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Cancer Biology and Genetics for Non-Biologists
Published in Trevor F. Cox, Medical Statistics for Cancer Studies, 2022
Your cells have to communicate, and they do not all live in isolation. Cells send and receive messages via signalling molecules. The signals can tell a cell to grow, produce particular proteins, produce a metabolic response or to die (apoptosis). The signals sent and received are usually called ligands and can be molecules, proteins or ions. Signals can be received from other nearby cells or from afar, the four types being, Paracrine signalling: Signalling by nearby cells allowing similar cells to act similarly• Synaptic signalling: Signalling by electrical impulses through nerve cellsAutocrine signalling: Signalling of a cell to itselfEndocrine signalling: Signalling from distant endocrine cells, e.g. the pancreas
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Cytokines are specifically released by cells to exert an effect on other cells in the body and can be involved in autocrine signaling. In the body they are produced by a wide range of cells, including immune cells such as macrophages, B lymphocytes, T lymphocytes, and mast cells, as well as by fibroblasts, endothelial cells, and various stromal cells. Any given cytokine may be produced by more than one cell type. They exert their effect through receptors and are important in the modulation of the immune system where they modulate the balance between humoral and cell-based immune responses, and also regulate the growth, maturation, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines through elaborate inhibition and feedback mechanisms.
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.
Female infertility caused by organophosphates: an insight into the latest biochemical and histomorphological findings
Published in Toxin Reviews, 2023
Mohammad Samare-Najaf, Ali Samareh, Bahia Namavar Jahromi, Navid Jamali, Sina Vakili, Majid Mohsenizadeh, Cain C. T. Clark, Ali Abbasi, Nastaran Khajehyar
Both para and autocrine signaling, along with an organized cross-talk between flaggings derived from oocytes and somatic cells, coordinate cellular interactions using gap junctional communication. This highly regulated process leads to the development of folliculogenesis and supports the appropriate acquisition of maturational competence by the oocyte (Biswas et al.2020, Tesfaye et al.2020, Dompe et al.2021). Furthermore, downstream from the surge in gonadotrophins, which is accompanied by the increment in LH, complex cell-cell signaling pathways initiate the development of oocyte nuclear maturation and ovulation (Prasasya and Mayo 2019, Gershon and Dekel 2020). The biosynthesis of sex steroids is dependent on hormonal homeostasis and functional interaction between somatic and germ cells within the follicle.
Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis
Published in Annals of Medicine, 2021
A. Borrajo, C. Spuch, M. A. Penedo, J. M. Olivares, R. C. Agís-Balboa
Peripheral system macrophages are a microglial cell type that presents antigens and secretes cytokines [32–36] involved in the physiological processes implemented to combat pathogens and repair tissues. Cytokines are low molecular weight proteins that are generally classified as pro- or anti-inflammatory. While pro-inflammatory cytokines can elicit a sustained immune response, anti-inflammatory cytokines downregulate immune responses by binding to receptors expressed in the microglia to initiate an autocrine signalling process. Cytokines have several effects on the function of the CNS such as promoting the growth and proliferation of astrocytes and oligodendrocytes [33] and modulating the release of neurotransmitters [31]. Recent studies have shown low levels of pro-inflammatory cytokines are expressed in the healthy brain, while they are expressed in high levels in brain and cerebrospinal fluid (CSF) samples from patients with Parkinson disease, Alzheimer disease [37,38], or other psychiatric diseases like schizophrenia [39].
Epidermal growth factor receptor ligands: targets for optimizing treatment of metastatic colorectal cancer
Published in Growth Factors, 2019
Siavash Foroughi, Jeanne Tie, Peter Gibbs, Antony Wilks Burgess
Perturbation of growth factor signaling is a major driver of CRC (and many other cancers). In many patients, constitutive, elevated, autocrine signaling appears to be a major driver of the uncontrolled growth of the tumor cell population (Bernat-Peguera et al. 2019). However, other steps in the ligand/receptor stimulating system are also perturbed by mutation of transcriptional control or processing. Where these perturbations lead to ligand deprivation, the cellular responses inevitably up regulate other members of signaling pathways to compensate or overcome the availability of ligand (Sun and Bernards 2014). There is increasing evidence that the overexpression and dysregulation of ADAMs play an important role in cancer. For example, overexpression of ADAMs 9, 10 15, 17 and 19 have been observed in both primary and metastatic CRC tumors when compared with normal colonic tissue (Merchant et al. 2008). The processing of the pro-ligands relies on cleavage by the ADAM proteases (Zhou et al. 2005). If pro-ligand levels are reduced, an increase in the levels of specific ADAMS may drive the production of more active ligand in the tumor environment. Analysis of the mRNA expression levels for CRC patients in the TCGA database (http://cancergenome.nih.gov/abouttcga) (National Cancer Institute 2018) indicates elevated levels for ADAMs 9, 15 and 19, so these enzymes might be significant targets for inhibiting autocrine ligand production and consequential EGFR activation in CRC.