Response of Skin-Derived and Metastatic Human Malignant Melanoma Cell Lines to Thymoquinone and Thymoquinone-Loaded Liposomes.

Thymoquinone has been proved to be effective against neoplasms, including skin cancer. Its high lipophilicity, however, may limit its potential use as a drug. Melanoma remains the deadliest of all skin cancers worldwide, due to its high heterogeneity, depending on the stage of the disease. Our goal was to compare the anti-cancer activity of free thymoquinone and thymoquinone-loaded liposomes on two melanoma cell lines that originated from different stages of this cancer: skin-derived A375 and metastatic WM9. We evaluated the proapoptotic effects of free thymoquinone by flow cytometry and Western blot, and its mitotoxicity by means of JC-1 assay. Additionally, we compared the cytotoxicity of free thymoquinone and thymoquinone in liposomes by WST-1 assay. Our results revealed a higher antiproliferative effect of TQ in WM9 cells, whereas its higher proapoptotic activity was observed in the A375 cell line. Moreover, the thymoquinone-loaded liposome was proved to exert stronger cytotoxic effect on both cell lines studied than free thymoquinone. Differences in the response of melanoma cells derived from different stages of the disease to thymoquinone, as well as their different responses to free and carrier-delivered thymoquinone, are essential for the development of new anti-melanoma therapies. However, further research is required to fully understand them.

Lipid rich plaque, female gender and proximal coronary stent edge dissections.

We hypothesized that women are more prone to develop coronary dissections during PCI due to potential balloon-oversizing or gender specific plaque and vascular characteristics. To date, a gender related difference in edge dissection has not been systematically studied. The Massachusetts General Hospital Optical Coherence Tomography (MGH OCT) Registry is an international registry of patients undergoing OCT procedures. We identified 206 consecutive patients (159 men, 47 women) with stable or unstable coronary syndromes demonstrating adequate OCT images for gender specific comparison in areas of non-overlapping stents. Presence of proximal edge dissection, its characteristics, plaque composition at stent borders and luminal diameters were assessed. A multivariate logistic regression model was applied to determine if female gender was predictive of proximal coronary dissection after adjusting for clinical, procedural and plaque characteristics. Proximal coronary dissection was significantly more common in women as compared to men (30.6 vs 15.6%, p = 0.02). No gender differences were observed in age, presentation, and stents per patient or plaque characteristics. The characteristics of edge dissections were different in women compared to men with a significant female predisposition to more complex proximal coronary dissection. In multivariable analysis, female gender was not a predictor of coronary dissection; on the other hand, stent oversizing and especially lipid rich plaque at proximal edge were independent predictors of proximal dissection. OCT confirms that female gender is associated with a greater than twofold increased risk of developing proximal coronary edge dissections as compared to men. But, the most potent independent predictor of proximal coronary edge dissection is the presence of a proximal lipid rich plaque.