Identification and evaluation of specific molecular markers is of great importance for reliable diagnostics and outcome prediction of renal neoplasms
High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas.
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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 SamplesTranscriptome and translatome analyses of 6 and 24 hours imbibed seeds dormant and non-dormant seeds of NILDOG1-Cvi with and without addition of the transcription inhibitor Cordycepin. NILDOG1-Cvi is the Ler WT containing an introgression of the Cvi accession on chromosome 5, which includes the DOG1 gene (Bentsink et al., 2006).
Combined transcriptome and translatome analyses reveal a role for tryptophan-dependent auxin biosynthesis in the control of DOG1-dependent seed dormancy.
Specimen part, Treatment
View SamplesAbove ground tissue of 10 day old Arabidopsis seedlings of Col wild-type, 35S-ARR7, arr7, 35S-ARR15 was treated with Cytokinin (benzyladenine), Auxin (indole-3-acetic acid) or both.
Hormonal control of the shoot stem-cell niche.
Age, Specimen part, Treatment
View SamplesThe rate of transcription elongation plays important roles in the timing of expression of full-length transcripts as well as for the regulation of alternative splicing. In this study we coupled Bru-Seq technology with 5,6-dichlorobenzimidazole 1-ß-D-ribofuranoside (DRB) to estimate the elongation rates of over 2,000 individual genes in human cells. This technique, BruDRB-Seq, revealed gene-specific differences in elongation rates with a median rate of around 1.5 kb/min. We found that genes with fast elongation rates showed higher densities of H3K79m2 and H4K20me1 marks compared to slower elongating genes. Furthermore, fast elongation rates had a positive correlation with gene length, low complexity DNA sequence and distance from nearest active transcription unit. Features that negatively correlated with elongation rate included exon density and the number of LINE sequences in the gene. The BruDRB-Seq technique offers new opportunities to interrogate mechanisms of regulation of transcription elongation. Overall design: Measurement of RNA Pol II elogation rate. Normal fibroblasts (HF1 and TM), Cockayne syndrome group B fibroblasts, K562 and MCF-7 cells were exposed to DRB for 60 minutes, after which a washout was performed. Nascent RNA was labeled using bromouridine for 10 minutes immediately after the washout. The genomic region extending from actice Trancription Start Sites was used to determine the gene''s elongation rate. Please note that the nf_0h_3* samples are duplicated sample records of GSM1062445 and GSM1062446, for the convenient retrieval of the complete raw data from SRA.
Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications.
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View SamplesFibroblast growth factor-23 (FGF23), a circulating protein produced in bone, causes renal inorganic phosphate (Pi) wasting by down-regulation of sodium phosphate co-transporter 2a (Npt2a). The mechanism behind this action is unknown. We have previously generated transgenic mice (TG) expressing human wild-type FGF23 under the control of the 1 (I) collagen promoter. In this study we performed a large scale gene expression study of kidneys from TG mice and wild-type littermates. Several genes that play a role in Pi regulation had decreased expression levels, such as Npt2a, but also Pdzk1 which is a scaffolding protein known to interact with NPT2a. Importantly, the Klotho gene, a suggested crucial co-factor for FGF23 receptor binding and activation, was the most affected decreased gene. However, other genes proposed to regulate Pi levels, such as secreted Frizzled Related Protein 4 (sFRP4), Na+/H+ exchanger regulatory factor 1 (NHERF1) and the FGF-receptors 1-4, revealed no changes. Interestingly, expression levels of inflammatory response genes were increased and histological analysis revealed tubular nephropathy in the TG mice kidneys. In conclusion, FGF23 TG mice have altered kidney gene expression levels of several genes thought to be part of Pi homeostasis and an increase in inflammatory response genes, data supported by histological analysis. These findings may lead to further understanding of how FGF23 mediates its actions on renal Pi regulation.
Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23.
Age
View SamplesComparison of Arabidopsis seedlings with disturbed function of CDKB2;1 and CDKB2;2 by either overexpression or knock-down
Requirement of B2-type cyclin-dependent kinases for meristem integrity in Arabidopsis thaliana.
Specimen part
View SamplesAtIPT8/pga22 seedlings (gain-of-function mutant in Ws background; Sun et al. 2003, Plant Physiology 131, pp167-176) were grown on vertical plates for 7 days in LD. The seedlings were then incubated directly on the plate with medium containing 5 uM 17-beta-estradiol (for induction of the IPT8 gene) or 5 uM trans-zeatin for 12 and 24 h. 5 mm primary root tips were harvested from the seedlings and pooled for microarray analysis. Total RNA was isolated from the samples with the RNeasy Plant Mini Kit from Qiagen.
Cytokinin regulation of auxin synthesis in Arabidopsis involves a homeostatic feedback loop regulated via auxin and cytokinin signal transduction.
Specimen part, Treatment
View SamplesPurpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia.
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