The tyrosine kinase ErbB2 positive breast tumors have more aggressive tumor growth, poorer clinical outcome, and more resistance to radiotherapy, chemotherapy and hormone therapy. A humanized anti-ErbB2 monoclonal antibody Herceptin and a small molecules inhibitor Lapatinib were developed and approved by FDA to treat patients with ErbB2 amplification and overexpression. Unfortunately, most ErbB2+ breast cancers do not respond to Herceptin and Lapatinib, and the majority of responders become resistant within 12 months of initial therapy (defined as secondary drug resistance). Such differences in response to Lapatinib treatment is contributed by substantial heterogeneity within ErbB2+ breast cancers. To address this possibility, we carried out transcriptomic analysis of mammary tumors from genetically diverse MMTV-ErbB2 mice. This will help us to have a better understanding of the heterogeneous response to ErbB2 targeted therapy and permit us to design better and more individualized (personalized) treatment strategies for human ErbB2 positive breast cancer.
Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.
Specimen part
View SamplesThe yeast PMR1 (ATP2C1) gene codes for the eukaryotic prototype of a high affinity P-type ATPase required for Ca2+/Mn2+ transport into the Golgi. Cells lacking PMR1 exhibit multiple genetic interactions with genes involved in DNA recombination and replication, a fact that is not yet understood. We find that deletion of PMR1 causes a delay in DNA replication initiation, progression and G2/M transition and induces the transcriptional up-regulation of genes involved in cell cycle regulation, including CLB5 and SWE1. Interestingly, pmr1 clb5 double mutants exhibit a dramatic delay in DNA replication and increased DNA breakage, while endoreplication and the formation of multi-nucleated, giant yeast is observed in pmr1 swe1 cells. Because these phenotypes can be attributed to impeded Mn2+-pump function, we provide a model in which Mn2+ interferes with Mg2+ in the nucleus, and vice versa, Mg2+ interferes with Mn2+ in the Golgi. Consequently, cell cycle progression is challenged by aberrant catalytic activities of enzymes involved in replication and protein glycosylation.
Impaired manganese metabolism causes mitotic misregulation.
No sample metadata fields
View SamplesWe sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.
Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
No sample metadata fields
View SamplesObesity is a chronic, complex and multifactorial disease that has reached pandemia levels and is becoming a serious health problem. Intestinal microbiota is considered a main factor that affects body weight and fat mass, which points toward a critical role in the development of obesity. In this sense, probiotic bacteria might modulate the intestinal microbiota and the mucosal-associated lymphoid tissue. The aim of this study was to investigate the effects of L. paracasei, L. rhamnosus and B. breve feeding on the intestinal mucosa gene expression in a genetic animal model of obesity.
Adamdec1, Ednrb and Ptgs1/Cox1, inflammation genes upregulated in the intestinal mucosa of obese rats, are downregulated by three probiotic strains.
Specimen part
View SamplesTGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma.
TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.
Specimen part, Treatment
View SamplesDiffuse large B-cell lymphoma (DLBCL) has striking clinical and molecular variability. Although a more precise identification of the multiple determinants of this variability is still under investigation, there is a consensus that high-clinical-risk DLBCL cases require a risk-adapted therapy, since intensification of chemotherapy with autologous stem-cell transplantation (ASCT) has been shown to improve the prognosis for high-risk patients in randomised clinical trials.
Identification of biological markers of sensitivity to high-clinical-risk-adapted therapy for patients with diffuse large B-cell lymphoma.
No sample metadata fields
View SamplesYerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related in inflammation. The aim of this work was to study the effect of YM in cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells in vitro with phitohemaglutinin in the presence of yerba mate and determined their activation measuring the the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component.
Yerba mate (Ilex paraguariensis) inhibits lymphocyte activation in vitro.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Specimen part
View SamplesCritical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Specimen part
View SamplesCritical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Specimen part
View Samples