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An avian embryo patient-derived xenograft model for preclinical studies of human breast cancers.

ABSTRACT: Lack of preclinical patient-derived xenograft (PDX) cancer models in which to conduct large scale molecular studies seriously impairs the development of effective personalized therapies. We report here on an in vivo concept consisting of implanting human tumor cells in targeted tissues of an avian embryo, delivering therapeutics, evaluating their efficacy by measuring tumors using light sheet confocal microscopy, and conducting large scale RNAseq analysis to characterize therapeutic-induced changes in gene expression. The model was established to recapitulate triple negative breast cancer (TNBC) and validated using TNBC standards of care (SOCs) and an investigational therapeutic agent.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172218 | GEO | 2021/11/17

REPOSITORIES: GEO

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Cancer patient and family perception of the usefulness of a question prompt sheet during important consultation

Project description:Interventions: Hospital introduction sheet + Question prompt sheet Hospital introduction sheet Primary outcome(s): The usefulness of a question prompt sheet/ hospital introduction sheet (3 items; 11 Likert scale) ‘ To understand the treatment plan, the sheet helped me to ask questions to the physician.’ ‘ To understand the treatment plan, the sheet was helpful.’ ‘ I will use the sheet again.&quot Study Design: Parallel Randomized

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Project description:Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets. We identified and confirmed four distinct, stable TNBC subtypes: (1) Luminal-AR (LAR); 2) Mesenchymal (MES); 3) Basal-Like Immune-Suppressed (BLIS), and 4) Basal-Like Immune-Activated (BLIA). RNA profiling analysis was conducted on 198 TNBC tumors (ER-negativity defined as Allred Scale value â¤2) with >50% cellularity (discovery set: n=84; validation set: n=114)

2015-12-18 | E-GEOD-76124 | biostudies-arrayexpress

SOCS-3 in muscle

Project description:Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. Methods We generated transgenic mice constitutively expressing SOCS-3 in skeletal muscle to define whether the sole expression of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 expression, several genes had deregulated expression, among them other members of the SOCS family. This could maintain the insulin signal into skeletal muscle. Interestingly, we found that SOCS-3 interacts with calcineurin, which has been implicated in muscle contractility. In SOCS-3 transgenic muscle, this leads to delocalisation of calcineurin to the fibre periphery. Relevant to this finding, SOCS-3 transgenic animals had dilatation of the sarcoplasmic reticulum associated with swollen mitochondria and decreased voluntary activity. Conclusions/interpretation Our results show that constitutive SOCS-3 expression in skeletal muscle is not in itself sufficient to induce the establishment of metabolic disorders such as diabetes. In contrast, we reveal a novel role of SOCS-3, which appears to be important for muscle integrity and locomotor activity. (Patricia Lebrun et al, Diabetologia, 2009)

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E-PROT-57

Project description:The Mount Sinai cohort of large-scale proteomic data in Alzheimer's disease

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Epigenetic heterogeneity and transcriptional drivers of triple-negative breast cancer

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Project description:NHGRI Large Scale Sequencing Program

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Project description:Large-Scale CLL Genome Analysis

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Expression data from tibialis anterior muscle

Project description:We generated transgenic mice expressing constitutively SOCS-3 specifically in skeletal muscle. SOCS proteins are implicated in the negative regulation of various pathways including insulin signaling pathway. Our transgenic mice are predisposed to obesity and systemic insulin resistance compared to control mice. We used microarrays to detail the variations of gene expression in muscle from transgenic mice versus controls. Keywords: transgenic, tibialis anterior, SOCS-3

2009-03-01 | GSE11105 | GEO

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