Tumor suppressor gene silencing through cytosine methylation contributes to cancer formation. Whether DNA demethylation enzymes counteract this oncogenic effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine demethylation, is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. Consistently, enforced expression of TET1 reduces cell invasion and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell invasion through its dioxygenase and DNA binding activities. Furthermore, TET1 maintains the expression of tissue inhibitors of metalloproteinase (TIMP) family proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical samples. Together, these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation.
The InGaZnO taken as switching layer in resistive nonvolatile memory is proposed in this paper. The memory cells composed of Ti/InGaZnO/TiN reveal the bipolar switching behavior that keeps stable resistance ratio of 102 with switching responses over 100 cycles. The resistance switching is ascribed to the formation/disruption of conducting filaments upon electrochemical reaction near/at the bias-applied electrode. The influence of electrode material on resistance switching is investigated through Pt/InGaZnO/TiN devices, which perform the unipolar and bipolar behavior as applying bias on Pt and TiN electrode, respectively. Experimental results demonstrate that the switching behavior is selective by the electrode.
In this letter, we investigate the impact of the light illumination on the stability of indium–gallium–zinc oxide thin film transistors under positive gate-bias stress. The noticeable decrease in threshold voltage (Vt) shift more than 5.5 V under illuminated positive gate-bias stress indicates a superior reliability in contrast with the dark stress. The accelerated Vt recovery characteristic compared with dark recovery demonstrates that the charge detrapping effect was enhanced under illumination. Furthermore, the average effective energy barrier of charge trapping and detrapping was derived to verify that illumination can excite the trapped charges and accelerate the charge detrapping process.
A post-treatment using N2O-plasma is applied to enhance the electrical characteristics of amorphous indium gallium zinc oxide thin film transistors. Improvements in the field-effect mobility and the subthreshold swing demonstrate that interface states were passivated after N2O-plasma treatment, and a better stability under positive gate-bias stress was obtained in addition. The degradation of mobility, resulted from bias stress, reduces from 6.1% (untreated devices) to 2.6% (N2O-plasma treated devices). Nevertheless, a strange hump characteristic occurs in transfer curve during bias stress, inferring that a parasitic transistor had been caused by the gate-induced electrical field.
Purpose: Wedelia chinensis is a common ingredient of anti-inflammatory herbal medicines in Taiwan and southern China. Inflammation is involved in promoting tumor growth, invasion, and metastasis. This study aims to test the biological effects in vivo of W. chinensis extract on prostate cancer. Experimental Design: The in vivo efficacy and mechanisms of action of oral administration of a standardized extract of W. chinensis were analyzed in animals bearing a subcutaneous or orthotopic prostate cancer xenograft. Results: Exposure of prostate cancer cells to W. chinensis extract induced apoptosis selectively in androgen receptor (AR)-positive prostate cancer cells and shifted the proportion in each phase of cell cycle toward G 2 -M phase in AR-negative prostate cancer cells. Oral herbal extract (4 or 40 mg/kg/d for 24-28 days) attenuated the growth of prostate tumors in nude mice implanted at both subcutaneous (31% and 44%, respectively) and orthotopic (49% and 49%, respectively) sites. The tumor suppression effects were associated with increased apoptosis and lower proliferation in tumor cells as well as reduced tumor angiogenesis. The antitumor effect of W. chinensis extract was correlated with accumulation of the principle active compounds wedelolactone, luteolin, and apigenin in vivo. Conclusion: Anticancer action of W. chinensis extract was due to three active compounds that inhibit the AR signaling pathway. Oral administration of W. chinensis extract impeded prostate cancer tumorigenesis. Future studies of W. chinensis for chemoprevention or complementary medicine against prostate cancer in humans are thus warranted. (Clin Cancer Res 2009;15(17):5435-44) Carcinoma of the prostate gland is the most common malignancy in males in the western world (1). Despite the low incidence of prostate cancer in oriental countries, statistics from Taiwan reveal prostate cancer deaths have continued to increase in the past two decades.5 Androgen ablation therapy remains the most effective means of treating metastatic prostate cancer tumors (2, 3). This therapy often induces apoptosis in the majority of prostate cancer cells by blocking testosterone signaling at the androgen receptor (AR) and lowering the expression of AR-regulated genes including prostate-specific antigen (PSA), a serologic biomarker up-regulated by androgens (4, 5). The CWR22 tumor model, based on implantation of a human prostate cancer in an athymic nude mouse, progresses in the same androgen-dependent manner as observed in clinical prostate cancer tumors. Further development from castrationrelapsed CWR22 tumors created subline tumors and a cell line, 22Rv1, which retain expression of AR and show androgen stimulation of neoplasia (6, 7). Earlier, we devised the androgeninduced PSA-luciferase activity in prostate cancer 22Rv1 cells and a derived stable clone, 103E, as a cell-based assay to detect any AR modulator effect of herbal extract or compounds (8-10). To determine whether herbal remedies or compounds can inhibit prostate cancer growth in o...
This letter investigates the degradation mechanism of amorphous indium-gallium-zinc oxide thin-film transistors under gate-bias stress. The larger Vt shift under positive AC gate-bias stress when compared to DC operation indicates that an extra electron trapping mechanism occurs during rising/falling time during the AC pulse period. In contrast, the degradation behavior under illuminated negative gate-bias stress exhibits the opposite degradation tendency. Since electron and hole trapping are the dominant degradation mechanisms under positive and illuminated negative gate-bias stress, respectively, the different degradation tendencies under AC/DC operation can be attributed to the different trapping efficiency of electrons and holes.
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