Feeding animals with either concentrates supplemented with vitamin E or alfalfa grazing has been proven to reduce the oxidative process that occurs in meat products. Indoor-kept lambs were fed a standard concentrate (n=7, C) or concentrate supplemented with vitamin E (n=7, VE) for 30 days before slaughtering all animals at 2224 kg of live weight. Simultaneously, 7 unweaned lambs grazed in alfalfa paddocks (ALF) with their dams. Global transcriptomic data of longissimus thoracis (LT) muscle and subcutaneous fat (SF) with the Affymetrix Ovine Gene 1.1 microarray was used. In LT muscle when ALF group was compared with C group, were identified 41 genes differentially expressed. Among these genes 32 were down- regulated and 9 were up- regulated. Meanwhile when VE treatment was compared with C group were identified a total of 29 genes, 26 were down- regulated and 3 genes were up- regulated. In SF when ALF treatment was compared with C, were identified only 4 genes differentially expressed, all of them up-regulated in ALF group. Meanwhile when VE treatment was compared with C group, were identified a total of 330 genes. Among them, 295 genes were up- regulated and 35 were down- regulated. In LT muscle the clusters corresponding to gene expression profiles from treatments ALF, C and VE were clearly separated from each other. In SF, ALF group, overlap with VE and C treatments, however, VE and C clearly were separate in different clusters. These differentially expressed genes were selected for a functional analysis by using DAVID. In LT muscle some of the identified significant biological processes were catabolic and lipid process (down-regulated, except CPT1B) (CPT1B, PLA2G16, SPSB1, LRTOMT, PLCD4, FBXO9, CNBP and CYP27A1) and muscle organ differentiation (down-regulated) (CPT1B, MYOD1, MYLK2 and MSTN) in ALF; whereas intracellular signaling cascade (IGF1R, DEF8, AKAP7 and CISH) was down-regulated. In SF, vitamin E supplementation had an important effect; most of the genes were up-regulated. DAVID analysis showed that biosynthesis lipid pathway was the most represented with 20 genes, such as EBP, MVD, CYP51A1, DHCR7, HMGCS1, LSS and FDFT1 implicated in cholesterol synthesis. Further exploration of the links between these genes and vitamin E will lead to a better understanding of how vitamin E affects the oxidative process that occurs in meat products.
Genome-wide expression profiling in muscle and subcutaneous fat of lambs in response to the intake of concentrate supplemented with vitamin E.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.
Sex, Age, Specimen part, Disease, Cell line
View SamplesThis 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 SamplesThe mechanisms of resistance to the antibody-drug conjugate, T-DM1, were studied on clones derived from breast cancer cell line, BT474.
No associated publication
Cell line
View SamplesRobles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells.
A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia.
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 SamplesThe 1q gain is related to poor survival, and to a profile of cell cycle deregulation in Ewing's Sarcoma (ES). Tumor samples with 1q gain overexpress the gene DTL.
1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma.
Disease, Cell line
View SamplesThe in vivo effects of Ocoxin Oral solution (OOS) were evaluated on acute myeloid leukemia mice models. With that purpose RNA from 3 control untreated animals and 3 daily-OOS treated animals was purified and their gene expression profiles compared using the Affimetrix Transcriptome Analysis console.
No associated publication
No sample metadata fields
View SamplesDespite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described more than 30 years ago, the phenotype of MM-CSC is still a matter of debate, especially with respect to the expression of syndecan- 1 (CD138). Here, we demonstrate the presence of two subpopulations - CD138++ (95-99%) and CD138low (1-5%) - in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 surface expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are also phenotypically interconvertible. Overall, our results differ from previously published data which attribute a B-cell phenotype to MM-CSC and urge the need to explore more reliable markers to discriminate true clonogenic myeloma cells.
Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
Disease, Cell line
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