To examine irreversible changes in the developing brain following seizures, juvenile inbred mice were intraperitoneally injected with kainate and nicotine.
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.
No sample metadata fields
View SamplesAltered gene expression in the sphingosine 1-phosphate receptor 2 (S1P2)-deficient or sphingosine 1-phosphate receptor 3 (S1P3)-deficient brain.
Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2.
No sample metadata fields
View SamplesAs part of a clinical trial of the MDM2 inhibitor DS-3032b, 41 primary tumor samples were obtained before treatment from 38 patients newly diagnosed with AML, or relapsed or refractory to standard induction chemotherapy
Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition.
Specimen part, Disease, Disease stage
View SamplesCdh1 regulates not only mitotic phase and G1 phase, but also G2 checkpoint under irradiation-induced DNA damage. Despite several reports indicating its potential as tumor suppressor, how Cdh1 affects tumorigenesis or tumor progression and its clinical implementation has yet to be evaluated. Considering the pivotal role of Cdh1 on DNA repair, we hypothesized that Cdh1 loss also causes fragility of tumor cells to DNA damage under oncogenic stress or chemotherapy. To test this hypothesis, we established a Cdh1 gene-trapped B cell acute lymphoblastic leukemia (B-ALL) mouse model. Cdh1-deficient B-ALL mice survived longer than Cdh1-intact group, with higher susceptibility to DNA damage. Consistently, reverse phase protein array-based analysis of more than 200 human adult B-ALL samples showed that low Cdh1 was associated with high complete remission rates and long remission durations. Furthermore, the clinical benefit with lower Cdh1 expression diminished after relapse, supported by mouse experiments showing that secondary/tertiary transplants of Cdh1-deficient B-ALL cells developed more progressive/resistant disease than Cdh1-intact group. This indicated that prolonged inactivation of Cdh1 eventually develops resistant clones. Our results collectively demonstrated that Cdh1 is a potential predictive biomarker of B-ALL chemosensitivity, but also alerting that synthetic lethality by targeting DNA repair system may eventually induce resistant disease due to genetic instability.
FZR1 loss increases sensitivity to DNA damage and consequently promotes murine and human B-cell acute leukemia.
No sample metadata fields
View SamplesSharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-B signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here, we report novel mechanisms of HCC progression through Sharpin overexpression. Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in stably Sharpin-expressing cells. Versican expression increased in the majority of HCC tissues and knocking down of versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of versican transcription synergistically with Wnt/-catenin pathway activation. Furthermore, Sharpin overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes versican expression synergistically with the Wnt/-catenin pathway, potentially contributing to HCC development. A Sharpin/versican axis could be an attractive therapeutic target for this currently untreatable cancer.
Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.
Specimen part
View SamplesThe Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-third of these rats develop lens opacity within 10-11-weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR is poorly understood.
Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat.
Specimen part, Disease
View SamplesTo assess RNA regulation in FALS for gene expression and alternative processing of RNA in the motor neuron precurssors (MPCs)
Establishment of In Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis.
Specimen part
View SamplesPurpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).
Clinical significance of osteoprotegerin expression in human colorectal cancer.
Specimen part
View SamplesPurpose: The purpose of this study is to identify a novel biomarker related with distant metastases of colorectal cancer (CRC).
Identification of NUCKS1 as a colorectal cancer prognostic marker through integrated expression and copy number analysis.
Specimen part
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