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Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.

The unique characteristic of head and neck squamous cell carcinoma (HNSCC) is that local invasion rather than distant metastasis is the major route for dissemination. Therefore, targeting the locally invasive cancer cells is more important than preventing systemic metastasis in HNSCC and other invasive-predominant cancers. We previously demonstrate a specific mechanism for HNSCC local invasion: the epithelial-mesenchymal transition (EMT) regulator Twist1 represses microRNA let-7i expression, leading to the activation of the small GTPase Rac1 and engendering the mesenchymal-mode movement in three-dimensional (3D) culture. However, targeting the EMT regulator is relatively difficult because of its transcription factor nature and the strategy for confining HNSCC invasion to facilitate local treatment is limited. Imipramine blue (IB) is a newly identified anti-invasive compound that effectively inhibits glioma invasion. Here we demonstrate that in HNSCC cells, a noncytotoxic dose of IB represses mesenchymal-mode migration in two-and-a-half-dimensional/3D culture system. IB suppresses EMT and stemness of HNSCC cells through inhibition of Twist1-mediated let-7i downregulation and Rac1 activation and the EMT signalling. Mechanistically, IB inhibits reactive oxygen species-induced nuclear factor-κB pathway activation. Importantly, IB promotes degradation of the EMT inducer Twist1 by enhancing F-box and leucine-rich repeat protein 14 (FBXL14)-mediated polyubiquitination of Twist1. Together, this study demonstrates the potent anti-invasion and EMT-inhibition effect of IB, suggesting the potential of IB in treating local invasion-predominant cancers.

BackgroundTo evaluate the possible association between paediatric head computed tomography (CT) examination and increased subsequent risk of malignancy and benign brain tumour.MethodsIn the exposed cohort, 24 418 participants under 18 years of age, who underwent head CT examination between 1998 and 2006, were identified from the Taiwan National Health Insurance Research Database (NHIRD). Patients were followed up until a diagnosis of malignant disease or benign brain tumour, withdrawal from the National Health Insurance (NHI) system, or at the end of 2008.ResultsThe overall risk was not significantly different in the two cohorts (incidence rate=36.72 per 100 000 person-years in the exposed cohort, 28.48 per 100 000 person-years in the unexposed cohort, hazard ratio (HR)=1.29, 95% confidence interval (CI)=0.90-1.85). The risk of benign brain tumour was significantly higher in the exposed cohort than in the unexposed cohort (HR=2.97, 95% CI=1.49-5.93). The frequency of CT examination showed strong correlation with the subsequent overall risk of malignancy and benign brain tumour.ConclusionsWe found that paediatric head CT examination was associated with an increased incidence of benign brain tumour. A large-scale study with longer follow-up is necessary to confirm this result.

We present a method for learning feature descriptors using multiple images, motivated by the problems of mobile robot navigation and localization. The technique uses the relative simplicity of small baseline tracking in image sequences to develop descriptors suitable for the more challenging task of wide baseline matching across significant viewpoint changes. The variations in the appearance of each feature are learned using kernel principal component analysis (KPCA) over the course of image sequences. An approximate version of KPCA is applied to reduce the computational complexity of the algorithms and yield a compact representation. Our experiments demonstrate robustness to wide appearance variations on non-planar surfaces, including changes in illumination, viewpoint, scale, and geometry of the scene.

We present a method for learning feature descriptors using multiple images, motivated by the problems of mobile robot navigation and localization. The technique uses the relative simplicity of small baseline tracking in image sequences to develop descriptors suitable for the more challenging task of wide baseline matching across significant viewpoint changes. The variations in the appearance of each feature are learned using kernel principal component analysis (KPCA) over the course of image sequences. An approximate version of KPCA is applied to reduce the computational complexity of the algorithms and yield a compact representation. Our experiments demonstrate robustness to wide appearance variations on non-planar surfaces, including changes in illumination, viewpoint, scale, and geometry of the scene.

A gap exists between students' employment needs and higher education offerings. Thus, developing the capability to meet the learning needs of students in supporting their future aspirations should be facilitated. To bridge this gap in practice, this study uses multiple methods (i.e., nominal group technique and instructional systems development) and robust tests (e.g., reliability and validity) to develop a diagnosis system of work-related capabilities. The research participants are twofold. At the early stage, this study invites three professors and three senior Human Resources managers to join the panel and help this study develop required capabilities. At the design and implementation stages, the research participants are freshman students at a famous university in Taiwan. This system enables college students to evaluate their capability scores by comparing themselves with the performances of prior students. The diagnosis results not only help students make learning plans during their university education, but also assist educators in adjusting the structure of the curriculum. Future studies are invited to use or adapt the assessment of work-related capabilities, as well as proposed system procedure and architecture this study developed.