scholarly journals Targeting Tissue Factor to Tumor Vasculature to Induce Tumor Infarction

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2841
Author(s):  
Andrew F. Berdel ◽  
Christian Schwöppe ◽  
Caroline Brand ◽  
Saliha Harrach ◽  
Kathrin Brömmel ◽  
...  
Keyword(s):  
Tumor Vasculature ◽  
Vascular Wall ◽  
Aminopeptidase N ◽  
Therapeutic Modality ◽  
Drug Candidate ◽  
Vessel Occlusion ◽  
Multiple Structures ◽  
Membrane Antigens ◽  
Vascular Adhesion ◽  
Ng2 Proteoglycan

Besides its central functional role in coagulation, TF has been described as being operational in the development of malignancies and is currently being studied as a possible therapeutic tool against cancer. One of the avenues being explored is retargeting TF or its truncated extracellular part (tTF) to the tumor vasculature to induce tumor vessel occlusion and tumor infarction. To this end, multiple structures on tumor vascular wall cells have been studied at which tTF has been aimed via antibodies, derivatives, or as bifunctional fusion protein through targeting peptides. Among these targets were vascular adhesion molecules, oncofetal variants of fibronectin, prostate-specific membrane antigens, vascular endothelial growth factor receptors and co-receptors, integrins, fibroblast activation proteins, NG2 proteoglycan, microthrombus-associated fibrin-fibronectin, and aminopeptidase N. Targeting was also attempted toward cellular membranes within an acidic milieu or toward necrotic tumor areas. tTF-NGR, targeting tTF primarily at aminopeptidase N on angiogenic endothelial cells, was the first drug candidate from this emerging class of coaguligands translated to clinical studies in cancer patients. Upon completion of a phase I study, tTF-NGR entered randomized studies in oncology to test the therapeutic impact of this novel therapeutic modality.

scholarly journals Atherosclerosis is attenuated by acacetin via Sirt1-mediated activation of AMPK/Sirt3 signals in diabetic ApoE-/- mice

2020 ◽  
Author(s):  
Wei-Min Han ◽  
Xu-Chang Chen ◽  
Yan Wang ◽  
Gui-Rong Li
Keyword(s):  
Carotid Artery ◽  
Mitochondrial Function ◽  
Umbilical Vein ◽  
Vascular Wall ◽  
Cardiovascular Disorder ◽  
Signaling Molecules ◽  
Drug Candidate ◽  
Dependent Manner ◽  
Wall Movement ◽  
Patients With Diabetes

Abstract BackgroundThe strategy of decreasing atherosclerotic cardiovascular disorder is imperative to reduce premature death and improve quality of life in patients with diabetes mellitus. The present study was designed to investigate whether the natural flavone acacetin could improve diabetes- accelerated atherosclerotic lesions.MethodsDiabetic model was established in 7-week-old ApoE−/− mice by intraperitoneal injection of STZ (daily 50 mg/kg) for 5 days. Animals of control, control with acacetin treatment, STZ-diabetes, STZ-diabetes with acacetin treatment received acacetin prodrug subcutaneously (20 mg/kg, b.i.d.) or equivolume saline for 12 weeks, and the elasticity of carotid artery and the ability of vascular wall movement were determined with ultrasound and magnetic resonance imaging. Human umbilical vein endothelial cells (HUVECs) were cultured with medium containing 5.5 mM or 33 mM glucose and treated with acacetin or vehicle. Changes of related aortic lesions and signaling molecules were determined by biochemical and molecular approaches in animals and cultured HUVECs.ResultsIt was found that acacetin significantly suppressed atherosclerotic lesions and neointima hyperplasia, improved the elasticity of carotid artery and the ability of vascular wall movement without reducing blood glucose level and reversed the impaired signaling molecules (i.e. SOD, Bcl2, PGC-1α, pAMPK, Sirt3 and Sirt1) in artery tissues in diabetic mice. In cultured HUVECs, high glucose-induced cell viability reduction, ROS over-production, decrease of anti-oxidation, increase of apoptosis, and impairment of mitochondrial function were countered by acacetin (0.3-3 µM) in a concentration-dependent manner. Moreover, acacetin relies on Sirt1 activation by increasing NAMPT and NAD+ followed by Sirt3, pAMPK and PGC-1α activation. Silencing Sirt1 abolished acacetin-induced activation of Sirt3, pAMPK, and PGC-1α.ConclusionsThese results indicate that Sirt1-mediated activation of pAMPK/Sirt3 signals is involved in protective effects of acacetin against atherosclerosis in diabetes by preserving mitochondrial function via reducing mitochondrial apoptosis and ROS production and enhancing its biogenesis, which suggests that acacetin may be a drug candidate for reducing atherosclerotic cardiovascular disorder in patients with diabetes.

scholarly journals Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 291 ◽  
Author(s):  
Emma Martínez-Alonso ◽  
Alejandro Escobar-Peso ◽  
Maria I. Ayuso ◽  
Rafael Gonzalo-Gobernado ◽  
Mourad Chioua ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Death ◽  
Infarct Volume ◽  
Free Radical Scavengers ◽  
Neuroprotective Activity ◽  
Drug Candidate ◽  
Dependent Manner ◽  
Vessel Occlusion ◽  
Pharmacological Characterization

Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.

scholarly journals Effect of TAK-218, a novel neuroprotective drug candidate, in a rat four-vessel-occlusion model of transient forebrain ischemia.

1996 ◽  
Vol 71 ◽  
pp. 172
Author(s):  
Tadatoshi Hashimoto ◽  
Takahiro Nakayama ◽  
Shin-ichi Yoshikubo ◽  
Kohji Fukatsu ◽  
Naohisa Fukuda ◽  
...  
Keyword(s):  
Drug Candidate ◽  
Forebrain Ischemia ◽  
Vessel Occlusion ◽  
Transient Forebrain Ischemia ◽  
Occlusion Model

scholarly journals Current treatment of Acute Ischemic Stroke in Vojvodina

2017 ◽  
Vol 70 (11-12) ◽  
pp. 459-464 ◽  
Author(s):  
Zeljko Zivanovic ◽  
Aleksandra Lucic ◽  
Biljana Radovanovic ◽  
Svetlana Ruzicka-Kaloci ◽  
Mirjana Jovicevic ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Large Vessel ◽  
Therapeutic Modality ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Mortality And Morbidity

Intravenous Thrombolysis in Acute Ischemic Stroke. Acute ischemic stroke is a major cause of mortality and morbidity in the world. Intravenous thrombolysis with recombinant tissue plasminogen activator remains the standard treatment for acute ischemic stroke for any patient presenting within 4.5 hours from symptom onset. However, it is more effective and safe when treatment starts early. This therapy for acute ischemic stroke has been administered in Vojvodina since 2008. Various factors influence the outcome after intravenous thrombolysis. Timely recanalization and reperfusion is associated with better clinical outcomes. Mechanical Thrombectomy - a New Therapeutic Modality for the Treatment of Acute Ischemic Stroke. Nevertheless, the rate of recanalization and favorable outcomes for patients with acute ischemic stroke due to large vessel occlusion are low after intravenous thrombolysis. In such patients mechanical thrombectomy has demonstrated significantly higher rates of recanalization and improved outcomes compared with intravenous thrombolysis alone. This endovascular reperfusion therapy began to be implemented in Vojvodina in 2016. Conclusion. Intravenous thrombolysis continues to play a key role in the treatment of all acute ischemic stroke patients, but mechanical thrombectomy should be the ?gold standard? in the cases with large vessel occlusion.

scholarly journals Structure of the vasculitides observed in the Clinic of Rheumatology

2020 ◽  
Vol 28 (3) ◽  
pp. 7-24
Author(s):  
Tzvetelina Yoneva ◽  
Yana Zdravkova ◽  
Georgi Kotov ◽  
Rasho Rashkov ◽  
Ivan Sheytanov
Keyword(s):  
Connective Tissue ◽  
Lupus Erythematosus ◽  
Correct Diagnosis ◽  
Connective Tissue Diseases ◽  
Vascular Wall ◽  
Vascular Pathology ◽  
Vessel Occlusion ◽  
Tissue Ischemia ◽  
The One ◽  
Destructive Inflammation

Systemic vasculitides are a heterogenic group of disorders characterized by destructive inflammation and fibrinoid necrosis of the vascular wall, vessel occlusion and tissue ischemia. Vasculitides presenting with necrosis are included in neither of the contemporary classifications, even though this type of vascular pathology is the one with the most dramatic manifestations in rheumatology. There have been no analyses of the nosological association, clinical features and therapeutic management of the vasculitides with necrosis in the pertinent literature. The aim of the present study was to analyze vasculitides in the Bulgarian population in terms of their nosological association; to examine the portion that ANCA-associated vasculitides represent out of all vasculitic syndromes on the one hand, and to make an analysis of the vasculitides with necrosis according to their nosological association on the other. In the present study, we included 388 patients with vasculitis, 251 of whom were female and 137 male. We conducted a prospective and retrospective analysis which covered the patients with vasculitis who were admitted to the Clinic of Rheumatology over the period 2009-2018. ANCA-associated vasculitides were the most often diagnosed vasculitides in the Clinic of Rheumatology. Vasculitic manifestations over the course of connective tissue diseases (most often systemic lupus erythematosus and systemic sclerosis) were the second most common group. Life-threatening cases of vasculitis with necrosis were mainly the result of flares of different connective tissue diseases. The major necrotizing vasculitides (Wegener’s granulomatosis and microscopic polyangiitis) were responsible for 12.6% of the cases of vasculitis with necrosis. In order to establish the correct diagnosis and start the suitable treatment, it is of vital importance to recognize the different vasculitic syndromes and their wide differential diagnosis. Most of them respond well to the currently available therapeutic options, especially if the correct diagnosis has been established early.

An electron microscopic study of the intra-myocardial lesions in cases of acute myocardial infarction

1978 ◽  
Vol 36 (2) ◽  
pp. 484-485
Author(s):  
Masahiro Ono ◽  
Kaoru Aihara ◽  
Gompachi Yajima
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Vessels ◽  
Vascular Wall ◽  
Vascular Changes ◽  
Electron Microscopic ◽  
Main Trunk ◽  
Mechanical Destruction ◽  
Transmission Electron ◽  
Myocardial Lesions

The pathogenesis of the arteriosclerosis in the acute myocardial infarction is the matter of the extensive survey with the transmission electron microscopy in experimental and clinical materials. In the previous communication,the authors have clarified that the two types of the coronary vascular changes could exist. The first category is the case in which we had failed to observe no occlusive changes of the coronary vessels which eventually form the myocardial infarction. The next category is the case in which occlusive -thrombotic changes are observed in which the myocardial infarction will be taken placed as the final event. The authors incline to designate the former category as the non-occlusive-non thrombotic lesions. The most important findings in both cases are the “mechanical destruction of the vascular wall and imbibition of the serous component” which are most frequently observed at the proximal portion of the coronary main trunk.

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