Background Angiogenesis is the formation of new vascular networks from preexisting ones through the migration and proliferation of differentiated endothelial cells. Available evidence suggests that while antiangiogenic therapy could inhibit tumour growth, the response to these agents is not sustained. The aim of this paper was to review the evidence for anti-angiogenic therapy in cancer therapeutics and the mechanisms and management of tumour resistance to antiangiogenic agents. We also explored the latest advances and challenges in this field. Main body of the abstract MEDLINE and EMBASE databases were searched for publications on antiangiogenic therapy in cancer therapeutics from 1990 to 2020. Vascular endothelial growth factor (VEGF) is the master effector of the angiogenic response in cancers. Anti-angiogenic agents targeting the VEGF and HIF-α pathways include monoclonal antibodies to VEGF (e.g. bevacizumab), small-molecule tyrosine kinase inhibitors (TKIs) e.g. sorafenib, decoy receptor or VEGF trap e.g. aflibercept and VEGFR2 inhibitors (e.g. ramucirumab). These classes of drugs are vascular targeting which in many ways are advantageous over tumour cell targeting drugs. Their use leads to a reduction in the tumour blood supply and growth of the tumour blood vessels. Tumour resistance and cardiovascular toxicity are important challenges which limit the efficacy and long-term use of anti-angiogenic agents in cancer therapeutics. Tumour resistance can be overcome by dual anti-angiogenic therapy or combination with conventional chemotherapy and immunotherapy. Emerging nanoparticle-based therapy which can silence the expression of HIF-α gene expression by antisense oligonucleotides or miRNAs has been developed. Effective delivery platforms are required for such therapy. Short conclusion Clinical surveillance is important for the early detection of tumour resistance and treatment failure using reliable biomarkers. It is hoped that the recent interest in mesenchymal cell-based and exosome-based nanoparticle delivery platforms will improve the cellular delivery of newer anti-angiogenics in cancer therapeutics.
Atrial fibrillation globally affects roughly 33.5 million people, making it the most common heart rhythm disorder. It is a crucial arrhythmia, as it is linked with a variety of negative outcomes such as strokes, heart failure and cardiovascular mortality. Atrial fibrillation can reduce quality of life because of the potential symptoms, for instance exercise intolerance, fatigue, and palpitation. There are different types of treatments aiming to prevent atrial fibrillation and improve quality of life. Currently, the primary treatment for atrial fibrillation is pharmacology therapy, however, these still show limited effectiveness, which has led to research on other alternative strategies. Catheter ablation is considered the second line treatment for atrial fibrillation when the standard treatment has failed. Moreover, catheter ablation continues to show significant results when compared to standard therapy. Hence, this review will argue that catheter ablation can show superiority over current pharmacological treatments in different aspects. It will discuss the most influential aspects of the treatment of atrial fibrillation, which are recurrence and burden of atrial fibrillation, quality of life, atrial fibrillation in the setting of heart failure and mortality and whether catheter ablation can be the first line treatment for patients with atrial fibrillation.
Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodiumglucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.
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