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Cancer Metastasis Reviews Sep 2018Tumor tissue is composed of tumor cells and surrounding non-tumor endothelial and immune cells, collectively known as the tumor microenvironment. Tumor cells manipulate... (Review)
Review
Tumor tissue is composed of tumor cells and surrounding non-tumor endothelial and immune cells, collectively known as the tumor microenvironment. Tumor cells manipulate tumor microenvironment to obtain sufficient oxygen and nutrient supply, and evade anti-tumor immunosurveillance. Various types of signaling molecules, including cytokines, chemokines, growth factors, and lipid mediators, are secreted, which co-operate to make up the complex tumor microenvironment. Prostaglandins, cyclooxygenase metabolites of arachidonic acid, are abundantly produced in tumor tissues. Ever since treatment with nonsteroidal anti-inflammatory drugs showed anti-tumor effect in mouse models and human patients by inhibiting whole prostaglandin production, investigators have focused on the importance of prostaglandins in tumor malignancies. However, most studies that followed focused on the role of an eminent prostaglandin, prostaglandin E, in tumor onset, growth, and metastasis. It remained unclear how other prostaglandin species affected tumor malignancies. Recently, we identified prostaglandin D, a well-known sleep-inducing prostaglandin, as a factor with strong anti-angiogenic and anti-tumor properties, in genetically modified mice. In this review, we summarize recent studies focusing on the importance of prostaglandins and their metabolites in the tumor microenvironment.
Topics: Animals; Humans; Neoplasms; Neovascularization, Pathologic; Prostaglandins; Tumor Microenvironment
PubMed: 29926309
DOI: 10.1007/s10555-018-9740-2 -
Annales D'endocrinologie Jun 2016The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery... (Review)
Review
The mechanisms involved in human pregnancy maintenance and parturition are highly complex and involve mother, fetus and placenta. The "final common pathway" to delivery is composed by inflammatory and endocrine interactive paths that tip the balance in favor of coordinated uterine contractility and cervical dilation. These mechanisms involve a shift from progesterone to estrogen dominance, CRH action, increased sensitivity to oxytocin, gap junction formation, and increased prostaglandins activity. Complementary changes in the cervix involve a decrease in progesterone dominance and the actions of prostaglandins and relaxin, via connective tissue alterations, leading to cervical softening and dilation. Neuronal, hormonal, inflammatory and immune pathways participate in initiation of labor and the utero-placental unit plays a major role in the synthesis and release of parturition mediators.
Topics: Estrogens; Female; Fetus; Hormones; Humans; Parturition; Placenta; Pregnancy; Progesterone; Prostaglandins
PubMed: 27155774
DOI: 10.1016/j.ando.2016.04.025 -
International Journal of Molecular... Jun 2023Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two... (Review)
Review
Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two main groups of molecules, the prostaglandins (PG) and the cytokines, have been discovered and play a major role in inflammatory processes. The activation of prostaglandins PGE2, PGD2 and PGI2 results in prominent symptoms during cardiovascular and rheumatoid diseases. The balance between pro- and anti-inflammatory compounds is nowadays a challenge for more targeted therapeutic approaches. The first cytokine was described more than a century ago and is now a part of different families of cytokines (38 interleukins), including the IL-1 and IL-6 families and TNF and TGFβ families. Cytokines can perform a dual role, being growth promotors or inhibitors and having pro- and anti-inflammatory properties. The complex interactions between cytokines, vascular cells and immune cells are responsible for dramatic conditions and lead to the concept of cytokine storm observed during sepsis, multi-organ failure and, recently, in some cases of COVID-19 infection. Cytokines such as interferon and hematopoietic growth factor have been used as therapy. Alternatively, the inhibition of cytokine functions has been largely developed using anti-interleukin or anti-TNF monoclonal antibodies in the treatment of sepsis or chronic inflammation.
Topics: Humans; Prostaglandins; Cytokines; Tumor Necrosis Factor Inhibitors; COVID-19; Inflammation; Interleukins; Prostaglandins, Synthetic; Anti-Inflammatory Agents
PubMed: 37298597
DOI: 10.3390/ijms24119647 -
Cells Jun 2021The prostaglandins constitute a family of lipids of 20 carbon atoms that derive from polyunsaturated fatty acids such as arachidonic acid. Traditionally, prostaglandins... (Review)
Review
The prostaglandins constitute a family of lipids of 20 carbon atoms that derive from polyunsaturated fatty acids such as arachidonic acid. Traditionally, prostaglandins have been linked to inflammation, female reproductive cycle, vasodilation, or bronchodilator/bronchoconstriction. Recent studies have highlighted the involvement of these lipids in cancer. In this review, existing information on the prostaglandins associated with different types of cancer and the advances related to the potential use of them in neoplasm therapies have been analyzed. We can conclude that the effect of prostaglandins depends on multiple factors, such as the target tissue, their plasma concentration, and the prostaglandin subtype, among others. Prostaglandin D2 (PGD) seems to hinder tumor progression, while prostaglandin E2 (PGE) and prostaglandin F2 alpha (PGF) seem to provide greater tumor progression and aggressiveness. However, more studies are needed to determine the role of prostaglandin I2 (PGI) and prostaglandin J2 (PGJ) in cancer due to the conflicting data obtained. On the other hand, the use of different NSAIDs (non-steroidal anti-inflammatory drugs), especially those selective of COX-2 (cyclooxygenase 2), could have a crucial role in the fight against different neoplasms, either as prophylaxis or as an adjuvant treatment. In addition, multiple targets, related to the action of prostaglandins on the intracellular signaling pathways that are involved in cancer, have been discovered. Thus, in depth research about the prostaglandins involved in different cancer and the different targets modulated by them, as well as their role in the tumor microenvironment and the immune response, is necessary to obtain better therapeutic tools to fight cancer.
Topics: Chemotherapy, Adjuvant; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Neoplasm Proteins; Neoplasms; Prostaglandins; Signal Transduction
PubMed: 34199169
DOI: 10.3390/cells10061487 -
Cancer Research Mar 2022Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development... (Review)
Review
Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development and progression. Understanding the molecular mechanisms of PG actions has potential clinical relevance for cancer prevention and therapy. This review focuses on the current status of PG signaling pathways in modulating cancer progression and aims to provide insights into the mechanistic actions of PGs and their receptors in influencing tumor progression. We also examine several small molecules identified as having anticancer activity that target prostaglandin receptors. The literature suggests that targeting PG pathways could provide opportunities for cancer prevention and therapy.
Topics: Humans; Neoplasms; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Receptors, Prostaglandin; Signal Transduction
PubMed: 34949672
DOI: 10.1158/0008-5472.CAN-21-2297 -
British Journal of Pharmacology Feb 2019Chronic inflammation underlies various debilitating disorders including autoimmune, neurodegenerative, vascular and metabolic diseases as well as cancer, where aberrant... (Review)
Review
Chronic inflammation underlies various debilitating disorders including autoimmune, neurodegenerative, vascular and metabolic diseases as well as cancer, where aberrant activation of the innate and acquired immune systems is frequently seen. Since non-steroidal anti-inflammatory drugs exert their effects by inhibiting COX and suppressing PG biosynthesis, PGs have been traditionally thought to function mostly as mediators of acute inflammation. However, an inducible COX isoform, COX-2, is often highly expressed in tissues of the chronic disorders, suggesting an as yet unidentified role of PGs in chronic inflammation. Recent studies have shown that in addition to their short-lived actions in acute inflammation, PGs crosstalk with cytokines and amplify the cytokine actions on various types of inflammatory cells and drive pathogenic conversion of these cells by critically regulating their gene expression. One mode of such PG-mediated amplification is to induce the expression of relevant cytokine receptors, which is typically observed in Th1 cell differentiation and Th17 cell expansion, events leading to chronic immune inflammation. Another mode of amplification is cooperation of PGs with cytokines at the transcription level. Typically, PGs and cytokines synergistically activate NF-κB to induce the expression of inflammation-related genes, one being COX-2 itself, which makes PG-mediated positive feedback loops. This signalling consequently enhances the expression of various NF-κB-induced genes including chemokines to macrophages and neutrophils, which enables sustained infiltration of these cells and further amplifies chronic inflammation. In addition, PGs are also involved in tissue remodelling such as fibrosis and angiogenesis. In this article, we review these findings and discuss their relevance to human diseases.
Topics: Animals; Cytokines; Humans; Inflammation; Inflammation Mediators; Prostaglandins
PubMed: 30381825
DOI: 10.1111/bph.14530 -
Biological & Pharmaceutical Bulletin 2022Prostanoids are a group of typical lipid mediators that are biosynthesized from arachidonic acid by the actions of cyclooxygenases and their subsequent terminal... (Review)
Review
Prostanoids are a group of typical lipid mediators that are biosynthesized from arachidonic acid by the actions of cyclooxygenases and their subsequent terminal synthases. Prostanoids exert a wide variety of actions through their specific membrane receptors on target cells. In addition to their classical actions, including fever, pain, and inflammation, prostanoids have been shown to play pivotal roles in various biological processes, such as female reproduction and the maintenance of vascular and gut homeostasis. Moreover, recent research using mice deficient in each of the prostanoid receptors, or using agonists/antagonists specific for each receptor clarified novel actions of prostanoids that had long been unknown, and the mechanisms therein. In this review, we introduce recent advances in the fields of metabolic control by prostanoid receptors such as in adipocyte differentiation, lipolysis, and adipocyte browning in adipose tissues, and discuss the potential of prostanoid receptors as a treatment target for metabolic disorders.
Topics: Adipocytes; Animals; Female; Inflammation; Lipolysis; Mice; Prostaglandins; Receptors, Prostaglandin
PubMed: 35908909
DOI: 10.1248/bpb.b22-00270 -
Pharmacological Research Nov 2019Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links... (Review)
Review
Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links PG to the modulation of the quality and magnitude of immune responses. T cells, as a core part of the immune system, respond readily to inflammatory cues from their environment, and express a diverse array of PG receptors that contribute to their function and phenotype. Here we put in context our knowledge about how PG affect T cell biology, and review advances that bring light into how specific T cell functions that have been newly discovered are modulated through PG. We will also comment on drugs that target PG metabolism and sensing, their effect on T cell function during disease, and we will finally discuss how we can design new approaches that modulate PG in order to maximize desired therapeutic T cell effects.
Topics: Animals; Autoimmune Diseases; Cell Differentiation; Drug Discovery; Humans; Immunity; Inflammation; Prostaglandins; T-Lymphocytes
PubMed: 31553935
DOI: 10.1016/j.phrs.2019.104456 -
Prostaglandins, Leukotrienes, and... Apr 2021Cyclooxygenase (COX)-derived prostaglandin E (PGE) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from...
OBJECTIVE
Cyclooxygenase (COX)-derived prostaglandin E (PGE) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from lipoxygenases (LOX) have also been implicated in neoplastic processes in the colon. In this study we aimed to characterize lipid mediators, so called oxylipins, in human colon adenomatous polyps.
DESIGN
We quantified oxylipins in healthy colon tissue and colorectal adenoma tissue procured during routine colonoscopy examinations. Lipid metabolite profiles were analyzed by liquid chromatography-tandem mass spectrometry.
RESULTS
Adenoma tissue showed a distinct prostaglandin profile as compared to normal colon mucosa. Interestingly, PGE was not higher in adenoma tissue as compared to normal mucosa. In contrast, we found significantly lower levels of prostaglandin D, prostaglandin J, and prostaglandin D in adenoma tissue. Furthermore, levels of 5-LOX and 12-LOX pathway products were clearly increased in adenoma biopsy samples. We also investigated the effect of aspirin treatment on prostaglandin profiles in adenoma tissue in a subset of patients and found a trend towards decreased prostaglandin levels in response to aspirin.
CONCLUSION
The human data presented here show specific changes of oxylipin profiles in colon adenoma tissue with decreased prostaglandin D levels as well as increased 5- and 12-LOX metabolites.
Topics: Adenoma; Aged; Arachidonate 5-Lipoxygenase; Case-Control Studies; Colon; Colonic Neoplasms; Cyclooxygenase 2; Female; Humans; Male; Oxylipins; Pilot Projects; Prostaglandin D2; Prostaglandins D
PubMed: 33812217
DOI: 10.1016/j.plefa.2021.102269 -
European Journal of Clinical... Nov 2020COVID-19 is a highly contagious viral disease. In this study, we tried to define and discuss all the findings on the potential association between arachidonic acid (AA)... (Review)
Review
BACKGROUND AND OBJECTIVE
COVID-19 is a highly contagious viral disease. In this study, we tried to define and discuss all the findings on the potential association between arachidonic acid (AA) pathway and COVID-19 pathophysiology.
METHODS
A literature search across PubMed, Scopus, Embase, and Cochrane database was conducted. A total of 25 studies were identified.
RESULTS
The data elucidated that COX-2 and prostaglandins (PGs), particularly PGE, have pro-inflammatory action in COVID-19 pathophysiology. Arachidonic acid can act as endogenous antiviral compound. A deficiency in AA can make humans more susceptible to COVID-19. Targeting these pro-inflammatory mediators may help in decreasing the mortality and morbidity rate in COVID-19 patients.
CONCLUSIONS
PGE levels and other PGs levels should be measured in patients with COVID-19. Lowering the PGE levels through inhibition of human microsomal prostaglandin E synthase-1 (mPGES-1) can enhance the host immune response against COVID-19. In addition, the hybrid compounds, such as COX-2 inhibitors/TP antagonists, can be an innovative treatment to control the overall balance between AA mediators in patients with COVID-19.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Betacoronavirus; COVID-19; Coronavirus Infections; Cyclooxygenase 2; Humans; Inflammation; Pandemics; Phospholipases A2; Pneumonia, Viral; Prostaglandin-E Synthases; Prostaglandins; Protein-Lysine 6-Oxidase; SARS-CoV-2; Sex Factors
PubMed: 32583353
DOI: 10.1007/s00228-020-02941-w