This SuperSeries is composed of the SubSeries listed below.
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Specimen part, Cell line, Treatment
View SamplesKinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. Results: Filanesib showed in vitro and in vivo synergy with all IMiDs plus dexamethasone treatment, particularly with the pomalidomide combination (PDF). Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and it was shown to be mediated by impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, PDF increased the activation of the proapoptotic protein Bax, which has been previously associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Conclusions: Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone and es-tablished the basis for a recently activated trial being conducted by the Spanish MM group investigating this combination in relapsed MM patients.
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Specimen part, Treatment
View SamplesKinesin spindle protein (KSP) inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (Arry-520), a KSP inhibitor, has demonstrated activity in heavily pretreated multiple myeloma (MM) patients. The aim of this work was to investigate the activity of filanesib in combination with an IMiDs plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. Results: Filanesib showed in vitro and in vivo synergy with all IMiDs plus dexamethasone treatment, particularly with the pomalidomide combination (PDF). Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and it was shown to be mediated by impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, PDF increased the activation of the proapoptotic protein Bax, which has been previously associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Conclusions: Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone and es-tablished the basis for a recently activated trial being conducted by the Spanish MM group investigating this combination in relapsed MM patients.
The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.
Cell line, Treatment
View SamplesRecent work suggests that imprinted genes may regulate the signalling function of the placenta by modulating the size of the endocrine compartment. Our work provides in vivo evidence that this hypothesis is well founded.
The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources.
Specimen part
View SamplesPrevious work has suggested that the imprinted gene Phlda2 regulates the signalling function of the placenta by modulating the size of the endocrine compartment. This study investigated the affect that Phlda2 mutant placenta has upon the brains of the wildtype dams carrying different placenta and consequently offspring.
Maternal care boosted by paternal imprinting in mammals.
Specimen part
View SamplesThe first T cells to arrive in the liver were mostly T regulatory (Treg) cells and metabolically active, highly proliferative T conventional (Tconv) cells. The Tconv cells had unusually high expression of PD-1 and the IL-33 receptor, ST2. As these PD-1+ Tconv cells accumulated in the tissue, they gradually lost their expression of ST2, ceased to proliferate and acquired an anergic phenotype. Overall design: Gene expression profiles of flow cytometry sorted DAPI negative CD45 positive TCRb positive CD4 positive Foxp3 negative cells from liver of 5- and 10-day-old B6.Aire-KO mice
T cell anergy in perinatal mice is promoted by T reg cells and prevented by IL-33.
Age, Specimen part, Cell line, Subject
View SamplesThe use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be normalized, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples are at times the sole means of addressing specific questions – e.g., samples collected in the course of fieldwork.
RNA-seq: impact of RNA degradation on transcript quantification.
No sample metadata fields
View SamplesWe have addressed the question of how different rodent species cope with the life-threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus (SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function-related plasticity in this nucleus. In addition we have identified many genes that are differentially expressed in a species-specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species-specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data.
Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways.
Sex, Specimen part
View SamplesCue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones.
Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.
Specimen part
View SamplesWe focused on RNA-seq-based full transcriptome responses to PtrSND1-B1 overexpression at 7, 12, and 25 h in stem defferentiating xylem (SDX) protoplasts Overall design: We transfected PtrSND1-B1 and sGFP into stem differentiating xylem protoplasts and performed RNA-seq to reveal the whole transcriptome.
SND1 transcription factor-directed quantitative functional hierarchical genetic regulatory network in wood formation in Populus trichocarpa.
Specimen part, Subject
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