Asahi Kasei · therapeutic agent
plasminogen activator is a therapeutic agent developed by Asahi Kasei. It is approved for therapeutic indications via injectable (others) or intravenous (iv).
| Brand Names | tisokinase, tisokinase, Kowa, Hapase |
| Company | Asahi Kasei |
| Route | Injectable (Others), Intravenous (IV) |
| Status | Approved |
plasminogen activator is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Cardiac disorders | Myocardial infarction | ✓ Approved |
Waśniowska Anna A, Natorska Joanna J, Konieczyńska Małgorzata M, Matusik Paweł T PT et al.
Yao Jinfen J, Chen Jie J
The present study aimed to explore the risk factors for abdominal adhesion during hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer via logistic regression analysis. The present study is a retrospective analysis involving 165 patients with ovarian cancer treated at The Department of Gynecology, Shanghai First Maternity and Infant Hospital (Shanghai, China) from February 2021 to June 2023. All patients were treated with HIPEC or adjuvant therapy. During the treatment, the patients were divided into the control (n=61) and observation (n=104) groups according to the presence of abdominal adhesion. The results of the present study highlighted the notable role of monitoring biomarkers such as C-reactive protein and plasminogen activator inhibitor-1 in predicting the risk of abdominal adhesions in patients with ovarian cancer treated with HIPEC. By optimizing surgical techniques, controlling inflammatory reactions, adopting anti-adhesion strategies and implementing detailed preoperative assessment and preventive measures for patients undergoing HIPEC, the incidence of adhesions may be effectively reduced and treatment safety improved.
Wu Jheng-Yan JY, Lee Keng-Wei KW, Kao Chia-Li CL, Hung Kuo-Chuan KC et al.
To evaluate the association between tirzepatide use and 1-year risk of major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease, compared with GLP-1 (glucagon-like peptide-1) receptor agonists. We conducted a retrospective, propensity score-matched cohort study using the TriNetX network. A total of 16 402 patients with type 2 diabetes and atherosclerotic cardiovascular disease initiating tirzepatide or GLP-1 receptor agonists between January 1, 2022, and March 31, 2025 were matched 1:1. The primary outcome was 1-year major adverse cardiovascular events; secondary outcomes included all-cause mortality, acute myocardial infarction, major adverse limb events, and tissue plasminogen activator use. Tirzepatide was associated with a lower risk of major adverse cardiovascular events (hazard ratio [HR], 0.75 [95% CI, 0.63-0.91]) and reduced risks of all-cause mortality (HR, 0.69 [95% CI, 0.53-0.90]), major adverse limb events (HR, 0.59 [95% CI, 0.39-0.88]), and acute myocardial infarction (HR, 0.70 [95% CI, 0.53-0.93]), compared with GLP-1 receptor agonists. Results were robust across subgroups and sensitivity analyses. Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a significantly reduced 1-year risk of major adverse cardiovascular events and other cardiovascular outcomes compared with GLP-1 receptor agonists. These findings support the cardiometabolic potential of tirzepatide, warranting further prospective validation.
Morrow Kaleb K, Karamanova Nina N, Woltjer Randy R, Krajbich Victoria V et al.
Age is the most important risk factor for coronary artery disease (CAD) independent of traditional risk factors. Aging induces classic pro-inflammatory and prothrombotic vascular phenotypic changes whose molecular mediators remain poorly understood. Medin is a common cleavage product protein that accumulates in vasculature with aging and shown to cause endothelial dysfunction. Its role in CAD is unknown. The study aimed to evaluate the effects of medin on human coronary artery endothelial cell (HCAEC) pro-inflammatory and prothrombotic activation and establish the relationship between medin and coronary atherosclerosis in human decedents. HCAECs were exposed to physiologic dose of medin (5 µM) for 20 hours and ribonucleic acid sequencing (RNAseq) with signaling pathway analyses and reverse transcription polymerase chain reaction of select pro-inflammatory and prothrombotic genes performed. Corresponding protein expression was measured by Western blot or enzyme linked immunosorbent assay in HCAECs exposed to medin (5 µM) without or with nuclear factor-κB (NFκB) inhibitor RO106-9920 (10 µM). Coronary arteries from 40 deceased individuals underwent immunohistochemistry and medin and plaque burden were quantified and their relationship evaluated. RNAseq showed predominant pro-inflammatory gene expression changes induced by medin. HCAECs treated with medin showed increased phosphorylated NFκB, elevated protein expression of interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and plasminogen activator inhibitor (PAI)-1 and reduced protein expression of thrombomodulin; these changes were reversed by RO106-9920 co-treatment. In human tissues, coronary artery medin strongly correlated with plaque burden (R=0.76, p<0.0001) and coronary macrophage content (R=0.72, p<0.0001). Coronary arteries from decedents with myocardial infarction had higher medin than those without (5.53±2.67% versus 0.02±0.02%, p=0.0005). Medin induced NFκB-mediated endothelial cell pro-inflammatory and prothrombotic activation and was strongly associated with coronary plaque burden and inflammation. Medin is a novel candidate mediator linking aging and coronary atherosclerosis.
Yu LianHui L, Cheng Shih-Tsung ST, Liu Fang F, Liu HsiaoQian H et al.
To evaluate the feasibility and early outcomes of a hybrid pharmacomechanical strategy combining emergent endovascular revascularization with adjunctive systemic thrombolysis for the treatment of acute limb ischemia (ALI). This retrospective single-center pilot study included 20 consecutive patients presenting with ALI within 96 hours of symptom onset who underwent primary endovascular revascularization between 2016 and 2018. Mechanical thrombectomy and angioplasty were performed as first-line interventions. In cases of incomplete reperfusion, adjunctive intravenous systemic urokinase infusion was administered followed by repeat angiographic assessment within 48 to 72 hours. Technical success, limb salvage, complications, and in-hospital mortality were evaluated. Initial mechanical endovascular intervention achieved successful reperfusion in 13 patients (65%). Seven patients with persistent low-flow states received adjunctive systemic thrombolysis, resulting in additional successful reperfusion in 5 cases. The overall technical success rate was therefore 90%. Two patients required fasciotomy for compartment syndrome. One patient developed severe ischemia-reperfusion injury resulting in multiorgan failure and death. Limb salvage was achieved in 18 of 20 patients during the index hospitalization. Mean clinical follow-up was (145.1 ± 182.3) days (median: 65 days). A staged hybrid pharmacomechanical strategy incorporating adjunctive systemic thrombolysis following mechanical endovascular revascularization was associated with a feasible treatment option for selected patients with ALI when initial mechanical intervention results in incomplete reperfusion. Larger studies are required to determine the comparative effectiveness of this approach in contemporary endovascular practice.Clinical ImpactFor patients with acute limb ischemia and suboptimal flow (TIMI 0-1) after initial endovascular mechanical thrombectomy-defined angiographically as TIMI 0 (no antegrade flow beyond the occlusion) or TIMI 1 (minimal penetration of contrast without distal bed filling), analogous to coronary grading-adjunctive systemic thrombolysis was associated with successful salvage in 83% of otherwise refractory cases in this pilot study, raising overall technical success from 65% to 90%. This staged hybrid strategy offers a practical "bail-out" option before resorting to repeat intervention or open surgery. Urokinase was delivered as a peripheral intravenous infusion; although not available in all regions (it has not been Food and Drug Administration-approved in the United States since 2010), the principle may be applied with alternative agents such as tissue plasminogen activator. The innovation lies in its simplicity: a predefined protocol using systemic urokinase without specialized catheter-directed systems. Clinicians should consider this approach in hemodynamically stable patients with persistent low-flow states, potentially reducing the need for immediate reintervention while achieving acceptable limb salvage and mid-term amputation-free survival.
Luo Chaodi C, Luo Wenjie W, Zheng Tingting T, Wang Ping P et al.
The favorable cardiovascular effects of sodium-glucose co-transporter 2 inhibitors in diabetes are well established, but their potential to ameliorate obesity-related cardiac dysfunction remains unclear. Pericardial adipose tissue (PAT)-derived adipocytokines, particularly leptin, contribute to obesity-associated cardiac remodeling. We investigated the detrimental effects of PAT-derived leptin on cardiac remodeling and whether dapagliflozin confers cardioprotection by reducing and counteracting PAT-derived leptin in obese rodents. Male Wistar rats, C57BL/6J mice, and ob/ob mice were fed a normal or high-fat diet for 20 weeks, with or without dapagliflozin (1 mg/kg per day) for the final 8 weeks. PAT adipocytes from 8-week-old rats were isolated and induced to insulin resistance. Primary cardiac fibroblasts and cardiomyocytes were exposed to PAT-conditioned medium, leptin antagonist, dapagliflozin (10 μM), reactive oxygen species scavenger N-acetylcysteine (50 mM), pNaKtide (10 μM), Src inhibitor PP2 (10 μM). Na+-K+-ATPase expression and activity, mitochondrial membrane potential, and mitochondrial permeability transition pore opening were assessed. The intervention of dapagliflozin to high-fat diet-fed Wistar rats could reduce body weight and improve metabolic disorders. Furthermore, dapagliflozin significantly alleviated the adipocyte hypertrophy of PAT, cardiac fibrosis and apoptosis, as well as the leptin production and secretion from PAT. In vitro, dapagliflozin inhibits the leptin production and secretion in insulin-resistant adipocytes of PAT by regulating the phosphoinositide 3-kinase/protein kinase B and extracellular signal-regulated kinase 1/2 signaling pathway. Meanwhile, dapagliflozin could counteract the profibrotic effect of PAT-derived leptin via inhibiting the signal transducer and activator of transcription 3-reactive oxygen species/Na+-K+-ATPase/Src oxidative stress loop signaling pathway. Meanwhile, dapagliflozin could also attenuate cardiomyocytes apoptosis induced by PAT-derived leptin via suppressing Janus kinase 2/signal transducer and activator of transcription 3-Bax and inhibiting reactive oxygen species/Na+-K+-ATPase/Src oxidative stress loop. Dapagliflozin reduced PAT-derived leptin via phosphoinositide 3-kinase/protein kinase B and extracellular signal-regulated kinase 1/2 signaling and mitigated PAT-derived leptin-induced myocardial fibrosis and apoptosis by inhibiting signal transducer and activator of transcription 3-mediated reactive oxygen species/Na+-K+-ATPase/Src oxidative stress signaling.
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