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Cancer-Associated Thrombosis: Pathophysiology, Laboratory Assessment, and Current Guidelines.

Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Convent

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… Inflammatory cytokines interfere with hemostasis in various ways, as they can downregulate thrombomodulin production, inhibit the release of nitric oxide and prostacyclin by endothelial cells, and stimulate PAI-1 production [ 4 ]. …

Cell Therapy as a Way to Increase the Effectiveness of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a standard method for treating a number of pathologies, primarily blood diseases. Timely restoration of the immune system after HSCT is a critical factor associated with the development of complications such as relapses or secondary tumors and various infections, as well as the graft-versus-host reaction in allogeneic transplantation, which ultimately affects the survival of patients. Introduction into the recipient's body of immune system cells that are incapable of sensitization by recipient antigens during the period of immune reconstitution

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… Platelet and red blood cell transfusion support are positively correlated with plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and soluble thrombomodulin levels [ 18 ] and do not increase the risk of developing aGVHD. …

Septic Hyperinflammation-Is There a Role for Extracorporeal Blood Purification Techniques?

This manuscript investigates the role of extracorporeal blood purification techniques in managing septic hyperinflammation, a critical aspect of sepsis characterized by an uncontrolled immune response leading to multiorgan dysfunction. We provide an overview of sepsis, focusing on the dynamics of immune response, the involvement of neutrophils, and the role of the endothelium in the disease's progression. It evaluates the effectiveness of various blood purification methods, including high-cut-off membranes, high-volume hemofiltration, adsorption techniques, and albumin dialysis, in removing cy

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… For example, the expression of surface-bound thrombomodulin can be reduced, leading to an increase in tissue factor (TF) expression. This, in combination with leukocytic microparticles and monocytes that also carry TF, triggers the activation of the coagulation cascade [ 28 ]. …

Артериальный тромбоэмболизм

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The Saudi Consensus for the Management of Cancer-Associated Thromboembolism: A Modified Delphi-Based Study.

Background Cancer is a well-known risk factor of preventable thromboembolic disease. This study aims to provide guidance on the prevention and management of cancer-associated thrombosis (CT) that tailors prophylactic and therapeutic options for medical and surgical oncology patients presenting to health care settings in Saudi Arabia. Methods The present consensus was developed in concordance with the modified Delphi-based approach, which incorporates a face-to-face meeting between two voting rounds to gain experts' feedback on the proposed statements. All experts were either oncologists, hemat

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… Local vascular invasion and overexpression of interleukin-1, soluble E-selectin, soluble thrombomodulin, and von Willebrand factor cause abnormalities in blood vessels. 4 Tissue factor production, which increases thrombin generation, may be increased by tumor cells. …

Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.

Neuropathic pain causes plasticity in the nervous system, which is often associated with altered protein synthesis. Proteins are the key executors of cellular functions, and their alteration is closely related to the occurrence of neuropathic pain. Protein synthesis is a finely regulated process involving the interaction of multiple biomolecules. Among them, the eukaryotic translation initiation factors (eIFs) are a group of key regulatory proteins that control the initiation phase of protein translation and thus influence the rate and type of protein synthesis. Recent studies have shown that

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… Role of high-mobility group box 1 and its modulation by thrombomodulin/thrombin axis in neuropathic and inflammatory pain . Br J Pharmacol . ( 2021 ) 178 : 798 – 812 . doi: 10.1111/bph.15091 , PMID: 32374414 101. Yu X Liu H Hamel KA Morvan MG Yu S Leff J . …

Development of Targeted Alpha Particle Therapy for Solid Tumors.

Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prosta

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… These particles were prepared with functionalized surfaces that facilitated the attachment of 201B mAb, which targets murine thrombomodulin on lung epithelium. … Biodistribution and small animal single-photon emission computed tomography (SPECT) studies revealed the specific targeting of murine thrombomodulin within the lung epithelium that was reduced upon the administration of non-radioactive 201b mAb. …

Cancer-Associated Thrombosis in Patients Treated with Immune Checkpoint Inhibitors.

The incidence of cancer-associated thrombosis has increased in recent years. While the association between venous thromboembolism (VTE) and chemotherapy is well established, there is no clear link between immune checkpoint inhibitors (ICIs) and VTE risk. Many risk assessment models (RAMs) have been developed to identify high-risk patients who need prophylaxis. However, these models are validated in patients undergoing chemotherapy, while they are scarce in those receiving immunotherapy. Moreover, the mechanisms linking ICIs to thrombosis are still a matter of debate. They include the upregulat

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… The inflammatory microenvironment also results in a decrease in the production of anticoagulant and fibrinolytic molecules, including thrombomodulin and tissue plasminogen activator (tPA). …

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

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… Chemotherapy-induced endothelial damage reduces the expression and function of key anticoagulant molecules, such as thrombomodulin, protein C , and antithrombin, impairing normal control of thrombin generation. …

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Tra

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… The downregulation of thrombomodulin (TM) and endothelial protein C receptor expression is attributed to the conversion of protein C to APC under inflammatory conditions ( Levi and Poll, 2015 ). …

Program-Abstracts

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… -11/stromelysin-3 09:34 Corinne Bousquet, Toulouse, France Forced Hemidesmosome Assembly as a Novel Mechanism for Somatostatin Receptor sst2 Tumor Suppressive Activity in Pancreatic Cancer 09:46 Vincent Frontera , Marseille, France Anti-JAM-C Tumor Growth Inhibition Occurs through Modulation of Thrombomodulin …

Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

Комплексное исследование двустороннего взаимодействия между микробиомами человека и злокачественными заболеваниями крови и гематологическими условиями: акцент на новых терапевтических стратегиях.

Микробиота человека играет ключевую роль в поддержании хомостаза, регулируя иммунную реакцию, метаболизм и гематопоисис. Микробиальный дисбиоз все чаще ассоциируется с иммунной дисфункцией, воспалением и аномалиями костного мозга, которые могут привести к гематологическим заболеваниям. В настоящем обзоре резюмируются текущие данные о роли микробиота в нормальном гематопоисе и ее потенциальной причастности к доброкачественным и злокачественным гематологическим расстройствам.МЕТОДЫ: Обзор описательной литературы был проведен на основе всестороннего поиска основных научных баз данных без временны

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… NETs also precipitate serine proteases—which in turn inactivate important anticoagulants such as TFPI and thrombomodulin; as a result, excessive coagulation occurs. …

Hematology

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… binding Platelet aggregation (unstable) by vWF and fibrinogen binding to the activated GPIIb/IIIa complex Platelet fibrin clot formation—fibrin–fibrin crosslinked by factor XIII and platelet–fibrin via GPIIb/IIIa Anticoagulation Pathways Antithrombin binds to thrombin and inhibits it Thrombin binds to thrombomodulin …

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and conseq

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… It also exerts antithrombotic effects by increasing thrombomodulin (TM) expression and downregulating tissue factor (TF) expression [ 92 ]. …

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) ne

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… Int J Cancer ( 2020 ) 146 : 2810–21 . 10.1002/ijc.32652 31465111 42 Tsubota M Fukuda R Hayashi Y Miyazaki T Ueda S Yamashita R Role of non-macrophage cell-derived HMGB1 in oxaliplatin-induced peripheral neuropathy and its prevention by the thrombin/thrombomodulin system in rodents: negative impact of …

Biocompatibility in hemodialysis: artificial membrane and human blood interactions.

Hemodialysis, a cornerstone therapy for chronic kidney disease, represented a crucial advance in the evolution of artificial organs. While its success is largely due to its efficiency in removing uremic toxins, an equally important challenge is to uphold the primum non nocere principle by minimizing the harmful effects of membrane-blood interactions. This review examines the complex mechanisms and key interactions underlying membrane biocompatibility, including complement activation, inflammation, and coagulation disturbances, paving the way for their clinical implications. We also summarize r

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… Primary hemostasis Adsorbed proteins promote platelet adhesion by binding to glycoprotein IIb/IIIa receptors, followed by platelet activation with morphological changes and pseudopod generation, release of phosphatidylserine and choline via the flip-flop mechanism, secretion of granular content (β-thrombomodulin …

Hematology

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… binding Platelet aggregation (unstable) by vWF and fibrinogen binding to the activated GPIIb/IIIa complex Platelet fibrin clot formation—fibrin–fibrin crosslinked by factor XIII and platelet–fibrin via GPIIb/IIIa ANTICOAGULATION PATHWAYS Antithrombin binds to thrombin and inhibits it Thrombin binds to thrombomodulin …

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbio

Abstract

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