The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

To compare the short-and long-term effect of two minimal invasive surgical therapies including keyhole approach endoscopic surgery(KAES)and stereotactic aspiration plus urokinase(SAU)in treating basal ganglia hypertensive intracerebral hemorrhage(hICH). The clinical data of 117 hICH patients(63 received KAES and 54 received SAU)were retrospectively analyzed.The operation time,blood loss during surgery,and drainage time were compared between two groups.The residual hematoma volume,hematoma clearance rate(HCR),Glasgow coma scale(GCS)score,and National Institute of Health Stroke Scale(NIHSS)score were recorded at baseline and in the ultra-early stage,early stage,and sub-early stage after surgery.The 30-day mortality and serious adverse events were assessed and the 6-month modified Rankin scale(mRS)score was rated. Baseline data showed no significant difference between these two groups.Compared with the SAU group,the KAES group had significantly longer operation time,more intraoperative blood loss,and shorter drainage time(all <0.001).In the ultra-early stage after surgery,HCR was significantly higher in the KAES group(<0.001),whereas in the early and sub-early stage,HCR showed no significant differences(all >0.05).In the ultra-early and early stage,the GCS and NIHSS scores showed no significant differences between two groups(all >0.05),whereas in the sub-early stage,the NIHSS score was better in the SAU group(=0.034).The 30-day mortality and incidences of serious adverse events showed no significant difference(all >0.05).The good recovery(mRS≤3)at 6-months follow-up showed no significant difference between the two groups(=0.413). Both KAES and SAU are safe and effective in treating basal ganglia hICH.In the ultra-early stage after surgery,KAES achieves better residual hematoma volume and HCR,and patients undergoing SAU quickly catch up.The short-and long-term effectiveness of SAU is comparable or even superior to KAES.
Basal Ganglia ; Humans ; Intracranial Hemorrhage, Hypertensive ; Retrospective Studies ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

OBJECTIVE: The principle operation of acute subdural hematoma (ASDH) is a craniotomy with hematoma removal, but a trephination with hematoma evacuation may be another method in selected cases. Trephine drainage was performed for ASDH patients in subacute stage using urokinase (UK) instillation, and its results were evaluated. METHODS: Between January 2016 and December 2018, the trephine evacuation using UK was performed in 9 patients. The interval between injury and operation was from 1 to 2 weeks. We underwent a burr hole trephination with drainage initially, and waited until the flow of liquefied hematoma stopped, then instilled UK for the purpose of clot liquefaction. RESULTS: The mean age of patients was 71.6 years (range, 38–90 years). The cause of ASDH was trauma in 8 cases, and supposed a complication of anticoagulant medication in 1 case. Four out of 8 patients took antiplatelet medications and one of them was a chronic alcoholism. The range of the Glasgow Coma Scale score before surgery was from 13 to 15. Most of patients, main symptom was headache at admission. The Glasgow Outcome Scale score was 5 in 8 cases and 3 in 1 case. CONCLUSION: It is thought to be a useful operation method in selected patients with ASDH that the subdural drainage in subacute stage with UK instillation. This method might be another useful option for the patients with good mental state regardless of age and the patients with a risk of bleeding due to antithrombotic medications.
Alcoholism ; Craniotomy ; Drainage ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Headache ; Hematoma ; Hematoma, Subdural, Acute ; Hematoma, Subdural, Chronic ; Hemorrhage ; Humans ; Methods ; Trephining ; Urokinase-Type Plasminogen Activator

Mesenteric venous thrombosis has a low prevalence and nonspecific clinical symptoms, and it may cause bowel infarction and death. Early diagnosis and prompt surgical intervention with anticoagulants are important to patients. We examined a 27-year-old woman complaining of diffuse abdominal pain and hematochezia, and diagnosed extensive mesenteric venous thrombosis with intestinal infarction and pulmonary thromboembolism. In light of the patient's symptoms, an operation seemed necessary. However, because of the high risk of mortality, we decided to look for another option. The patient was successfully treated with intensive medical care and a radiological procedure in spite of intestinal infarction.
Abdominal Pain ; Adult ; Anticoagulants ; Early Diagnosis ; Female ; Gastrointestinal Hemorrhage ; Humans ; Infarction ; Mesenteric Ischemia ; Mesenteric Vascular Occlusion ; Mortality ; Prevalence ; Pulmonary Embolism ; Thrombectomy ; Thrombolytic Therapy ; Thrombosis ; Urokinase-Type Plasminogen Activator

We describe the case of a patient with an acute subdural hematoma (SDH) that was removed using urokinase irrigation after burr hole trephination in a limited situation where craniotomy was not possible. A 90-year-old woman was admitted to our hospital with a stuporous mental status. Computed tomography (CT) scans revealed a chronic SDH, and a burr hole procedure was performed. The patient's postoperative progression was good until the third day after surgery when we found that the acute SDH had increased on CT scans. The patient's guardian refused further surgery, and thus we drained the blood from the hematoma by injecting urokinase through a drainage catheter. We used urokinase for two days, and removed the catheter after confirming via CT scans that the hematoma was almost alleviated. The patient recovered gradually; she was discharged with few neurological deficits.
Aged, 80 and over ; Catheters ; Craniotomy ; Drainage* ; Female ; Hematoma ; Hematoma, Subdural, Acute* ; Humans ; Stupor ; Tomography, X-Ray Computed ; Trephining ; Urokinase-Type Plasminogen Activator*

Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.
Child ; Diagnosis ; Female ; Glomerulosclerosis, Focal Segmental* ; Humans ; Hypoalbuminemia ; Immunologic Factors ; Kidney Failure, Chronic ; Kidney Transplantation ; Methylprednisolone* ; Nephrotic Syndrome ; Plasmapheresis* ; Prognosis ; Proteinuria ; Recurrence ; Urokinase-Type Plasminogen Activator ; Young Adult

OBJECTIVE: Aneurysm clipping and simultaneous hematoma evacuation through open craniotomy is traditionally recommended for ruptured cerebral aneurysms accompanied by intracerebral or intrasylvian hemorrhages. We report our experience of adapting a less invasive treatment strategy in poor-grade patients with intracerebral or intrasylvian hemorrhages associated with ruptured cerebral aneurysms, where the associated ruptured cerebral aneurysms were managed by endovascular coil embolization, followed by stereotactic aspiration of hematomas (SRH) using urokinase. MATERIALS AND METHODS: We retrospectively analyzed 112 patients with ruptured cerebral aneurysms. There were accompanying intracerebral or intrasylvian hemorrhages in 36 patients (32.1%). The most common site for these ruptured aneurysms was the middle cerebral artery (MCA) (n = 15; 41.6%). Endovascular coil embolization followed by SRH using urokinase was performed in 9 patients (25%). RESULTS: In these 9 patients, the most common site of aneurysms was the MCA (n = 3; 33.4%); the hematoma volume ranged from 19.24 to 61.68 mL. Four patients who were World Federation of Neurological Surgeons (WFNS) grade-IV on admission, achieved favorable outcomes (Glasgow Outcome Score [GOS] 4 or 5) at 6-months postoperatively. In the five patients who were WFNS grade-V on admission, one achieved a favorable outcome, whereas 4 achieved GOS scores of 2 or 3, 6-months postoperatively. There was no mortality. CONCLUSION: If immediate hematoma evacuation is not mandated by clinical or radiological signs of brain herniation, a less invasive strategy, such as endovascular coil embolization followed by SRH using urokinase, may be a good alternative in poor-grade patients with intracerebral or intrasylvian hemorrhages associated with ruptured cerebral aneurysms.
Aneurysm ; Aneurysm, Ruptured ; Brain ; Cerebral Hemorrhage ; Craniotomy ; Embolization, Therapeutic* ; Hematoma* ; Hemorrhage ; Humans ; Intracranial Aneurysm* ; Middle Cerebral Artery ; Mortality ; Neurosurgeons ; Retrospective Studies ; Urokinase-Type Plasminogen Activator*

PURPOSE: Genetically engineered stem cells may be advantageous for gene therapy against various human cancers due to their inherent tumor-tropic properties. In this study, genetically engineered human neural stem cells (HB1.F3) expressing Escherichia coli cytosine deaminase (CD) (HB1.F3.CD) and human interferon-β (IFN-β) (HB1.F3.CD.IFN-β) were employed against lymph node–derived metastatic colorectal adenocarcinoma. MATERIALS AND METHODS: CD can convert a prodrug, 5-fluorocytosine (5-FC), to active 5-fluorouracil, which inhibits tumor growth through the inhibition of DNA synthesis,while IFN-β also strongly inhibits tumor growth by inducing the apoptotic process. In reverse transcription polymerase chain reaction analysis, we confirmed that HB1.F3.CD cells expressed the CD gene and HB1.F3.CD.IFN-β cells expressed both CD and IFN-β genes. RESULTS: In results of a modified trans-well migration assay, HB1.F3.CD and HB1.F3.CD.IFN-β cells selectively migrated toward SW-620, human lymph node–derived metastatic colorectal adenocarcinoma cells. The viability of SW-620 cells was significantly reduced when co-cultured with HB1.F3.CD or HB1.F3.CD.IFN-β cells in the presence of 5-FC. In addition, it was found that the tumor-tropic properties of these engineered human neural stem cells (hNSCs) were attributed to chemoattractant molecules including stromal cell-derived factor 1, c-Kit, urokinase receptor, urokinase-type plasminogen activator, and C-C chemokine receptor type 2 secreted by SW-620 cells. In a xenograft mouse model, treatment with hNSC resulted in significantly inhibited growth of the tumor mass without virulent effects on the animals. CONCLUSION: The current results indicate that engineered hNSCs and a prodrug treatment inhibited the growth of SW-620 cells. Therefore, hNSC therapy may be a clinically effective tool for the treatment of lymph node metastatic colorectal cancer.
Adenocarcinoma* ; Animals ; Chemokine CXCL12 ; Colorectal Neoplasms ; Cytosine Deaminase* ; Cytosine* ; DNA ; Escherichia coli ; Flucytosine ; Fluorouracil ; Genetic Therapy ; Heterografts* ; Humans ; Interferon-beta ; Lymph Nodes ; Lymphatic Metastasis ; Mice* ; Neural Stem Cells* ; Polymerase Chain Reaction ; Reverse Transcription ; Stem Cells ; Urokinase-Type Plasminogen Activator

PURPOSE: In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. METHODS: Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. RESULTS: Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). CONCLUSION: Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating ; Diagnosis ; Estrogens ; Hormone Replacement Therapy ; Humans ; Lymph Nodes* ; Neoplasm Metastasis* ; Plasminogen Activator Inhibitor 1 ; Prognosis ; Skin ; Thoracic Wall ; Urokinase-Type Plasminogen Activator*