Filters
Technology
Platform
SRP102431
Mus musculus
9 Downloadable Samples
Ion Torrent Proton
Description
Analysis of murine cardiomyocyte cell line HL-1 treated with Ivermectin or Importazole. Results provide insight into the pathways regulated by the treatments. Overall design: RNA-seq of mouse HL-1 cardiomyocytes treated with vehicle (DMSO), Ivermectin, or Importazole for 24 hours, in triplicate, using Ion Proton System.
Publication Title
Antihypertrophic Effects of Small Molecules that Maintain Mitochondrial ATP Levels Under Hypoxia.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Aim: Differentiation of cardiac fibroblasts (Fb) into myofibroblasts (MyoFb) is responsible for connective tissue buildup in myocardial remodeling. We examined reversibility of MyoFb differentiation. Methods and Results: Adult rat cardiac Fb were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different Fb phenotypes. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fiber formation decorated with alpha-smooth muscle actin (-SMA). Transforming growth factor-1 (TGF-1) promoted terminal differentiation into -SMA positive MyoFb showing near absence of proliferation i.e. non-p-MyoFb (2-fold increase in cell number after 12 days vs 11-fold for p-MyoFb). SD-208, a TGF--receptor-I kinase blocker, inhibited p-MyoFb differentiation as shown by stress fiber absence, low levels of -SMA protein expression, and high levels of proliferation (32-fold increase after 12 days). Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and 4-fold contraction. Fb produced low levels of collagen and secreted high levels of IL-10. Non-p-MyoFb showed high collagen production and high MCP-1 and TIMP-1 secretion. Transcriptome analysis indicated differential gene expression between all phenotypes. Dedifferentiation of p-MyoFb, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress, shown by stress fiber de-polymerization in 30% of p-MyoFb vs in 8% of non-p-MyoFb. Stress fiber de-polymerization could be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2 day culture in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D culture. Conclusions: Both reduction in mechanical strain and TGF--receptor-I kinase inhibition can reverse p-MyoFb differentiation but not in non-p-MyoFb.
Publication Title
Reversible and irreversible differentiation of cardiac fibroblasts.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Organ transplant recipients (OTRs) on Cyclosporine A (CSA) are prone to catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer-targeting systemic treatments are unavailable. We have shown increased risk for catastrophic SCC in OTRs via CSA-mediated induction of Interleukin-22 (IL-22). Herein, we found CSA drives SCC proliferation and tumor growth through IL-22 and JAK/STAT pathway induction. We in turn inhibited SCC growth with an FDA-approved JAK 1/2 inhibitor, Ruxolitinib. In human SCC cells, greatest proliferative response to IL-22 and CSA treatment occurred in non-metastasizing lines. IL-22 treatment upregulated JAK1 and STAT1/3 in A431 SCC cells. JAK/STAT pathway genes were highly expressed in tumors from a cohort of CSA-exposed OTRs, and in SCC with high risk for metastasis. Compared to immunocompetent SCC, genes associated with innate immunity, response to DNA damage and p53 regulation were differentially expressed in SCC from OTRs. In nude mice engrafted with human A431 cells, IL-22 and CSA treatment increased tumor growth and upregulated IL-22 receptor, JAK1 and STAT 1/3 expression. Ruxolitinib treatment significantly reduced tumor volume and reversed the accelerated tumor growth. CSA and IL-22 exacerbate aggressive behavior in SCC. Targeting the IL-22 axis via selective JAK/STAT inhibition may reduce the progression of aggressive SCC in OTRs, without compromising immunosuppression.
Publication Title
Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PD-L1 suppresses host immunity and promotes tumor growth. We investigated how IFN- regulates PD-L1 in the ovarian cancer microenvironment. In clinical samples, the number of stromal CTLs in peritoneally disseminated tumors was correlated with PD-L1 expression on the tumor cells, and the lymphocyte number was significantly related to the IFN- signature score. In mouse models, PD-L1 was induced in peritoneal disseminated tumors, where lymphocytes were prominent, but not in subcutaneous tumors. Depleting IFNGR1 resulted in lower PD-L1 expression and longer survival in peritoneal dissemination model. Injection of IFN- into subcutaneous tumors increased PD-L1 expression and tumor size, and PD-L1 depletion abrogated tumor growth. These data suggest that IFN- works as a tumor progressor through PD-L1 induction. The source of IFN- in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN- and expression microarray analysis was performed, and probes showing significantly higher values in IFN--added group were termed IFN- signature genes (295 probes). We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN- signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN- in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN--rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment.
Publication Title
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The patients with locally advanced squamous cervical cancer (SCC) were examined in this study. All patients received neoadjuvant chemotherapy followed by radical hysterectomy. Tumor response against NAC was determined based on RECIST criterior. Gene-expression profiles of SCC were determined using Human Genome GeneChip arrays U133.
Publication Title
Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The source of IFN- in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN- and expression microarray analysis was performed, and probes showing significantly higher values in IFN--added group were termed IFN- signature genes (295 probes). We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN- signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN- in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN--rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment.
Publication Title
IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 138 Downloadable Samples
Description
Multiple myeloma (MM) is a malignant plasma cell disorder with well-defined clonal genetic/cytogenetic abnormalities. However, cellular heterogeneity is a key factor in MM's progression, therapeutic decision, and response to treatment. Single cell whole transcriptome profiling (scRNA-Seq) offers an opportunity to dissect this molecular heterogeneity during MM progression to better understand the disease and guide rational therapy. Here, we examined 597 CD138 positive cells from 15 patients at different stages of MM progression using scRNA-Seq. We selected 790 genes based on a Coefficient of Variation (CV) approach which organized cells into four clusters (L1-L4) based on unsupervised clustering. Plasma cells from each patient contained a mixed population of plasma cells at different state of aggressiveness based on gene expression signature reflecting the inter-cellular heterogeneous nature of MM. Cells in the L1 group is characterized by low level expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathway having most cells from MGUS patients (p < 1.2x10-14). In contrast, low level of these genes in L1 group increased progressively and were the highest in the L4 group containing only cells from high-risk MM patients with t(4;14) translocations. Furthermore, 44 genes consistently overexpressed by pair-wised comparisons of the four groups strongly associated with a reduced overall survival in MM patients (APEX trial, p < 0.0001; Hazard Ratio (HR), 1.83; 95% CI, 1.33 to 2.52), particularly those in the bortezomib treated group (p < 0.0001; HR, 2.00; 95% CI, 1.39 to 2.89). No survival significance was observed for the dexamethasone treated group. Our study at the resolution of single cells showed that there is a mixed population of cells in each patient at different stages of MM progression and these cells can be organized into four different subgroups (L1 to L4). Consistent overexpression of the 44 genes from L1 to L4 groups is associated with patient outcome and treatment response. Our results show that oxidative phosphorylation, Myc target, and mTORC1 signaling genes are significant pathways for MM progression and affect MM prognosis and treatment stratification. Overall design: 597 single cell libraries passed QC and were included in the downstream analysis
Publication Title
Molecular signatures of multiple myeloma progression through single cell RNA-Seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination.
Publication Title
PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor beta (TGF-) superfamily. By regulating target gene transcription, BMPs control various cellular processes, such as proliferation, differentiation, apoptosis and migration.
Publication Title
The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-A potential therapeutic target.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention.
Publication Title
Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis.
Sample Metadata Fields
Specimen part, Subject
View Samples