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https://www.readbyqxmd.com/read/28962123/whole-genome-gene-expression-changes-and-hematological-effects-of-rikkunshito-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-chemotherapy
#1
Yung-Che Chen, An-Shen Lin, Yu-Chiang Hung, Kuang-Den Chen, Ching-Yuan Wu, Chien-Hao Lie, Chang-Chun Hsiao, Chung-Jen Chen, Shih-Feng Liu, Wen-Feng Fang, Jen-Chieh Chang, Ting-Ya Wang, Yi-Hsi Wang, Yu-Hsiu Chung, Tung-Ying Chao, Sum-Yee Leung, Mao-Chang Su, Meng-Chih Lin
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28954929/neutrophil-macroaggregates-promote-widespread-pulmonary-thrombosis-after-gut-ischemia
#2
Yuping Yuan, Imala Alwis, Mike C L Wu, Zane Kaplan, Katrina Ashworth, David Bark, Alan Pham, James Mcfadyen, Simone M Schoenwaelder, Emma C Josefsson, Benjamin T Kile, Shaun P Jackson
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation in distant organs. The mechanisms linking hemodynamic changes in the gut to remote organ thrombosis remain ill-defined. We demonstrate that gut ischemia in the mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These neutrophil aggregates lead to widespread occlusion of pulmonary arteries, veins, and the microvasculature. A similar pulmonary neutrophil-rich thrombotic response occurred in humans with the acute respiratory distress syndrome...
September 27, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28951241/protection-from-psoriasis-related-thrombosis-following-inhibition-of-il-23-or-il-17a
#3
Yumeng Li, Jackelyn B Golden, Maya I Camhi, Xiufen Zhang, Yi Fritz, Doina Diaconu, Tammy L Ivanco, Daniel I Simon, Kristine Kikly, Thomas S McCormick, Yunmei Wang, Nicole L Ward
Psoriasis patients experience chronic systemic skin inflammation and develop cardiovascular comorbidities that shorten their lifespan. Whether cardiovascular disease is improved by treatment with current biologics that target disease-specific pathways is unclear. KC-Tie2 mice develop psoriasiform skin inflammation with increases in IL-23 and IL-17A and proinflammatory monocytosis and neutrophilia that precedes development of carotid artery thrombus formation. To examine whether targeted blockade of IL-23 or IL-17A in KC-Tie2 psoriasis mice improves cardiovascular outcomes, mice were treated systemically for 6 weeks with antibodies targeting IL-17A, IL-17RA, IL-12/23p40, or IL-23p19...
September 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28950949/g-protein-coupled-kinin-receptors-and-immunity-against-pathogens
#4
Julio Scharfstein, Pablo I P Ramos, Manoel Barral-Netto
For decades, immunologists have considered the complement system as a paradigm of a proteolytic cascade that, acting cooperatively with the immune system, enhances host defense against infectious organisms. In recent years, advances made in thrombosis research disclosed a functional link between activated neutrophils, monocytes, and platelet-driven thrombogenesis. Forging a physical barrier, the fibrin scaffolds generated by synergism between the extrinsic and intrinsic (contact) pathways of coagulation entrap microbes within microvessels, limiting the systemic spread of infection while enhancing the clearance of pathogens by activated leukocytes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28931754/activated-signature-of-antiphospholipid-syndrome-neutrophils-reveals-potential-therapeutic-target
#5
Jason S Knight, He Meng, Patrick Coit, Srilakshmi Yalavarthi, Gautam Sule, Alex A Gandhi, Robert C Grenn, Levi F Mazza, Ramadan A Ali, Paul Renauer, Jonathan D Wren, Paula L Bockenstedt, Hui Wang, Daniel T Eitzman, Amr H Sawalha
Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils - neutrophil extracellular traps (NETs), in particular - in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28917273/mechanisms-and-risk-factors-of-thrombosis-in-cancer
#6
REVIEW
Anna Falanga, Laura Russo, Viola Milesi, Alfonso Vignoli
The close relationship between cancer and thrombosis is known since more than a century. Venous thromboembolism (VTE) may be the first manifestation of an occult malignancy in an otherwise healthy individual. Cancer patients commonly present with abnormalities of laboratory coagulation tests, indicating an ongoing subclinical hypercoagulable condition. The results of laboratory tests demonstrate that a process of fibrin formation and removal parallels the development of malignancy, which is of particular interest since fibrin and other clotting products are important for both thrombogenesis and tumor progression...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28870575/usefulness-of-platelet-to-lymphocyte-and-neutrophil-to-lymphocyte-ratios-in-predicting-the-presence-of-cerebral-venous-sinus-thrombosis-and-in-hospital-major-adverse-cerebral-events
#7
Yesim Eylev Akboga, Hesna Bektas, Omer Anlar
BACKGROUND: Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) as recently emerging thrombo-inflammatory indicators were significantly associated with both major cerebrovascular/cardiovascular adverse events (MACE) and mortality. Therefore, we aimed to assess the effects of combinations of PLR and NLR in predicting the presence of CVST and in-hospital MACE. METHODS: A total of 277 participants comprising 80 patients with evidence of CVST and 197 controls with similar baseline characteristics were included in this retrospective study...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28837206/neutrophil-extracellular-traps-are-increased-in-patients-with-acute-ischemic-stroke-prognostic-significance
#8
Juana Vallés, Aída Lago, María Teresa Santos, Ana María Latorre, José I Tembl, Juan B Salom, Candela Nieves, Antonio Moscardó
Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes...
October 5, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28837205/triggering-receptor-expressed-on-myeloid-cells-1-a-new-player-in-platelet-aggregation
#9
Lucie Jolly, Jeremie Lemarie, Kevin Carrasco, Batric Popovic, Marc Derive, Amir Boufenzer, Sebastien Gibot
Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an immunoreceptor initially known to be expressed on neutrophils and monocytes/macrophages. TREM-1 acts as an amplifier of the inflammatory response during both infectious and aseptic inflammatory diseases. Another member of the TREM family, The Triggering receptor expressed on myeloid cells Like Transcript-1 (TLT-1) is exclusively expressed in platelets and promotes platelet aggregation. As the gene that encodes for TLT-1 is located in the TREM-1 gene cluster, this prompted us to investigate the expression of TREM-1 on platelets...
August 30, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28833583/cell-free-dna-and-dnase-activity-in-dogs-with-immune-mediated-hemolytic-anemia
#10
U Jeffery, L Ruterbories, R Hanel, D N LeVine
BACKGROUND: Immune-mediated hemolytic anemia (IMHA) in dogs has a high risk of thrombosis and is associated with marked neutrophilia and necrosis. Cell death and release of neutrophil extracellular traps contribute to increased serum concentrations of cell-free DNA, and in human autoimmune disease reduced DNase activity further increases cell-free DNA. Free DNA in blood has prothrombotic properties and could contribute to hypercoagulability in IMHA. HYPOTHESIS: Cell-free DNA is elevated and DNase activity reduced in dogs with IMHA compared to healthy dogs...
September 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28807983/cancer-associated-pathways-and-biomarkers-of-venous-thrombosis
#11
Yohei Hisada, Nigel Mackman
Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we will summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets and tissue factor-positive (TF+) microvesicles are all potential factors that alone or in combination increase cancer-associated thrombosis. Lung and colorectal cancer patients often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28795678/-neutrophil-extracellular-traps-and-coagulation-dysfunction-in-sepsis
#12
Fangxiao Zhang, Zhidan Zhang, Xiaochun Ma
Neutrophil extracellular traps (NETs) are net-like structure composed of DNA and nuclear proteins, which are produced by activated neutrophils under the circumstances of a variety of pathogens or drugs. As part of defensive mechanism, NETs have been proved to restrict the spread of pathogens and release of antimicrobial molecules. NETs can not only strengthen the adhesion between neutrophils and platelets, promote platelet mediated procoagulant reaction, but also lead to endothelial cell damage and coagulopathy in sepsis...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28775074/stasis-promotes-erythrocyte-adhesion-to-von-willebrand-factor
#13
Michel W J Smeets, Marjon J Mourik, Hans W M Niessen, Peter L Hordijk
OBJECTIVE: Venous thromboembolism is a major contributor to global disease burden. Leukocytes and platelets initiate thrombogenesis on blood stasis and initiate the formation of a fibrin, VWF (von Willebrand factor), and neutrophil extracellular trap scaffold for erythrocytes. However, there is little knowledge on how erythrocytes become stably incorporated into this scaffold. Recently, we described the adhesion of calcium-loaded erythrocytes to endothelial-derived VWF strings. Because VWF is part of the scaffold of venous thrombi, we questioned whether reduced flow or stasis promotes the adhesion of normal erythrocytes to VWF and whether venous thrombi show evidence of erythrocyte-VWF interactions...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28760115/a-model-of-acute-antibody-mediated-renal-allograft-rejection-in-the-sensitized-rata
#14
Sharmila Ramessur Chandran, William R Mulley, John Kanellis, David J Nikolic-Paterson, Frank Y Ma
OBJECTIVES: Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. MATERIALS AND METHODS: We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1av1 and Lewis RT1l), which develop aggressive rejection...
July 31, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28743887/tumor-derived-exosomes-induce-the-formation-of-neutrophil-extracellular-traps-implications-for-the-establishment-of-cancer-associated-thrombosis
#15
Ana C Leal, Daniella M Mizurini, Tainá Gomes, Natalia C Rochael, Elvira M Saraiva, Marcos S Dias, Claudio C Werneck, Micheli S Sielski, Cristina P Vicente, Robson Q Monteiro
Cancer patients are at an increased risk of developing thromboembolic complications. Several mechanisms have been proposed to explain cancer-associated thrombosis including the release of tumor-derived extracellular vesicles and the activation of host vascular cells. It was proposed that neutrophil extracellular traps (NETs) contribute to the prothrombotic phenotype in cancer. In this study, we evaluated the possible cooperation between tumor-derived exosomes and NETs in cancer-associated thrombosis. Female BALB/c mice were orthotopically injected with 4T1 breast cancer cells...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28741500/immunity-gone-astray-nets-in-cancer
#16
Jessica Cedervall, Anna-Karin Olsson
Neutrophil extracellular traps (NETs) have emerged as significant contributors to cancer-associated pathologies such as metastasis, thrombosis, and organ dysfunction in preclinical models. We review recent discoveries of the involvement of NETs in human cancers and suggest tumor-induced NET formation as an interesting potential therapeutic target in oncology.
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28730407/venous-thromboembolism-thrombosis-inflammation-and-immunothrombosis-for-clinicians
#17
REVIEW
Eduardo Vazquez-Garza, Carlos Jerjes-Sanchez, Aline Navarrete, Jorge Joya-Harrison, David Rodriguez
Venous thromboembolism (VTE) is a worldwide disease related with mortality, cardiovascular disability, impaired quality of life and, cause major long-term complications. Clinicians related to the acute and long-term patients care must be involved in the molecular mechanisms of thrombosis. The vessel wall and its inner lining of the endothelium are critical to the maintenance of a patent vasculature. After endothelial disruption, collagen (first line of endothelial defense) and intravascular tissue factor (second line of endothelial defense) are exposed to blood flow, starting the formation of a thrombus...
July 20, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28727215/neutrophil-extracellular-traps-coincide-with-a-pro-coagulant-status-of-microcirculatory-endothelium-in-burn-wounds
#18
H Ibrahim Korkmaz, Magda M W Ulrich, Sanne Vogels, Tim de Wit, Paul P M van Zuijlen, Paul A J Krijnen, Hans W M Niessen
Burn-induced tissue loss is partly related to secondary expansion of necrosis into vital dermis neighboring the initial burn injury. An important factor herein is the severe loss of perfusion of the burn wound, probably caused by microvascular damage induced by the intense local inflammatory responses as well as burn-induced hypercoagulation. We hypothesize that the formation of neutrophilic extracellular traps (NETs) play an important role in this. The purpose of this study was to investigate postburn intravascular thrombosis, NETs formation and the coagulant state in the microvasculature of burns in both animal models and patients...
July 20, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28687627/phase-ii-trial-of-sorafenib-in-combination-with-capecitabine-in-patients-with-hepatocellular-carcinoma-inst-08-20
#19
Yehuda Patt, Cristhiam Rojas-Hernandez, Houman Mohammad Fekrazad, Pranshu Bansal, Fa Chyi Lee
LESSONS LEARNED: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn...
October 2017: Oncologist
https://www.readbyqxmd.com/read/28684614/ubiquinol-effects-on-antiphospholipid-syndrome-prothrombotic-profile-a-randomized-placebo-controlled-trial
#20
RANDOMIZED CONTROLLED TRIAL
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Ábalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio González-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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