The Aurora kinase family comprises three serine/threonine kinases, Aurora-A, -B and -C. Among these, Aurora-A and -B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases have been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis.Aurora kinases therefore represent promising targets for anticancer therapeutics. So far, a number of Aurora kinase inhibitors (AKIs) have been generated, of which some are currently undergoing clinical trials. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in contributing tumorigenesis, the recent preclinical and clinical AKI data and potential alternative routes for Aurora-A kinase inhibition.Key words: Aurora-A; Aurora kinase inhibitors (AKIs); targeted cancer therapy; mitosis; tumorigenesis 3 In mammals, the Aurora family of serine/threonine kinases consists of Aurora-A, -B and -C, which share a highly conserved catalytic domain containing auto-phosphorylating sites. The catalytic domain is flanked by a very short C-terminal tail and an N-terminal domain of variable lengths 1,2 . In the C-terminal regions of Auroras, there exists a short amino-acid peptide motif called "destruction box" (D-box). The D-box is recognized by the anaphase-promoting complex/cyclosome (APC/C) for degradation through the ubiquitin/proteasome-dependent pathway ( Fig. 1A). Despite their structural similarities, the expression patterns, cellular localization and physiological functions of these three Aurora kinases are largely distinct.Aurora-A and -B are commonly expressed in most cell types whereas Aurora-C is specially expressed in the testis. Both Aurora-A and -B play key roles in regulating cell-cycle progression from G2 through to cytokinesis. Aurora-C has a unique physiological role in spermatogenesis and functions as a chromosomal passenger protein similar to Aurora-B in mitosis 2 .Overexpression of Aurora-A and -B have been found in multiple types of cancer (Table 1), which function as oncogenes to promote tumorigenesis, providing potential targets for cancer therapy.However, comparatively little information is available regarding the roles of Aurora-C in cancer.In this review, we will focus on recent progress as well as the main unresolved issues associated with Aurora-A in cancer.4 1 FUNCTIONS OF AURORA-A In normal cells a. MitosisIn G1 phase, the level of Aurora-A is rarely detectable. During S phase, a small proportion of Aurora-A is first detected at centrosomes. At late G2 phase, Aurora-A accumulates evidently at centrosomes and becomes activated 3 . During prometaphase and metaphase, active Aurora-A localizes on bipolar spindles and spindle poles after...

Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress–induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A–dependent (LDHA-dependent) metabolic rewiring. Chronic stress–induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress–induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer.

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Drawing on affective events theory (AET) and workplace incivility spiral, this study tested a conditional process model to explain, when and how, affective workplace events (workplace ostracism and workplace incivility) affect employees’ emotions and work effort. Data for this cross-sectional study were collected via an online survey from 251 employees at three public sector universities in Quetta, Pakistan. Results indicated that both ostracism and incivility encumber work effort, and that one way via which ostracism negatively affects work effort is by provoking targets’ negative affect (NA). Results also revealed that workplace incivility exacerbated positive relationship of ostracism and NA such that this relationship was stronger when incivility was high and weaker when incivility was low. Moreover, the indirect effects of ostracism on work effort were also contingent on workplace incivility. Practical implications are discussed at the end.

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This study explores the research paradigms of contemporary business ethics research in 2001–2008. With citation data from the top two business ethics journals included in the Social Sciences Citation Index, this study conducts citation and co‐citation analysis to identify the most important publications, scholars, and research themes in the business ethics area and then maps the intellectual structure of business ethics studies between 2001 and 2008. The results show that current business ethics studies cluster around four major research themes, including morality and social contract theory, ethical decision making, corporate social responsibility, and stakeholder theory. This study helps profile the invisible network of knowledge production in business ethics and provides important insights on current research paradigms of business ethics studies.

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Background: Cancer patients suffer from diverse symptoms, including depression, anxiety, pain, and fatigue and lower quality of life (QoL) during disease progression. This study aimed to evaluate the benefits of Traditional Chinese Medicine psychobehavioral interventions (TCM PBIs) on improving QoL by meta-analysis.