更新于：2024-05-01
uPA
尿激酶型纤维蛋白溶酶原激活因子
更新于：2024-05-01
基本信息
别名 尿激酶型纤维蛋白酶原激活剂、plasminogen activator, urokinase、PLAU + [7] |
简介 Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
Combination Therapy With Liposomal Doxorubicin and Withaferin A (Ashwagandha, ASWD) in Recurrent Ovarian Cancer
Master Protocol for Early Treatment and Post-Exposure Prophylaxis of COVID-19 Adaptive Platform Trial PROTECT-APT 1
A Phase II Clinical Trial of Standardized Withaferin-A for the treatment of Steroid Refractory acute Graft versus Host Disease.
100 项与 uPA 相关的临床结果
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100 项与 uPA 相关的转化医学
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2024-02-22Arteriosclerosis, thrombosis, and vascular biology
Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution.
Article
作者: Julia B Kral-Pointner ; Patrick Haider ; Petra L Szabo ; Manuel Salzmann ; Mira Brekalo ; Karl H Schneider ; Waltraud C Schrottmaier ; Christoph Kaun ; Sonja Bleichert ; Attila Kiss ; Romana Sickha ; Christian Hengstenberg ; Kurt Huber ; Christine Brostjan ; Helga Bergmeister ; Alice Assinger ; Bruno K Podesser ; Johann Wojta ; Philipp Hohensinner
BACKGROUND:
Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated cell interactions.
METHODS:
Thrombosis was induced by inferior vena cava stenosis through ligation in mice. After 1 day, a P-selectin-blocking antibody or isotype control was administered and thrombus composition and resolution were analyzed.
RESULTS:
Localizing neutrophils and macrophages in thrombotic lesions of wild-type mice revealed that these cells enter the thrombus and vessel wall from the caudal end. Neutrophils were predominantly present 1 day and monocytes/macrophages 3 days after vessel ligation. Blocking P-selectin reduced circulating platelet-neutrophil and platelet-Ly6Chigh monocyte aggregates near the thrombus, and diminished neutrophils and Ly6Chigh macrophages in the cranial thrombus part compared with isotype-treated controls. Depletion of neutrophils 1 day after thrombus initiation did not phenocopy P-selectin inhibition but led to larger thrombi compared with untreated controls. In vitro, P-selectin enhanced human leukocyte function as P-selectin-coated beads increased reactive oxygen species production by neutrophils and tissue factor expression of classical monocytes. Accordingly, P-selectin inhibition reduced oxidative burst in the thrombus and tissue factor expression in the adjacent vessel wall. Moreover, blocking P-selectin reduced thrombus density determined by scanning electron microscopy and increased urokinase-type plasminogen activator levels in the thrombus, which accelerated caudal fibrin degradation from day 3 to day 14. This accelerated thrombus resolution as thrombus volume declined more rapidly after blocking P-selectin.
CONCLUSIONS:
Inhibition of P-selectin-dependent activation of monocytes and neutrophils accelerates venous thrombosis resolution due to reduced infiltration and activation of innate immune cells at the site of thrombus formation, which prevents early thrombus stabilization and facilitates fibrinolysis.
2024-02-12Rheumatology and therapy
Real-World Use and Effectiveness Outcomes in Patients with Rheumatoid Arthritis Treated with Upadacitinib: An Analysis from the CorEvitas Registry.
Article
作者: Joshua F Baker ; Patrick Zueger ; Mira Ali ; Denise Bennett ; Miao Yu ; Yolanda Munoz Maldonado ; Robert R McLean
INTRODUCTION:
Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA.
METHODS:
Data were collected from the CorEvitas® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy.
RESULTS:
Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy.
CONCLUSIONS:
UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.
2024-02-11International journal of hematology
Dysregulated hemostasis in acute promyelocytic leukemia.
Review
作者: Yohei Hisada
Acute promyelocytic leukemia (APL) is associated with a high incidence of early death, which occurs within 30 days of diagnosis. The major cause of early death in APL is severe bleeding, particularly intracranial bleeding. Although APL is known to be associated with activation of coagulation, hyperfibrinolysis, and thrombocytopenia, the precise mechanisms that cause bleeding have not yet been elucidated. I propose that a combination of four pathways may contribute to bleeding in APL: (1) tissue factor, (2) the urokinase plasminogen activator/urokinase plasminogen activator receptor, (3) the annexin A2/S100A100/tissue plasminogen activator, and (4) the podoplanin/C-type lectin-like receptor 2. A better understanding of these pathways will identify new biomarkers to determine which APL patients are at high risk of bleeding and allow the development of new treatments for APL-associated bleeding.
分析
对领域进行一次全面的分析。
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