Correlation between the Surface Undulation and Luminescence Characteristics in Semi-Polar 112¯2 InGaN/GaN Multi-Quantum Wells.

Surface undulation was formed while growing InGaN/GaN multi-quantum wells on a semi-polar m-plane (1-100) sapphire substrate. Two distinct facets, parallel to 112¯2 and 011¯1, were formed in the embedded multi-quantum wells (MQWs). The structural and luminescence characteristics of the two facets were investigated using transmission electron microscopy equipped with cathodoluminescence. Those well-defined quantum wells, parallel and slanted to the growth plane, showed distinct differences in indium incorporation from both the X-ray yield and the contrast difference in annular darkfield images. Quantitative measurements of concentration in 011¯1 MQWs show an approximately 4 at% higher indium incorporation compared to the corresponding 112¯2 when the MQWs were formed under the same growth condition.

Ulipristal acetate induces cell cycle delay and remodeling of extracellular matrix.

Uterine leiomyoma is a benign tumor that grows within the muscle tissue of the uterus. Ulipristal acetate (UPA) is a pre­operative drug used to reduce the size of leiomyoma. The aim of the present study was to examine the in vitro mechanistic details of action of UPA on uterine leiomyomas. Primary cultures of leiomyoma cells were isolated from patient myomectomy specimens and incubated in the presence or absence of UPA at various concentrations. The proliferation, cell viability and doubling time properties of the treated cells were analyzed. In addition, the mRNA and protein expression levels of p21, p27, cyclin E, cyclin­dependent kinase 2 (CDK2), matrix metalloproteinase (MMP)­2 and MMP­9 were examined, as well as the structure of F­actin in the primary­cultured leiomyoma cells. The results demonstrated that UPA exerted inhibitory effects on proliferation of primary­cultured leiomyoma cells. Expression of p21 and p27 was upregulated, while cyclin E and CDK2 were downregulated in UPA­treated primary­cultured leiomyoma cells. An increased expression of MMP­2 was observed in primary­cultured leiomyoma cells and a leiomyoma tissue sample of a patient with previous history of UPA treatment. Furthermore, a pronounced formation of F­actin stress fibers was observed in leiomyoma cells of the UPA­treated patient. These data suggest that UPA treatment attenuated the proliferation of uterine fibroid cells via upregulation of p21 and p27, resulting in cell cycle delay. The findings in the current study also suggest that UPA may cause extracellular matrix constriction, leading to the shrinkage in size of the leiomyoma possibly via stimulation of MMP­2 expression and induction of actin stress fibers.

Antitumor effects of flavopiridol on human uterine leiomyoma in vitro and in a xenograft model.

Dysregulated cyclin-dependent kinases (CDKs) are considered a potential target for cancer therapy. Flavopiridol is a potent CDK inhibitor. In this study, the antiproliferative effect of the flavonoid compound flavopiridol and its mechanism in human uterine leiomyoma cells were investigated. The present study focused on the effect of flavopiridol in cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry was performed to determine the effect of flavopiridol on cell cycle. The expression of cell cycle regulatory-related proteins was evaluated by Western blotting. Cell viability and proliferation of uterine leiomyoma cells were significantly reduced by flavopiridol treatment in a dose-dependent manner. Flow cytometry results showed that flavopiridol induced G1 phase arrest. Flavopiridol-induced growth inhibition in uterine leiomyoma cells was associated with increased expression of p21(cip/wafl) and p27(kip1) in a dose-dependent manner. Downregulation of CDK2/4 and Cyclin A with a concomitant increase in dephosphorylation of retinoblastoma was observed. This study demonstrates that flavopiridol inhibits cell proliferation by initiating G1 cell cycle arrest in human uterine leiomyoma. We also found that flavopiridol is effective in inhibiting xenografted human uterine leiomyoma growth. These results indicate that flavopiridol could prove to be a promising chemopreventive and therapeutic agent for human uterine leiomyoma.