Never in Mitosis (NIMA) Related Kinase 2 (NEK2) plays a key role in regulating mitotic processes, including centrosome duplication and separation, microtubule stabilization, kinetochore attachment and spindle assembly checkpoint. NEK2 is aberrantly overexpressed in a wide variety of human cancers and has been implicated in various aspects of malignant transformation, including tumorigenesis, drug resistance and tumor progression. The close relationship between NEK2 and cancer has made it an attractive target for anticancer therapeutic development; however, the mechanisms of how NEK2 coordinates altered signaling to malignant transformation remains unclear. In this paper, we discuss the functional roles of NEK2 in cancer development; highlight some of the significant NEK2 signaling in cancer, and summarize recent advances in the development of NEK2 inhibitors.

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Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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Campaigns designed to promote sun protection often fail to induce long-term changes in behaviour. There is limited information on patients with low compliance to sun protection recommendations from dermatologists.
To characterize dermatology patients at higher risk of low compliance to sun protection measures, and to investigate the relationship between sun protection behaviour, knowledge about accurate sun protection recommendations, ultraviolet (UV)-associated risks and level of UV exposure.
An anonymous self-administered multiple-choice questionnaire was distributed by dermatologists to patients receiving a sunscreen prescription. Four domains were explored: sun protection behaviour, sun protection knowledge, level of UV exposure and knowledge about UV-associated risks. We modelled sun protection behaviour and determined factors associated with low compliance to sun protection measures.
In total 2215 questionnaires were analysed. Patients stratified by risk who better complied with sun protection measures had a better knowledge of UV-associated risks (mean score 14·45 ± 3·20 vs. 12·75 ± 3·29 and 11·20 ± 3·80, P < 0·0001) and sun protection measures (mean score 12·08 ± 2·79 vs. 10·68 ± 3·11 and 9·00 ± 3·63, P < 0·0001). Patients who better complied with sun protection measures also reported higher levels of sun exposure (mean score 4·24 ± 2·26 vs. 4·02 ± 2·05 and 3·34 ± 2·14, P < 0·0001). Factors associated with low adherence to sun protection behaviour were age below 20 or over 64 years, male sex, lower knowledge about accurate sun protection recommendations and UV-associated risks, and low UV exposure.
This study shows the complex relationship between UV exposure, knowledge about UV-associated risks, and knowledge about sun protection recommendations and behaviour. Future skin cancer prevention programmes should focus on specific populations with low sun protection behaviour and high UV exposure.
© 2014 British Association of Dermatologists.

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Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.
Copyright © 2013 American Society for Bone and Mineral Research.

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Our purpose was to characterize the occurrence of gastrointestinal (GI) events among women on oral bisphosphonate therapy.
This was a retrospective cohort study that used a United States (US) claims database. The study period was from January 1, 2000, to December 31, 2011. The index date was the date of the first oral bisphosphonate (alendronate, ibandronate, or risedronate) prescription and occurred between January 1, 2001, and December 31, 2010. The pre- and post-index periods were the 1-year periods before and after the index date, respectively. The analysis included women with osteoporosis aged ≥55 years at the index date who were naive to all osteoporosis treatments before the index date and were continuously enrolled in the health plan for at least 1 year before and 1 year after the index date. Patients with a diagnosis of malignant neoplasm during the pre- or post-index periods or a diagnosis of Paget disease anytime in the claims history were excluded. The occurrence of GI events (defined as esophagitis; gastroesophageal reflux disease; ulcer, stricture, perforation, or hemorrhage of the esophagus; gastric, duodenal, or peptic ulcer; acute gastritis; duodenitis; GI hemorrhage; nausea/vomiting; or dysphagia) was assessed during the pre-index period and at 3, 6, and 12 months in the post-index period. The rate of GI events was defined as the percentage of patients having at least 1 GI event in each analysis period (ie, pre-index and post-index periods). GI events in the post-index period were also stratified by the presence of GI events in the pre-index period.
A total of 75,593 women were included in the analysis. The average age at the index date was 64.4 years. Gastroprotective agents were used by 17.9% of patients. Approximately one fourth of patients (26.6%; n = 20,073) had ≥1 GI events in the pre-index period. Approximately the same proportion of patients (28.0%; n = 21,142) experienced GI events in the post-index period. The cumulative rate of GI events during the post-index period was higher among patients who had GI events in the pre-index period (51.2%) than among patients without a GI event in the pre-index period (19.6%).
Among women with osteoporosis enrolled in a US commercial plan, GI events were common regardless of bisphosphonate use. Approximately one fourth of US women on bisphosphonate therapy experienced GI events within the year after initiation of therapy, and one half of US women with a previous GI event had another event while taking bisphosphonates.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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