The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate as compared to chemotherapy plus either trastuzumab or lapatinib. An extensive biomarker programme was prospectively planned to identify potential predictors of sensitivity to different treatments and evaluate treatment effect on tumor biomarkers.
Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer.
Specimen part, Disease, Disease stage
View SamplesTo investigate the role of the circadian clock gene Bmal1 in skeletal muscle, we compared the circadian transcriptomes of fast tibialis anterior (TA) and slow soleus (SOL) skeletal muscles from muscle-specific Bmal1 KO (mKO) and their control Cre- littermates (Ctrl).
Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock.
Sex, Specimen part, Time
View SamplesTo investigate the time-dependent and coordinated sequence of inflammation-related events, and the dynamic features of macrophage polarisation/activation, we build and validated an in vitro model based on primary human monocytes
Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View SamplesTumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Analyzing the cytokines affecting myelo-monocytic differentiation produced by various experimental tumors, we found that GM-CSF, G-CSF, and IL-6 allowed a rapid generation of MDSCs from precursors present in mouse and human bone marrow (BM). BM-MDSCs induced by GM-CSF+IL-6 possessed the highest tolerogenic activity, as revealed by the ability to impair the priming of IFN- -producing CD8+ T cells upon in vivo adoptive transfer. Moreover, adoptive transfer of syngeneic, GM-CSF+IL-6-conditioned MDSCs to diabetic mice transplanted with allogeneic pancreatic islets resulted in long term acceptance of the allograft and correction of the diabetic status. Cytokines inducing MDSCs acted on a common molecular pathway. Immunoregulatory activity of both tumor-induced and BM-derived MDSCs was entirely dependent on C/EBP transcription factor, a key component of the emergency myelopoiesis triggered by stress and inflammation. Adoptive transfer of tumor antigen-specific CD8+ T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBP in myeloid compartment. These data unveil another link between inflammation and cancer and identify a novel molecular target to control tumor-induced immune suppression.
Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth.
Specimen part, Cell line
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesBy restraining T cell activation and promoting regulatory T cell (Treg) expansion, myeloid-derived suppressor cells (MDSC) and tolerogenic dendritic cells (DC) (tDC) can control self-reactive and anti-graft effector T cells in autoimmunity and transplantation. Their therapeutic use and characterization, however, is limited by their scarce availability in the peripheral blood of tumor-free donors. In the present study we describe and characterize a novel population of myeloid suppressor cells, named fibrocytic MDSC (f-MDSC), that are differentiated from umbilical cord blood (UCB) precursors by a 4 day culture with FDA approved cytokines (rh-GM-CSF and rh-G-CSF). This MDSC subset, characterized by the expression of MDSC-, DC-, and fybrocyte-s associated markers, promotes Treg regulatory cells expansion and promote normoglycemia in a xenogeneic model of Type 1 Diabetes (T1D). In order to exert their pro-tolerogenic function, fibrocytic MDSC require direct contact with activated T cells, which leads to the induction and secretion of indoleamine 2,3 deoxygenase (IDO). This new myeloid subset may represent an important tool for the in vitro and in vivo production of Treg for the treatment of autoimmune diseases, and either prevention or control of allograft rejection.
No associated publication
Specimen part, Cell line, Treatment
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