The objective of this study was to characterise a small panel of differentially expressed genes in the muscle that could be utilised to authenticate animals raised on pasture versus animals raised indoors on a concentrate based diet.
The application of transcriptomic data in the authentication of beef derived from contrasting production systems.
Specimen part
View SamplesActivating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GISTs). Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable. Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined. The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines in the presence or absence of added FGF2 in vitro, and delayed tumor regrowth in vivo. In addition, inhibition of mitogen-activated protein kinase (MAPK) signaling by imatinib was not sustained in GIST cells. An extracellular signal-regulated kinase (ERK) rebound occurred through activation of FGF signaling, and was repressed by FGFR1 inhibition. Downregultation of Sprouty proteins played a role in the imatinib-induced feedback activation of FGF signaling in GIST cells.
FGFR-Mediated Reactivation of MAPK Signaling Attenuates Antitumor Effects of Imatinib in Gastrointestinal Stromal Tumors.
Cell line
View SamplesThe RPMI-8226 human multiple myeloma cell line was stably infected with either a validated shRNA against BMI1 or a control shRNA. RNA was prepared from these lines, +/- doxycycline induction and at various time points post-induction. Samples were hybridized on the Affymetrix U133plus2 human genome expression microarray.
The Polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells.
Cell line
View SamplesWe utilized whole genome sequencing of mRNA (RNA-seq) to understand the extent to which the senescence-associated secretory phenotype is regulated by p38MAPK Overall design: Examination of replicates of young, senescent or p38MAPK-inhibited senescent BJ human foreskin fibroblasts.
p38MAPK plays a crucial role in stromal-mediated tumorigenesis.
No sample metadata fields
View SamplesLNCaP-derived MDV3100-resistant clones were treated with MDV3100 for 24h prior to collection
An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).
Cell line
View SamplesGenetically engineered LNCaPs overexpressing various AR alleles were treated with 0.1% DMSO or 10uM MDV3100 for 24h prior to collection
An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).
Cell line
View SamplesMutations 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.
Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma.
Treatment
View SamplesMCL cell lines were treated with DMSO or 5uM AFN700 for 20hrs
Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma.
Cell line, Treatment
View SamplesMCL lines (biological replicates) were treated with DMSO or 2.5uM Sotrastaurin for 3hrs
Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma.
No sample metadata fields
View SamplesMCL lines were treated with or without 100ng/ml doxycycline for 7 days
Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma.
Cell line, Treatment
View Samples