Inflammation and immune activation of the cervicovaginal mucosa are considered factors that increase susceptibility to HIV infection. It is essential to screen candidate anti-HIV microbicides for potential mucosal immunomodulatory/inflammatory effects prior to further clinical development. The goal of this study was to develop an in vitro method for preclinical evaluation of the inflammatory potential of new candidate microbicides. We compared transcriptomes of human vaginal cells (Vk2/E6E7) treated with well-characterized pro-inflammatory (PIC) and non-inflammatory (NIC) compounds. Microarraray comparative analysis allowed us to generate a panel of 20 genes that were consistently deregulated by all PICs compared to NICs, thus distinguishing between these two groups.
Gene Expression Profiling of Human Vaginal Cells In Vitro Discriminates Compounds with Pro-Inflammatory and Mucosa-Altering Properties: Novel Biomarkers for Preclinical Testing of HIV Microbicide Candidates.
Specimen part, Cell line
View SamplesWe performed gene expression analysis using the SCRB-Seq method from cervical and peripheral blood antigen presenting cells that were collected from women with different cervicovaginal bacterial community types. Overall design: Cervical and peripheral blood antigen presenting cells were FACS sorted using the gating strategy: FSC vs. SSC -> Singlets -> Live CD45+ -> HLA-DR+ -> CD11c+ or CD14+. The genital bacterial microbiomes were characterized in the same women and categorized into Lactobacillus dominance, Gardnerella dominance, or Prevotella dominance.
Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.
No sample metadata fields
View SamplesThis study was performed to check that ESR1 and BMI1 are biologically active after lentiviral transduction of primary human mammary epithelial cells (HMECs) with lentiviral vectors expressing ESR1 and BMI1 from the human PGK promoter. ESR1 targets like PGR, PRLR and GREB1, but not TFF1 and XBP1, were induced by estradiol in the ESR1-expressing cells. BMI1 targets like BMI1, NEFL and CCND2 were repressed in the BMI1-expressing cells. BMI1 suppressed genes associated with squamous and neural differentiation in the ESR1 plus BMI1-expressing cells.
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Specimen part
View SamplesA high percentage of potential oncology drugs fail in clinical trials, partly because preclinical models used to test them are inadequate. Breast cancer is the leading cause of cancer-related death among women worldwide but we lack appropriate in vivo models for the ER+ subtypes, which represent more than 75% of all cases. We address these issues by xenografting tumor cells to their site of origin, the milk ducts. All ER+ cell lines and patient-derived xenografts grow mimicking their clinical counterparts. Disease progresses with invasion and metastasis, which become amenable to study. The action of hormones, important in breast carcinogenesis, can now be studied in a relevant context. Importantly, these open opportunities for development and evaluation of therapies.
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Specimen part
View SamplesA high percentage of potential oncology drugs fail in clinical trials, partly because preclinical models used to test them are inadequate. Breast cancer is the leading cause of cancer-related death among women worldwide but we lack appropriate in vivo models for the ER+ subtypes, which represent more than 75% of all cases. We address these issues by xenografting tumor cells to their site of origin, the milk ducts. All ER+ cell lines and patient-derived xenografts grow mimicking their clinical counterparts. Disease progresses with invasion and metastasis, which become amenable to study. The action of hormones, important in breast carcinogenesis, can now be studied in a relevant context. Importantly, these open opportunities for development and evaluation of therapies.
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Specimen part
View SamplesEORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet.
Identification of molecular apocrine breast tumours by microarray analysis.
No sample metadata fields
View SamplesHead and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
No sample metadata fields
View SamplesSignal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC) and Barretts adenocarcinomas (BAC) revealed similar STAT3 expression in ESCCs and BACs, but preferentially activated P-STAT3 in ESCCs. In vitro, strong STAT3 activation was seen by EGF-stimulation in OE21 (ESCC) cells, whilst OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 and OE33 cells and reduced cell migration in OE33, but not in OE21 cells. Transcriptome analysis identified STAT3-knockdown associated down-regulation of cell cycle processes and the selective down-regulation of cyclins and cyclin dependent kinaes associated genes in both OE21 and OE33 cells. Moreover, the transcriptome response showed changes in cell migration/invasion related genes that correlated with the associated phenotype measurements. This study demonstrates the importance of STAT3 expression and activation in esophageal carcinomas, whereby the extent differs between ESCCs and BACs. STAT3 knockdown significantly reduces cell proliferation in both types of esophageal cancer cells and inhibits migration in BAC cells. Thus, STAT3 may be further exploited as potential novel therapeutic target for esophageal cancers.
STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett's adenocarcinomas.
Cell line, Treatment
View SamplesThree ALCL cell lines DEL, FEPD and K299 were induced with an IRF4-specific shRNA for up to 96 hours.
Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma.
Cell line
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