To identify the gene expression changes that are specific to SBMA, we prepared total mRNA samples from the spinal cords of transgenic mice carrying a full-length human AR with 97 CAGs (AR-97Q), transgenic mice bearing a wild-type allele of AR with 24 CAGs (AR-24Q), and the wild-type littermates of the AR-97Q mice (C57BL/6). We used AR-97Q (Line #7-8) male mice because they show progressive muscular atrophy and weakness as well as SBMA-like pathology such as the accumulation of the pathogenic androgen receptor in the nucleus of motor neurons.
Naratriptan mitigates CGRP1-associated motor neuron degeneration caused by an expanded polyglutamine repeat tract.
Sex
View SamplesCUGBP1 and MBNL1 are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. Using HITS-CLIP anlysis, we found CUGBP1 and MBNL1 preferentially bind to alternatively spliced introns and exons, as well as to the 3' UTRs.
CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
Specimen part, Cell line
View SamplesLiver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks
Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles.
Specimen part
View SamplesThe gene expression profling between Control and 300 mg/kg PhIP treatment in ventral prostate lobe of male F344 rats
Early detection of prostate carcinogens by immunohistochemistry of HMGB2.
Specimen part
View SamplesNon-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.
Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer.
Cell line
View SamplesThe purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors.
GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer.
Age, Specimen part, Disease stage
View SamplesEndometrial cancer is one of the most common gynecologic malignancies, and patients with high grade disease, especially serous papillary subtype (SPEC) are often related to the poor outcomes. Recent genome-wide analyses have revealed that SPEC exhibits gene expression profiles that are distinct from the endometrioid histologic subtype; therefore, it is important to identify the SPEC driver genes or pathways responsible for the inherently aggressive phenotypes and to develop SPEC-specific therapies to target these driver genes or pathways.
STAT1 drives tumor progression in serous papillary endometrial cancer.
Specimen part, Cell line
View SamplesOvarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination.
PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction.
Age, Specimen part
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 SamplesWe comprehensively searched for the factors that may attribute to hepatic insulin sensitivity in the patients with NAFLD. Forty-three NAFLD patients were assessed for putative biomarkers in blood and urine, body composition, tissue lipid content, tissue insulin sensitivity by hyperinsulinemic-euglycemic clamp, hepatic histology and gene expressions using liver biopsies, and life styles. In results, the higher levels of plasma adiponectin, muscle insulin sensitivity, and adipose tissue insulin sensitivity positively, but the higher levels of HbA1c, ALT, and log converted high-sensitive CRP negatively correlated with hepatic insulin sensitivity. Interestingly, whole liver volume and hepatic lean volume corrected by body surface area (cm3/m2) showed significant negative correlation with hepatic insulin sensitivity, specifically in patients with T2DM.
No associated publication
Specimen part, Disease
View Samples