Non-doped solid-state white light-emitting electrochemical cells employing the microcavity effect.

Solid-state white light-emitting electrochemical cells (LECs) have attracted research attention owing to their advantages of simple device structure, low operation voltage and compatibility with solution processes. In this work, we demonstrate a simple approach to obtain white electroluminescence (EL) from non-doped LECs based on a blue-emitting complex. With a relatively thicker emissive layer, red emission can be additionally enhanced by the microcavity effect when the recombination zone moves to appropriate positions. Hence, white EL can be harvested by combining blue emission from the complex and red emission from the microcavity effect. These non-doped white LECs show external quantum efficiencies and power efficiencies up to 5% and 12 lm W(-1), respectively. These results show that efficient white EL can be obtained in simple non-doped LECs.

Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma.

Aurora kinases such as Aurora A and Aurora B are key regulators of mitosis and have been reported to be overexpressed in various malignancies. However, the expression and localization of Aurora kinases in normal and neoplastic endometrial tissues remain undetermined. In the present study, immunohistochemical expression of Aurora A and B was examined in 40 normal, 30 hyperplastic, and 73 malignant endometria. The data were compared with the expression of Ki-67 and patient survivals. The expression of Aurora A and B at protein and messenger RNA levels was also examined using Western blotting and the reverse transcriptase polymerase chain reaction. The expression of Aurora A in normal endometrium was observed mainly in the proliferative phase and was decreased in the secretory phase. The Aurora A expression was significantly increased in carcinomas compared with normal proliferative endometrium; however, there was no correlation of Aurora A expression with Ki-67 expression or patient survival. The expression of Aurora B in normal endometrium was significantly higher in the proliferative phase than in the secretory phase. In endometrial carcinomas, the expression of Aurora B was correlated with Ki-67 expression and was significantly increased in high-grade tumors. In addition, patients with Aurora B-positive carcinoma showed poor prognosis compared with those with Aurora B-negative carcinoma (P = .0135). Accordingly, the present study indicates the aberrant expression of Aurora A and Aurora B in endometrial carcinomas and the clinical importance of Aurora B expression in relationship to patient prognosis.

Intratumoral heterogeneous expression of p53 correlates with p53 mutation, Ki-67, and cyclin A expression in endometrioid-type endometrial adenocarcinomas.

To further elucidate the significance of p53 mutation in endometrial carcinoma, we investigated it in endometrioid-type endometrial carcinomas showing intratumoral heterogeneous p53 expression. In addition, we also examined the correlation of p53 mutation and cyclin A expression, because we previously reported a topological correlation between the expression of p53 and cyclin A. The p53 mutation in exons 5-8 in 54 cases of endometrial carcinoma showing immunohistochemical expression of p53 was examined using microdissected tissue DNAs. Of the 54 p53-positive endometrial carcinomas, 23 (43%) had p53 mutation with a tendency in histologically higher grade tumors. Ten of the 54 showed a heterogeneous p53 expression, and in 9 of the 10 cases, p53 mutation was present only in p53-positive sites, which were often found in histologically less differentiated areas with elevated Ki-67 in the same tumor. Cyclin A expression was topologically observed in p53-positive areas; however, it was noted in both tumors with (12/23, 52%) and without (18/31, 58%) p53 mutation. These results suggest that p53 mutation is a late event and plays an important role in the acquisition of malignant potentials in endometrioid-type endometrial adenocarcinomas. Unexpectedly, accumulation of the p53 protein itself may be important in cyclin A overexpression.

Cyclic changes in the expression of steroid receptor coactivators and corepressors in the normal human endometrium.

To examine the sex steroid-dependent growth mechanisms of the human endometrium, the expression of steroid receptor coactivators [steroid receptor coactivator-1 (SRC-1) and p300/CREB-binding protein (p300/CBP)] and corepressors (nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors) was examined by immunohistochemistry, using 50 samples of normal endometria, and was compared with that of estrogen receptors (ER), progesterone receptors (PR), and proliferation marker Ki-67. In addition, actual binding of the coactivators to ER or PR was analyzed by immunoprecipitation. The expression of SRC-1 was diffusely observed in glandular and stromal cells in the proliferative phase and drastically decreased in the secretory phase. Such change in the expression pattern of SRC-1 resembled that of ER, PR, and Ki-67. On the other hand, p300/CBP expression was relatively constant throughout the menstrual cycle, with slight predominance in the proliferative phase. The expression of corepressors nuclear receptor corepressor and silencing mediator for retinoid and thyroid hormone receptors was focal in the endometrium. Immunoprecipitation, using tissue samples of both proliferative and secretory phases, revealed the complex formation between the coactivators and receptors. Binding of SRC-1 to ER was observed in the proliferative (but not in the secretory) endometrium. In contrast, binding p300/CBP to ER was noted in the endometria of both phases. Complex formation between p300/CBP and PR was noted in the secretory endometrium, whereas that between SRC-1 and PR was not apparent. Accordingly, we showed the expression pattern of steroid receptor coactivators and corepressors in the normal endometrium. Cyclic change in the expression of SRC-1 during the menstrual cycle might be important in the estrogen-action for the glandular and stromal cells.

Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, Ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator.

Although aberrant expression of several cell-cycle regulators has been reported in endometrial carcinoma, correlations among these factors and their prognostic significance have not fully been elucidated. In the present study, expression of cyclins (D1, E, A, and B1), cyclin-dependent kinases (cdk2, cdk4, and cdc2), and tumor-suppressor gene products (p53, p21, and p27) were systematically examined by immunohistochemistry in 82 cases of endometrial carcinoma and 20 normal endometria. Results were compared with the expression of Ki-67, sex steroid receptor status, clinicopathological parameters, and patient outcomes. Positive staining for cyclin D1, cyclin E, cyclin A, cyclin B1, cdk2, cdk4, cdc2, p53, p21, and p27 was observed in 63%, 66%, 31%, 32%, 51%, 77%, 71%, 43%, 35%, and 60% of the 82 carcinomas, respectively. Among these factors, positive staining for cyclin D1, cdk4, and p53 was significantly frequent in advanced-stage tumors, and that for cyclin D1, cyclin A, cdk4, p21, and p53 was more frequent in higher-grade tumors. High correlation was found between cyclin A and p53 expression, between cyclin D1 and cdk4 expression, between cdk4 and Ki-67 expression, and between p21 and Ki-67 expression. Multivariate analysis showed that the factors for poor prognosis were advanced stage and cyclin A positivity. These findings suggest that various cell-cycle regulators are involved in activated cell growth of endometrial carcinoma, and that positive staining for cyclin A could be a useful marker for unfavorable patient prognosis.

Immunohistochemical expression of E-cadherin and beta-catenin in the normal and malignant human endometrium: an inverse correlation between E-cadherin and nuclear beta-catenin expression.

BACKGROUND: The E-cadherin/beta-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. We previously reported aberrant expression of beta-catenin in endometrial carcinomas. However, the expression and correlation of E-cadherin and beta-catenin in normal and malignant endometrial tissues are not fully understood. MATERIALS AND METHODS: Immunohistochemical expression of E-cadherin and beta-catenin was detected in 30 cases of normal endometrium and 73 cases of endometrial carcinoma. RESULTS: In the normal endometrium, the expression of E-cadherin and cytoplasmic beta-catenin in glandular cells was predominantly observed in the proliferative phase, and decreased in the secretory phase. In endometrial carcinomas, the expression of E-cadherin and cytoplasmic beta-catenin decreased compared to that in the normal proliferative endometrial glands. The expression of E-cadherin and cytoplasmic beta-catenin tended to be reduced in histologically high-grade tumors compared to low-grade tumors. Nuclear expression of beta-catenin was observed in the glandular cells in the late proliferative and early secretory phases, as well as in high-grade endometrial carcinomas. Interestingly, nuclear beta-catenin expression was associated with the loss of E-cadherin expression in normal and carcinoma cells, indicating an inverse correlation. CONCLUSION: The cyclic expression of E-cadherin and beta-catenin in the normal endometrium suggests that the adhesion complex may act to maintain the endometrial architectures. In addition, nuclear beta-catenin expression associated with loss of E-cadherin expression may be involved in the acquisition of aggressive biological behavior, especially in high-grade tumors.

Nuclear localization of beta-catenin is correlated with the expression of cyclin D1 in endometrial carcinomas.

BACKGROUND: beta-catenin has recently been reported to act as a cell growth promoter through cyclin D1 transcription. However, the correlation between beta-catenin and cyclin D1 expressions is not fully understood in endometrial tissues. MATERIALS AND METHODS: Immunohistochemical expression of beta-catenin was examined in normal endometria (32 cases) and endometrial carcinomas (82 cases), and its expression was compared with that of cyclins (D1, E, A, B1). RESULTS: Sporadic nuclear staining of beta-catenin and cyclins was observed from proliferative phase of early secretory phase endometria, however, spacial correlations between beta-catenin and cyclins were not evident. In endometrial carcinomas, positivity for nuclear beta-catenin and cyclins increased compared to the normal endometria. Topologically, the cyclin D1-positive cells were frequently found in nuclear beta-catenin-positive cells. In addition, Spearman's rank correlation analysis revealed that the nuclear expression of beta-catenin correlated positively with that of cyclin D1 (p < 0.0001). CONCLUSION: The beta-catenin-cyclin D1 pathway might be involved in the growth of endometrial carcinomas.

Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression.

BACKGROUND: To examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC-1] and p300/cyclic AMP-response element-binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid-hormone receptors [SMRT]), were investigated. METHODS: The expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki-67. RESULTS: In samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC-1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC-1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC-1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC-1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8). CONCLUSIONS: The current study showed that expression levels of the steroid receptor coactivators SRC-1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR.