The objective of the study was to better understand the mechanism behind scar formation by identifying ECM factors and other unique genes differentially expressed during rat ligament healing via microarray. Rat medial collateral ligaments (MCL) were surgically transected or left intact. MCLs were collected at day 3 or 7 post-injury and used for microarray analysis. Results were compared to the normal intact ligaments.
Gene profiling of the rat medial collateral ligament during early healing using microarray analysis.
Sex, Specimen part
View SamplesHistidine-rich glycoprotein (HRG) is a 75 kDa heparin-binding plasma protein which has been implicated in regulation of tumor angiogenesis and growth. To exert some of its biological functions, HRG acts on macrophages.This study was performed to assess changes in gene expression in peritoneal macrophages treated with HRG using oligonucleotide microarrays
Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization.
Specimen part, Disease, Treatment, Time
View SamplesIn order to identify the processes altered in T regulatory cells (Treg) by Zoledronic acid (ZA), we examined RNA expression by RNA-seq in Treg treated with and without ZA. We identified gene expression alterations in ZA-treated Treg that were essential to Treg function. Overall design: Human T regulatory cells isolated from healthy donors (n=6) were cultured overnight with IL-2 and OKT3 (anti-CD3) in the presence or absence of ZA. RNA sequencing (Illumina HiSeq2500) was performed to identify differential gene expression induced by ZA treatment of Treg.
Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer.
Specimen part, Disease, Treatment, Subject
View SamplesChronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, but the underlying molecular mechanisms are unknown. We hypothesized that lung stromal cells activate pathological gene expression programs supporting oncogenesis. To identify molecular mechanisms operating in the lung stroma that support development of lung cancer. Study subjects included patients with- or without- lung cancer across a spectrum of lung function. We conducted multi-omics analysis of non-malignant lung tissue to quantify the transcriptome, translatome and proteome. Cancer-associated gene expression changes predominantly manifested as alterations in the efficiency of mRNA translation modulating protein levels in the absence of corresponding changes in mRNA levels. The molecular mechanisms driving these cancer-associated translation programs differed based on lung function. In subjects with normal to mildly impaired lung-function, the mammalian target of rapamycin (mTOR) pathway served as an upstream driver; whereas in severe airflow obstruction, pathways downstream of pathological extracellular matrix (ECM) emerged. Consistent with a role during cancer initiation, both the mTOR and ECM gene expression programs paralleled activation of previously identified pro-cancer secretomes. Furthermore, in situ examination of lung tissue documented that stromal fibroblasts express cancer-associated proteins from the two pro-cancer secretomes including IL6 in mild or no airflow obstruction and BMP1 in severe airflow obstruction. Two distinct stromal gene expression programs promoting cancer initiation are activated in lung cancer patients depending on lung function. Our work has implications both for screening strategies and personalized approaches to cancer treatment. Overall design: Polysome-profiling of non-cancerous lung stroma tissue samples from patients with or without lung cancer across a range of forced expiratory volume in one second (FEV1)
Distinct Cancer-Promoting Stromal Gene Expression Depending on Lung Function.
Specimen part, Subject
View SamplesTwo major subsets of rat natural killer (NK) cells can be distinguished based on their expression of either the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors.
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines.
Specimen part
View SamplesDiabetes and obesity are widespread diseases with signifciant socioeconomic implications. We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients.
Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
Specimen part, Race
View SamplesOxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior. Overall design: The mRNA profiles from hippocampus of WT, Ogg1-/-, Mutyh-/- and Ogg1-/- Mutyh-/- C57BL/6 mice at 6month of age were generated by RNA sequencing using Illumina Hiseq 2000
Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice.
Age, Specimen part, Cell line, Subject
View SamplesBarretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease, Subject
View SamplesBarretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Transplantation of transformed Barretts stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease
View SamplesBarretts esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barretts have been stymied by our inability to identify the Barretts stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Genomic analyses of Barretts stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barretts stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barretts develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease, Disease stage
View Samples