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The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease
TLDR
The first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules is created, and it is demonstrated that this “Connectivity Map” resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. Expand
Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning
TLDR
Genes implicated in DLBCL outcome included some that regulate responses to B-cell–receptor signaling, critical serine/threonine phosphorylation pathways and apoptosis, and identify rational targets for intervention. Expand
Gene expression correlates of clinical prostate cancer behavior.
TLDR
The results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis. Expand
A molecular signature of metastasis in primary solid tumors
TLDR
It is found that solid tumors carrying the gene-expression signature were most likely to be associated with metastasis and poor clinical outcome, suggesting that the metastatic potential of human tumors is encoded in the bulk of aPrimary tumor, thus challenging the notion that metastases arise from rare cells within a primary tumor that have the ability to metastasize. Expand
Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer.
TLDR
Enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets. Expand
Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins.
TLDR
Results indicate that a critical function of AR in PTEN-deficient prostate cancer cells is to support the pathologic activation of mTOR, possibly by increasing the expression of proteins that enhance nutrient availability and thereby prevent feedback inhibition of m TOR. Expand
Transcriptional control of autophagy–lysosome function drives pancreatic cancer metabolism
TLDR
The results identify the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrate that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy. Expand
Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators.
TLDR
This work identifies new modes of HSP90 modulation through a gene expression-based strategy that is similar to celastrol and gedunin and blocks the ability of androgen receptor (AR) signaling states to be modulated. Expand
Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: implications for insulin resistance.
TLDR
It is demonstrated that TNF-alpha antagonizes the actions of insulin, at least in part, through regulation of adipocyte gene expression including reduction in ACRP30 mRNA and induction of lipolysis resulting in increased plasma FFAs. Expand
Gene expression–based high-throughput screening(GE-HTS) and application to leukemia differentiation
TLDR
In screening 1,739 compounds, it is identified 8 that reliably induced the differentiation signature and, furthermore, yielded functional evidence of bona fide differentiation, indicating that GE-HTS may be a powerful, general approach for chemical screening. Expand
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