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Long non-coding RNAs (lncRNAs) govern gene expression by competitively binding to microRNA response elements (MREs). Although they were initially considered as transcriptional noise, lncRNAs have attracted increased attention in oncology. Dysregulation of lncRNAs occurs in various types of human tumor, including esophageal adenocarcinoma (EAC). However, the functions of these cancer-associated lncRNAs and of their related competitive endogenous RNA (ceRNA) network in EAC remains unknown. To determine the relevant potential mechanisms, the present study analyzed the transcriptome sequencing data and clinical information of 79 patients with EAC, including 79 tumor samples and 11 normal samples, which were obtained from The Cancer Genome Atlas esophageal cancer project. The edgeR v3.25.0 software was used for differential gene expression analysis. The results exhibited 561 cancer-associated lncRNAs with a >2.0-fold change and a false discovery rate-adjusted P<0.01. Among these lncRNAs, 26 were significantly associated with patient overall survival. According to data from bioinformatics databases and differentially expressed RNAs, an lncRNA-regulated ceRNA network for EAC was constructed. The results demonstrated that the aberrantly expressed lncRNA-associated ceRNA network included 37 EAC cancer-associated lncRNAs, five miRNAs and 13 mRNAs. In conclusion, the present study identified novel lncRNAs as candidate prognostic biomarkers and revealed a potential regulatory network of gene expression in EAC., (Copyright: © Yu et al.)

Non-small cell lung cancer (NSCLC), as the most common histological type of lung cancer with high mortality rates, has been widely treated by Compound Kushen Injection (CKI) in China. Among various active components with many pharmacologic properties, matrine, oxymatrine, sophoridine, oxysophocarpine and N-methylcytisine, are the main bioactive alkaloids of CKI. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify the five alkaloids in nude rat plasma in this study. With aminopyrine as internal standard (IS), plasma samples were extracted by alkalified chloroform and then separated on an Agela Venusil MP C18 column (2.1 mm × 100 mm, 3 μm) using gradient elution. Water containing 10 mmol/L ammonium acetate (adjusted to pH 8.0 with ammonia water, A) and methanol (B) constituted the mobile phase system. Notably, the analysis was rapid and accurate due to a short running time of 6 min and a stereoisomer separation between matrine and sophoridine. Detection was implemented in MRM mode with an electrospray positive ionization source. Validation parameters were all in accordance with current criterion. The established method has been effectively employed to compare the pharmacokinetic behaviors of five alkaloids between normal and NSCLC nude rats. Results indicated that the pharmacokinetic behaviors of oxymatrine, sophoridine and N-methylcytisine from CKI could be changed when it was intravenously administrated to the NSCLC model rats, and possible reasons have been proposed. This study could provide meaningful reference for further clinical medication of CKI when combined with time-effect curve and clinical symptoms., (Copyright © 2019. Published by Elsevier B.V.)

In recent years, biological nanomedicine-based biomaterials have an extreme attention for biomedical uses, herein we examined a novel kind advance of photoluminescent Graphene quandum dots encapsulated mesoporous nanoparticles (GND@MSNs) encapsulated by well-known anticancer drugs Doxorubicin (DOX) and Cyclosporin (CsA) for lung carcinoma. Electron microscopic technique exhibit the nanostructure and spherical morphology of GND@MSNs+DOX+CsA with mean size ≈110 nm. Moreover, Dynamic Light Scattering (DLS) exposed that blended GND@MSNs+DOX+CsA nanoparticles were highly stable with extremely negatively charged nanoparticles. Raman investigation was done on the all naturally dynamic nanoparticles containing shed graphene to survey the blend condition of the graphene inside the silica mesoporous nanoparticles. GND@MSNs+DOX+CsA provided an outstanding anti-cancer efficiency against the lung cancer cell lines (i.e., A549 and HEL-299). MTT assay monitored that GND@MSNs, GND@MSNs+DOX and GND@MSNs+DOX+CsA have a robust toxicity behaviour on the A549 and HEL-299 model lung cancer cell lines. Additionally, investigation of the cell death was found on AO-EB, Hoechst 33452 staining and flowcytometry techniques. Furthermore, the DNA damage were confirmed by cell cycle arrest and comet assay. Hence, we suggesting that these GND@MSNs+DOX+CsA could be applied as auspicious drug vesicles for novel lung cancer therapeutic potential and new openings to solve the complexity of lung cancer in the care of cancer patients., (Copyright © 2019. Published by Elsevier B.V.)

The epidemiological and prognostic data focusing on clear cell renal cell carcinoma (ccRCC) are rarely presented. This study was aimed to define the frequency, incidence, and survival outcomes of ccRCC in the United States.The Surveillance, Epidemiology, and End Results (SEER) database was searched for patients with ccRCC from 1973 to 2014. Two patient cohorts were utilized: patient cohorts of SEER 18 registries and 9 registries. Overall survival was determined with Kaplan-Meier method and compared across groups with log-rank test.The incidence rate of ccRCC increased with advancing age, peaked in individuals aged 60 to 79 years, and declined in individuals aged ≥80 years. The incidence rate of ccRCC was significantly higher in males than females (1.94: 1, P < .0001), in Whites than Blacks or others (1:0.79:0.91, P < .0001). The incidence rate of ccRCC with right side as primary origin was slightly but significantly higher than that with left side as primary origin (1:0.96, P = .0006). The incidence rate of ccRCC in Grade II was higher than other grades. Generally, the incidence rates of ccRCC in most circumstances started to surge in the middle 1990s. Survival outcomes of ccRCC worsened with advancing age at diagnosis, tumor grade, and stage. A better prognosis was observed in females than males, in Whites than Blacks, and in individuals diagnosed in 2006 to 2014 than 1973 to 2005.To the best of our knowledge, the present study firstly presented long-term and updated epidemiological and prognostic data concerning ccRCC in the United States. Significant differences in incidence rates and survival outcomes stratified by different variables were identified.

Whistles emitted by Indo-Pacific humpback dolphins in Zhanjiang waters, China, were collected by using autonomous acoustic recorders. A total of 529 whistles with clear contours and signal-to-noise ratio higher than 10 dB were extracted for analysis. The fundamental frequencies and durations of analyzed whistles were in ranges of 1785-21 675 Hz and 30-1973 ms, respectively. Six tonal types were identified: constant, downsweep, upsweep, concave, convex, and sine whistles. Constant type was the most dominant tonal type, accounting for 32.51% of all whistles, followed by sine type, accounting for 19.66% of all whistles. This paper examined 17 whistle parameters, which showed significant differences among the six tonal types. Whistles without inflections, gaps, and stairs accounted for 62.6%, 80.6%, and 68.6% of all whistles, respectively. Significant intraspecific differences in all duration and frequency parameters of dolphin whistles were found between this study and the study in Malaysia. Except for start frequency, maximum frequency and the number of harmonics, all whistle parameters showed significant differences between this study and the study conducted in Sanniang Bay, China. The intraspecific differences in vocalizations for this species may be related to macro-geographic and/or environmental variations among waters, suggesting a potential geographic isolation among populations of Indo-Pacific humpback dolphins.

This study explores important factors of assistive technology (AT) and evaluates their relative impact on AT effectiveness and retention. Questionnaire based survey is used for data collection from 327 people with dementia (PWD). This empirical study uses statistical techniques including exploratory factor analysis for factor identification, linear regression for impact study, Kruskal Wallis H and Mann Whitney U tests for the statistical significant study in terms of demographic and characteristics. The exploratory factor analysis results into 11 factors: operational support, physical support, psychological support, social support, cultural match, reduced external help, affordability, travel help, compatibility, effectiveness and retention. The results reveal that social support, psychological support and travel help and reduced external help strongly impact on AT effectiveness and retention. The users are motivated by socialization support through using AT without any external help. The use of AT during travelling improves confidence of the PWD and helps them psychologically.

Objectives: The objectives of this study were to investigate new nurses' experiences of workplace incivility; verify the mediating role of work ability in the relationship between workplace incivility and job performance and examine the moderating role of career expectations in the relationship between workplace incivility and job performance., Design: This cross-sectional survey was conducted in China in May 2016., Settings: The research settings included 54 cities across 29 provinces of China., Participants: Of the 903 participants recruited, 696 new nurses (<3 years of nursing experience) agreed to complete the online questionnaire of the study. The effective response rate was 77.1%. The inclusion criteria were voluntary participation, <3 years of nursing experience and recognition as a registered nurse. The exclusion criteria were refusal to participate, >3 years of nursing experience or not recognised as a registered nurse., Results: New nurses (60.7%) experienced some level of workplace incivility in the previous year, and it was more frequent among those with higher educational degrees. Work ability mediated the relationship between workplace incivility and job performance, and this relationship was moderated by career expectations., Conclusion: Incivility towards new nurses was relatively common in the workplace. Workplace incivility impairs job performance by weakening the work ability of new nurses. Higher career expectations may buffer workplace incivility and contribute to the maintenance of job performance by buffering the detrimental effects of workplace incivility., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this study is to describe the current state of workplace violence (WPV) and compassionate behaviour towards nurses and to explain how they affect nurses' stress, sleep quality and subjective health status., Design: A cross-sectional online survey study., Setting: The survey was conducted across eight provinces in China., Participants: A total of 1024 nurses were recruited to complete an online questionnaire survey from February to May 2016 in China., Results: Approximately 75.4% participants had experienced some form of violence. Most of the participants experienced WPV such as verbal violence (65.2%), made difficulties (54.5%), tarnished reputation (37.5%), mob behaviour (34.9%), intimidation behaviour (18.8%), physical violence (14.6%) and sexual harassment (5.9%). In this study, 92.4% participants experienced compassionate behaviour from their coworkers (84.9%), supervisors (67.3%), and from their patients (65.3%). The results show that the exposure to WPV behaviour significantly affected the psychological stress (β=0.295, p<0.01), sleep quality (β=-0.198, p<0.01) and subjective health status (β=-0.252, p<0.01) of nurses. The exposure to compassionate behaviour significantly affected the psychological stress (β=-0.229, p<0.01), sleep quality (β=0.326, p<0.01) and subjective health status (β=0.342, p<0.01) of nurses. The results of the mediation analysis showed that psychological stress is a partial mediator in the relationship between violence and sleep quality (β=-0.458, p<0.01) and between violence and subjective health (β=-0.425, p<0.01). Moreover, psychological stress also partially mediated the relationship between compassionate behaviour and sleep quality (β=-0.473, p<0.01), and between compassionate behaviour and subjective health (β=-0.405, p<0.01)., Conclusion: In China, most nurses have experienced different forms of WPV from patients and/or their relatives, as well as experiencing various forms of compassionate behaviour from their coworkers, supervisors and/or patients. This study investigates the prevalence of the different types of WPV and compassionate behaviour. Several aspects of harm to nurses from exposure to violence is confirmed. We found that WPV can damage nurses' health outcomes, while compassionate behaviours were beneficial to their health outcomes. A harmonious nursing environment should be provided to minimise threats to nurses' health status., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Increasing evidence indicates that microRNAs dysregulation contributes to the development and progression of various human cancers, including oral squamous cell carcinoma (OSCC). However, little is known about the potential role of microRNA-92a (miR-92a) in OSCC. Thus, the aim of this study was to investigate the effects of miR-92a expression on OSCC cell growth, apoptosis and tumorigenesis. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-92a in primary tumor tissues and OSCC cell lines. The effects of miR-92a on cell proliferation, cell cycle, apoptosis and tumorigenesis of OSCC cells were explored after miR-92a expression was increased or decreased in the UM1 and Tca-8113 cells, respectively. The 3'-untranslated region (3'-UTR) of FOXP1 combined with miR-92a was analyzed with dual-luciferase reporter assays. The level of miR-92a expression was significantly up-regulated in the OSCC tissues and cell lines. The up-regulation of miR-92a expression promoted UM1 cell proliferation, cell cycle progression in vitro and tumor growth in nude mice, but its expression reduction inhibited these processes and induced apoptosis in Tca-8113 cells. Additionally, miR-92a expression was inversely correlated with FOXP1 protein expression in the OSCC tissues and cell lines. Furthermore, FOXP1 was identified as a functional downstream target of miR-92a by directly targeting the 3'-UTR of FOXP1. These findings indicate that miR-92a may act as a tumor inducer in OSCC by suppressing FOXP1 expression, and it could serve as a potential therapeutic target for OSCC treatment., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background and Aim: Some cancer-specific miRNAs are dysregulated in pancreatic adenocarcinoma (PAAD) and involved in cell autophagy, differentiation, proliferation, migration, invasion, and malignant transformation. The aim of our study was to determine a panel of new diagnostic and prognostic biomarkers for PAAD., Methods: We conducted a comprehensive analysis of global miRNA-expression profiles and corresponding prognosis information of 168 PAAD patients from the Cancer Genome Atlas data set. A total of 16 differentially expressed miRNAs were identified as aberrantly expressed in PAAD, and six of these were evaluated for use as diagnostic markers for PAAD. Next, we confirmed a two-miRNA signature significantly associated with PAAD patient diagnosis and outcome prediction., Results: The panel of two miRNAs showed outstanding diagnostic performance, with sensitivity of 100% and specificity of 87.5%. Finally, we divided the PAAD patients into high-risk and low-risk groups based on the expression profile of the two miRNAs. Kaplan-Meier analysis demonstrated that patients in the high-risk group had significantly worse prognosis than patients in the low-risk group. Univariate and multivariate Cox regression analysis showed that the two-miRNA signature was an independent prognostic factor for the overall survival of PAAD patients., Conclusion: Taken together, the two-miRNA signature may serve as an accurate and sensitive biomarker for diagnosis and PAAD-outcome prediction, facilitating the diagnosis and potentially improving treatment outcome of PAAD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Breast cancer was a malignant tumor seriously threatening the life of women in the world. But the prognosis of breast cancer patients was not so satisfactory due to the limited effective therapeutics. The heterogeneity decided that more than one gene or one signaling pathway was responsible for the initiation or progression of breast cancer. DDX51 gene was a member of RNA helicases family in charge of regulation of RNA metabolism. And DDX51 gene was shown to promote proliferation in NSCLC. But we firstly reported the abundant expression of DDX51 gene in both the breast cancer tissues and cell lines in this study. And DDX51 expression was shown to be associated with TNM stage and prognosis in breast cancer patients. When DDX51 was successfully knocked down, either proliferation or DNA synthesis of MCF-7 cells was inhibited. But the ability of migration and invasion of MCF-7 cells was not affected by DDX51 gene. Furthermore, DDX51 knockdown was accompanied by inhibition of Wnt/β-catenin signaling because expression of critical members such as β-catenin, cyclin D1, TCF/LEF, and DKK1 were all affected. Therefore, this study proved that DDX51 gene promoted proliferation in MCF-7 cells by regulating Wnt/β-catenin signaling pathway and showed clinical significance in breast cancer. This study provides us a new promising hope for treatment of patients with breast cancer., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: This study presents an overview of recent research activities in assistive technology (AT) for people with dementia. Bibliometric studies are used to explore breadth and depth of different research areas, yet this method has not yet been fully utilised in AT research for people with dementia., Methods: The bibliometric method was used for collecting studies related to AT. Based on inclusion/exclusion criteria, the AT studies with a focus on people with dementia are considered., Study Scope: The study is based on factors such as number of publications, citations per paper, collaborative research output, P-Index, major research and application areas and national dementia strategies., Data Collection: Data were collected from 2000 to 2014 in AT research. The top 10 countries are selected based on their research outputs., Results: USA emerged as the leading contributor with 503 publications and an annual growth rate of 16%, followed by UK with 399 publications and growth rate of 22%. Germany with 101 publications is on the 6th place, but it has a higher citation rate 16.43% as compared to USA (13.34%). Although all 10 countries show good collaborative research output, Italy, Spain and the Netherlands emerge as top collaborative research contributors with high percentages (84%, 84% and 79%). All the top 10 countries, except Canada, Germany and Spain, have national dementia strategies in place., Conclusion: The overall analysis shows that USA and UK are working extensively in AT research for people with dementia. Both these countries also have well established national dementia strategies., (© 2017 Health Libraries Group.)

In wireless body area sensor networks (WBASNs), Quality of Service (QoS) provision for patient monitoring systems in terms of time-critical deadlines, high throughput and energy efficiency is a challenging task. The periodic data from these systems generates a large number of small packets in a short time period which needs an efficient channel access mechanism. The IEEE 802.15.4 standard is recommended for low power devices and widely used for many wireless sensor networks applications. It provides a hybrid channel access mechanism at the Media Access Control (MAC) layer which plays a key role in overall successful transmission in WBASNs. There are many WBASN's MAC protocols that use this hybrid channel access mechanism in variety of sensor applications. However, these protocols are less efficient for patient monitoring systems where life critical data requires limited delay, high throughput and energy efficient communication simultaneously. To address these issues, this paper proposes a frame aggregation scheme by using the aggregated-MAC protocol data unit (A-MPDU) which works with the IEEE 802.15.4 MAC layer. To implement the scheme accurately, we develop a traffic patterns analysis mechanism to understand the requirements of the sensor nodes in patient monitoring systems, then model the channel access to find the performance gap on the basis of obtained requirements, finally propose the design based on the needs of patient monitoring systems. The mechanism is initially verified using numerical modelling and then simulation is conducted using NS2.29, Castalia 3.2 and OMNeT++. The proposed scheme provides the optimal performance considering the required QoS.

Many studies use surface electromyogram (sEMG) signals to estimate the joint angle, for control of upper-limb exoskeletons and prostheses. However, several practical factors still affect its clinical applicability. One of these factors is the load variation during daily use. This paper demonstrates that the load variation can have a substantial impact on performance of elbow angle estimation. This impact leads an increase in mean RMSE (Root-Mean-Square Error) from 7.86 ° to 20.44 ° in our experimental test. Therefore, we propose three methods to address this issue: 1) pooling the training data from all loads together to form the pooled training data for the training model; 2) adding the measured load value (force sensor) as an additional input; and 3) developing a two-step hybrid estimation approach based on load and sEMG. Experiments are conducted with five subjects to investigate the feasibility of the proposed three methods. The results show that the mean RMSE is reduced from 20.44 ° to 13.54 ° using method one, 10.47 ° using method two, and 8.48 ° using method three, respectively. Our study indicates that 1) the proposed methods can improve performance and stability on joint angle estimation and 2) sensor fusion (sEMG sensor and force sensor) is an efficient way to resolve the adverse effect of load variation.

Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer., Competing Interests: The authors declare no conflicts.

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer.

With the advent of new agents targeting CD20, Bruton's tyrosine kinase, and phosphoinositol-3 kinase for chronic lymphoid leukemia (CLL), more treatment options exist than ever before. B-cell lymphoma-2 (BCL-2) plays a major role in cellular apoptosis and is a druggable target. Small molecule inhibitors of BCL-2 are in active clinical studies. ABT-199 (venetoclax, RG7601, GDC-0199) has been granted breakthrough designation by FDA for relapsed or refractory CLL with 17p deletion. In this review, we summarized the latest clinical development of ABT-199/venetoclax and other novel agents targeting the BCL-2 proteins.

Anaplastic lymphoma kinase 1 (ALK-1) is a member of the insulin receptor tyrosine kinase family. ALK-1 was initially found in anaplastic large cell lymphoma (ALCL). ALK mutations have also been implicated in the pathogenesis of non-small cell lung cancer (NSCLC) and other solid tumors. Multiple small molecule inhibitors with activity against ALK and related oncoproteins are under clinical development. Two of them, crizotinib and ceritinib, have been approved by FDA for treatment of locally advanced and metastatic NSCLC. More agents (alectinib, ASP3026, X396) with improved safety, selectivity, and potency are in the pipeline. Dual inhibitors targeting ALK and EGFRm (AP26113), TRK (TSR011), FAK (CEP-37440), or ROS1 (RXDX-101, PF-06463922) are under active clinical development.

Research on the effects of entrepreneurial stressors is limited, especially regarding its relation to the burnout that frequently occurs in the process of starting and growing a venture. The effect of the role of entrepreneurial stressors (workload, competitive comparison, demands-of-knowledge, managing responsibility, and resource requirements) on burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) was examined in a Chinese sample of entrepreneurs. Entrepreneurial stressors emerged as a significant predictor of burnout in the process of entrepreneurship in a sample of 289 entrepreneurs (63.8% men; M age = 26.2 yr.; 39.6% of their parents have been self-employed). The findings clarify the functional relationship between entrepreneurial stressors and burnout. Entrepreneurial stressors played multiple roles. Managing responsibility was an active contributor to the sense of achievement and to emotional exhaustion. Workload was an active contributor to emotional exhaustion. Demands-of-knowledge negatively affected three of the dimensions of burnout. Theoretical and practical implications for management of the effect of these relationships are discussed.

Activity recognition of an elderly person can be used to provide information and intelligent services to health care professionals, carers, elderly people, and their families so that the elderly people can remain at homes independently. This study investigates the use and contribution of wrist-worn multisensors for activity recognition. We found that accelerometers are the most important sensors and heart rate data can be used to boost classification of activities with diverse heart rates. We propose a genetic algorithm-based fusion weight selection (GAFW) approach which utilizes GA to find fusion weights. For all possible classifier combinations and fusion methods, the study shows that 98% of times GAFW can achieve equal or higher accuracy than the best classifier within the group.

Dysregulation of the nucleo-cytoplasmic transport of proteins plays an important role in carcinogenesis. The nuclear export of proteins depends on the activity of transport proteins, exportins. Exportins belong to the karyopherin β superfamily. Exportin-1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), mediates transport of around 220 proteins. In this review, we summarized the development of a new class of antitumor drugs, collectively known as selective inhibitors of nuclear export (SINE). KPT-330 (selinexor) as an oral agent is showing activities in early clinical trials in both solid tumors and hematological malignancies.

Objective: To investigate the correlation between Angle's class III patients' occlusion plane and anterior overbite by controlling the changes in occlusion plane during orthodontic treatment., Methods: In total, 90 Angle's class III adult orthodontic patients were selected as the experimental group, and 30 normal adults were selected as the control group. According to the overbite, the class III patients were divided into three groups, and 14 indicators were measured. ANOVA and multiple comparison analysis were used to analyze the difference between class III patients, and linear analysis was used to analyze the correlation between anterior overbite and anterior-posterior occlusion plane., Results: In class Ill patients, posterior occlusion plane and anterior overbite size were negatively correlated (r = -0.24, P < 0.05), whereas anterior occlusal plane and anterior overbite size were positive correlated (r = 0.23, P < 0.05)., Conclusion: The shape of the occlusion plane varies in different anterior overbite patients. During orthodontic treatment in different overbite class III patients, the vertical height of the posterior teeth and the rotation of the occlusion plane should be controlled.

Combination of phenethyl isothiocyanate (PEITC) and paclitaxel (taxol) has been shown to work synergistically to increase apoptosis and cell cycle arrest in breast cancer cells. In this report, we further explored the mechanisms for the synergistic activity of PEITC and taxol in MCF7 and MDA-MB-231 (MB) breast cancer cell lines. By Western blotting analysis, treatment of MCF7 cells with both PEITC and taxol led to a 10.4-fold and 5.96-fold increase in specific acetylation of alpha-tubulin over single agent PEITC and taxol, respectively. This synergistic effect on acetylation of alpha-tubulin was also seen in MB cells. The combination of PEITC and taxol also reduced expressions of cell cycle regulator Cdk1, and anti-apoptotic protein bcl-2, enhanced expression of Bax and cleavage of PARP proteins. In conclusion, this study provided biochemical evidence for the mechanism of synergistic effect between the epigenetic agent PEITC and the chemotherapeutic agent taxol.

This study examined whether combining paclitaxel (taxol) with a novel epigenetic agent phenethyl isothiocyanate (PEITC) will yield a synergistic effect on inhibiting breast cancer cells. Two drug-resistant breast cancer cell lines, MCF7 and MDA-MB-231, were treated with PEITC and taxol. Cell growth, cell cycle, and apoptosis were examined. The combination of PEITC and taxol significantly decreased the IC50 of PEITC and taxol over each agent alone. The combination also increased apoptosis by more than two fold over each single agent in both cell lines. A significant increase of cells in the G2/M phases was detected. In conclusion, the combination of PEITC and taxol exhibits a synergistic effect on growth inhibition in breast cancer cells. This combination deserves further study in vivo.

Rituximab (RTX), a monoclonal antibody (mAb) against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP) remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin's lymphoma (NHL). Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106), ocrelizumab (PRO70769), and third-generation mAbs, AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutumumab).

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.

Aberrant epigenomic alterations include incorrect histone modifications involving altered expression of chromatin-modifying proteins. They contribute to gene silencing and carcinogenesis. The nature of the epigenomic alterations occurring with prostate cancer remains to be fully identified. The acetylation status of histone H3 in human prostate cancer cells was assessed with multiple acetylation sites at N-termini. In contrast to the non-malignant prostatic cell lines RC165N/h and RC170N/h which possess stem cell properties, cancer cell lines LNCaP, DU-145, and PC-3 were either not acetylated or reduced in density (50-70%), at N-termini lysines 9, 14, 18, and 23 of histone H3. Deficient acetylation of histone H3 was similarly detected with clinical prostatic adenocarcinomas as compared to normal tissues. Cancer cell lines and adenocarcinomas exhibited varied acetylation status at particular lysines, indicating the possible presence of deacetylation patterns reflecting individual cancer cell clones. A significantly elevated activity of histone deacetylases (HDACs) was determined in both cancer cell lines and adenocarcinomas. Inhibition of HDACs enhanced histone acetylation and p21 gene expression, indicating that excessive HDAC activity is a requisite for deficient histone acetylation. Deficient histone acetylation involving excessive HDAC activity may represent epigenomic features of prostate cancer cells, and the aberrant enzyme activity is probably an underlying cause of disrupting the epigenomes of normal prostatic cells.

Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22. Around 5-8% of CML develop complex variant Ph translocations involving one or more chromosomal regions besides 9 and 22. Chromosome 3 is not frequently involved in complex translocations in CML. We report in this study a case of CML displaying a t(3;9;22) 3-way translocation. A review of the literature appears to indicate that CML patients with this translocation tend to have an aggressive course and poor outcome. Additional 3-way chromosome translocations associated with CML are also reviewed.

DNA methylation and histone acetylation are two well known epigenetic chromatin modifications. Epigenetic agents leading to DNA hypomethylation and histone hyperacetylation have been approved for treatment of hematological disorders. The first histone deacetylase inhibitor, vorinostat, has been licensed for cutaneous T cell lymphoma treatment. More than 11 new epigenetic agents are in various stages of clinical development for therapy of multiple cancer types. In this review we summarize novel histone deacetylase inhibitors and new regimens from clinical trials for epigenetic therapy of cancer.

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them.

Objective: To understand the relationship between vegetable intake and risk of lung cancer in the Tin Corporation (YTC) miners in Yunnan., Methods: The reproducibility and validity of frequency of vegetable intake in Food Frequency Questionnaire (FFQ) were studied and the correlations between different vegetable intake and frequency and lung cancer relative risk among high risk population of lung cancer by Chi-square, single- and multi-Cox regression were analyzed., Results: Results showed that the reproducibility and validity of wax gourd, cucumber, spinach, wild celery, fresh bush pepper, fresh soybean, sweet potatoes, asparagus, fresh bamboo shoot were good (r = 0.20 - 0.33, P < 0.05); There were significantly different incidences of lung cancer in different frequencies of wax gourd, cucumber, wild celery, fresh bush pepper out of 11 vegetables intake, and also in different total vegetable intakes (chi(2) = 8.83 - 30.64, P < 0.05). 11 vegetables and total vegetable intake were significantly negatively correlated with risks of lung cancer (RR < 1, P < 0.05). Only 2 vegetable frequencies were negatively correlated with risk of lung cancer by adjusting confounders such as age, occupational history, and smoking (P < 0.05)., Conclusion: This suggested that vegetables intake may have a role in decreasing the incidence of lung cancer.