GIST is considered to invariably arise through gain-of-function KIT or PDGFRA mutation of the interstitial cells of Cajal (ICC). However, the genetic basis of the malignant progression of GIST is poorly understood.
Distinct gene expression-defined classes of gastrointestinal stromal tumor.
Sex, Age
View SamplesOur previous investigation indicated that high-virulence C. gattii (C. gattii TIMM 4097) tend to reside in the alveoli, whereas low-virulence C. gattii (C. gattii TIMM 4903) tend to be washed out from the alveoli and move into the central side of the respiratory system. To test this hypothesis, we performed microarray assay.
How histopathology can contribute to an understanding of defense mechanisms against cryptococci.
Sex, Specimen part
View SamplesErbB receptor ligands, epidermal growth factor (EGF) and heregulin (HRG), induce dose-dependent transient and sustained intracellular signaling, proliferation and differentiation of MCF-7 breast cancer cells, respectively. In an effort to delineate the ligand-specific cell determination mechanism, we investigated time-course gene expressions induced by EGF and HRG that induce distinct cellular phenotypes in MCF-7 cells. To analyze the effects of ligand dosage and time for the gene expression independently, we developed a statistical method for decomposing the expression profiles into the two effects. Our results indicated that signal transduction pathways devotedly convey quantitative properties of the dose-dependent activation of ErbB receptor to early transcription. The results also implied that moderate changes in the expression levels of numbers of genes, not the predominant regulation of a few specific genes, might cooperatively work at the early stage of the transcription for determining the cell fate. However, the EGF- and HRG-induced distinct signal durations resulted in the ligand-oriented biphasic induction of proteins after 20 min. The selected gene list and HRG-induced prolonged signaling suggested that transcriptional feedback to the intracellular signaling results in a graded to biphasic response in the cell determination process, and that each ErbB receptor is inextricably responsible for the control of amplitude and duration of cellular biochemical reactions.
Quantitative transcriptional control of ErbB receptor signaling undergoes graded to biphasic response for cell differentiation.
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 SamplesWe recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. The breakpoints accumulated frequently adjacent to the T cell receptor alpha/delta chain locus (TCR/) with chromosomal deletions at 14q11 and a recurrent 0.9 Mb interstitial deletion was identified at a region including part of the TCR/ locus. Because leukemia-associated genes are frequently located near the breakpoint cluster regions, we then analyzed the gene expression profiles of ATL cells and identified N-myc downstream regulated gene 2 (NDRG2) as one of the genes that are down-regulated in ATLL cells among the 25 genes mapped to the region adjacent to the recurrently deleted regions at 14q11.
Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.
Specimen part
View SamplesZinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon.
Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain.
Specimen part
View SamplesPaper abstract: The transcription factors Abrupt (Ab) and Knot (Kn) act as selectors of distinct dendritic arbor morphologies in two classes of Drosophila sensory neurons, termed class I and class IV, respectively. We performed binding-site mapping and transcriptional profiling of isolated these neurons. Their profiles were similarly enriched in cell-type-specific enhancers of genes implicated in neural development. We identified a total of 429 target genes, of which 56 were common to Ab and Kn; these targets included genes necessary to shape dendritic arbors in either or both of the two sensory subtypes. Furthermore, a common target gene, encoding the cell adhesion molecule Ten-m, was expressed more strongly in class I than IV, and this differential was critical to the class-selective directional control of dendritic branch sprouting or extension. Our analyses illustrate how differentiating neurons employ distinct and shared repertoires of gene expression to produce class-selective morphological traits.
Sensory-neuron subtype-specific transcriptional programs controlling dendrite morphogenesis: genome-wide analysis of Abrupt and Knot/Collier.
Specimen part
View SamplesThere is a continuing need for driver strains to enable cell type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (http://enhnacertrap.bio.brandeis.edu). Overall design: Examination of 6 cortical mouse neuronal cell types. 5 of which are in layer 6 in 3 different cortical regions.
A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types.
Sex, Cell line, Subject
View SamplesCollismycin A is a microbial product. We used microarrays to examine the effect of collismycin A on gene expression of HeLa cells.
Proteomic profiling reveals that collismycin A is an iron chelator.
Specimen part, Cell line
View SamplesThe agonistic anti-human CD3 antibody , OKT-3, has been used to control acute transplant rejection. The in vivo administration of OKT-3 was previously shown to induce the partial depletion of T cells and anergy in the remaining CD4+ T cells. However, this therapy is also associated with the systemic release of several cytokines, which leads to a series of adverse side effects. We established a novel anti-human CD3 Ab, 20-2b2 (#1 abs), which recognized a close, but different determinant on the CD3 molecule from that recognized by OKT3. 20-2b2 was non-mitogenic for human CD4+ T cells, could inhibit the activation of T cells in vitro, and induced T cell anergy in in vivo experiments using humanized mice. Cytokine release in humanized mice induced by the administration of 20-2b2 was significantly less than that induced by OKT-3. Our results indicated that the CD3 molecule is still an attractive, effective, and useful target for the modulation of T cell responses. The establishment of other Abs that recognize CD3, even though the determinant recognized by those Abs may be close to or different from that recognized by OKT-3, may represent a novel approach for the development of safer Ab therapies using anti-CD3 Abs, in addition to the modification of OKT-3 in terms of the induction of cytokine production.
Modulation of the human T cell response by a novel non-mitogenic anti-CD3 antibody.
Specimen part, Disease, Disease stage
View Samples