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https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#1
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27876232/hypercoagulation-and-complement-connected-players-in-tumor-development-and-metastases
#2
REVIEW
Silvia Guglietta, Maria Rescigno
Hypercoagulation is a common feature of several tumors to the extent that individuals with coagulation defects often present with occult visceral cancers. Recent evidence has shown that hypercoagulation is not just a mere secondary effect due to the presence of the tumor, rather it actively contributes to tumor development and dissemination. Among the numerous mechanisms that can contribute to cancer-associated hypercoagulation, the ones involving immune-mediated processes are gaining increasing attention. In particular, complement cascade and hypercoagulation are one inducing the other in a vicious circle that involves neutrophil extracellular traps (NETs) formation...
November 18, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27824278/modulation-of-porcine-intestinal-epitheliocytes-immunetranscriptome-response-by-lactobacillus-jensenii-tl2937
#3
H Kobayashi, L Albarracin, N Sato, P Kanmani, A K M H Kober, W Ikeda-Ohtsubo, Y Suda, T Nochi, H Aso, S Makino, H Kano, S Ohkawara, T Saito, J Villena, H Kitazawa
In order to evaluate probiotic strains applicable for the beneficial immunomodulation of the porcine gut (immunobiotics), we previously developed a porcine intestinal epitheliocyte cell line (PIE cells). Here, transcriptomic studies using PIE cells were performed considering that this information would be valuable for understanding the mechanisms involved in the protective activity of the immunobiotic strain Lactobacillus jensenii TL2937 against intestinal inflammatory damage in pigs. In addition, those studies would provide criteria for selecting biomarkers for the screening of new immunobiotic strains...
November 8, 2016: Beneficial Microbes
https://www.readbyqxmd.com/read/27824218/coagulopathy-in-sepsis-a-new-look-at-an-old-problem
#4
Małgorzata Lipinska-Gediga
Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis...
November 8, 2016: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/27782319/dangerous-liaisons-complement-coagulation-and-kallikrein-kinin-cross-talk-act-as-a-linchpin-in-the-events-leading-to-thromboinflammation
#5
REVIEW
Kristina N Ekdahl, Yuji Teramura, Osama A Hamad, Sana Asif, Claudia Duehrkop, Karin Fromell, Elisabet Gustafson, Jaan Hong, Huda Kozarcanin, Peetra U Magnusson, Markus Huber-Lang, Peter Garred, Bo Nilsson
Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27766055/platelets-and-platelet-adhesion-molecules-novel-mechanisms-of-thrombosis-and-anti-thrombotic-therapies
#6
Xiaohong Ruby Xu, Naadiya Carrim, Miguel Antonio Dias Neves, Thomas McKeown, Tyler W Stratton, Rodrigo Matos Pinto Coelho, Xi Lei, Pingguo Chen, Jianhua Xu, Xiangrong Dai, Benjamin Xiaoyi Li, Heyu Ni
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27758696/immune-inflammatory-activation-in-acute-coronary-syndromes-a-look-into-the-heart-of-unstable-coronary-plaque
#7
Giovanni Cimmino, Francesco S Loffredo, Alberto Morello, Saverio D Elia, Raffaele De Palma, Plinio Cirillo, Paolo Golino
In the last twenty years, our comprehension of the molecular mechanisms involved in formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration...
October 13, 2016: Current Cardiology Reviews
https://www.readbyqxmd.com/read/27637304/postorthopedic-surgery-joint-replacement-surgery-venous-thromboembolism-prophylaxis
#8
REVIEW
Louis M Kwong, Jon A Kimball
Elective total hip or knee arthroplasty places patients at risk for venous thromboembolism (VTE). As our understanding of the pathophysiology of VTE after joint arthroplasty has increased, pharmacologic strategies have been developed to target different aspects of the coagulation cascade. Various approaches have been used as risk reduction strategies. In 2011 and 2014 the Food and Drug Administration approved rivaroxaban and apixaban as new oral antithrombotic agents. Although controversies remain with regard to the ideal VTE pharmacoprophylactic agent, this class of novel oral anticoagulants has been demonstrated to be safe and to be more effective than enoxaparin...
October 2016: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27574188/disulfide-hmgb1-derived-from-platelets-coordinates-venous-thrombosis-in-mice
#9
Konstantin Stark, Vanessa Philippi, Sven Stockhausen, Johanna Busse, Antonella Antonelli, Meike Miller, Irene Schubert, Parandis Hoseinpour, Sue Chandraratne, Marie-Luise von Brühl, Florian Gärtner, Michael Lorenz, Alessandra Agresti, Raffaele Coletti, Daniel J Antoine, Ralf Heermann, Kirsten Jung, Sven Reese, Iina Laitinen, Markus Schwaiger, Axel Walch, Markus Sperandio, Peter P Nawroth, Christoph Reinhardt, Sven Jäckel, Marco E Bianchi, Steffen Massberg
Deep venous thrombosis (DVT) is one of the most common cardiovascular diseases, but its pathophysiology remains incompletely understood. While sterile inflammation has recently been shown to boost coagulation during DVT, the underlying molecular mechanisms are not fully resolved, which could potentially identify new anti-inflammatory approaches to prophylaxis and therapy of DVT. Using a mouse model of venous thrombosis induced by flow reduction in the vena cava inferior we identified blood-derived high-mobility group box 1 protein (HMGB1) - a prototypical mediator of sterile inflammation - to be a master regulator of the prothrombotic cascade involving platelets and myeloid leukocytes fostering occlusive DVT formation...
August 29, 2016: Blood
https://www.readbyqxmd.com/read/27566655/meningiomas-and-proteomics-focus-on-new-potential-biomarkers-and-molecular-pathways
#10
Rosaria Viola Abbritti, Francesca Polito, Maria Cucinotta, Claudio Lo Giudice, Maria Caffo, Chiara Tomasello, Antonino Germanò, Mohammed Aguennouz
Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein...
September 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27513209/inhibition-of-coagulation-proteases-xa-and-iia-decreases-ischemia-reperfusion-injuries-in-a-preclinical-renal-transplantation-model
#11
Solenne Tillet, Sébastien Giraud, Thomas Kerforne, Thibaut Saint-Yves, Sandrine Joffrion, Jean-Michel Goujon, Jerôme Cau, Gérard Mauco, Maurice Petitou, Thierry Hauet
Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation...
July 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27497655/analytical-comparison-of-a-us-generic-enoxaparin-with-the-originator-product-the-focus-on-comparative-assessment-of-antithrombin-binding-components
#12
Pierre A J Mourier, Fréderic Herman, Philippe Sizun, Christian Viskov
Enoxaparin sodium, a low-molecular-weight heparin (LMWH) prepared from porcine intestinal heparin, is widely used for the prevention and treatment of venous thromboembolism. The antithrombotic activity of heparin is mediated mainly through its activation of antithrombin (AT) and subsequent inhibition of coagulation factors. Heparin is a complex heteropolymer and the sulfation pattern of its alternating uronic acid and glucosamine sugar units is a major factor influencing its biological activity. The manufacturing process itself is associated with the introduction of exogenous microheterogeneities that may further affect its biological efficacy...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27470592/inhibitory-serpins-new-insights-into-their-folding-polymerization-regulation-and-clearance
#13
REVIEW
Peter G W Gettins, Steven T Olson
Serpins are a widely distributed family of high molecular mass protein proteinase inhibitors that can inhibit both serine and cysteine proteinases by a remarkable mechanism-based kinetic trapping of an acyl or thioacyl enzyme intermediate that involves massive conformational transformation. The trapping is based on distortion of the proteinase in the complex, with energy derived from the unique metastability of the active serpin. Serpins are the favoured inhibitors for regulation of proteinases in complex proteolytic cascades, such as are involved in blood coagulation, fibrinolysis and complement activation, by virtue of the ability to modulate their specificity and reactivity...
August 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27456888/the-effects-of-thrombomodulin-and-activated-protein-c-on-the-pathogenesis-of-multiple-sclerosis
#14
Ece Balkuv, Asuman Orhan Varoglu, Nihal Isik, Banu Isbilen, Saadettin Duruyen, Recep Basaran, Abdulkadir Kocer
BACKGROUND: Various molecules of the coagulation cascade are thought to have varying roles in the pathophysiology of multiple sclerosis (MS). We aimed to find new information about the effects of the coagulation cascade molecules to develop new therapeutic strategies for MS. MATERIALS AND METHODS: Patients with MS were chosen from among patients who were followed up at our hospital. We examined the thrombomodulin (TM) and activated protein C (APC) serum levels in patients with MS and the healthy controls...
July 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27372899/role-of-heparin-and-non-heparin-binding-serpins-in-coagulation-and-angiogenesis-a-complex-interplay
#15
REVIEW
Teena Bhakuni, Mohammad Farhan Ali, Irshad Ahmad, Shadabi Bano, Shoyab Ansari, Mohamad Aman Jairajpuri
Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression...
August 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27354721/the-role-of-leukocytes-in-thrombosis
#16
REVIEW
Laura L Swystun, Patricia C Liaw
In recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage-associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways...
August 11, 2016: Blood
https://www.readbyqxmd.com/read/27321583/plasma-based-proteomics-reveals-immune-response-complement-and-coagulation-cascades-pathway-shifts-in-heat-stressed-lactating-dairy-cows
#17
Li Min, Jianbo Cheng, Shengguo Zhao, He Tian, Yangdong Zhang, Songli Li, Hongjian Yang, Nan Zheng, Jiaqi Wang
UNLABELLED: Heat stress (HS) has an enormous economic impact on the dairy industry. In recent years, many researchers have investigated changes in the gene expression and metabolomics profiles in dairy cows caused by HS. However, the proteomics profiles of heat-stressed dairy cows have not yet been completely elucidated. We compared plasma proteomics from HS-free and heat-stressed dairy cows using an iTRAQ labeling approach. After the depletion of high abundant proteins in the plasma, 1472 proteins were identified...
September 2, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27282765/platelets-are-versatile-cells-new-discoveries-in-hemostasis-thrombosis-immune-responses-tumor-metastasis-and-beyond
#18
Xiaohong Ruby Xu, Dan Zhang, Brigitta Elaine Oswald, Naadiya Carrim, Xiaozhong Wang, Yan Hou, Qing Zhang, Christopher Lavalle, Thomas McKeown, Alexandra H Marshall, Heyu Ni
Platelets are small anucleate blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. At the site of vascular injury, platelet adhesion, activation and aggregation constitute the first wave of hemostasis. Blood coagulation, which is initiated by the intrinsic or extrinsic coagulation cascades, is the second wave of hemostasis. Activated platelets can also provide negatively-charged surfaces that harbor coagulation factors and markedly potentiate cell-based thrombin generation...
December 2016: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/27203170/-vascular-calcifications-the-hidden-side-effects-of-vitamin-k-antagonists
#19
Youssef Bennis, Subashini Vengadessane, Sandra Bodeau, Valérie Gras, Giampiero Bricca, Saïd Kamel, Sophie Liabeuf
Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA...
September 2016: Thérapie
https://www.readbyqxmd.com/read/27192799/-anti-thrombotic-properties-of-high-density-lipoprotein
#20
REVIEW
Makoto Kurano
Along with the established evidence on the association between a low HDL cholesterol level and arterial thrombosis, several limited studies have suggested that low HDL cholesterol is also a risk factor for venous thrombosis, such as deep vein thrombosis and pulmonary embolism. As well as emerging evidence from clinical studies, basic research has proposed the interaction between HDL and key molecules in the field of thrombosis and hemostasis; HDL interacts with megakaryocytes to affect the production of platelets, suppresses the aggregation of platelets, protects against the injury of endothelial cells, and inhibits coagulation and fibrinolysis cascades...
January 2016: Rinsho Byori. the Japanese Journal of Clinical Pathology
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