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Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Autocrine signalling involves cells secreting signalling molecules that can bind to its own receptors and coordinate decisions between groups of identical cells. This generates the “community effect” observed between cells and enhances the effect of signalling when groups of cells carry out the response simultaneously. Activity can also be coordinated between cells through gap junctions, which can form between cells with closely apposed plasma membranes, where the cytoplasm of neighbouring cells are joined directly by narrow water-filled channels. This enables the exchange of small intracellular signalling molecules, such as Ca2+ and cyclic AMP, therefore gap junctions allow cells to communicate directly unrestricted by the barrier presented by intervening plasma membranes.
Placental Biosynthesis, Metabolism, and Transport of Eicosanoids
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
The primary function of the placenta is to support a viable fetus throughout gestation and, as such, it serves to supply oxygen and nutrients to the fetus and remove carbon dioxide and waste products from it. As an organ of exchange, the placenta is highly vascularized, and the eicosanoids appear to play a part in the control of this vasculature. The placenta is also an extremely active endocrine organ, producing a wide variety of peptide, steroid, and other hormones, including the eicosanoids. Many of these hormones will fulfill autocrine or paracrine functions in addition to their exocrine effects. The eicosanoids are highly suitable for such functions, being potent, short-acting bioregulators. A further function of the placenta may be as an immunological barrier, serving to protect the fetal allograft from rejection. The placenta fulfills all of its functions in a remarkably short life span, during which it proliferates, matures, and achieves a variety of differentiated functions. During the lifetime of the placenta, the hormonal milieu to which its cells are subjected changes markedly as its endocrine functions change. This means that many autocrine or paracrine mechanisms may be operating within the placenta at various times to regulate eicosanoid metabolism.
Erythroleukemia Cell Secretion and Erythroid Cell Differentiation-Inhibiting Factors
Published in Velibor Krsmanović, James F. Whitfield, Malignant Cell Secretion, 2019
Velibor Krsmanović, Jean-Michel Biquard
The blockage of cell differentiation or the reduced differentiation response associated with oncogenesis does not appear to depend exclusively on an autocrine mechanism.152 Several nonerythroid cell types have been shown to secrete differentiation-inhibiting factors which act on normal erythroid progenitors and erythroleukemia cells. Endotoxin-stimulated macrophages, murine embryonal carcinoma cells, and bone marrow stromal cells are known to modulate erythroid differentiation by the factors that they secrete.153-156 For instance, several established murine macrophage cell lines incubated with endotoxin in a serum-free medium, as well as murine embryonal carcinoma cells, secrete a 40-to 43-kDa erythroid inhibitory activity (EIA) which inhibits DMSO-induced erythroid differentiation of FLC.154,155 The differentiation-inhibiting activity secreted by murine macrophage cell lines is different from other known macrophage monokines such as IL-1, TGF-β, FGF, G-CSF, hepatocyte stimulating factor, interferon, PDGF, and cachectin/TNF.154
Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion
Published in Expert Review of Anticancer Therapy, 2022
Michael H. Storandt, Zhaohui Jin, Amit Mahipal
Human FGFRs include a family of four receptor tyrosine kinases (1–4) located on the cell membrane, which when activated by its ligand, fibroblast growth factor (FGF), dimerize leading to autophosphorylation of the intracellular kinase domain and downstream signal transduction pathways (Figure 1) [27–30]. FGFs are a family of 18 secreted proteins and 4 intracellular proteins that function through autocrine/paracrine signaling and control of voltage gated sodium channels respectively [31]. Autocrine and paracrine FGFs function in cell proliferation and survival, and play an important role in organogenesis during embryonic development. Additionally, three endocrine FGFs have been shown to function in phosphate regulation, bile acid production, and carbohydrate and lipid metabolism [31]. FGFs are held in the extracellular matrix by heparan sulfate proteoglycans (HPSG) and are released by heparinases or other proteases allowing for binding to the FGFR, with this interaction further stabilized by cell surface HPSGs [32,33] or the klotho co-receptor [34].
Curcumin reverses hepatic epithelial mesenchymal transition induced by trichloroethylene by inhibiting IL-6R/STAT3
Published in Toxicology Mechanisms and Methods, 2021
Weiya Cao, Yinci Zhang, Amin Li, Pan Yu, Li Song, Jiaojiao Liang, Niandie Cao, Jiafeng Gao, Ruyue Xu, Yongfang Ma, Xiaolong Tang
We observed that the tumor size of curcumin group mice was significantly reduced compared with the TCE group. Environmental factors may play a key role in the carcinogenesis of liver tissue. Chronic inflammation is closely related to the progress of the process. The release of inflammatory factors is an important reason for tumor occurrence and development. Chronic inflammation can activate the inflammation-related pathway by autocrine, and promote cell proliferation, which leads to the development of tumors (Wehbe et al. 2006). Many studies have shown that downregulation or knockout of the gene expression encoding carcinogenic inflammatory factors can effectively reduce the occurrence and invasion of tumor (Udden et al. 2019). In order to confirm our observation, we carried out a series of quantitative analyses. He staining and Western blotting analysis showed that curcumin significantly reduced the extensive infiltration of inflammatory cells. In the control group, the liver structure was intact, and no abnormal proliferation or inflammatory cell infiltration was observed in the epithelium, and the expression of JAK2, STAT3, snail, and N-cadherin induced by TCE was significantly inhibited. The expression of CyclinD1 and survivin is closely related to cell proliferation. With the proliferation of cells, the expression of CyclinD1 and Survivin also increased, which is inevitable in the process of the cell cycle. In addition, curcumin can effectively reduce the inflammatory cytokines IL-6R and gp130.
Endocrine fibroblast growth factors as potential biomarkers for chronic kidney disease
Published in Expert Review of Molecular Diagnostics, 2020
Yuichiro Kondo, Hirotaka Komaba, Masafumi Fukagawa
Fibroblast growth factors (FGFs) are a family of peptide growth factors that share a number of biological functions, including cell growth and differentiation, angiogenesis, embryonic development, wound healing, and metabolic regulation [1–3]. The human FGF family comprise 22 members, from FGF1 to FGF23, except FGF15, which is the mouse orthologue of human FGF19. FGF family members are grouped into six subfamilies based on differences in sequence homology and developmental characteristics. The majority of FGFs work as autocrine and paracrine factors that regulate tissue and organogenesis during embryonic development. These canonical FGFs transmit intracellular signals through four tyrosine kinase FGF receptors (FGFR1-4), via a high-affinity interaction with heparin or heparan sulfate [4,5].