The discovery of molecules with anti-angiogenic properties has led to promising new strategies for the treatment of diseases characterized by excessive new vessel growth, such as cancer and haemangioma. We have assessed the effects of DNA-damaging and cytoskeletal-disrupting agents in vitro on several endothelial cell functions. We report that bleomycin, mitomycin C and cytoskeletal-disrupting drugs (2-methoxyestradiol, taxol, vincristine, vinblastine, colchicine, nocodazole, and cytochalasin D) exhibit anti-angiogenic activities of varying potency. Bleomycin and the various cytoskeletal-disrupting drugs inhibited endothelial cell migration, while mitomycin C had a marginal effect. Both DNA-damaging and cytoskeletal-disrupting drugs decreased endothelial cell growth in a dose-dependent manner, and this was accompanied by the induction of apoptosis. The growth inhibitory and apoptotic effects of cytoskeletal-disrupting drugs were the most pronounced. We also show that both classes of drugs inhibited capillary-like tube formation in an assay of in vitro angiogenesis, with cytoskeletal-disrupting agents inhibiting in vitro angiogenesis with greater potency. A targeted approach incorporating several compounds with different mechanisms of action may be useful for the treatment of angiogenesis-dependent diseases such as hemangiomas of infancy.

The vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) axis is indispensable in the process of angiogenesis and has been implicated as a key driver of tumor vascularization. Consequently, several strategies that target VEGF and its cognate receptors, VEGFR-1 and VEGFR-2, have been designed to treat cancer. While therapies targeting full-length VEGF have resulted in an improvement in both overall survival and progression-free survival in various cancers, these benefits have been modest. In addition, the inhibition of VEGFRs is associated with undesirable off-target effects. Moreover, VEGF splice variants that modulate sprouting and non-sprouting angiogenesis have been identified in recent years. Cues within the tumor microenvironment determine the expression patterns of these variants. Noteworthy is that the mechanisms of action of these variants challenge the established norm of VEGF signaling. Furthermore, the aberrant expression of some of these variants has been observed in several cancers. Herein, developments in the understanding of the VEGF/VEGFR axis and the splice products of these molecules, as well as the environmental cues that regulate these variants are reviewed. Furthermore, strategies that incorporate the targeting of VEGF variants to enhance the effectiveness of antiangiogenic therapies in the clinical setting are discussed.

Breast cancer remains a burden in both developed and developing countries, with higher mortality in developing countries. Attempts to eradicate cancer have not been successful despite the progress made in the development of more novel chemotherapeutic drugs. Reactive-oxygen-species-mediated oxidative stress is known to play a role in breast cancer pathogenesis via genetic and epigenetic modifications, resulting in uncontrolled cell proliferation. Phytochemicals could provide leads for the development of alternative therapeutic agents due to their antioxidant activity, as well as their ability to induce apoptosis in cancer cells. However, most of the studies carried out using in vitro models do not continue with further studies in estrogen-receptor-positive in vivo breast cancer models, or fail to examine the possible biochemical mechanisms of phytochemical-based amelioration. This review examines oxidative-stress-mediated carcinogenesis and the potential of phytochemicals as anticancer agents.

The C-3 brominated and iodinated derivatives were prepared from the corresponding 2-arylquinolin-4(1H)-ones and their NMe-4-oxo derivatives using pyridinium tribromide in acetic acid or iodine-Na 2 CO 3 mixture in THF. The results of further studies of chemical transformation of the prepared α-haloenones and preliminary antitumour activity of the 3-bromo NH-4-oxo and NMe-4-oxo derivatives are also described.

Background Hemangiomas are benign vascular tumors that are characterised by excessive