Circadian rhythm study on transcriptional responses to i.v. administered 90 kBq iodine-131 after 24h in mouse kidney cortex and medulla, liver, lungs, spleen, and thyroid.
Circadian rhythm influences genome-wide transcriptional responses to (131)I in a tissue-specific manner in mice.
Sex, Specimen part, Time
View SamplesTranscriptomic profiling of normal mouse thyroid tissue following 211At irradiation
Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles.
Specimen part
View SamplesRNA microarray analysis of low-dose and dose rate responses versus time after i.v. administration of 211At.
Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after <sup>177</sup>Lu[Lu]-octreotate therapy.
Time
View SamplesTranscriptomic profiling of human breast tumors using RNA sequencing Overall design: Evaluation of common fusion transcripts, genetic variants, and gene expression patterns in 8p11-p12 amplified breast carcinomas
Genome-wide multi-omics profiling of the 8p11-p12 amplicon in breast carcinoma.
Age, Specimen part, Subject
View SamplesThe radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In vitro and preclinical in vivo studies have shown that irradiation can up-regulate the expression of somatostatin receptors and thereby give an increased uptake of 177Lu-octreotate. The cellular processes that underlie positive treatment response to 177Lu-octreotate are otherwise largely unknown. Genome-wide analysis of tumor cell responses in this successful mouse model offers a venue to identify critical treatment parameters and to optimize clinical effectiveness of 177Lu-octreotate therapy. Combining 177Lu-octreotate with other anti-tumor agents has also been proposed as a strategy for optimization. Some studies have shown synergistic effects in tumor cell killing and volume reduction The hedgehog signaling pathway is involved in embryonic development and tissue regeneration and can be/is abnormally activated in various cancers. Inhibition of the hedgehog signaling pathway has yielded promising therapeutic effects on NE tumors and may potentially enhance the effects of 177Lu-octreotate treatment in patients.
Priming increases the anti-tumor effect and therapeutic window of <sup>177</sup>Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
Time
View SamplesThe radiolabelled somatostatin analogue 177Lu-octreotate is a promising treatment option for malignant neuroendocrine tumors that overexpress somatostatin receptors. The human small intestine neuroendocrine tumor cell line GOT1 and Medullary thyroid carcinoma model GOT2 have shown promising treatment response to 177Lu-octreotate in xenografted mice. In clinical studies, however, only low cure rates have been achieved to date. In xenografted tumors, the human stromal components have been replaced with mouse stroma, which may have an impact in the treatment response of the xenografts.
Priming increases the anti-tumor effect and therapeutic window of <sup>177</sup>Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
Time
View SamplesBromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mTOR inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of BRD4 inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains antiproliferative activity of JQ1 in OS cells.
Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma.
Specimen part, Cell line
View SamplesAnalysis of histone acetyl transferases (HATs) from the MYST and GNAT families in S. pombe to identify functional differences or overlap with regard to gene expression. Mutations were made to Elp3 and Gcn5 (GNAT family), and to Mst2 (MYST family). Mutants showed distinct phenotypes which were repressed or enhanced by mutant combinations.
Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation.
Cell line, Treatment
View SamplesPublic transcriptomics studies have shown that several genes display pronounced gender differences in their expression in the human brain, and these differences may influence the clinical manifestations and risk for neuronal disorders. While disease relevant implications have already been proposed for gender differences in hormone levels, life style and genetic diversity, a systems level analysis of brain gene expression disparities between the genders in the context of brain disorders like Alzheimers disease (AD) has not yet been conducted.
Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies.
Specimen part, Treatment
View Samples