chronic myeloid leukemia (cml) is a myeloproliferative disease of the hematopoietic stem cells, characterized by the presence of the philadelphia (ph) chromosome. although imatinib inhibits the bcr-abl kinase activity, clinical experiences confirm that imatinib may not target cml stem cells in vivo. the identification of signaling pathways responsible for the self-renewal properties of leukemic...

Intestinal fibrosis is the main pathological process in Crohn's disease (CD); acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but the regulatory mechanism remains unknown. The present study observed the effect of moxibustion on the extracellular signal-regulated kinase (ERK) signaling pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf-1,...

Melatonin, secreted mainly by the pineal gland, plays roles in various physiological functions including protecting cell death. We showed in previous study that the proliferation and differentiation of precursor cells from the adult mouse subventricular zone (SVZ) can be modulated by melatonin via the MT1 melatonin receptor. Since melatonin and epidermal growth factor receptor (EGFR) share some...

Endothelial cells exhibit an autonomous proliferative response to hypoxia, independent of paracrine effectors. In cultured endothelial cells of porcine aorta, we analyzed the signaling of this response, with a focus on the roles of redox signaling and the MEK/ERK pathway. Transient hypoxia (1 hour) stimulated proliferation by 61+/-4% (n=16; P<0.05 versus control), quantified after 24 hours norm...

Heat shock protein (HSP)90 inhibitors have shown significant anti-tumor activities in preclinical settings in both solid and hematological tumors. We previously reported that the novel, orally available HSP90α/β inhibitor TAS-116 shows significant anti-MM activities. In this study, we further examined the combination effect of TAS-116 with a RAS-RAF-MEK-ERK signaling pathway inhibitor in RAS- o...

Soluble human leukocyte antigen-G (HLA-G) is a non-classical class Ib HLA molecule that is secreted from blastocysts. Soluble HLA-G modulates the immune tolerance of the mother and can be used as a prognostic factor for the clinical pregnancy rate. However, the underlying mechanism of how soluble HLA-G5 affects pregnancy remains largely unknown. We hypothesized that soluble HLA-G5 promotes succ...

The accurate joining of DNA double-strand breaks by homologous recombination repair (HRR) is critical to the long-term survival of the cell. The three major mitogen-activated protein (MAP) kinase (MAPK) signaling pathways, extracellular signal-regulated kinase (ERK), p38, and c-Jun-NH(2)-kinase (JNK), regulate cell growth, survival, and apoptosis. To determine the role of MAPK signaling in HRR,...

Glutamate, as an essential neurotransmitter, has been thought to have different roles in the central nervous system (CNS), including nerve regeneration, synaptogenesis, and neurogenesis. Excessive glutamate causes an up-regulation of the multiple signaling pathways, including phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), Akt/mammalian target of rapamycin (mTOR) protein, mitogen-activat...

Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have similar levels of phosphorylated ERK, but only the former depend on ERK signaling for proliferation. The mitogen-activated protein kinase, extracellular signal-regulated kinase kinase (MEK)/ERK-dependent transcriptional output was defined as the genes whose expression changes significantly 8 h after MEK inhibi...

Self-renewal and differentiation of embryonic stem cells (ESCs) are controlled by intracellular transcriptional factors and extracellular factor-activated signaling pathways. Transcription factor Oct4 is a key player maintaining ESCs in an undifferentiated state, whereas the Erk/MAPK pathway is known to be important for ESC differentiation. However, the manner in which intracellular pluripotenc...