Patients with palliative SCCHN were treated with figitumumab, an IGF-1R inhibitor. This receptor plays an important role in cell growth, proliferation and differentiation and is often overexpressed in SCCHN. No significant clinical activity was observed in our study
Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02).
Specimen part
View SamplesPURPOSE. During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. METHODS. Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several deregulated genes were assessed by RT-qPCR. Protein expression level and retinal cellular localization were determined by western-blot and immunohistochemistry, respectively. RESULTS. Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. CONCLUSIONS. This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathological conditions. Overall design: Retinal samples were harvested from C57Bl6/J and rd10 mouse retina at postnatal days 30 for whole transcriptome sequencing (RNAseq). Each sample included 2 frozen retina and experiments were performed in triplicate. RNA-seq transcriptome libraries were constructed from 1 ug of total RNA.
Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.
Specimen part, Cell line, Subject
View SamplesGlioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature it cannot be completely removed. We have recently shown that the WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is downregulated in glioblastoma and acts as strong tumor suppressor. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. MALAT1, a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knock-down of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation.
WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Specimen part, Cell line, Treatment
View SamplesComparison of laminin binding and laminin non-binding germ cells
Defining the spermatogonial stem cell.
No sample metadata fields
View SamplesRat germ cells
Defining the spermatogonial stem cell.
No sample metadata fields
View SamplesAnalysis of the influence of celiac disease-associated bacteria and gluten on intestinal epithelial cells
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Cell line, Treatment
View SamplesAnalysis of the influence of celiac disease-associated bacteria and gluten on intestinal epithelial cells
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Cell line, Treatment
View SamplesAnalysis of the influence of celiac disease-associated bacteria on intestinal epithelial cells
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Cell line, Treatment
View SamplesAnalysis of role of small intestinal intraepithelial lymphocytes (IELs) in the immunopathology of celiac disease
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Specimen part
View Samples