A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects.
The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression.
Sex
View SamplesAdenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands, with an incidence of 4.5 per 1,000,000. It can also arise in glandular tissue closely related to salivary glands in the lacrimal gland, nasal passages and tracheobronchial tree, as well as in glands of the breast and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform or tubular patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis and/or spread along peripheral nerves. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACC, and recently it has been discovered that in a majority of ACC the MYB gene on chromosome 6 is fused to the 3 terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation. Recently it has been determined that most cell lines with attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB-NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and pre-clinical models systems of ACC, we have for several years been establishing xenograft tumor lines from clinical samples of ACC. We describe our experience with these models and their characterization here.
Development and characterization of xenograft model systems for adenoid cystic carcinoma.
Specimen part
View SamplesUpstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the non-coding RNA roX plays key roles in the control of X-chromosome dosage compensation in both sexes. In order to investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of non-coding RNAs in a sex-specific fashion. Overall design: Two replicates of UNR IP were performed in D.melanogaster adult males and females, and enrichment in either sex was compared with IgG IP as control. To correlate sex-specific UNR binding with sex-specific transcription and splicing we performed RNA-Seq experiments in males and females.
Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR.
Specimen part, Subject
View SamplesThis study examined the gene expression effects of treating androgen-deprived C4-2 prostate cancer cells with the ACLY inhibitor BMS-303141 and the AR antagonist enzalutamide. Overall design: Cells were treated with vehicle control, ACLY inhibitor alone, Enzalutamide alone, and ACLY-inhibitor and Enzalutamide combined together for 24 hours under androgen-depleted conditions (RPMI + 5% charcoal stripped serum). Biological triplicate samples were prepared.
Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.
Subject
View SamplesThe basic unit of genome packaging is the nucleosome, and nucleosomes have long been proposed to restrict DNA accessibility both to damage and to transcription. However, nucleosome number in cells was considered fixed, and no condition was described where nucleosome number was reduced. We show here that mammalian cells lacking High Mobility Group Box 1 protein (HMGB1) contain a reduced amount of core, linker and variant histones, and a correspondingly reduced number of nucleosomes. Yeast nhp6 mutants lacking NHP6A and B proteins, which are related to HMGB1, also have a reduced amount of histones and fewer nucleosomes. Nucleosome limitation in both mammalian and yeast cells increases the sensitivity of DNA to damage, increases transcription globally, and the relative expression of about 10% of genes. In yeast nhp6 cells the loss of more than one nucleosome in four does not affect the location of nucleosomes and their spacing, but nucleosomal occupancy. The decrease in nucleosomal occupancy is non-uniform, and our results can be modelled assuming that different nucleosomal sites compete for the available histones: sites with high affinity are almost always packaged into nucleosomes both in wt and nucleosome-depleted cells, whereas sites with low affinity are less frequently packaged in nucleosome-depleted cells. We suggest that by modulating the occupancy of nucleosomes histone availability may constitute a novel layer of epigenetic regulation.
Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output.
No sample metadata fields
View SamplesMelanoma is an aggressive neoplasm with increasing incidence that is classified by the NCI as a recalcitrant cancer, i.e., a cancer with poor prognosis, lacking progress in diagnosis and treatment. In addition to conventional therapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints. As drug resistance remains a major obstacle to treatment success, advanced therapeutic approaches based on novel targets are still urgently needed. We reasoned that the base excision repair enzyme Thymine DNA Glycosylase (TDG) could be such a target for its dual role in safeguarding the genome and the epigenome, by performing the last of the multiple steps in DNA demethylation. Overall design: Six samples : cells treated with shTDG and cells treated with shControl both in triplicates.
Thymine DNA glycosylase as a novel target for melanoma.
Cell line, Treatment, Subject
View SamplesThalidomide-dexamethasone (TD) combination is an effective induction therapy for newly diagnosed multiple myeloma patients, candidates for subsequent autologous stem cell transplantation (ASCT). Since maximization of tumor response before ASCT may favorably affect the clinical outcomes, we designed a study to identify a gene expression profile (GEP) signature predictive of attainment of complete response to TD induction therapy. CD138+ bone marrow samples obtained at diagnosis from 112/311 patients were analyzed. Two subsequent time phases were planned. Firstly, a GEP supervised analysis, performed on a training set of 32 patients, allowed to identify 157 probe sets differentially expressed in complete responder + near complete responder (CR+nCR) versus partial responder patients. Than, we generated an 8-gene GEP signature predicting at diagnosis the probability to achieve CR+nCR to TD induction therapy. The performance of this assay was subsequently validated in an 80 patients training set. The 8-gene signature provide a negative predictive value of 93% and a positive predictive value of 44%. The 8 genes were down-regulated in patients who achieved at least a nCR. These results could be an important first step to adopting a diagnostic assay, used to determine, at diagnosis, patients who will respond more favourably to a particular treatment strategy.
Correlation between eight-gene expression profiling and response to therapy of newly diagnosed multiple myeloma patients treated with thalidomide-dexamethasone incorporated into double autologous transplantation.
Age, Specimen part, Disease, Disease stage
View SamplesT84 cells were treated with DMSO, 30nM trametinib (MEKi), 1µM JQ1 (BRD4i) or the combination of trametinib and JQ1 (combo) for 24h. Overall design: 3 replicates per condition were analyzed by RNA-seq.
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
Cell line, Treatment, Subject
View SamplesHCT116 cells were treated with with increasing concentrations of trametinib over 2 months. Drug-resistant clones emerged and were cultured in the presence of 30 nmol/L trametinib. These cells exhibited a greater than 10-fold increase in the GI50 for trametinib compared to the parental cell line. RNA-seq of the resistant clone HCT116_R4 versus the parental cells identified differentially expressed genes potentially involved in resistance. Overall design: For the parental and resistant clone, 3 replicates each were analysed by RNA-seq.
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
Treatment, Subject
View SamplesSeed germination is a critical developmental process in plant propagation. Knowledge of the gene expression patterns in this critical process is important in order to understand the main biochemical reactions involved in successful germination, specially for economically relevant plants such as Maize.
Expression profile of maize (Zea mays L.) embryonic axes during germination: translational regulation of ribosomal protein mRNAs.
Treatment, Time
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