On metronomic chemotherapy: Modulation of angiogenesis mediated by VEGE-A

Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

“…acting on the microtubules. We have previously reported that metronomic paclitaxel treatment (19 mg/kg/week) for 7 days in rats results in a strong antiangiogenic response, with VA reduced to 44% and MVL to 61% of controls [3]. This is an almost identical antiangiogenic response to that seen in response to 2.0 mg/kg/ week of vinblastine presented here.…”

“…infusion) using several chemotherapeutics of various classes in the same experimental setting, the very strong antiangiogenic effects exerted by vinblastine, as observed here, with a statistically significant reduction in both microvessel spatial extension (vascularized area, VA) and density (microvessel length, MVL), have previously only been observed following treatment with paclitaxel and cyclophosphamide, but at doses that affected the physiologic body-weight gain to a lesser degree [3]. It is noteworthy that the present model compares well with other in vivo angiogenesis models in terms of biological, technical and ethical features and that differences in outcome between in vivo angiogenesis models should not be entirely unexpected because of differences in test tissue, species, experimental performance and measuring power [24].…”

“…In a recent study, we made observations suggesting that radical oxygen species (ROS) following chemotherapy may occasionally stimulate angiogenesis in vivo [3]. The question is whether an even more pronounced antiangiogenic effect could have been achieved with vinblastine by including a ROS scavenger in the formulation of the vehicle, thereby reducing the effect of the suggested proangiogenic drive from chemotherapy-induced ROS.…”

“…However, in the extreme of metronomic chemotherapy scheduling (i.e. using a continuous infusion schedule), a dose-response relationship is sometimes not present, as recently reported in the case of doxorubicin [3]. Information of this kind is fundamental when designing optimal treatment schedules that are subsequently going to be transferred to clinical trials.…”

“…The central part of each window is often avascular in untreated animals and the surrounding fatty tissue distinctly delineates each window. The entire vasculature of each intact mesenteric window was visualized immunohistochemically using a primary monoclonal antibody against rat endothelium [3,41].…”