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GSE10575
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The regeneration of diseased hyaline cartilage remains a great challenge, mainly because degeneration activities after major injury or due to age-related processes overwhelm the self-renewal capacity of the tissue. We show that repair tissue from human articular cartilage of late stages of osteoarthritis harbor a unique progenitor cell population, termed chondrogenic progenitor cells exhibiting stem cell characteristics, such as multipotency, lack of immune system activation and, in particular, migratory activity. The isolated CPC exhibit a high chondrogenic potential and were able to populate diseased tissue in vivo. Moreover, down-regulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9 and consequently the matrix synthesis potential of chondrogenic progenitor cells. Our results, while offering new insight into the biology of progenitor cells from diseased cartilage tissue, might assist future strategies to treat late stages of osteoarthritis.
Publication Title
Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The epithelial expression of the insulin receptor in the colon is previously reported to correlate with the extent of colonic inflammation. Here, we investigated the effect of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer. We report increased susceptibility to chemically-induced colitis together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we show that topically administered insulin in inflamed colons of wildtype mice reduces inflammation-induced weight loss and improves remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and developed significantly fewer and smaller tumors compared with the control group receiving phosphate-buffered saline only. Rectal insulin therapy can potentially be a novel treatment targeting the epithelial layer to enhance mucosal healing in the ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.
Publication Title
Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 58 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Deregulation of the translational machinery is emerging as a critical contributor to lymphomagenesis. Various miRNA alterations have been identified in lymphoma, but their role in disrupting the cap-dependent translation regulation complex remains poorly understood. Here, we demonstrate the translation initiation factor, eIF4GII, as a direct target and major mediator of miR-520c-3p function through 3UTR of eIF4GII mRNA. We established that elevated miR-520c-3p represses translation, initiates premature senescence and blocks cell proliferation in diffuse large B-cell lymphoma (DLBCL). Moreover, miR-520c-3p overexpression diminishes DLBCL cells colony formation and reduces tumor growth in a lymphoma xenograft mouse model. miR-520c-3p overexpressing cells display lowered eIF4GII levels. Consequently, downregulation of eIF4GII by siRNA induces cellular senescence, decreases cell proliferation and ability to form colonies. Our in vitro and in vivo findings we further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally highly up-regulated eIF4GII protein expression. In contrast, normal donor B-cell lymphocytes had low levels of eIF4GII protein and elevated miR-520c-3p levels. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of cap-dependent translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. These findings may have implications for therapeutic interventions in patients with DLBCL.
Publication Title
Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma.
Publication Title
p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cardiac-specific PPARalpha transgenic (Tg-PPARalpha) mice show mild cardiac hypertrophy and systolic dysfunction. The failing heart phenotypes observed in Tg-PPARalpha are exacerbated by crossing with cardiac-specific Sirt1 transgenic (Tg-Sirt1) mice, whereas Tg-Sirt1 mice themselves do not show any cardiac hypertrophy or systolic dysfunction. To investigate the mechanism leading to the failing heart phenotypes in TgPPARalpha/Tg-Sirt1 bigenic mice, microarray analyses were performed. The microarray analyses revealed that many ERR target genes were downregulated in Tg-PPARalpha and in Tg-Sirt1, and they were further downregulated in the Tg-PPARalpha/Tg-Sirt1 bigenic mice.
Publication Title
PPARα-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We harvested the heart from transgenic mice with cardiac specific overexpression of Sirt1 (Tg-Sirt1) and non-transgenic (NTg) control littermate at 3 months of age and then microarray analyses were conducted.
Publication Title
Sirt1 regulates aging and resistance to oxidative stress in the heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In this data, we examined Transcriptome detection and expression in 8 samples of Retinoblastoma. We found a central core shared by all samples .
Publication Title
Discovery of a transcriptomic core of genes shared in 8 primary retinoblastoma with a novel detection score analysis.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Muscle atrophy F-box (MAFbx) is an E3 ubiquitin ligase which plays a critical role in mediating skeletal muscle atrophy. We investigated the effect of MAFbx KO in cardiac hypertrophy in response to pressure overload. A DNA microarray analysis was conducted using total RNA prepared from wild type and MAFbx KO mouse hearts subject to transverse aortic constriction (TAC). Results provide insight into the molecular mechanism to mediate the effect of MAFbx upon pathological hypertrophy.
Publication Title
Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
To determine the global effects of ASCT2 inhibition, we used next generation sequencing to determine mRNA expression changes in PC-3 cells treated with BenSer or GPNA for 48 h. Overall design: Examination of two different ASCT2 inhibitors BenSer and GPNA in prostate cancer cell line PC-3.
Publication Title
Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Stable knockdown of NET1, a RhoGEF, was achieved in AGS Gastric Cancer cells. This gene is known to be overexpressed in the disease.
Publication Title
A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer.
Sample Metadata Fields
Cell line
View Samples