This SuperSeries is composed of the SubSeries listed below.
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesThe goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesPrevious studies have suggested that CD133+ cells isolated from human kidney biopsies have the potential to ameliorate injury following intravenous (IV) administration in rodent models of kidney disease by integrating into damaged renal tissue and generating specialised renal cells. However, whether renal engraftment of CD133+ cells is prerequisite for ameliorating injury has not yet been unequivocally resolved. Here, we have established a cisplatin-induced nephropathy model in immunodeficient rats to assess the efficacy of CD133+ human kidney cells in restoring renal health, and to determine the fate of these cells after systemic administration. Specifically, following IV administration, we evaluated the impact of the CD133+ cells on renal function by undertaking longitudinal measurements of the glomerular filtration rate using a novel transcutaneous device. Furthermore, using histological assays, we assessed whether the human kidney cells could promote renal regeneration, and if this was related to their ability to integrate into the damaged kidneys. Our results show that both CD133+ and CD133- cells improve renal function and promote renal regeneration to a similar degree. However, this was not associated with engraftment of the cells into the kidneys. Instead, after IV administration, both cell types were exclusively located in the lungs, and had disappeared by 24 hours. Our data therefore indicate that renal repair is not mediated by CD133+ cells homing to the kidneys and generating specialised renal cells. Instead, renal repair is likely to be mediated by paracrine or endocrine factors.
Human Kidney-Derived Cells Ameliorate Acute Kidney Injury Without Engrafting into Renal Tissue.
Specimen part, Disease stage
View SamplesDue to the urgent need of new targeting strategies in PCa, AR interacting proteins should be considered. In this study we aimed to test the effect of a long-term knockdown of NCOA1, an AR coactivator, in PCa progression and metastatogenesis and whether NCOA1 could be used as a possible therapeutic target. To test the consequences of NCOA1 knockdown on proliferation, we performed by 3H thymidine incorporation assays revealing a strong reduction in castration resistant MDA PCa 2b and androgen-dependent LNCaP cells, without affecting AR negative PC3 cells. Furthermore, Boyden chamber assays revealed a strong decrease in migration and invasion upon NCOA1 knockdown. Using a cDNA microarray, we identified protein kinase D1 (PRKD1) as one prominent upregulated gene in MDA PCa 2b, which was not seen in PC3 cells. Knockdown of PRKD1 clearly reverted the reduced migratory potential. Moreover, we found phospholipase A2, group7 (PLA2G7) and eukaryotic translation initiation factor 5A2 (EIF5A2), which might be involved in migration of PC3 cells. Further, we can clearly demonstrate that PRKD1 is negatively regulated by the AR/NCOA1 complex. In addition, immunhistochemical staining revealed a strong increase in NCOA1 expression in matched and unmatched patients samples, respectively between normal prostate and primary tumor. Regarding the PRKD1 staining, no final conclusion can be drawn in terms of a tumor suppressor function. Thus, our findings directly associate NCOA1/AR complex with PRKD1 regulation and further suggest NCOA1 as a potential therapeutic target also due to the effect on PC3 cell migration.
The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1.
Cell line
View SamplesThese experiments were done to compare the gene expression profiles in CD4+ T cells responding to antigen presented by dendritic cells transiently or persistently. Some treatments include the activation of the dendritic cells by CD40 engagement.
Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation.
Specimen part
View SamplesProstate cancer (PCa) development and progression are associated with chronic inflammation. The cytokine interleukin (IL)-6 can influence progression, differentiation, survival, and angiogenesis of PCa. To identify novel pathways that are triggered by IL-6, we performed a gene expression profiling of two PCa cell lines, LNCaP and MDA PCa 2b, under treatment with 5 ng/ml IL-6. Interferon regulatory factor (IRF)9 was identified as one of the most prevalent IL-6 regulated genes in both cell lines. IRF9 is a mediator of type I interferon signaling and acts together with signal transduction and activator of transcription (STAT)1 and 2 to activate transcription of interferon responsive genes. The IL-6 regulation of IRF9 was confirmed at mRNA and protein levels by quantitative real-time PCR and Western blot, respectively, in both cell lines and could be blocked by the anti-IL-6 antibody Siltuximab. Three PCa cell lines with an autocrine IL-6 loop, PC3, DU145, and LNCaP-IL-6+, showed a high expression of IRF9. A tissue microarray with 36 malignant and adjacent 36 benign areas from prostate cancer specimens showed that IRF9 protein expression is moderately elevated in malignant areas and positively correlates with the tissue expression of IL-6. Downregulation and overexpression of IRF9 provided evidence for an interferon-independent role of IRF9 on cellular proliferation of different PCa cell lines. Furthermore, expression of IRF9 was essential to mediate the antiproliferative effects of IFN-2. We concluded that IL-6 is an inducer of IRF9 expression in prostate cancer and a sensitizer for the antiproliferative effects of IFN2.
IL6 sensitizes prostate cancer to the antiproliferative effect of IFNα2 through IRF9.
Cell line, Treatment
View SamplesThe aim of our study was to discover a miR marker panel prognostic of 5-year survival in OSCC patients that may be utilized in parallel with the current clinical covariates. We assessed differential expression of miRNAs genome-wide via deep sequencing in 20 tumor tissue samples. We also attempted to identify deregulated miR expression signatures that may serve as the prognostic marker of cancer survival. Selected miR marker-based panel then may serve as a guide for selection of appropriate follow-up chemo/radiation treatment, significantly improving the clinical management of OSCC and the overall survival rate. Overall design: Identify miRs differentially expressed in the poor prognosis group compared to the good prognosis group
Prognostic value of miR-375 and miR-214-3p in early stage oral squamous cell carcinoma.
No sample metadata fields
View SamplesOvariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
Specimen part
View SamplesThe CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein (pRb). It is known that cyclin D1 regulates ER transactivation using heterologous reporter systems, the significance of this observation to E2 dependent gene activation is unknow. E2 stimulated MCF7 cells treated with cyclin D1 siRNA in order to analyze the genes regulated by estradiol in a cyclin D1 dependent manner. Hormone deprived MCF7 cells were treated with cyclin D1 siRNA or control siRNA and stimulated with E2 or vehicle
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
Cell line, Treatment
View SamplesMurine prostate epithelial cells (PECs) were obtained from Ccnd1-/- and Ccnd1+/+ FvB mice (2-3 months of age). RNA extracted from PECs (3 technical replicates for each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells.
No sample metadata fields
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