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https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#1
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28492702/low-plasma-fvii-c-and-activated-fvii-as-predictive-markers-for-overt-disseminated-intravascular-coagulation
#2
Surapong Lertthammakiat, Nattachai Anantasit, Usanarat Anurathapan, Nongnuch Sirachainan, Praguywan Kadegasem, Ampaiwan Chuansumrit
In sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with tissue factor is the key step of coagulation resulting in disseminated intravascular coagulation (DIC). We conducted a prospective cohort study among 47 septic patients, aged 8 months to 18.8 years. They were initially divided into three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57 % (interquartile range [IQR] 41-80)] and overt DIC groups [33 % (23-52)] than that in the no DIC group [65 % (44-87)]...
May 11, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28460818/neutral-macrocyclic-factor-viia-inhibitors
#3
Nicholas R Wurtz, Brandon L Parkhurst, Indawati DeLucca, Peter W Glunz, Wen Jiang, Xiaojun Zhang, Daniel L Cheney, Jeffrey M Bozarth, Alan R Rendina, Anzhi Wei, Tim Harper, Joseph M Luettgen, Yiming Wu, Pancras C Wong, Dietmar A Seiffert, Ruth R Wexler, E Scott Priestley
Factor VIIa (FVIIa) inhibitors have shown strong antithrombotic efficacy in preclinical thrombosis models with limited bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful due to the requirement of a basic P1 group to interact with Asp189 in the S1 binding pocket, limiting their membrane permeability. We have combined recently reported neutral P1 binding substituents with a highly optimized macrocyclic chemotype to produce FVIIa inhibitors with low nanomolar potency and enhanced permeability...
April 19, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28437748/rational-and-timely-haemostatic-interventions-following-cardiac-surgery-coagulation-factor-concentrates-or-blood-bank-products
#4
Mariann Tang, Christian Fenger-Eriksen, Per Wierup, Jacob Greisen, Jørgen Ingerslev, Vibeke Hjortdal, Benny Sørensen
BACKGROUND: Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery...
April 5, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28420729/factor-v-anticoagulant-cofactor-activity-that-targets-the-early-phase-of-coagulation
#5
Salvatore Santamaria, Natalia Reglińska-Matveyev, Magdalena Gierula, Rodney M Camire, James T B Crawley, David A Lane, Josefin Ahnström
Tissue factor pathway inhibitor (TFPI), the main inhibitor of initiation of coagulation, exerts an important anticoagulant role through the factor Xa (FXa)-dependent inhibition of tissue factor/factor VIIa (FVIIa). Protein S is a TFPI cofactor, enhancing the efficiency of FXa inhibition. TFPI can also inhibit prothrombinase assembly by directly interacting with coagulation factor V (FV) which has been activated by FXa. Since full-length TFPI associates with FV in plasma, we hypothesized that FV may influence TFPI inhibitory function...
April 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28417928/potential-coagulation-factor-driven-pro-inflammatory-responses-in-ovarian-cancer-tissues-associated-with-insufficient-o%C3%A2-and-plasma-supply
#6
REVIEW
Shiro Koizume, Yohei Miyagi
Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII). The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic blood coagulation process. Interactions between cancer cells and immune cells via coagulation factors and adhesion molecules can promote progression of cancer, including epithelial ovarian cancer (EOC). This process is not necessarily advantageous, as tumor tissues generally undergo hypoxia due to aberrant vasculature, followed by reduced access to plasma components such as coagulation factors...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28381691/autoimmune-bullous-disease-and-hashimoto-s-disease-complicated-by-acquired-hemophilia-a
#7
Nobuko Nishiura, Daisuke Ujimoto, Jiro Fujita, Tetsuo Maeda, Yukinobu Nakagawa, Hirokazu Kashiwagi, Kenji Oritani, Yoshiaki Tomiyama, Yuzuru Kanakura
A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28360881/hemostasis-in-intracranial-hemorrhage
#8
REVIEW
Deepak Gulati, Dharti Dua, Michel T Torbey
Spontaneous non-traumatic intracerebral hemorrhage (ICH) is associated with high morbidity and mortality throughout the world with no proven effective treatment. Majority of hematoma expansion occur within 4 h after symptom onset and is associated with early deterioration and poor clinical outcome. There is a vital role of ultra-early hemostatic therapy in ICH to limit hematoma expansion. Patients at risk for hematoma expansion are with underlying hemostatic abnormalities. Treatment strategy should include appropriate intervention based on the history of use of antithrombotic use or an underlying coagulopathy in patients with ICH...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28245651/molecular-dynamics-simulation-of-cytotoxicity-of-graphene-nanosheets-to-blood-coagulation-protein
#9
Byeong Cheol Jo, Hyun Jung Yoon, Myoung-Ryul Ok, Sangwook Wu
Graphene is a nanomaterial that is widely used in electronics, biomedicine, and drug-delivery systems. Although it has many industrial applications, the cytotoxicity of graphene has not been sufficiently studied. In this study, the authors used molecular dynamics simulation to investigate how a graphene nanosheet affects a blood-coagulation protein, namely, a tissue factor/FVIIa binary complex bound to a lipid bilayer membrane, in a 4:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-l-serine lipid bilayer mixture...
February 28, 2017: Biointerphases
https://www.readbyqxmd.com/read/28223242/fviia-prevents-the-progressive-hemorrhaging-of-a-brain-contusion-by-protecting-microvessels-via-formation-of-the-tf-fviia-fxa-complex
#10
Qiang Yuan, Dalong Zhang, Sirong Wu, Jian Yu, Lei Yu, Yirui Sun, Zhuoying Du, Zhiqi Li, Liangfu Zhou, Xing Wu, Jin Hu
Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant human activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions...
February 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28219621/topical-application-of-recombinant-activated-factor-vii-during-cesarean-delivery-for-placenta-previa
#11
Birgit T B G Schjoldager, Emmeli Mikkelsen, Malene R Lykke, Jørgen Præst, Anne-Mette Hvas, Lars Heslet, Niels J Secher, Jannie D Salvig, Niels Uldbjerg
BACKGROUND: During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. OBJECTIVE: We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation...
February 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28195355/factor-vii-and-incidence-of-myocardial-infarction-in-a-japanese-population-the-jichi-medical-school-cohort-study
#12
Takuya Shiraishi, Shizukiyo Ishikawa, Kazuomi Kario, Kazunori Kayaba, Eiji Kajii
BACKGROUND: The role of factor VII (FVII) as a risk factor in myocardial infarction (MI) has been the subject of numerous studies. However, it remains uncertain whether the FVII levels are associated with development of MI. METHODS: The subjects were 4142 men and women whose activated FVII (FVIIa) and FVII coagulant (FVIIc) levels were measured in the Jichi Medical School Cohort Study. Subjects were divided into tertiles by FVIIa and FVIIc levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for MI...
February 13, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28150568/structural-modulation-of-factor-viia-by-full-length-tissue-factor-tf1-263-implication-of-novel-interactions-between-egf2-domain-and-tf
#13
Ramesh Prasad, Prosenjit Sen
Tissue factor (TF)-mediated factor VII (FVII) activation and a subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As a result of unresolved crystal structure of the full-length TF1-263-FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear...
February 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28148395/tissue-factor-factor-viia-complex-triggers-protease-activated-receptor-2-dependent-growth-factor-release-and-migration-in-ovarian-cancer
#14
Alice Chanakira, Pamela R Westmark, Irene M Ong, John P Sheehan
OBJECTIVE: Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. METHODS: TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines...
April 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28105277/design-and-synthesis-of-novel-meta-linked-phenylglycine-macrocyclic-fviia-inhibitors
#15
Jeremy M Richter, Daniel L Cheney, J Alex Bates, Anzhi Wei, Joseph M Luettgen, Alan R Rendina, Timothy M Harper, Rangaraj Narayanan, Pancras C Wong, Dietmar Seiffert, Ruth R Wexler, E Scott Priestley
Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089408/the-various-assays-for-measuring-activity-states-of-factor-viia-in-plasma-and-therapeutic-products-diagnostic-value-and-analytical-usefulness-in-various-pathophysiological-states
#16
REVIEW
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms...
February 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28035745/one-amino-acid-in-mouse-activated-factor-vii-defines-its-endothelial-protein-c-receptor-epcr-binding-and-modulates-its-epcr-dependent-hemostatic-activity-in-vivo
#17
G Pavani, S M Zintner, L Ivanciu, J C Small, K A Stafford, J H Szeto, P Margaritis
Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. SUMMARY: Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences...
December 30, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28033108/tissue-factor-promotes-breast-cancer-stem-cell-activity-in-vitro
#18
Hudhaifah Shaker, Hannah Harrison, Robert Clarke, Goran Landberg, Nigel J Bundred, Henri H Versteeg, Cliona C Kirwan
Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/27994741/discovery-of-phenylglycine-lactams-as-potent-neutral-factor-viia-inhibitors
#19
Nicholas R Wurtz, Brandon L Parkhurst, Wen Jiang, Indawati DeLucca, Xiaojun Zhang, Vladimir Ladziata, Daniel L Cheney, Jeffrey R Bozarth, Alan R Rendina, Anzhi Wei, Joseph M Luettgen, Yiming Wu, Pancras C Wong, Dietmar A Seiffert, Ruth R Wexler, E Scott Priestley
Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27899993/predictive-value-of-microparticle-associated-tissue-factor-activity-for-permeability-glycoprotein-mediated-multidrug-resistance-in-cancer
#20
Antonio Angelini, Sebastiano Miscia, Maria Antonietta Centurione, Roberta Di Pietro, Lucia Centurione
Multidrug resistance (MDR) protein 1, which is also known as permeability glycoprotein (Pgp), and tissue factor (TF) are recurrently overexpressed on the surface of cancer cells, likely in response to stimuli such as chemotherapy. Microparticles (MPs) released from cancer cells into the bloodstream express tumour markers on their surface that may be useful as predictive biomarkers for evaluating disease progression. The present study measured the level of TF/factor VII (FVII)-dependent coagulation of MPs isolated from the plasma of cancer patients with various tumours, who were undergoing chemotherapy...
November 2016: Oncology Letters
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