We assess if distinct biological processes might be associated with chemotherapy sensitivity in the different clinical subsets of breast cancers.
Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer.
Age, Specimen part
View SamplesThis is Phase II Trial of 4courses of 5-fluorouracil, doxorubicin and cyclophosphamide follwed by 4 additional courses of weekly docetaxel and capecitabine administered as Preoperative Therapy for Patients with Locally Advanced Breast Cancer, Stages II and III by US oncology (PROTOCOL 02-103)
Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer.
Age, Disease stage
View SamplesCD8 T cells play an importart role in adaptive immunity to intracellular pathogens. Nave CD8 T cells , that have not encountered antigen previously can be identified by virtue of their distinct phenotype. Upon antigenic encounter, they proliferate rapidly and undergo massive reprograming to differentiate to cytotoxic T lymphocytes. The yellow fever live virus vaccine (YF-17D) provides a model primary acute viral infection that can be used to follow this response.Here we characterize the resting, non-activated naive CD8 T cells in nine healthy adults and YF-specific CD8 T cells elicited in response to YF-17D vaccination from the same donors during the effector (2 weeks after vaccination) and memory (5-8 months later) stages.
Origin and differentiation of human memory CD8 T cells after vaccination.
Specimen part, Subject
View SamplesThese 14 samples originate from peripheral blood mononuclear cells (PBMC) from donors at different times after they were vaccinated with the YF-17D vaccine. Overall design: 10,000 to 100,000 tetramer+ CD8 T cells specific for the NS4B-214 epitope in YFV-17D were purified by flow cytometry based sorting, from 8 vaccinees. Total Naive (CD45RA+ CD8+) CD8 t cells were also sorted from these donors. Subsets were defined based on the time after vaccination. The subsets (cell types) include: Naive CD8 T cells (n=6); YFV-specific Effector CD8 T cells (day 14 after vaccination, n =3) and YFV-specific long term memory CD8 T cells (4 to 12 years after vaccination, n=5).
Origin and differentiation of human memory CD8 T cells after vaccination.
Specimen part, Subject
View SamplesNuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with its Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing at the Mediator level. In sum, we provide insight into how NPC-associated adaptor complexes can access the core transcription machinery. Overall design: RNAseq was performed from WT, sac3?, cdk8? and Sac3 R288D mutant cells. For each strain triplicates were analyzed. WT strain was sac3? transformed with pRS315 SAC3 WT
The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.
Subject
View SamplesTranscriptome analysis of RNAs extracted from 2 hour-TGF-b-treated or untreated LX-2 cells with or without STAT3 knockdown
Transforming Growth Factor-β (TGF-β) Directly Activates the JAK1-STAT3 Axis to Induce Hepatic Fibrosis in Coordination with the SMAD Pathway.
Treatment, Time
View SamplesMouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). Following hair regeneration, SCs within the bulge and its vicinity (upper ORS which becomes the bulge for the next cycle) briefly self-renew to replenish expended SCs and ensure long-term tissue regeneration.
An RNA interference screen uncovers a new molecule in stem cell self-renewal and long-term regeneration.
Sex, Specimen part
View SamplesGenome-wide RNAi screens in mice identified Ctnnb1 and Mllt6 as physiological regulators of HrasG12V-dependent epidermal hyperplasia. To probe the consequences of Ctnnb1 and Mllt6 on HrasG12V-dependent oncogenic growth, we examined how their depletion impacts gene expression in the HrasoncoX2 epidermis. We performed RNA-seq analysis of FACS-purified embryonic epidermal cells, followed by network analysis of differentially regulated transcripts. Whether Ctnnb1 or Mllt6, knockdown markedly enhanced activity of genes restricting growth, and decreased expression of genes promoting epidermal proliferation. This contrasted with known transcriptional changes that typically follow epidermal expression of oncogenic Hras. Moreover, there was a significant overlap in genes whose expression was affected by Mllt6 and ß-catenin, further implying a level of shared function. Overall design: Transcriptional profiles of epidermal progenitors of embryonic day 18.5 animals of wild-type, HrasG12V, and HrasG12V depleted of Ctnnb1 or Mllt6 backgrounds.
RNAi screens in mice identify physiological regulators of oncogenic growth.
Cell line, Subject
View SamplesPurpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia.
No sample metadata fields
View SamplesBackground: Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH) with those from healthy individuals.
Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism.
Specimen part, Disease, Disease stage
View Samples