Update for: Thrombin Inhibition Preoperatively (TIP) in Early Breast Cancer, the first clinical trial of DOACs as an anti-cancer agent

Introduction: Tumour expression of extrinsic clotting pathway markers are increased in oestrogen receptor (ER) negative, high Ki67, more aggressive breast cancer subtypes. In in vitro and in vivo studies, the extrinsic clotting pathway promotes cancer growth and metastasis.  Cancer stem-like cells (CSCs) are a subpopulation of cancer cells that are resistant to chemotherapy, endocrine therapy and radiotherapy and play a role in recurrence. In vitro, Direct Oral Anticoagulants inhibit breast cancer stem cell activity.
Source: Thrombosis Research - Category: Hematology Authors: Tags: PO-56 Source Type: research

Related Links:

DiscussionLaboratory evidence supports an anti-cancer role for anticoagulants; however, this has failed to translate into survival benefit when trialled in patients with metastatic disease or poor prognosis cancers, such as lung cancer. Subgroup analysis supported a potential survival benefit in better prognosis advanced disease patients. This is the first study to investigate the anti-cancer effects of anticoagulants in early breast cancer.Trial registrationUK National Research Ethics Service (NRES) approval 15/NW/0406, MHRA Clinical Trials Authorisation 48380/0003/001-0001. The sponsor is Manchester University NHS Founda...
Source: Trials - Category: Research Source Type: clinical trials
In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2,ABCB1,CYP3A4*22,CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2  years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variantABCG2 c.421C  >  A, and sex predicted higher apixaban concentrations whe...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
Since the Women's Health Initiative (WHI) has been stopped 2002 due to increased risk of venous thromboembolism, myocardial infarction, stroke and breast cancer, safety issues have got great concern using hormone replacement therapy (HRT). However, using lower dosages, other hormonal components and/or transdermal instead of oral application can reduce those risks although not demonstrated in a placebo-controlled study comparable to WHI. However, this has been shown in large case/control- and cohort-studies reflecting more practical conditions in contrast to WHI.
Source: Maturitas - Category: Primary Care Authors: Tags: INV65 Source Type: research
In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differenti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Vit Weinberger1, Marketa Bednarikova2, Jitka Hausnerova3, Petra Ovesna4, Petra Vinklerova1, Lubos Minar1, Michal Felsinger1, Eva Jandakova3, Marta Cihalova3 and Michal Zikan5* 1Department of Gynecology and Obstetrics, University Hospital in Brno and Masaryk University, Brno, Czechia2Department of Internal Medicine – Hematology and Oncology, University Hospital in Brno and Masaryk University, Brno, Czechia3Department of Pathology, University Hospital in Brno and Masaryk University, Brno, Czechia4Faculty of Medicine, Institute of Biostatistics and Analyses, Masaryk University, Brno, Czechia5Institute of Biostati...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractTo investigate the occurrence of thrombotic events (myocardial infarction, deep vein thrombosis or ischemic stroke) in a group of 39 cases of severe FXII deficiency during a mean 22.5  years follow-up. All patients seen in Padua during the years 1968–2006 will the object of this investigation. FXII was less than or 1% of normal in all cases. Factor FXII activity in unaffected family members was 98% (range 90–140%). No patient or control had a thrombotic event in the past and none were on anticoagulant therapy. FV Leiden was present in one patient and in two controls whereas the G to A20210 prothrom...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
Coagulation signaling through protease activated receptors (PARs) participates in inflammation and immunity. In cancer, tissue factor (TF) driven signaling via PAR2 promotes tumor progression, but effective pharmacological strategies to inhibit the PAR2 activating proteases for clinical anti-cancer benefit are currently unknown. To gain a better understanding of signaling by coagulation proteases, we generated PAR2 mouse strains with mutations that abolish canonical proteolysis by all proteases including FVIIa (PAR2 R38E) or create specific resistance to cleavage by the TF-FVIIa-Xa signaling complex (PAR2 G37I) that requir...
Source: Blood - Category: Hematology Authors: Tags: 321. Blood Coagulation and Fibrinolytic Factors: The Clotting System in Inflammation, Immunity, and Cancer Source Type: research
CONCLUSIONS: In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients. This article is protected by copyright. All rights reserved. PMID: 30240508 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
Abstract Transition to menopause is associated with an increase in cardiovascular disease (CVD) risk, mainly attributed to lipid and glucose metabolism dysregulation, as well as to body fat redistribution, leading to abdominal obesity. Indeed, epidemiological evidence suggests that both early menopause (EM, defined as age at menopause
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research
Introduction: It has been well-established that cancer results in a hypercoagulable state and an increased risk for venous thromboembolism (VTE). More recently, it has been suggested that coagulation may also affect cancer progression and metastasis. Cancer patients with VTE are currently treated with the anticoagulant low molecular weight heparins (LMWHs). Preclinical studies have shown that LMWHs can inhibit metastasis formation in several types of cancer, but beneficial effects of LMWHs on survival have not been consistently found in clinical trials.
Source: Thrombosis Research - Category: Hematology Authors: Tags: PO-50 Source Type: research
More News: Breast Cancer | Cancer | Cancer & Oncology | Chemotherapy | Clinical Trials | Endocrine Therapy | Oral Cancer | Stem Cell Therapy | Stem Cells | Study | Thrombosis