This SuperSeries is composed of the SubSeries listed below.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesBackground: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesPhytochromes are red/far red photosensors regulating numerous developmental programs in plants. Among them phytochrome A (phyA) is essential to enable seedling de-etiolation in continuous far-red (FR) light a condition mimicking the environment under a dense canopy. The ecological relevance of this response is demonstrated by the high mortality rate of phyA mutants germinating in deep vegetational shade. phyA signaling involves a direct interaction of the photoreceptor with members of the bHLH transcription factor family, PIF1 and PIF3 (Phytochrome Interacting Factor). Here we investigated the involvement of PIF4 and PIF5 in phyA signaling and found that they redundantly control de-etiolation in FR light. The pif4pif5 double mutant is hypersensitive to low fluence rates of FR light. This phenotype is dependent on FR light perception by phyA but does not rely on alterations of the phyA level. Our microarrays analysis shows that PIF4 and PIF5 are part of an inhibitory mechanism repressing the expression of some light-responsive genes in the dark and are also needed for full expression of several growth-related genes in the light. Unlike PIF1 and PIF3, PIF4 and PIF5 are not degraded in response to FR light indicating that they are light-regulated by a different mechanism. Our genetic analysis suggests that this is achieved through the sequestration of these PIFs by the closely related bHLH transcription factor HFR1 (long Hypocotyl in FR light).
Phytochrome interacting factors 4 and 5 redundantly limit seedling de-etiolation in continuous far-red light.
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View SamplesThe stomach is often considered a single compartment, but morphological differences among different areas are well known. Oxyntic mucosa (OXY) is primarily equipped for acid secretion, while it is not enough clear if gastric functional control are shared with other areas.
Differential gene expression in the oxyntic and pyloric mucosa of the young pig.
Sex, Specimen part
View SamplesPressure overload-induced cardiac hypertrophy was examined in IL-18 knockout and littermate control mice.
Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.
Specimen part
View SamplesSerum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass. We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy. Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.
Treatment
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization and early life feeding of medium chain triglycerides on the maturation of the porcine gastric mucosa are largely unknown.
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Specimen part
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the maturation of the porcine gastric mucosa are largely unknown.
The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.
Specimen part
View SamplesOvarian cancer has a high mortality rate due, in part, to the lack of early detection and incomplete understanding of the origin of the disease. The hen is the only spontaneous model of ovarian cancer, and can therefore aid in the identification and testing of early detection strategies and therapeutics. To our knowledge, no studies to date have examined global gene expression in ovarian cancer of the hen. Our aim was to combine the use of the hen animal model and microarray technology to identify differentially expressed genes in ovarian tissue from normal hens compared to hens with ovarian cancer.
Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin?
Specimen part, Disease, Disease stage
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the gut barrier upon the further encounter of favorable bacteria or not, are largely unknown.
Molecular networks affected by neonatal microbial colonization in porcine jejunum, luminally perfused with enterotoxigenic Escherichia coli, F4ac fimbria or Lactobacillus amylovorus.
Specimen part, Treatment
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