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 SamplesThe ability to regenerate or recover from injuries varies greatly not only between species but also between tissues and organs or developmental stages of the same species. The mechanisms behind these different regenerative capabilities are ultimately dependent on the control of genome activity, determined by a complex interplay of regulatory elements functioning at the level of chromatin. Resetting of gene expression patterns during injury responses is, thus, shaped by the coordinated action of genomic regions (enhancers, silencers) that integrate the activity of multiple sequence-specific DNA binding proteins (transcription factors and cofactors). Using genome- wide approaches to interrogate chromatin function here we identify the regulatory elements governing tissue recovery in Drosophila wing imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings point to a global co-regulation of gene expression and provide evidence for Damage Responding Regulatory Elements (DRRE), some of which are novel whereas others are also used in other tissues or developmental stages. Overall design: We collected data at different time points (0, 15 and 25h) after apoptosis induction. These time periods were selected because they included the most important transcriptional responses to apoptosis, ranging from the earliest gene expression up to complete re-patterning. Discs kept at the same conditions without inducing cell death were used as controls.
Damage-responsive elements in <i>Drosophila</i> regeneration.
Specimen part, Subject
View SamplesContinuous contact with self-major histocompatibility complex ligands is essential for the survival of naive CD4 T cells. We have previously shown that the resulting tonic TCR signaling also influences their fate upon activation by increasing their ability to differentiate into induced regulatory T cells. To decipher the molecular mechanisms governing this process, microarray data comparing highly (Ly-6C-) and lowly (Ly-6C+) Self-reactive naive CD4 T cells were obtained.
Calcium-mediated shaping of naive CD4 T-cell phenotype and function.
Specimen part
View SamplesSince bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions.
Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis.
Specimen part, Cell line
View SamplesTo find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen part
View SamplesTranscriptome analysis of 12 zebrafish tissues
Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database.
No sample metadata fields
View SamplesThis study supports an active role for PLZF and RAR-PLZF in leukemogenesis, identifies upregulation of CRABPI as a novel mechanism contributing to retinoid resistance and reveals the ability of the reciprocal fusion gene products to mediate distinct
RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
No sample metadata fields
View SamplesDe novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood fatality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models,we found that Asxl1 global loss or conditional deletion in osteoblasts and their progenitors in mice leads to significant bone loss and markedly decreased numbers of marrow mesenchymal stem/progenitor cells (MSPCs) compared with wild-type (WT) littermates. Asxl1-/- MSPCs displayed impaired self-renewal and skewed differentiation-away from osteoblasts and favoring adipocytes. RNA-seq analysis reveals the altered expression of genes involved in cell proliferation, skeletal development and morphogenesis. Furthermore, gene set enrichment analysis showed a decreased gene expression of stem cell self-renewal signature,suggesting the role of Asxl1 in regulating the stemness of MSPCs. Importantly, introducing Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1-/- MSPCs. Our study unveils a pivotal role of ASXL1 in maintenance of MSPC functions and skeletal development. Overall design: Examination of mRNA profiles in wild type and Asxl1-/- MSPCs by deep sequencing
Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice.
Specimen part, Subject
View SamplesTransforming growth factor- (TGF-) is a key factor for the development of prostate cancer metastases in bone. In breast cancer and melanoma, studies have shown how TGF- regulates gene expression to allow cancer cells to adapt to the bone microenvironment.
The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone.
Specimen part, Cell line, Treatment
View SamplesGrb14 is an endogenous inhibitor of insulin signaling
Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance.
Specimen part, Treatment
View Samples