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Current Medicinal Chemistry 2011Tumor-induced dysfunction of immune cells is a common problem in cancer. Tumors induce immune suppression by many different mechanisms, including accumulation of... (Review)
Review
Tumor-induced dysfunction of immune cells is a common problem in cancer. Tumors induce immune suppression by many different mechanisms, including accumulation of regulatory T cells (Treg). Adaptive Treg (Tr1) generated in the tumor microenvironment express CD39 and CD73 ectonucleotidases, produce adenosine and are COX2+PGE2+. Adenosine and PGE2 produced by Tr1 or tumor cells bind to their respective receptors on the surface of T effector cells (Teff) and cooperate in up-regulating cytosolic 3'5'-cAMP levels utilizing adenylyl cyclase isoform 7 (AC-7). In Teff, increased cAMP mediates suppression of anti-tumor functions. Treg, in contrast to Teff, seem to require high cAMP levels for mediating suppression. This differential requirement of Treg and Teff for cAMP offers an opportunity for pharmacologic interventions using selected inhibitors of the adenosine/PGE2 pathways. Blocking of adenosine/PGE2 production by Tr1 or blocking binding of these factors to their receptors on T cells or inhibition of cAMP synthesis in Teff all represent novel therapeutic strategies that used in combination with conventional therapies could restore anti-tumor functions of Teff . At the same time, these inhibitors could disarm Tr1 cells by depriving them of the factors promoting their generation and activity or by down-regulating 3'5'-cAMP levels. Thus, the pharmacologic control of Treg-Teff interactions offers a novel strategy for restoration of anti-tumor Teff functions and silencing of Treg. Used in conjunction with anti-cancer drugs or with immune therapies, this strategy has a potential to improve therapeutic effects by preventing or reversing tumor-induced immune suppression.
Topics: Adenosine; Animals; Dinoprostone; Humans; Immune Tolerance; Neoplasms; T-Lymphocytes, Regulatory; Tumor Microenvironment
PubMed: 22087822
DOI: 10.2174/092986711798184334 -
PloS One 2020To compare effectiveness and safety of oral misoprostol (50 μg every four hours as needed), low dose vaginal misoprostol (25 to 50 μg every six hours as needed), and... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To compare effectiveness and safety of oral misoprostol (50 μg every four hours as needed), low dose vaginal misoprostol (25 to 50 μg every six hours as needed), and our established dinoprostone vaginal gel (one to two mg every six hours as needed) induction.
MATERIALS AND METHODS
Consenting women with a live term single cephalic fetus for indicated labor induction were randomized (3N = 511). Prior uterine surgery or non-reassuring fetal surveillance were exclusions. Concealed computer generated randomization was stratified and blocked. Newborns were assessed by a team unaware of group assignment. The primary outcome was time from induction at randomization to vaginal birth for initial parametric analysis. Sample size was based on mean difference of 240 minutes with α2 = 0.05 and power 95%. Non-parametric analysis was also pre-specified ranking cesareans as longest vaginal births.
RESULTS
Enrollment was from April 1999 to December 2000. Demographics were similar across groups. Analysis was by intent to treat, with no loss to follow up. Mean time (±SD) to vaginal birth was 1356 (±1033) minutes for oral misoprostol, 1530 (±3249) minutes for vaginal misoprostol, and 1208 (±613) minutes for vaginal dinoprostone (P = 0.46, ANOVA). Median times to vaginal birth were 1571, 1339, and 1451 minutes respectively (P = 0.46, Kruskal-Wallis). Vaginal births occurred within 24 hours in 44.9, 53.5 and 47.7% respectively (P = 0.27, χ2). There were no significant differences in Kaplan Meier survival analyses, cesareans, adverse effects, or maternal satisfaction. The newborn who met birth asphyxia criteria received vaginal misoprostol, as did. all three other newborns with cord artery pH<7.0 (P = 0.04, Fisher Exact).
CONCLUSION
There was no significant difference in effectiveness of the three groups. Profound newborn acidemia, though infrequent, occurred only with low dose vaginal misoprostol.
Topics: Administration, Intravaginal; Administration, Oral; Adult; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Oxytocics; Patient Satisfaction; Pregnancy; Treatment Outcome; Young Adult
PubMed: 31923193
DOI: 10.1371/journal.pone.0227245 -
Medical Archives (Sarajevo, Bosnia and... Feb 2022Induction of labor (IOL) is a technique to establish vaginal delivery when the risks for continuing the pregnancy for mother or baby are higher than the risks of...
BACKGROUND
Induction of labor (IOL) is a technique to establish vaginal delivery when the risks for continuing the pregnancy for mother or baby are higher than the risks of delivery. It is usually performed in high-risk pregnancies, but can also be beneficial in low-risk populations, as shown in the ARRIVE trial.
OBJECTIVE
To evaluate the effectiveness and safety of slow-release vaginal dinoprostone (prostaglandin E2 10 mg) for labor induction in women with low-risk pregnancies.
METHODS
A prospective study was performed at Hanoi Obstetrics and Gynecology Hospital, Vietnam. We recruited women with low-risk pregnancies from 39 weeks + 0 days to 40 weeks + 6 days of gestation and an unfavorable cervix. Women who participated received 10 mg intravaginal slow-release dinoprostone (Propess) for induction of labor. Labor, deliveries, and post-partum management were performed according to the local protocol.
RESULTS
From September 2020 to March 2021, 102 low-risk women were eligible to participate in the study. Among these women, 67.6% had vaginal deliveries, 6.9% had postpartum bleeding, and 3.9% experienced tachysystole. All newborns were healthy, with good APGAR scores. None of the women needed respiratory support or intensive care unit admission. All other maternal or fetal complications were explored. The rate of cesarean section was 3.8 higher in nulliparous than multiparous women and 2.2 times higher in women who did not receive epidural analgesia than in those who did. The risk of cesarean section increased if the time between labor induction and active labor was greater than 12.5 hours.
CONCLUSION
Slow-release dinoprostone insert is safe and effective for the induction of labor in low-risk pregnant women. The risk of cesarean section was elevated in nulliparous patients and those who did not receive epidural analgesia during labor. As the time from labor induction to active labor increased, the risk of cesarean section increased.
Topics: Cesarean Section; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Oxytocics; Pregnancy; Prospective Studies
PubMed: 35422562
DOI: 10.5455/medarh.2022.76.39-44 -
Frontiers in Immunology 2022Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing...
Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of classical pro-inflammatory cytokines. A dose-dependent effect of WSS on potency is evidenced by production of prostaglandin E2 (PGE) and indoleamine 2,3 dioxygenase 1 (IDO1), as well as suppression of tumor necrosis factor-α (TNF- α) and interferon-γ (IFN-γ) production by activated immune cells. Consistent, reproducible licensing is demonstrated in adipose tissue and bone marrow human derived MSC without significant impact on cell viability, cellular yield, or identity. Transcriptome analysis of WSS-conditioned BM-MSC elucidates the broader phenotypic implications on the differential expression of immunomodulatory factors. These results suggest mechanotransduction as a viable, scalable pre-conditioning alternative to pro-inflammatory cytokines. Enhancing the immunomodulatory capacity of MSC biomechanical conditioning represents a novel cell therapy manufacturing approach.
Topics: Cytokines; Dinoprostone; Humans; Immunomodulation; Mechanotransduction, Cellular; Mesenchymal Stem Cells
PubMed: 35874742
DOI: 10.3389/fimmu.2022.874698 -
Immunity Dec 2018How macrophages convey extracellular signals by bridging metabolism and functions remains unclear. In this issue of Immunity, Sanin et al. (2018) report that...
How macrophages convey extracellular signals by bridging metabolism and functions remains unclear. In this issue of Immunity, Sanin et al. (2018) report that prostaglandin E2 (PGE2) treatment in interleukin-4-activated macrophages suppresses mitochondrial membrane potential to control voltage-regulated genes involved in proliferation and immune responses.
Topics: Dinoprostone; Gene Expression; Macrophages; Membrane Potential, Mitochondrial
PubMed: 30566885
DOI: 10.1016/j.immuni.2018.12.002 -
Cellular & Molecular Immunology May 2013The reciprocal activating crosstalk between dendritic cells (DCs) and natural killer (NK) cells plays a pivotal role in regulating immune defense against viruses and... (Review)
Review
The reciprocal activating crosstalk between dendritic cells (DCs) and natural killer (NK) cells plays a pivotal role in regulating immune defense against viruses and tumors. The cytokine-producing capacity, Th-cell polarizing ability and chemokine expression, migration and stimulatory functions of DCs are regulated by activated NK cells. Conversely, the innate and effector functions of NK cells require close interactions with activated DCs. Cell membrane-associated molecules and soluble mediators, including cytokines and prostaglandins (PGs), contribute to the bidirectional crosstalk between DCs and NK cells. One of the most well-known and well-studied PGs is PGE2. Produced by many cell types, PGE2 has been shown to affect various aspects of the immune and inflammatory responses by acting on all components of the immune system. There is emerging evidence that PGE2 plays crucial roles in DC and NK cell biology. Several studies have shown that DCs are not only a source of PGE2, but also a target of its immunomodulatory action in normal immune response and during immune disorders. Although NK cells appear to be unable to produce PGE2, they are described as powerful PGE2-responding cells, as they express all PGE2 E-prostanoid (EP) receptors. Several NK cell functions (lysis, migration, proliferation, cytokine production) are influenced by PGE2. This review highlights the effects of PGE2 on DC-NK cell crosstalk and its subsequent impact on immune regulations in normal and immunopathological processes.
Topics: Animals; Cell Communication; Dendritic Cells; Dinoprostone; Humans; Immune System Diseases; Immunity; Killer Cells, Natural
PubMed: 23524652
DOI: 10.1038/cmi.2013.1 -
Cancer Metastasis Reviews Dec 2011Many lines of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E(2) (PGE(2)) is often observed in... (Review)
Review
Many lines of evidence demonstrate that prostaglandins play an important role in cancer, and enhanced synthesis of prostaglandin E(2) (PGE(2)) is often observed in various human malignancies often associated with poor prognosis. PGE(2) synthesis is initiated with the release of arachidonic acid by phospholipase enzymes, where it is then converted into the intermediate prostaglandin prostaglandin H(2) (PGH(2)) by members of the cyclooxygenase family. The synthesis of PGE(2) from PGH(2) is facilitated by three different PGE synthases, and functional PGE(2) can promote tumor growth by binding to four EP receptors to activate signaling pathways that control cell proliferation, migration, apoptosis, and angiogenesis. An integral method of controlling gene expression is by posttranscriptional mechanisms that regulate mRNA stability and protein translation. Messenger RNA regulatory elements typically reside within the 3' untranslated region (3'UTR) of the transcript and play a critical role in targeting specific mRNAs for posttranscriptional regulation through microRNA (miRNA) binding and adenylate- and uridylate-rich element RNA-binding proteins. In this review, we highlight the current advances in our understanding of the impact these RNA sequence elements have upon regulating PGE(2) levels. We also identify various RNA sequence elements consistently observed within the 3'UTRs of the genes involved in the PGE(2) pathway, indicating these binding sites for miRNAs and RNA-binding proteins to be central regulators of PGE(2) synthesis and function. These findings may provide a rationale for the development of new therapeutic approaches to control tumor growth and metastasis promoted by elevated PGE(2) levels.
Topics: Animals; Base Sequence; Dinoprostone; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasms; Prostaglandin-Endoperoxide Synthases; RNA Processing, Post-Transcriptional; RNA-Binding Proteins; Receptors, Prostaglandin E; Regulatory Sequences, Ribonucleic Acid
PubMed: 22005950
DOI: 10.1007/s10555-011-9300-5 -
Cancer Metastasis Reviews Dec 2011One of the most common features of exposure of skin to ultraviolet (UV) light is the induction of inflammation, a contributor to tumorigenesis, which is characterized by... (Review)
Review
One of the most common features of exposure of skin to ultraviolet (UV) light is the induction of inflammation, a contributor to tumorigenesis, which is characterized by the synthesis of cytokines, growth factors and arachidonic acid metabolites, including the prostaglandins (PGs). Studies on the role of the PGs in non-melanoma skin cancer (NMSC) have shown that the cyclooxygenase-2 (COX-2) isoform of the cyclooxygenases is responsible for the majority of the pathological effects of PGE(2). In mouse skin models, COX-2 deficiency significantly protects against chemical carcinogen- or UV-induced NMSC while overexpression confers endogenous tumor promoting activity. Current studies are focused on identifying which of the G protein-coupled EP receptors mediate the tumor promotion/progression activities of PGE(2) and the signaling pathways involved. As reviewed here, the EP1, EP2, and EP4 receptors, but not the EP3 receptor, contribute to NMSC development, albeit through different signaling pathways and with somewhat different outcomes. The signaling pathways activated by the specific EP receptors are context specific and likely depend on the level of PGE(2) synthesis, the differential levels of expression of the different EP receptors, as well as the levels of expression of other interacting receptors. Understanding the role and mechanisms of action of the EP receptors potentially offers new targets for the prevention or therapy of NMSCs.
Topics: Animals; Dinoprostone; Humans; Inflammation; Prostaglandin-Endoperoxide Synthases; Receptors, Prostaglandin E; Skin; Skin Neoplasms
PubMed: 22012553
DOI: 10.1007/s10555-011-9317-9 -
Taiwanese Journal of Obstetrics &... Sep 2020To evaluate the factors associated with the successful induction of labor (IOL) in women treated with dinoprostone slow-released vaginal insert.
OBJECTIVE
To evaluate the factors associated with the successful induction of labor (IOL) in women treated with dinoprostone slow-released vaginal insert.
MATERIAL AND METHODS
A retrospective study was conducted between June 2017 and December 2017, enrolling 65 patients who underwent dinoprostone slow-released vaginal insert-induced labor. The correlation between the characteristics of the pregnant women and its success, as well as perinatal complications and adverse outcomes were analyzed.
RESULTS
Fifty-three of 65 (81.5%) achieved a successful vaginal delivery. Only multi-parous pregnant women were an independent predictor factor for successful induction after dinoprostone slow-released vaginal insert, since all of them succeeded after this strategy treatment (100%, n = 18), compared to 74.5% (35/47) of successful rate in the nulliparous pregnant women with a statistically significant difference (p = 0.018). There were no adverse events occurred in both mothers and their offspring.
CONCLUSION
Dinoprostone slow-released vaginal insert is a good choice for multiparous pregnant women who need IOL, regardless of which reasons are indicated. For nulliparous women, more studies might be needed to evaluate the effectiveness of PGE2 for IOL.
Topics: Administration, Intravaginal; Adult; Cervical Ripening; Delivery, Obstetric; Dinoprostone; Female; Humans; Labor, Induced; Oxytocics; Parity; Pregnancy; Retrospective Studies
PubMed: 32917325
DOI: 10.1016/j.tjog.2020.07.017 -
IUBMB Life Jul 2018Invasion of host cell by pathogens induce various intracellular signalling pathways. The host cell through the initiation of these signalling circuits desperately wants... (Review)
Review
Invasion of host cell by pathogens induce various intracellular signalling pathways. The host cell through the initiation of these signalling circuits desperately wants to get rid of the pathogen, whereas the pathogen tries to subvert these defence strategies to create an environment for their successful survival. Leishmania spp. is not an exception. Leishmania have to evolve a range of strategic mechanisms to neutralize macrophage defensive arsenals which enable the parasite to replicate within the phagolysosome of infected host. Understanding these signalling mechanisms in detail will not only improve our basic knowledge of host-pathogen interaction but will also help us to develop effective drug targets not only against leishmaniasis but also for many other macrophage associated diseases. © 2018 IUBMB Life, 70(7):593-601, 2018.
Topics: Antiprotozoal Agents; Apoptosis; Dinoprostone; Host-Pathogen Interactions; Humans; Immune Tolerance; Immunologic Factors; Inflammasomes; Leishmania donovani; Leishmaniasis, Visceral; Respiratory Burst; Signal Transduction; Toll-Like Receptors
PubMed: 29684241
DOI: 10.1002/iub.1759