Stress hormones have been implicated in both tumor initiation and progression. Human telomerase reverse transcriptase (hTERT) is overexpressed in cancer cells and associated with malignant tumor progression and poor outcome. We thus sought to determine whether the stress hormone norepinephrine (NE) could induce hTERT expression and subsequently ovarian cancer progression. Unexpectedly, NE induced hTERT transcript and protein expression, and subsequently ovarian cancer cell invasion. Pharmacologic inhibition of β2-adrenergic receptor 2 and protein kinase A, as well as silencing of hypoxia-inducible factor-1α and c-Myc expression, profoundly attenuated NE-induced hTERT expression. Strikingly, stimulation of the cells with NE or ectopic expression of hTERT induced expression of Slug, ovarian cancer cell epithelial-mesenchymal transition (EMT) and invasion. Silencing of hTERT expression abrogated NE-induced ovarian cancer cell invasion, EMT and Slug expression. In addition, silencing of Slug expression significantly inhibited NE- and hTERT-induced ovarian cancer cell EMT and invasion. Moreover, continuous exposure to NE was sufficient to enhance in vivo hTERT expression and metastasis of ovarian cancer cells to the lung. Finally, we provide evidence that hTERT links Src to Slug expression in NE-induced ovarian cancer EMT and metastasis. We thus demonstrate a novel role of hTERT in stress hormone-induced ovarian cancer aggressiveness through inducing Slug, providing novel biomarkers and potential therapeutic targets for ovarian cancer.

Multi-energy imaging is useful for contrast enhancement of lesions, quantitative analysis of specific materials and material separation in the human body. Generally, dual-energy methods are applied to discriminating two materials, but this method cannot discriminate more than two materials. Photon-counting detectors provide spectral information from polyenergetic X-rays using multiple energy bins. In this work, we developed triple-energy X-ray beams using a filter with K-edge energy and applied them experimentally. The energy spectra of triple-energy X-ray beams were assessed by using a spectrometer. The designed triple-energy X-ray beams were validated by measuring quantitative evaluations with mean energy ratio (MER), contrast variation ratio (CVR) and exposure efficiency (EE). Then, triple-energy X-ray beams were used to extract density map of three materials, iodine (I), aluminum (Al) and polymethyl methacrylate (PMMA). The results of the thickness density maps obtained with the developed triple-energy X-ray beams were compared to those acquired using the photon-counting method. As a result, it was found experimentally that the proposed triple-energy X-ray beam technique can separate the three materials as well as the photon-counting method.

Chest digital tomosynthesis (chest DTS) has been recently introduced to overcome the limitations for high patient dose of conventional X-ray radiography and of a cone-beam computed tomography (CBCT) in studies of overlap of anatomical structures. In the present study, we constructed chest DTS system with amorphous-silicon (a-Si) digital flat-panel detector with pixel pitch of 143 × 143 µm 2 based upon filtered backprojection (FBP) reconstruction methods We performed both experiments and systematic simulations using our chest DTS system. The image performances were evaluated by means of root-mean-square error (RMSE) and signal difference-to-noise ratio (SDNR) with respect to scan angles such as ±5 • , ±10 • , ±15 • , and ±20 • . We also performed experiments using our chest DTS system. According to the results, the image performances obtained from chest DTS are improved by using our wide scan angle approach The chest DTS slices showed an improvement in the depth resolution with increasing scan angle. It was found that the optimized filter with a Hanning window to limit the high-frequency components improves image performance because of noise reduction. The chest DTS slices showed an improvement in the depth resolution with increasing scan angle. Both simulation and experimental results showed the same tendency when image performances quantitatively compared. Based on our results, we successfully obtained chest DTS reconstruction images by using a FBP method and promising to application to field of medical imaging. KEYWORDS: Detector design and construction technologies and materials; Medical-image reconstruction methods and algorithms, computer-aided diagnosis; X-ray radiography and digital radiography (DR)