Did you mean: proptosis
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Signal Transduction and Targeted Therapy Mar 2021Currently, pyroptosis has received more and more attention because of its association with innate immunity and disease. The research scope of pyroptosis has expanded... (Review)
Review
Currently, pyroptosis has received more and more attention because of its association with innate immunity and disease. The research scope of pyroptosis has expanded with the discovery of the gasdermin family. A great deal of evidence shows that pyroptosis can affect the development of tumors. The relationship between pyroptosis and tumors is diverse in different tissues and genetic backgrounds. In this review, we provide basic knowledge of pyroptosis, explain the relationship between pyroptosis and tumors, and focus on the significance of pyroptosis in tumor treatment. In addition, we further summarize the possibility of pyroptosis as a potential tumor treatment strategy and describe the side effects of radiotherapy and chemotherapy caused by pyroptosis. In brief, pyroptosis is a double-edged sword for tumors. The rational use of this dual effect will help us further explore the formation and development of tumors, and provide ideas for patients to develop new drugs based on pyroptosis.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Immunity, Innate; Neoplasm Proteins; Neoplasms; Pore Forming Cytotoxic Proteins; Pyroptosis; Radiotherapy
PubMed: 33776057
DOI: 10.1038/s41392-021-00507-5 -
Cellular & Molecular Immunology May 2021Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination... (Review)
Review
Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination of immune responses and autoimmunity. In recent years, our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially. Different modalities of what has become known as 'programmed cell death' have been described, and some key players in these processes have been identified. We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death. These studies have highlighted the complex mechanisms tipping the balance between different cell fates. Here, we summarize the latest discoveries in the three most well understood modalities of cell death, namely, apoptosis, necroptosis, and pyroptosis, highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.
Topics: Animals; Apoptosis; Health; Humans; Inflammation; Models, Biological; Necroptosis; Pyroptosis
PubMed: 33785842
DOI: 10.1038/s41423-020-00630-3 -
Theranostics 2022Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main... (Review)
Review
Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection. However, excessive pyroptosis may cause immoderate and continuous inflammatory responses that involves in the occurrence of inflammatory diseases. Attractively, as immunogenic cell death, pyroptosis can serve as a new strategy for cancer elimination by inducing pyroptotic cell death and activating intensely antitumor immunity. To make good use of this double-edged sword, the molecular mechanisms, and therapeutic implications of pyroptosis in related diseases need to be fully elucidated. In this review, we first systematically summarize the signaling pathways of pyroptosis and then present the available evidences indicating the role of pyroptosis in inflammatory diseases and cancer. Based on this, we focus on the recent progress in strategies that inhibit pyroptosis for treatment of inflammatory diseases, and those that induce pyroptosis for cancer therapy. Overall, this should shed light on future directions and provide novel ideas for using pyroptosis as a powerful tool to fight inflammatory diseases and cancer.
Topics: Humans; Inflammasomes; Neoplasms; Pyroptosis; Signal Transduction
PubMed: 35673561
DOI: 10.7150/thno.71086 -
Journal of Hematology & Oncology Dec 2022Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death... (Review)
Review
Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments.
Topics: Humans; Cell Death; Neoplasms; Copper; Apoptosis; Ferroptosis; Pyroptosis; Necroptosis
PubMed: 36482419
DOI: 10.1186/s13045-022-01392-3 -
Trends in Pharmacological Sciences Aug 2022The nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome has emerged as a key mediator of... (Review)
Review
The nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome has emerged as a key mediator of pathological inflammation in many diseases and is an exciting drug target. Here, we review the molecular basis of NLRP3 inhibition by drug-like small molecules under development as novel therapeutics. We also summarize recent strategies to block pyroptosis as a novel approach to suppress chronic inflammation. Major recent developments in this area include the elucidation of mechanisms of action (MoAs) by which small molecules block NLRP3 inflammasome assembly and gasdermin D (GSDMD)-induced pyroptosis. We also discuss the status of clinical trials using agents that block specific components of the NLRP3 pathway, including their potential clinical applications for the treatment of many diseases.
Topics: Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis
PubMed: 35513901
DOI: 10.1016/j.tips.2022.04.003 -
Cell Jan 2024Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by... (Review)
Review
Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by eliminating infected cells. Cell death can be induced by the genetically programmed suicide mechanisms of apoptosis, necroptosis, and pyroptosis, or it can be a consequence of dysregulated metabolism, as in ferroptosis. Here, we review the signaling mechanisms underlying each cell-death pathway, discuss how impaired or excessive activation of the distinct cell-death processes can promote disease, and highlight existing and potential therapies for redressing imbalances in cell death in cancer and other diseases.
Topics: Humans; Apoptosis; Cell Death; Ferroptosis; Homeostasis; Pyroptosis; Signal Transduction
PubMed: 38242081
DOI: 10.1016/j.cell.2023.11.044 -
Immunological Reviews Sep 2020ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z-RNA... (Review)
Review
ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z-RNA produced during influenza virus infection induces cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). PANoptosis is a coordinated cell death pathway that is driven through a multiprotein complex called the PANoptosome and enables crosstalk and co-regulation among these processes. During influenza virus infection, a key step in PANoptosis and PANoptosome assembly is the formation of the ZBP1-NLRP3 inflammasome. When Z-RNA is sensed, ZBP1 recruits RIPK3 and caspase-8 to activate the ZBP1-NLRP3 inflammasome. Several other host factors have been found to be important for ZBP1-NLRP3 inflammasome assembly, including molecules involved in the type I interferon signaling pathway and caspase-6. Additionally, influenza viral proteins, such as M2, NS1, and PB1-F2, have also been shown to regulate the ZBP1-NLRP3 inflammasome. This review explains the functions of ZBP1 and the mechanistic details underlying the activation of the ZBP1-NLRP3 inflammasome and the formation of the PANoptosome. Improved understanding of the ZBP1-NLRP3 inflammasome will direct the development of therapeutic strategies to target infectious and inflammatory diseases.
Topics: Apoptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Necroptosis; Pyroptosis; RNA-Binding Proteins
PubMed: 32729116
DOI: 10.1111/imr.12909 -
Biomedicine & Pharmacotherapy =... Jan 2020Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines... (Review)
Review
Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1β. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.
Topics: Animals; Antineoplastic Agents; Cell Death; Humans; Inflammation Mediators; Neoplasms; Pyroptosis; Signal Transduction
PubMed: 31710896
DOI: 10.1016/j.biopha.2019.109595 -
Journal of Hematology & Oncology Aug 2020In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly... (Review)
Review
In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by the fact that only one third of patients with most types of cancer respond to these agents. The induction of cell death mechanisms other than apoptosis has gradually emerged as a new cancer treatment strategy because most tumors harbor innate resistance to apoptosis. However, to date, the possibility of combining these two modalities has not been discussed systematically. Recently, a few studies revealed crosstalk between distinct cell death mechanisms and antitumor immunity. The induction of pyroptosis, ferroptosis, and necroptosis combined with ICIs showed synergistically enhanced antitumor activity, even in ICI-resistant tumors. Immunotherapy-activated CD8+ T cells are traditionally believed to induce tumor cell death via the following two main pathways: (i) perforin-granzyme and (ii) Fas-FasL. However, recent studies identified a new mechanism by which CD8+ T cells suppress tumor growth by inducing ferroptosis and pyroptosis, which provoked a review of the relationship between tumor cell death mechanisms and immune system activation. Hence, in this review, we summarize knowledge of the reciprocal interaction between antitumor immunity and distinct cell death mechanisms, particularly necroptosis, ferroptosis, and pyroptosis, which are the three potentially novel mechanisms of immunogenic cell death. Because most evidence is derived from studies using animal and cell models, we also reviewed related bioinformatics data available for human tissues in public databases, which partially confirmed the presence of interactions between tumor cell death and the activation of antitumor immunity.
Topics: Adaptive Immunity; Alarmins; Animals; Antigens, Neoplasm; Autophagy; Ferroptosis; Humans; Immune Checkpoint Inhibitors; Lymphocyte Subsets; Lymphocytes, Tumor-Infiltrating; Mice; Models, Immunological; NF-kappa B; Necroptosis; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms; Protein Kinases; Pyroptosis
PubMed: 32778143
DOI: 10.1186/s13045-020-00946-7 -
Clinical and Translational Medicine Aug 2021In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger... (Review)
Review
In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.
Topics: Humans; Neoplasms; Pyroptosis; Tumor Microenvironment
PubMed: 34459122
DOI: 10.1002/ctm2.492