Metal Drugs and the Anticancer Immune Response

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(2), P. 1519 - 1624

Published: Nov. 29, 2018

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also prevent malignant transformation ("immune surveillance"). Hence, clinically apparent tumor already reflects selection for those cell clones capable evading recognition evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface can reverse important aspects evasion. This topic has recently gained intense attention based on combination approaches immunotherapy (e.g., checkpoint inhibitors), strategy delivering first exciting results in clinical settings. review summarizes promising still extremely fragmentary knowledge interplay metal drugs fidelity responses role adverse effects. It highlights that, at least some cases, induce long-lasting responses. Important steps this process comprise altered visibility susceptibility cancer cells toward immunity, as well direct impacts populations microenvironment. On basis gathered information, we suggest initiating joint multidisciplinary programs implement comprehensive analyses into strategies develop novel smart compounds.

Language: Английский

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Extracellular ATP: A Feasible Target for Cancer Therapy

Cells, Journal Year: 2020, Volume and Issue: 9(11), P. 2496 - 2496

Published: Nov. 17, 2020

Adenosine triphosphate (ATP) is one of the main biochemical components tumor microenvironment (TME), where it can promote progression or suppression depending on its concentration and specific ecto-nucleotidases receptors expressed by immune cancer cells. ATP be released from cells via both nonspecific pathways. A non-regulated release occurs dying damaged cells, whereas active involves exocytotic granules, plasma membrane-derived microvesicles, ATP-binding cassette (ABC) transporters membrane channels (connexin hemichannels, pannexin 1 (PANX1), calcium homeostasis modulator (CALHM1), volume-regulated anion (VRACs) maxi-anion (MACs)). Extracellular acts at P2 purinergic receptors, among which P2X7R a key mediator final ATP-dependent biological effects. Over years, receptor- ecto-nucleotidase-targeting for therapy has been proposed actively investigated, while comparatively fewer studies have explored suitability TME as target. In this review, we briefly summarize available evidence suggesting that central role in determining fate is, therefore, suitable target therapy.

Language: Английский

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Extracellular nucleotides and nucleosides as signalling molecules

Immunology Letters, Journal Year: 2018, Volume and Issue: 205, P. 16 - 24

Published: Nov. 12, 2018

Language: Английский

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Carotid body chemoreceptors: physiology, pathology, and implications for health and disease

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(3), P. 1177 - 1235

Published: Feb. 11, 2021

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 pH, eliciting reflex ventilatory, cardiovascular, humoral responses to maintain homeostasis. This review examines fundamental biology underlying CB function, its contribution integrated physiological responses, role in maintaining health potentiating disease. Emphasis placed on 1) transduction mechanisms (type I) cells, highlighting played by hypoxic inhibition of O2-dependent K+ channels mitochondrial oxidative metabolism, their modification intracellular molecules other ion channels; 2) synaptic linking type I cells petrosal nerve terminals, focusing proposed transmitters modulatory gases, participation glial regulation chemosensory process; 3) activation, emphasizing that differ dramatically depending nature physiological, pathological, or environmental challenges, interactions with reflexes optimizing oxygen delivery tissues; 4) enhanced discharge autonomic cardiorespiratory pathophysiology obstructive sleep apnea, congestive heart failure, resistant hypertension, metabolic diseases how modulation reactivity disease conditions may attenuate pathophysiology.

Language: Английский

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A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo

Neuron, Journal Year: 2021, Volume and Issue: 110(5), P. 770 - 782.e5

Published: Dec. 22, 2021

Language: Английский

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Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2021, Volume and Issue: 376(1821), P. 20190762 - 20190762

Published: Feb. 8, 2021

Transmitter signalling is the universal chemical language of any nervous system, but little known about its early evolution. Here, we summarize data distribution and functions neurotransmitter systems in basal metazoans as well outline hypotheses their origins. We explore scenario that neurons arose from genetically different populations secretory cells capable volume transmission integration behaviours without canonical synapses. The closest representation this primordial organization currently found Placozoa, disk-like animals with simplest cell composition complex behaviours. propose injury-related was evolutionary predecessor for integrative transmitters such nitric oxide, ATP, protons, glutamate small peptides. By contrast, acetylcholine, dopamine, noradrenaline, octopamine, serotonin histamine were recruited neurotransmitters relatively later animal evolution, only bilaterians. Ligand-gated ion channels often preceded establishment novel systems. Moreover, lineage-specific diversification receptors occurred parallel within Cnidaria several bilaterian lineages, including acoels. In summary, ancestral signal molecules provides unique microenvironments behaviour-driven innovations pave way to brain elementary cognition. This article part theme issue ‘Basal cognition: multicellularity, cognitive lens'.

Language: Английский

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Activation of immune signals during organ transplantation

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 11, 2023

Abstract The activation of host’s innate and adaptive immune systems can lead to acute chronic graft rejection, which seriously impacts survival. Thus, it is particularly significant clarify the signals, are critical initiation maintenance rejection generated after transplantation. response dependent on sensing danger stranger molecules. ischemia reperfusion grafts cell stress or death, followed by releasing a variety damage-associated molecular patterns (DAMPs), recognized pattern recognition receptors (PRRs) host cells activate intracellular signals induce sterile inflammation. In addition DAMPs, exposed ‘non-self’ antigens (stranger molecules) system, stimulating more intense further aggravating damage. polymorphism MHC genes between different individuals key for donor identify heterologous components in allogeneic xenogeneic organ antigen mediates host, resulting memory immunity trained graft, poses challenge long-term survival graft. This review focuses receptor patterns, alloantigens xenoantigens, described as model model. this review, we also discuss

Language: Английский

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ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain

Science Advances, Journal Year: 2023, Volume and Issue: 9(13)

Published: March 31, 2023

Following peripheral nerve injury, extracellular adenosine 5′-triphosphate (ATP)–mediated purinergic signaling is crucial for spinal cord microglia activation and neuropathic pain. However, the mechanisms of ATP release remain poorly understood. Here, we show that volume-regulated anion channel (VRAC) an ATP-releasing activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Mice with microglia-specific deletion Swell1 (also known as Lrrc8a), a VRAC essential subunit, had reduced injury–induced increase cord. The mutant mice also exhibited decreased microgliosis, dorsal horn neuronal hyperactivity, both evoked spontaneous pain–like behaviors. We further performed high-throughput screens identified FDA-approved drug dicumarol novel potent inhibitor. Intrathecal administration alleviated mechanical allodynia mice. Our findings suggest key determinant pain potential therapeutic target this debilitating disease.

Language: Английский

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Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation–induced surfactant secretion

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(5)

Published: Feb. 29, 2024

Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease tension and facilitate inspiration. Surfactant deficiency often seen in premature infants also children adults with respiratory distress syndrome. Mechanical stretch of type 2 epithelial (AT2) cells during lung expansion primary physiological factor that stimulates secretion; however, it unclear whether there mechanosensor dedicated for this process. Here we show loss mechanosensitive channels TMEM63A TMEM63B resulted atelectasis failure mice due deficit secretion. TMEM63A/B were predominantly localized at limiting membrane lamellar body, lysosome-related organelle stores pulmonary ATP AT2 cells. Activation cell facilitated release from bodies fused plasma membrane. The released evoked Ca2+ signaling potentiated exocytic fusion more bodies. Our study uncovered vital function TMEM63 channels, which makes ready first breath birth maintains respiration through life.

Language: Английский

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Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix

Chemical Reviews, Journal Year: 2019, Volume and Issue: 119(24), P. 12337 - 12374

Published: Nov. 18, 2019

Inorganic polyphosphates (polyP) consist of linear chains orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy polyP. However, the function and metabolism this long-neglected polymer scarcely known, especially in higher eukaryotes. In recent years, interest polyP experienced a renaissance, beginning with discovery phosphate source bone mineralization. Later, two discoveries placed into focus regenerative medicine applications. First, shows morphogenetic activity, i.e., induces cell differentiation via gene induction, and, second, acts an storage donor extracellular space. Studies on acidocalcisomes mitochondria provided first insights enzymatic basis eukaryotic formation. addition, concerted action alkaline phosphatase adenylate kinase proved crucial for ADP/ATP generation PolyP added extracellularly mammalian cells resulted 3-fold increase ATP. The importance mechanism phosphotransfer reaction energy-consuming processes matrix discussed. This review aims give critical overview about formation unique is capable storing useful energy.

Language: Английский

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