About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesT cell lymphoma
PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.
Sex, Specimen part, Cell line
View SamplesMany cancers rely on glycolytic metabolism to fuel rapid proliferation. This has spurred interest in designing drugs that target tumor glycolysis such as AZD3965, a small molecule inhibitor of Monocarboxylate Transporter 1 (MCT1) currently undergoing Phase I evaluation for cancer treatment. Since MCT1 mediates proton-linked transport of monocarboxylates such as lactate and pyruvate across the plasma membrane (Halestrap and Meredith, 2004), AZD3965 is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show that MCT1 inhibition impairs proliferation of glycolytic breast cancer cells that express MCT4 via disruption of pyruvate rather than lactate export. We found that MCT1 expression is elevated in glycolytic breast tumors and cell lines as well as in malignant breast and lung tissues. High MCT1 expression predicts poor prognosis in breast and lung cancer patients. Stable knockdown and AZD3965-mediated inhibition of MCT1 promote oxidative metabolism. Acute inhibition of MCT1 reduces pyruvate export rate but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that also express MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest that MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors that further supports their use as anti-cancer therapeutics.
MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.
Cell line, Treatment
View SamplesDysfunctions in mitochondria dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). Recently, it was shown that an inherited form of PD and dementia is caused by new mutations in the OPA1 gene, which encodes for a key player of mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1 mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectively rescued this survival deficit. Additionally, dampening necroptosis in MPTP treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both the early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a promising therapeutic target for PD. Overall design: 3 replicates for control and 3 replicates for OPA1 F38D mutant cells
Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson's Disease Models.
Specimen part, Subject
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesTranscriptome profiling using RNA-seq of MV+, a mouse lens epithelium cell line expressing Pax6 and RAG renal adenocarcinoma cell line which does not express Pax6. Overall design: Total RNA was collected and a Illumina sequencing libraries prepared from three biological replicates of cultured MV+ and RAG cells.
Polymer Simulations of Heteromorphic Chromatin Predict the 3D Folding of Complex Genomic Loci.
Cell line, Subject
View SamplesTranscriptomic studies revealed that hundreds of mRNAs show differential expression in the brains of sleeping versus awake rats, mice, flies, and sparrows. Although these results have offered clues regarding the molecular consequences of sleep and sleep loss, their functional significance thus far has been limited. This is because the previous studies pooled transcripts from all brain cells, including neurons and glia.
Effects of sleep and wake on oligodendrocytes and their precursors.
Specimen part
View SamplesTransient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View SamplesHuman medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
No sample metadata fields
View SamplesFour vehicle-treated and four HhAntag-treated pancreatic xenograft tumors were profiled for gene expression changes using Affymetrix U133 Plus 2.0 and Affymetrix Mouse Genome 430 2.0 arrays.
A paracrine requirement for hedgehog signalling in cancer.
No sample metadata fields
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