Gene expression profiles were recorded from rectal suction specimens of Cystic Fibrosis (CF) patients, carrying the CF-specific D508 mutated CFTR-allele. These profiles were compared with gene expression profiles from rectal suction specimens of non-CF subjects (control).
The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells.
Specimen part
View SamplesHere we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, non-invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a standard of care chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.
Preclinical models for neuroblastoma: establishing a baseline for treatment.
Specimen part
View SamplesPurpose: To identify the impact of thermoneutral housing as opposed to standard housing on gene expression profiles in the mouse peripheral blood mononuclear cells (PBMCs), focusing on proinflammatory immune responses and high-fat diet induced non-alcoholic fatty liver disease pathogenesis. Methods: Expression profiles from PBMCs collected from C57Bl6 mice fed chow or high-fat diet for 8 weeks, following 2 weeks at either standard or thermoneutral housing conditions. Sequencing was performed in duplicate, the Illumina HiSeq 2500. Transcripts that passed quality filters were analyzed at the gene level, using Strand NGS for accurate alignment and quantification. Results: We mapped approximately 20million reads per sample to the mm10 genome using annotations produced by Ensembl, which represented 36186 transcripts. Approximately 14000 genes exhibited reasonable expression in at least one experimental condition. The primary focus was the effect of housing temperature while holding diet consistent (i.e. thermoneutral vs standard, both on high-rat diet), where ~2700 genes exhibited differential regulation. Conclusions: We present the transcriptomic profile of PBMCs from mice fed chow of high-fat diets, following either standard or thermoneutral housing. We obseve an augmented proinflammatory immune response. Overall design: PBMC expression profiles were characterized following eight weeks of chow or high-fat diet, following two weeks of standard or thermoneutral housing.
Modulation of ambient temperature promotes inflammation and initiates atherosclerosis in wild type C57BL/6 mice.
Specimen part, Subject
View SamplesNasopharyngeal carcinoma (NPC) is a common cancer in southern China and South East Asia where more than 50,000 new cases are diagnosed each year.
The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma.
Disease, Disease stage
View SamplesThe transcriptional co-regulator IRF2BP1 gets de-SUMOylated after EGF treatment in Hela cells. SUMOylation of IRF2BP1 occurs at position K579.
Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling.
Cell line, Treatment
View SamplesWe addressed the clinical significance and mechanisms behind in vitro cellular responses to ionising radiation (IR)-induced DNA double strand breaks in 74 paediatric ALL patients. We found an apoptosis-resistant response in 36% of patients and an apoptosis-sensitive response in the remaining 64% of leukaemias. Global gene expression profiling of 11 apoptosis-resistant and 11 apoptosis-sensitive ALLs revealed abnormal up-regulation of multiple pro-survival pathways in response to IR in apoptosis-resistant leukaemias and differential post-transcriptional activation of the PI3-Akt pathway was observed in representative resistant cases. It is possible that abnormal pro-survival responses to DNA damage provide one of the mechanisms of primary resistance in ALL .
Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.
No sample metadata fields
View SamplesThe goal of this study is to define genes that are differentially expressed in Down syndrome leukemic blasts after treatment with valproic acid (VPA)
Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.
Disease, Disease stage
View SamplesNeurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth cause progressive hearing loss, and the standard treatment including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allows hearing test. Here we developed a cerebellopontine angle (CPA) schwannomas model that faithfully recapitulates the tumor-induced hearing loss. Using this model we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor HGF levels. cMET gene knockdown study independently confirmed the role of cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared to normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in NF2 patients.
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DOCK8 is critical for the survival and function of NKT cells.
Sex, Specimen part
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