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  • cytokine
  • On the other hand, GM-CSF deficiency leads to various immune dysfunctions and the current utilization of GM-CSF as haematopoietic factor might be an accurate but very incomplete indication for a cytokine with vast clinical potential. (springer.com)
  • The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. (springer.com)
  • osteoclastogenesis
  • To identify components of the MCSF receptor that is critical for osteoclastogenesis in beta(3)(-/-) cells, we retrovirally transduced authentic osteoclast precursors with chimeric c-Fms constructs containing various cytoplasmic domain mutations. (semanticscholar.org)
  • kinase
  • GM-CSF stimulated MAP kinase activation in both the undifferentiated and differentiated HL-60 cells. (ovid.com)
  • One such transcription factor is the cAMP-regulatory element-binding protein (CREB), which can be activated through phosphorylation by a number of kinases, including Akt, p90Rsk, protein kinase A, and calcium/calmodulin-dependent kinases and regulates genes whose deregulated expression promotes oncogenesis, including cyclins , Bcl-2 family members, and Egr-1 . (aacrjournals.org)
  • Although dramatic advances have been made through the use of kinase inhibitors such as Bcr-Abl inhibitors in chronic myeloid leukemia (CML) or epidermal growth factor receptor (EGFR) kinase inhibitors in non-small cell lung cancer, a number of hurdles have arisen. (aacrjournals.org)
  • For example, many kinase and cell-surface receptor-triggered pathways converge on transcription factors such as NF-κB or STAT family members. (aacrjournals.org)
  • antagonists
  • NDMA receptor antagonists such as amitriptyline and ketamine interfere with the role of NMDA receptors in the process of central sensitization in which NMDA receptors on spinal dorsal horn neurons are activated, resulting in an increase in synaptic efficacy and so an amplification of the response to sensory input. (cancer.gov)
  • Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling. (nih.gov)
  • Targets
  • Tumor necrosis factor-inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor-driven model of rheumatoid arthritis. (biomedsearch.com)
  • Although transcription factors have not been a central focus of drug development, recent advances suggest that CREB and other such proteins may be worthwhile targets for cancer therapy. (aacrjournals.org)
  • In considering other levels of control that may play an important role in malignant cellular behavior, and which may be important targets for therapy, increasing attention has focused on transcription factors. (aacrjournals.org)
  • alveolar
  • To investigate the role of PPARγ in alveolar macrophage homeostasis, we generated myeloidspecific PPARγ knockout mice using the Lys-Cre method to knock out the floxed PPARγ gene. (ecu.edu)
  • Similar to the GM-CSF-deficient mouse, absence of alveolar macrophage PPARγ resulted in development of lung pathology resembling PAP in 16-wk-old mice, along with excess M-CSF gene expression and secretion. (ecu.edu)
  • In ex vivo wild-type alveolar macrophages, we observed that M-CSF itself is capable of inducing foam cell formation similar to that seen in PAP. (ecu.edu)
  • Taken together, these data suggest that M-CSF is an important mediator of alveolar macrophage homeostasis, and that transcriptional control of M-CSF production is regulated by NF-κB and PPARγ. (ecu.edu)
  • Pathways
  • Although transcription factors are not often directly modified by mutations in cancer cells, they frequently become activated constitutively through mutations affecting "upstream" pathways. (aacrjournals.org)
  • Since normal cells are relatively insensitive to inhibition of these proteins due to redundancies in normal signaling pathways, inhibitors of these transcription factors hold the potential for having a very high therapeutic index. (aacrjournals.org)
  • assay
  • In contrast, mutation at Tyr 721 of Fms had no effect on invasion as measured in the in vitro assay but markedly abolished Fms-induced colony formation in soft agar and eradicated the metastatic potential of the transfected clones. (aacrjournals.org)
  • activation
  • Growth factors and cytokines can trigger cell-cycle progression and other cellular events through the rapid and transient activation of transcription factors that regulate the expression of genes such as cyclins. (aacrjournals.org)
  • The malignant phenotype in cancer is mediated by inappropriate expression of these same genes, often driven by continuous nonphysiological activation of the transcription factors that normally control their expression. (aacrjournals.org)
  • Thus, critical insight into the role of transcription factor activation in cancer arose from studying the regulation of genes in response to cytokines under normal conditions. (aacrjournals.org)
  • oncogenic
  • By continually driving the expression of key target genes, these oncogenic transcription factors play a central role in tumor pathogenesis. (aacrjournals.org)
  • Alternatively, transcription factors that display normal sequence and expression may still be critical mediators of oncogenic events occurring "upstream. (aacrjournals.org)
  • tumor
  • OBJECTIVE: To investigate how tumor necrosis factor (TNF)-inhibiting therapy affects bone destruction and inflammation in a TNF-driven mouse model of rheumatoid arthritis. (biomedsearch.com)
  • Altered function or expression of a transcription factor may occur as a central component of the molecular pathogenesis of a tumor. (aacrjournals.org)
  • Inhibition of these transcription factors can revert the malignant behavior of many tumor types. (aacrjournals.org)
  • estrogen
  • Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells. (nih.gov)
  • Signal
  • Much of our initial understanding of the role of transcription factors in oncogenesis arose from studies of normal signal transduction. (aacrjournals.org)
  • genes
  • We explored the transcriptional activity of HERV sequences as well as the antiviral restriction factor and interferon-inducible genes in the skin from LP patients and healthy control (HC) donors. (biomedsearch.com)
  • Other transcript expressions, such as the master regulator of type I interferon-dependent immune responses, STING (stimulator of interferon genes) and IRF-7 (interferon regulatory factor 7), IFN-β and the inflammassome NALP3, had increased levels in LP, when compared to HC group. (biomedsearch.com)
  • growth
  • Compared with parental cells, transfected cells expressing a wild-type CSF-1R invaded 100-fold more efficiently through a barrier of reconstituted basement membrane (Matrigel) and formed colonies in soft agar, whereas the cellular growth rate was only slightly increased. (aacrjournals.org)
  • Growth Factors. (springer.com)