ABSTRACT
Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.
PMID:32545233 | DOI:10.3390/cancers12061536
00:58
PubMed articles on: Cardio-Oncology
Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity
Lyra-Leite DM and Burridge PW. Curr Cardiol Rep 2020 - Review.
ABSTRACT
PURPOSE OF REVIEW: In this article, we review the different model systems based on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and how they have been applied to identify the cardiotoxic effects of anticancer therapies.
RECENT FINDINGS: Developments on 2D and 3D culture systems enabled the use of hiPSC-CMs as screening platforms for cardiotoxic effects of anticancer therapies such as anthracyclines, monoclonal antibodies, and tyrosine kinase inhibitors. Combined with computational approaches and higher throughput screening technologies, they have also enabled mechanistic studies and the search for cardioprotective strategies. As the population ages and cancer treatments become more effective, the cardiotoxic effects of anticancer drugs become a bigger problem leading to an increased role of cardio-oncology. In the past decade, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become an important platform for preclinical drug tests, elucidating mechanisms of action for drugs, and identifying cardioprotective pathways that could be further explored in the development of combined treatments. In this article, we highlight 2D and 3D model systems based on hiPSC-CMs that have been used to study the cardiotoxic effects of anticancer drugs, investigating their mechanisms of action and the potential for patient-specific prediction. We also present some of the important challenges and opportunities in the field, indicating possible future developments and how they could impact the landscape of cardio-oncology.
PMID:32562096 | DOI:10.1007/s11886-020-01325-x
00:58
PubMed articles on: Cancer & VTE/PE
In vivo performance of gold nanoparticle-loaded absorbable inferior vena cava filters in a swine model
Huang SY, et al. Biomater Sci 2020.
ABSTRACT
Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing protection against pulmonary embolism (PE) for patients contraindicated for anticoagulant therapy. However, because absorbable filters are not radiopaque, monitoring of the filter using conventional X-ray imaging modalities (e.g. plain film radiographs, computed tomography [CT] and fluoroscopy) during deployment and follow-up is not possible and represents a potential obstacle to widespread clinical integration of the device. Here, we demonstrate that gold nanoparticles (AuNPs) infused into biodegradable filters made up of poly-p-dioxanone (PPDO) may improve device radiopacity without untoward effects on device efficacy and safety, as assessed in swine models for 12 weeks. The absorbable AuNP-infused filters demonstrated significantly improved visualization using CT without affecting tensile strength, in vitro degradation, in vivo resorption, or thrombus-capturing efficacy, as compared to similar non-AuNPs infused resorbable IVCFs. This study presents a significant advancement to the development of imaging enhancers for absorbable IVCFs.
PMID:32558854 | DOI:10.1039/d0bm00414f
00:58
PubMed articles on: Cardio-Oncology
Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review
Upshaw JN. Curr Oncol Rep 2020 - Review.
ABSTRACT
PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies.
RECENT FINDINGS: Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.
PMID:32564220 | DOI:10.1007/s11912-020-00923-w
00:59
PubMed articles on: Cardio-Oncology
Cardiac effects and toxicity of chloroquine: a short update
Mubagwa K. Int J Antimicrob Agents 2020 - Review.
ABSTRACT
There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.
PMID:32565195 | PMC:PMC7303034 | DOI:10.1016/j.ijantimicag.2020.106057
00:59
PubMed articles on: Cancer & VTE/PE
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer
Alyami M, et al. Eur J Surg Oncol 2020.
ABSTRACT
BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC.
METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0.
RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC.
CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.
PMID:32561204 | DOI:10.1016/j.ejso.2020.05.021
00:59
PubMed articles on: Cardio-Oncology
High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease
Sparkenbaugh EM, et al. J Thromb Haemost 2020.
Comments
Post a Comment
اكتب تعليق حول الموضوع