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International Journal of Biological... 2022Gastric cancer (GC) is the most common gastrointestinal malignant tumor, and distant metastasis is a critical factor in the prognosis of patients with GC. Understanding...
Gastric cancer (GC) is the most common gastrointestinal malignant tumor, and distant metastasis is a critical factor in the prognosis of patients with GC. Understanding the mechanism of GC metastasis will help improve patient prognosis. Studies have confirmed that urokinase-type plasminogen activator receptor (PLAUR) promotes GC metastasis; however, its relationship with anoikis resistance and associated mechanisms remains unclear. In this study, we demonstrated that PLAUR promotes the anoikis resistance and metastasis of GC cells and identified transcription Factor 7 Like 2 (TCF7L2) as an important transcriptional regulator of PLAUR. We also revealed that TCF7L2 is highly expressed in GC and promotes the anoikis resistance and metastasis of GC cells. Moreover, we found that TCF7L2 transcription activates PLAUR. Finally, we confirmed that TCF7L2 is an independent risk factor for poor prognosis of patients with GC. Our results show that TCF7L2 and PLAUR are candidate targets for developing therapeutic strategies for GC metastasis.
Topics: Anoikis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Plasminogen Activators; Receptors, Urokinase Plasminogen Activator; Signal Transduction; Stomach Neoplasms; Transcription Factor 7-Like 2 Protein
PubMed: 35864968
DOI: 10.7150/ijbs.69933 -
Stroke Aug 2019
Topics: Endovascular Procedures; Humans; Stroke; Tissue Plasminogen Activator
PubMed: 31303154
DOI: 10.1161/STROKEAHA.119.025865 -
Anesthesiology Clinics Mar 2021Anesthesiologists provide care to acute and subacute ischemic stroke (IS) patients and stroke survivors in interventional radiology, intensive care, and operating rooms.... (Review)
Review
Anesthesiologists provide care to acute and subacute ischemic stroke (IS) patients and stroke survivors in interventional radiology, intensive care, and operating rooms. These encounters will become more frequent following studies that have extended the treatment window from last known well time for fibrinolytic and endovascular thrombectomy (EVT). The number of stroke centers certified to quickly and effectively initiate treatment of IS patients and the number of patients connected to them by telehealth continue to grow. This article reviews IS pathophysiology, assessment, treatment, pathology, and complications; anesthetic management during EVT; perioperative stroke management; and how anesthesia has an impact on patients with prior stroke.
Topics: Brain Ischemia; Endovascular Procedures; Fibrinolytic Agents; Humans; Ischemic Stroke; Stroke; Thrombectomy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33563375
DOI: 10.1016/j.anclin.2020.11.002 -
Circulation. Cardiovascular Quality and... Aug 2019
Topics: Humans; Percutaneous Coronary Intervention; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 31412736
DOI: 10.1161/CIRCOUTCOMES.119.005931 -
Journal of Thrombosis and Haemostasis :... Dec 2023Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is... (Review)
Review
Fibrinolysis is the system primarily responsible for removal of fibrin deposits and blood clots in the vasculature. The terminal enzyme in the pathway, plasmin, is formed from its circulating precursor, plasminogen. Fibrin is by far the most legendary substrate, but plasmin is notoriously prolific and is known to cleave many other proteins and participate in the activation of other proteolytic systems. Fibrinolysis is often overshadowed by the coagulation system and viewed as a simplistic poorer relation. However, the primordial plasminogen activators evolved alongside the complement system, approximately 70 million years before coagulation saw the light of day. It is highly likely that the plasminogen activation system evolved with its roots in primordial immunity. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allow plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, numerous pathogens express their own plasminogen activators or contain surface proteins that provide binding sites for host plasminogen. The fibrinolytic system has been harnessed for clinical medicine for many decades with the development of thrombolytic drugs and antifibrinolytic agents. Our refined understanding and appreciation of the fibrinolytic system and its alliance with infection and immunity and beyond are paving the way for new developments and interest in novel therapeutics and applications. One must ponder as to whether the nomenclature of the system hampered our understanding, by focusing on fibrin, rather than the complex myriad of interactions and substrates of the plasminogen activation system.
Topics: Humans; Fibrinolysis; Fibrinolysin; Plasminogen Activators; Plasminogen; Fibrin; Serine Proteases
PubMed: 38000850
DOI: 10.1016/j.jtha.2023.09.012 -
Neurotherapeutics : the Journal of the... Apr 2023Alteplase has been the primary thrombolytic used in the treatment of acute ischemic stroke since thrombolysis was first established as an effective treatment of acute... (Review)
Review
Alteplase has been the primary thrombolytic used in the treatment of acute ischemic stroke since thrombolysis was first established as an effective treatment of acute ischemic stroke in 1995. Tenecteplase, a genetically modified tissue plasminogen activator, has gained attention as an attractive alternative to alteplase given its practical workflow advantages and possible superior efficacy in large vessel recanalization. As more data is analyzed both from randomized trials and non-randomized patient registries, there is mounting support that tenecteplase appears to be at least equally, if not more, safe and potentially more effective than alteplase in the treatment of acute ischemic stroke. Randomized trials investigating tenecteplase in the delayed treatment window and with thrombectomy are ongoing, and their results are eagerly awaited. This paper provides an overview of completed and ongoing randomized trials and nonrandomized studies analyzing tenecteplase in the treatment of acute ischemic stroke. Results reviewed support the safe use of tenecteplase in clinical practice.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Ischemic Stroke; Stroke; Brain Ischemia; Fibrinolytic Agents
PubMed: 37273127
DOI: 10.1007/s13311-023-01391-3 -
Pharmacology 2023Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action.
OBJECTIVES
The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis.
METHODS
A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework.
RESULTS
A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10).
CONCLUSION
For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.
Topics: Humans; Fibrinolytic Agents; Tissue Plasminogen Activator; Tenecteplase; Urokinase-Type Plasminogen Activator; Network Meta-Analysis; Pulmonary Embolism; Heparin; Streptokinase; Hemorrhage; Anticoagulants
PubMed: 36603558
DOI: 10.1159/000527668 -
Biomolecules Nov 2020The Gram-negative bacterium causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. overcomes the innate immunity of... (Review)
Review
The Gram-negative bacterium causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. overcomes the innate immunity of its host thanks to many pathogenicity factors, including plasminogen activator, Pla. This factor is a broad-spectrum outer membrane protease also acting as adhesin and invasin. uses Pla adhesion and proteolytic capacity to manipulate the fibrinolytic cascade and immune system to produce bacteremia necessary for pathogen transmission via fleabite or aerosols. Because of microevolution, invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest phylogenetic groups. This mutation caused a better ability to activate plasminogen. In paradox with its fibrinolytic activity, Pla cleaves and inactivates the tissue factor pathway inhibitor (TFPI), a key inhibitor of the coagulation cascade. This function in the plague remains enigmatic. Pla (or ) had been used as a specific marker of , but its solitary detection is no longer valid as this gene is present in other species of . Though recovering hosts generate anti-Pla antibodies, Pla is not a good subunit vaccine. However, its deletion increases the safety of attenuated strains, providing a means to generate a safe live plague vaccine.
Topics: Animals; Antigens, Bacterial; Humans; Plague; Plague Vaccine; Plasminogen Activators; Point Mutation; Protein Interaction Maps; Protein Structure, Secondary; Yersinia pestis
PubMed: 33202679
DOI: 10.3390/biom10111554 -
International Journal of Molecular... Feb 2023Stressful events trigger a set of complex biological responses which follow a bell-shaped pattern. Low-stress conditions have been shown to elicit beneficial effects,... (Review)
Review
Glucocorticoid-Responsive Tissue Plasminogen Activator (tPA) and Its Inhibitor Plasminogen Activator Inhibitor-1 (PAI-1): Relevance in Stress-Related Psychiatric Disorders.
Stressful events trigger a set of complex biological responses which follow a bell-shaped pattern. Low-stress conditions have been shown to elicit beneficial effects, notably on synaptic plasticity together with an increase in cognitive processes. In contrast, overly intense stress can have deleterious behavioral effects leading to several stress-related pathologies such as anxiety, depression, substance use, obsessive-compulsive and stressor- and trauma-related disorders (e.g., post-traumatic stress disorder or PTSD in the case of traumatic events). Over a number of years, we have demonstrated that in response to stress, glucocorticoid hormones (GCs) in the hippocampus mediate a molecular shift in the balance between the expression of the tissue plasminogen activator (tPA) and its own inhibitor plasminogen activator inhibitor-1 (PAI-1) proteins. Interestingly, a shift in favor of PAI-1 was responsible for PTSD-like memory induction. In this review, after describing the biological system involving GCs, we highlight the key role of tPA/PAI-1 imbalance observed in preclinical and clinical studies associated with the emergence of stress-related pathological conditions. Thus, tPA/PAI-1 protein levels could be predictive biomarkers of the subsequent onset of stress-related disorders, and pharmacological modulation of their activity could be a potential new therapeutic approach for these debilitating conditions.
Topics: Humans; Tissue Plasminogen Activator; Plasminogen Activator Inhibitor 1; Glucocorticoids; Mental Disorders
PubMed: 36901924
DOI: 10.3390/ijms24054496 -
No Shinkei Geka. Neurological Surgery Dec 2020
Topics: Fibrinolytic Agents; Humans; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 33353872
DOI: 10.11477/mf.1436204333