecular analysis. Total RNA obtained from prostate tumors/tissues. Prostate tumors/tissues were harvested and processed for RNA isolation and transcriptome analysis using the MagMAX RNA isolation kit (Ambion). Total RNA was amplified and labelled for subsequent microarrays hybridization using the Illumina TotalPrep RNA Amplification Kit.
