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Jingjing Song, Da Ma, Xiangqi Liu, Yichen Chen, Juan Fang, Vivian Wai Yan Lui, Sijia Zhao, Juan Xia, Bin Cheng, Zhi Wang
Thrombomodulin (TM, also known as CD141), which functions as an anticoagulant, is widely expressed on cell surface of a variety of cell types, including human blood cells as well as certain immune cells. To determine whether TM could be a potential marker for OSCC diagnosis as well as a molecular target for OSCC therapy, we examined the expression of TM in an oral cancer tissue microarray with 153 oral cancer tissues. Further, we also analyzed the expression of TM on DCs of 36 OSCC patients and 36 healthy donors...
March 18, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Katrine Munk Begtrup, Johanne Andersen Hojbjerg, Birgitte Vrou Offersen, Anne-Mette Hvas
Cancer is associated with increased risk of venous thromboembolic disease. Venous thromboembolic disease accounts for a substantial addition to morbidity and mortality rates in cancer patients and is the second leading cause of death in cancer patients, exceeded only by the underlying cancer. Only few previous studies have investigated the influence of radiotherapy on hemostasis and whether radiotherapy in itself causes an increased risk of venous thromboembolic disease. The aim was to investigate if adjuvant radiotherapy affects hemostasis after surgery and chemotherapy in patients with breast cancer...
March 19, 2018: Platelets
Susumu Sakamoto, Hiroshige Shimizu, Takuma Isshiki, Keishi Sugino, Atsuko Kurosaki, Sakae Homma
BACKGROUND AND OBJECTIVES: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often-fatal condition associated with endothelial damage and abnormalities of the coagulation system. Recombinant human soluble thrombomodulin (rhTM) has anti-inflammatory effects and regulates the coagulation pathway. This study evaluated the effectiveness of rhTM for the treatment of AE-IPF. METHODS: This historically controlled study included 80 patients with AE-IPF admitted to our center during the period from 2006 through 2016...
March 2018: Respiratory Investigation
Kang An, Hang Yin, Ju Mei, Jiaquan Zhu, Min Tang
OBJECTIVES: We retrospectively analysed data from non-valvular atrial fibrillation (AF) patients who underwent minimally invasive surgical AF ablation at our centre. Our purpose was to explore the atrial endocardial expression of von Willebrand factor (vWF) and thrombomodulin (TM) and their association with rhythm results after the procedure. METHODS: From January 2014 to May 2015, 60 patients underwent minimally invasive surgical AF ablation at our centre. Left atrial appendage samples were obtained during the procedure and immunohistochemistry for endocardial markers including vWF and TM was performed and semi-quantitatively graded...
March 14, 2018: Interactive Cardiovascular and Thoracic Surgery
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
Jonathan V Martin, David M Liberati, Lawrence N Diebel
BACKGROUND: Hypernatremia is a common problem affecting critically ill patients, whether due to underlying pathology or the subsequent result of hypertonic fluid resuscitation. Numerous studies have been published suggesting that hypernatremia may adversely affect the vascular endothelial glycocalyx. Our study aimed to evaluate if high sodium concentration would impair the endothelial and glycocalyx barrier function and if stress conditions that simulate the shock microenvironment would exacerbate any observed adverse effects of hypernatremia...
March 12, 2018: Journal of Trauma and Acute Care Surgery
Kota Ouchi, Shin Takahashi, Sonoko Chikamatsu, Shukuei Ito, Yoshikazu Takahashi, Sadayuki Kawai, Akira Okita, Yuki Kasahara, Yoshinari Okada, Hiroo Imai, Keigo Komine, Ken Saijo, Masahiro Takahashi, Hidekazu Shirota, Masanobu Takahashi, Makio Gamoh, Chikashi Ishioka
BACKGROUND: Recombinant human soluble thrombomodulin (rTM) has been established and introduced in the clinic as a standard treatment for disseminated intravascular coagulation (DIC). However, the efficacy and safety of rTM for DIC associated with solid tumors (DIC-STs) have not been fully established. Here, we performed a retrospective analysis of the clinical outcomes of rTM for DIC-STs and considered a treatment strategy with rTM for DIC-STs. METHODS: Patients with DIC-STs between November 2009 and March 2016 in 2 cancer core hospitals were retrospectively analyzed...
March 7, 2018: International Journal of Clinical Oncology
Akiyuki Uzawa, Masahiro Mori, Hiroki Masuda, Ryohei Ohtani, Tomohiko Uchida, Satoshi Kuwabara
Recombinant thrombomodulin (rTM) has pleiotropic properties including anti-coagulation and anti-inflammation; however, its effectiveness as a treatment for multiple sclerosis (MS) has not been fully evaluated. High mobility group box 1 (HMGB1) and pro-inflammatory cytokines, working as an inflammatory mediator, are reportedly involved in the inflammatory pathogenesis of MS. The aim of this study was to determine whether rTM can be a potential therapeutic agent for experimental autoimmune encephalomyelitis (EAE)...
March 6, 2018: Clinical and Experimental Immunology
Yutaka Umemura, Kazuma Yamakawa, Mineji Hayakawa, Daisuke Kudo, Satoshi Fujimi
BACKGROUND: Antithrombin and recombinant human thrombomodulin (rhTM) are individually reported to improve survival in sepsis-induced disseminated intravascular coagulation (DIC). However, continuing controversy exists as to which agent is superior and whether concomitant therapy is superior to individual administration. METHODS: This post hoc analysis included adult patients with sepsis-induced DIC from a nationwide multicenter registry database in Japan. We categorized patients into 4 groups: patients who received (1) individual administration of antithrombin, (2) individual administration of rhTM, (3) both, and (4) neither...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
Hossam Taha Mohamed, Noura El-Husseiny, Eslam A El-Ghonaimy, Sherif Abdelaziz Ibrahim, Zainab A Bazzi, Dora Cavallo-Medved, Michael B Boffa, Mohamed El-Shinawi, Mona Mostafa Mohamed
Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM), encoded by THBD, is important for TAFI activation. CPB2 gene expression is influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10). Our previous results showed that tumor infiltrating monocytes/macrophages (CD14+ /CD16+ ) isolated from inflammatory breast cancer (IBC) patients' secrete high levels of IL-10...
January 10, 2018: Current Problems in Cancer
Vincent Chunpeng Pai, I-Chung Lo, Yan Wun Huang, I-Ching Tsai, Hui-Pin Cheng, Guey-Yueh Shi, Hua-Lin Wu, Meei Jyh Jiang
BACKGROUND: Thrombomodulin (TM), a transmembrane glycoprotein highly expressed in endothelial cells (ECs), is a potent anticoagulant maintaining circulation homeostasis. Under inflammatory states, TM expression is drastically reduced in ECs while vascular smooth muscle cells (VSMCs) show a robust expression of TM. The functional role of TM in VSMCs remains elusive. METHODS: We examined the role of TM in VSMCs activities in human aortic VSMCs stimulated with platelet-derived growth factor-BB (PDGF-BB)...
February 13, 2018: Journal of Biomedical Science
Martin Frydland, Sisse Rye Ostrowski, Jacob Eifer Møller, Edina Hadziselimovic, Lene Holmvang, Hanne Berg Ravn, Lisette Okkels Jensen, Anna Sina Pettersson, Jesper Kjaergaard, Matias Greve Lindholm, Pär Ingemar Johansson, Christian Hassager
BACKGROUND: Mortality in ST-elevation myocardial infarction (STEMI)-patients developing cardiogenic shock (CS) during hospitalization is high. Catecholamines, ischemia, and inflammation (parameters present in CS) affect the endothelium. We hypothesized that plasma level of biomarkers reflecting endothelial damage would be associated with CS and mortality. METHODS: In 96% of 1467 consecutive patients with suspected STEMI, biomarkers reflecting endothelial cell- (soluble thrombomodulin, sTM) and glycocalyx- (syndecan-1) damage were measured on admission...
February 12, 2018: Shock
Mitsutake Yano, Yuji Ikeda, Tomomi Kato, Mika Sakaki, Sho Sato, Akira Yabuno, Eito Kozawa, Masanori Yasuda
The present study presents a case of peritoneal malignant mesothelioma (PMM) following radiation therapy for cervical cancer. A 34-year-old Japanese woman, without asbestos exposure, was referred to the Department of Gynecologic Oncology, Saitama Medical University International Medical Center due to a cervical mass, and was diagnosed with cervical squamous cell carcinoma (SCC). The serum levels of tumor markers, including SCC antigen and cancer antigen 125 (CA125) were 229.0 ng/ml and 54.4 U/ml, respectively...
February 2018: Molecular and Clinical Oncology
Oliver Königsbrügge, Günter Weigel, Peter Quehenberger, Ingrid Pabinger, Cihan Ay
The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42)...
February 7, 2018: Clinical and Experimental Medicine
Satoshi Kaito, Sakiko Harada, Masao Tsukada, Akira Kojima, Kanichi Iwama, Kazunari Yamada, Kouichi Kajiwara, Kentaro Morikawa, Keiki Shimizu, Yasuji Kozai, Hideki Koudo
A 35-year-old man who previously underwent splenectomy for hereditary spherocytosis at age 29 visited our hospital complaining of fatigue that had started 7 days ago and right upper abdominal pain. Laboratory data showed increased white blood cell and eosinophil count accompanied by severe transaminitis and clotting abnormalities. Computed tomography scan showed multiple embolisms in the portal vein, superior mesenteric vein, right pulmonary artery, and inferior vena cava. Severe liver damage presumably caused by portal vein thrombosis was also observed...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Salvatore F Priore, Lauren E Schwartz, Jonathan I Epstein
Osteoclast-rich undifferentiated carcinoma of the urinary tract (ORUCUT) is a rare tumor composed of ovoid to spindle-shaped mononuclear cells with intermixed or focally clustered osteoclast-like giant cells. Previous studies have demonstrated that the mononuclear cells are neoplastic cells, while the giant cells are reactive cells of histiocytic lineage. The association between these tumors and classic urothelial carcinomas suggest that the mononuclear cells are derived from urothelial cells; however, no studies have been conducted to assess the immunohistochemical profile of ORUCUT with more specific urothelial markers...
February 6, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Xiaoxi Pan, Yun Yun Gong, Ya Xu, Robert A S Ariens, Michael N Routledge
BACKGROUND:  Particulate matter contained in ambient air pollution has been associated with cardiovascular diseases in several epidemiological studies. OBJECTIVE:  The aim of this study was to investigate the potential for urban particulate matter to induce changes in clot structure through interaction with vascular endothelial cells. METHODS:  We examined the structure of clots formed on human umbilical vascular endothelial cells that had been treated with various types of particles versus those formed on untreated cells...
February 2018: Thrombosis and Haemostasis
Magdalena Budzyń, Maria Iskra, Wojciech Turkiewicz, Zbigniew Krasiński, Bogna Gryszczyńska, Magdalena Paulina Kasprzak
BACKGROUND: Although the endothelial dysfunction is considered to be implicated in the pathogenesis of chronic venous insufficiency (CVI) the endothelial status in patients with venous disorders is still not fully evaluated. Therefore the aim of the study was to measure the concentration of selected markers of endothelial dysfunction: von Willebrand factor (vWf), soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM) and soluble VE-cadherin (sVE-cadherin) in CVI women who constitute the most numerous group of patients suffering from venous disease...
2018: PloS One
Sivaramakrishna P Rachakonda, Hao Dai, Olaf Penack, Olga Blau, Igor Wolfgang Blau, Aleksandar Radujkovic, Carsten Müller-Tidow, Rajiv Kumar, Peter Dreger, Thomas Luft
Purpose Endothelial vulnerability is a potential risk factor for complications after allogeneic stem-cell transplantation (alloSCT). The CD40/CD40 ligand (CD40L) axis contributes to inflammatory diseases and is upregulated in endothelial cells upon activation, suggesting a role in alloSCT biology. Here, we studied single nucleotide polymorphisms (SNPs) in the CD40L gene in recipients of alloSCT. Patients and Methods Three CD40L SNPs (rs3092920, rs3092952, rs3092936) were analyzed for association with transplant-associated thrombotic microangiopathy, overall nonrelapse mortality (NRM), and NRM after acute graft-versus-host disease in 294 recipients of alloSCT without statin-based endothelial prophylaxis (SEP)...
January 25, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Carlos H Villa, Daniel C Pan, Ian H Johnston, Colin F Greineder, Landis R Walsh, Elizabeth D Hood, Douglas B Cines, Mortimer Poncz, Don L Siegel, Vladimir R Muzykantov
Carriage of drugs by red blood cells (RBCs) modulates pharmacokinetics, pharmacodynamics, and immunogenicity. However, optimal targets for attaching therapeutics to human RBCs and adverse effects have not been studied. We engineered nonhuman-primate single-chain antibody fragments (scFvs) directed to human RBCs and fused scFvs with human thrombomodulin (hTM) as a representative biotherapeutic cargo (hTM-scFv). Binding fusions to RBCs on band 3/glycophorin A (GPA; Wright b [Wrb] epitope) and RhCE (Rh17/Hr0 epitope) similarly endowed RBCs with hTM activity, but differed in their effects on RBC physiology...
February 13, 2018: Blood Advances
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