We assessed genome-wide expression of available pretreatment specimens from CLL patients enrolled in REACH, a study of fludarabine and cyclophosphamide FC or R-FC (addition of rituximab to FC) in relapsed CLL, to understand the disease heterogeneity and explore genes that may be prognostic or predictive of benefit from R-FC treatment. REACH (NCT00090051) was registered at www.clinicaltrials.gov.
PTK2 expression and immunochemotherapy outcome in chronic lymphocytic leukemia.
Specimen part, Disease stage, Subject
View SamplesPyocyanin has been shown to engage in redox transfer of electrons from NADPH to oxygen to generate superoxide radicals. Transcriptional response to oxygen stress has been characterized in yeast and should be observable upon exposure to pyocyanin if this is the true mode of action.
Pyocyanin isolated from a marine microbial population: synergistic production between two distinct bacterial species and mode of action.
No sample metadata fields
View SamplesSmall ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Cell line, Treatment, Subject, Time
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling of exosomal RNA isolated from breast cancer patients before, during and after radiation therapy.
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Subject
View SamplesThe goal of this study is to investigate if endogenous RNA in exosomes activates RIG-I through unshielding. Overall design: transcription profiling for exosomal RNA isolated from stroma cell (MRC5) or stroma/breast cancer cell co-culture (MRC5 and 1833).
Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer.
Cell line, Subject
View SamplesThe highly conserved Wnt signaling pathway drives intestinal homeostasis across species. Apc is a negative regulator of Wnt signaling. Loss of function mutations in Apc are found in 80-90% of human colorectal cancers. Importantly, Apc loss is widely known as the key driving event in the disease.
Intestinal stem cell overproliferation resulting from inactivation of the APC tumor suppressor requires the transcription cofactors Earthbound and Erect wing.
Sex, Age, Specimen part
View SamplesThe tumorigenicity of human pluripotent stem cells (hPSCs) is a major safety concern for their application in regenerative medicine. Here we identify the tight-junction protein Claudin-6 as a specific cell surface marker of hPSCs that can be used to selectively remove Claudin-6-positive cells from mixed cultures. We show that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for hPSC survival and self-renewal. We use three different strategies to remove Claudin-6-positive cells from mixed populations: an antibody against Claudin-6; a cytotoxin-conjugated antibody that selectively targets undifferentiated cells; and clostridium perfringens enterotoxin, a toxin that binds several Claudins, including Claudin-6, and efficiently kills undifferentiated cells, thus eliminating the tumorigenic potential of hPSC-containing cultures. This work provides a proof of concept for the use of Claudin-6 to eliminate residual undifferentiated hPSCs from culture, highlighting a strategy that may increase the safety of hPSC-based cell therapies.
Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells.
Specimen part, Cell line
View SamplesPluripotent-specific inhibitors (PluriSIns) make a powerful tool for studying the mechanisms that control the survival of human pluripotent stem cells (hPSCs). Here we characterize PluriSIn#2 as a novel selective indirect inhibitor of topoisomerase II alpha (TOP2A). We find that TOP2A is uniquely expressed in undifferentiated hPSCs, and that its inhibition results in their rapid cell death. These findings reveal a dependency of hPSCs on the activity of TOP2A, which can be harnessed for their selective elimination from culture.
Brief reports: Controlling the survival of human pluripotent stem cells by small molecule-based targeting of topoisomerase II alpha.
Specimen part, Cell line, Treatment
View SamplesThe generation of induced pluripotent stem cells (iPSCs) and the direct conversion approach provide an invaluable resource of cells for disease modeling, drug screening, and patient-specific cell-based therapy. However, while iPSCs are stable and resemble ESCs in their transcriptome, methylome and function, the vast majority of the directly converted cells represent an incomplete reprogramming state as evident by their aberrant transcriptome and transgene dependency. This raises the question of whether complete and stable nuclear reprogramming can be achieved only in pluripotent cells. Here we demonstrate the generation of stable and fully functional induced trophoblast stem cells (iTSCs) by transient expression of Gata3, Tfap2c and Eomes. Similarly to iPSCs, iTSCs underwent a complete and stable reprogramming process as assessed by transcriptome and methylome analyses and functional assays such as the formation of hemorrhagic lesion and placenta contribution. Careful examination of the conversion process indicated that the cells did not go through a transient pluripotent state. These results suggest that complete nuclear reprograming can be attained in non-pluripotent cells. Overall design: Technical duplicates of 10 samples
Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.
Specimen part
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