In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A

Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy

The Effect of Subareolar Isosulfan Blue Injection on Pulse Oximeter Readings

WOS: 000335573100019PubMed ID: 24799789Besides several side effects including anaphylaxis, blue dyes are also known to cause false pulse oximeter readings. We aimed to examine the effects of subareolar isosulfan blue injection on pulse oximeter (SpO2) readings. The study group included 27 patients undergoing SLNB using both radiocolloid and isosulfan blue. Another group of 27 patients constituted the control group. Pulse oximeter readings were compared. SpO2 decline a parts per thousand yen4 % was defined as significant. All but one (96.2 %) of the patients in the study group showed SpO2 declines, compared to only one patient in the control group. Median +/- Interqartile Range (IR) SpO2 decrease was 3.0 +/- 4.0 % in the study and 0.0 +/- 1.0 % in the control group (p < 0.001). There were significant (a parts per thousand yen4 %) SpO2 decreases in 13 (48.1 %) patients in the study group. Statistically significant differences were noted between the two groups in all recordings between 15 and 180 min (p < 0.001). Initial time for SpO2 fall and the time to the lowest SpO2 recording were 10.0 +/- 10.0 and 40.0 +/- 30.0 min respectively. Using subareolar injection, the frequency of false readings is comparable with intraparenchymal injections, and is higher than intradermal injections. Time to peak SpO2 fall, and the recovery period, are delayed in the subareolar technique

Morphine and breast tumor metastasis: the role of matrix-degrading enzymes

Opioids including morphine are commonly used in pain management during and after cancer surgery but have been linked to a variety of pro- and anti-tumor effects. In the present study the effect of morphine administration on the localization and growth of breast tumor cells in lungs and the level of extracellular matrix (ECM) proteases were investigated. In a mouse syngeneic model of intravenously inoculated breast cancer cells, morphine administration led to a reduction in the localization and growth of tumors in the lungs and a reduction in circulating matrix metalloproteinase-9 (MMP-9) and urokinase-like plasminogen activator (uPA). To model the involvement of non-malignant cells of the tumor microenvironment in the changes we observed in the level of proteases, we co-cultured breast cancer cells with macrophages, endothelial cells and fibroblasts. We found a significant elevation of matrix proteases as well as matrix protease inhibitors in co-cultures of breast cancer cells with macrophages or endothelial cells. Interestingly, morphine treatment of these co-cultures reduced the level of MMP-9 and increased its endogenous inhibitor, TIMP-1, thereby altering the proteolytic profile. Morphine affected the level of enzymes in co-cultures but not in cells grown individually. This suggests that anti-tumor effects of morphine observed in our in vivo model could be mediated at least in part through modulation of paracrine communication between cancer cells and non-malignant cells in the tumor microenvironment