Anti-angiogenesis in cancer therapeutics: the magic bullet.

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. 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.

Cardiovascular Safety and Superiority of Anti-Obesity Medications.

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 sodium-glucose 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.

The Effect of Emotional Valence on Ventricular Repolarization Dynamics Is Mediated by Heart Rate Variability: A Study of QT Variability and Music-Induced Emotions.

BACKGROUND: Emotions can affect cardiac activity, but their impact on ventricular repolarization variability, an important parameter providing information about cardiac risk and autonomic nervous system activity, is unknown. The beat-to-beat variability of the QT interval (QTV) from the body surface ECG is a non-invasive marker of repolarization variability, which can be decomposed into QTV related to RR variability (QTVrRRV) and QTV unrelated to RRV (QTVuRRV), with the latter thought to be a marker of intrinsic repolarization variability. AIM: To determine the effect of emotional valence (pleasant and unpleasant) on repolarization variability in healthy volunteers by means of QTV analysis. METHODS: 75 individuals (24.5 ± 3.2 years, 36 females) without a history of cardiovascular disease listened to music-excerpts that were either felt as pleasant (n = 6) or unpleasant (n = 6). Excerpts lasted about 90 s and were presented in a random order along with silent intervals (n = 6). QTV and RRV were derived from the ECG and the time-frequency spectrum of RRV, QTV, QTVuRRV and QTVrRRV as well as time-frequency coherence between QTV and RRV were estimated. Analysis was performed in low-frequency (LF), high frequency (HF) and total spectral bands. RESULTS: The heart rate-corrected QTV showed a small but significant increase from silence (median 347/interquartile range 31 ms) to listening to music felt as unpleasant (351/30 ms) and pleasant (355/32 ms). The dynamic response of QTV to emotional valence showed a transient phase lasting about 20 s after the onset of each musical excerpt. QTV and RRV were highly correlated in both HF and LF (mean coherence ranging 0.76-0.85). QTV and QTVrRRV decreased during listening to music felt as pleasant and unpleasant with respect to silence and further decreased during listening to music felt as pleasant. QTVuRRV was small and not affected by emotional valence. CONCLUSION: Emotional valence, as evoked by music, has a small but significant effect on QTV and QTVrRRV, but not on QTVuRRV. This suggests that the interaction between emotional valence and ventricular repolarization variability is mediated by cycle length dynamics and not due to intrinsic repolarization variability.