bluuebunny/crossref_metadata_2025 huggingface dataset:
Ordering Chaos: The Performance Consequences of Budgetary Changes
Authors: Flink Carla M.
Published: April 2017

Literature on punctuated equilibrium theory has aimed to explain the causes of policy punctuations. What remain unknown are the consequences of those punctuations (and other size changes) for organizations. Specifically, this study analyzes how budgetary changes affect organizational performance. While the connection between financial resources and organization outcomes has been examined before, the analyses here expand upon previous work by considering the full spectrum of budgetary changes from negative punctuations to positive punctuations. This topic is important given today’s fiscal uncertainty. For managers and bureaucrats, they are expected to stabilize organization outputs no matter what policy inputs are established in the organization. At times, inputs can be erratic and unstable—successful organizations can find a way to maintain performance despite these obstacles. In the context of school districts, this study examines the performance consequences (measured by annual changes in the statewide standardized test pass rate) of different size alterations in instructional expenditures. Results indicate that, generally, organizations are able to dampen the impact of negative financial changes and improve upon budgetary increases in the translation to outcomes.
Lymphoma Classification in Goats
Authors: Kiser Patti K. , Löhr Christiane V.
Published: April 2017

Lymphoma has been described in individual cases for goats but not systematically characterized in a larger cohort. This study aimed to subtype caprine lymphoma based on topographic and subgross distribution, immunophenotype, and cellular morphology following the World Health Organization classification system for hematopoietic tumors in domestic animals. Fifteen caprine lymphoma cases were assessed with 6 submitted as biopsy and 9 for postmortem examination. Goats were predominantly young adult (median 3 years) and dwarf breeds (Pygmy and Pygora). The sexes were similarly represented. Nuclear size was measured relative to red blood cells (RBCs) and then adjusted for species-specific differences and designated small (<3× RBCs), intermediate (3–4× RBCs), or large (>4× RBCs). Using immunohistochemistry, 11 of 15 (73%) goats had T-cell lymphoma (TCL; CD3 positive, CD79α negative) and 4 of 15 (27%) had B-cell lymphoma (BCL; CD79α positive, CD3 negative). A multicentric distribution was most common. TCL generally involved the thoracic cavity and/or neck, suggestive of thymic origin or homing. TCLs were further classified as lymphoblastic lymphomas (3/11; 27%), large granular lymphocyte lymphoma (1/11; 9%), diffuse small lymphocytic lymphomas (3/11; 27%), or peripheral/mature T-cell lymphoma (PTCL) not otherwise specified (4/11 [36%], of which 3 were high grade and 1 intermediate grade). In 1 goat with PTCL, lymph nodes had either paracortical expansion or diffuse infiltrates suggesting transition from nodular to diffuse PTLC. BCLs were classified as diffuse large B-cell lymphoma (2/4; 50%) or B-cell lymphocytic lymphoma intermediate type (2/4; 50%). In contrast to dogs and horses, lymphomas in goats are predominantly TCL and frequently involve the mediastinum.
Optimizing spaceborne LiDAR and very high resolution optical sensor parameters for biomass estimation at ICESat/GLAS footprint level using regression algorithms
Authors: Dhanda P , Nandy S , Kushwaha SPS , Ghosh S , Murthy YVN Krishna , Dadhwal VK
Published: April 2017

Forests sequester large quantity of carbon in their woody biomass and hence accurate estimation of forest biomass is extremely crucial. The present study aims at combining information from spaceborne LiDAR (ICESat/GLAS) and high resolution optical data to estimate forest biomass. Estimation of aboveground biomass (AGB) at ICESat/GLAS footprint level was done by integrating data from multiple sensors using two regression algorithms, viz. random forest (RF) and support vector machine (SVM). The study used forest height and canopy return ratio (rCanopy) for determination of effective size of ICESat/GLAS footprints for field data collection. The forest height was predicted with root mean square error (RMSE) of 1.35 m. The study showed that six most important parameters derived from LiDAR, and passive optical data were able to explain 78.7% (adjusted) variation in the observed AGB with an RMSE of 13.9 Mg ha–1. It was also observed that 15 most important parameters were able to explain 83% (adjusted) variation in the observed AGB. It was found that SVM regression algorithm explained 88.7% of variation in AGB with an RMSE of 13.6 Mg ha–1 on the combined datasets while RF regression algorithm explained 83.5% of variation in AGB with an RMSE of 20.57 Mg ha–1. The study demonstrated that RF regression algorithm performs equally well on datasets irrespective of the correlation of underlying variables with the predicted variable whereas SVM regression was found to perform well on those datasets which had a subset of underlying variables that are correlated with the predicted variable. The study highlighted that sensor integration approach is more accurate than single sensor approach in predicting the AGB.
Evidence of an Intelligent Tutoring System as a Mindtool to Promote Strategic Memory of Expository Texts and Comprehension With Children in Grades 4 and 5
Authors: Wijekumar Kausalai (Kay) , Meyer Bonnie J. F. , Lei Puiwa , Cheng Weiyi , Ji Xuejun , Joshi R. M.
Published: April 2017

Reading and comprehending content area texts require learners to effectively select and encode with hierarchically strategic memory structures in order to combine new information with prior knowledge. Unfortunately, evidence from state and national tests shows that children fail to successfully navigate the reading comprehension challenges they face. Schools have struggled to find approaches that can help children succeed in this important task. Typical instruction in classrooms across the country has focused on procedural application of strategies or content-focused approaches that encourage rich discussions. Both approaches have achieved success but have limitations-related transparency and specificity of scaffolds and guidance for the teacher and learner in today’s diverse and complex classroom settings. The text structure strategy combines content and strategy to provide pragmatic, transparent, and scaffolded instruction addressing these challenges. A web-based intelligent tutoring system for the text structure strategy, named ITSS, was designed and developed to provide consistent and high-quality instruction to learners in Grades 4 and 5 about how to read, select main ideas, encode strategic memory structures, make inferences, and monitor comprehension during reading. In this article, we synthesize results from two recent large-scale randomized controlled studies to showcase how the ITSS supports selection and encoding of students’ strategic memory structures and how prior knowledge affects the memory structures. We provide greater depth of information about such processing than examined and reported in extant literature about overall increases in reading comprehension resulting from students using ITSS.
Constructing an Affective Tutoring System for Designing Course Learning and Evaluation
Authors: Wang Cheng-Hung , Lin Hao-Chiang Koong
Published: April 2017

Computers and the Internet are indispensable in modern life. Increasingly useful digital environments and technological developments have reshaped models of knowledge acquisition. Studies on the development of online learning have yielded valuable insights. In the design of online teaching systems that can replicate face-to-face teaching, user-friendly design is a key factor determining whether a system is immediately accepted by users. In this study, we designed an affective tutoring system (ATS) for curriculum teaching. Participants’ learning processes were recorded during ATS teaching sessions. Negative emotions in the participants were recognized in real time and recorded in a learning state database. We determined the learning outcomes of students who were taught using the ATS or normal online learning. The experimental results indicated that the ATS is an effective tool and significantly improves learning outcomes.
Moral economy, intermediaries and intensified competition in the labour market for function musicians
Authors: Umney Charles
Published: April 2017

This article examines the labour market for ‘function’ musicians in London. It shows how the market encompasses a chain of relationships between clients, intermediaries and musicians, considering how the idea of ‘moral economy’ – a subject of revived interest in employment sociology – fits empirical reality. It shows that function musicians have created a strong moral economy regulating the distribution of opportunities and resources within bands. However, other actors in the chain, particularly agents, are able to impose intensified labour competition on bands. This competition leads trust relationships to fray and social expectations about the distribution of resources to weaken. These tensions are embodied in the role of the fixer: a musician who uneasily straddles market and moral domains.
Efficiency of Executive Function: A Two-Generation Cross-Cultural Comparison of Samples From Hong Kong and the United Kingdom
Authors: Ellefson Michelle R. , Ng Florrie Fei-Yin , Wang Qian , Hughes Claire
Published: April 2017

Although Asian preschoolers acquire executive functions (EFs) earlier than their Western counterparts, little is known about whether this advantage persists into later childhood and adulthood. To address this gap, in the current study we gave four computerized EF tasks (providing measures of inhibition, working memory, cognitive flexibility, and planning) to a large sample ( n = 1,427) of 9- to 16-year-olds and their parents. All participants lived in either the United Kingdom or Hong Kong. Our findings highlight the importance of combining developmental and cultural perspectives and show both similarities and contrasts across sites. Specifically, adults’ EF performance did not differ between the two sites; age-related changes in executive function for both the children and the parents appeared to be culturally invariant, as did a modest intergenerational correlation. In contrast, school-age children and young adolescents in Hong Kong outperformed their United Kingdom counterparts on all four EF tasks, a difference consistent with previous findings from preschool children.
Introduction to the Special Issue on Liminal Hotspots
Authors: Stenner Paul , Greco Monica , F. Motzkau Johanna
Published: April 2017

This article introduces a special issue of Theory and Psychology on liminal hotspots. A liminal hotspot is an occasion during which people feel they are caught suspended in the circumstances of a transition that has become permanent. The liminal experiences of ambiguity and uncertainty that are typically at play in transitional circumstances acquire an enduring quality that can be described as a “hotspot”. Liminal hotspots are characterized by dynamics of paradox, paralysis, and polarization, but they also intensify the potential for pattern shift. The origins of the concept are described followed by an overview of the contributions to this special issue.
From paradox to pattern shift: Conceptualising liminal hotspots and their affective dynamics
Authors: Greco Monica , Stenner Paul
Published: April 2017

This article introduces the concept of liminal hotspots as a specifically psychosocial and sociopsychological type of wicked problem, best addressed in a process-theoretical framework. A liminal hotspot is defined as an occasion characterised by the experience of being trapped in the interstitial dimension between different forms-of-process. The paper has two main aims. First, to articulate a nexus of concepts associated with liminal hotspots that together provide general analytic purchase on a wide range of problems concerning “troubled” becoming. Second, to provide concrete illustrations through examples drawn from the health domain. In the conclusion, we briefly indicate the sense in which liminal hotspots are part of broader and deeper historical processes associated with changing modes for the management and navigation of liminality.
Permanent (trickster) liminality: The reasons of the heart and of the mind
Authors: Szakolczai Árpád
Published: April 2017

The term liminality is often used to celebrate escape from rigid structures or to promote creativity. However, the collapse of the stable frameworks of social life also generates anguishing conditions of uncertainty. This article introduces the term “permanent liminality” for situations in which the temporary suspension of normality becomes permanent. Such situations of entrapment within an interstitial dimension produce an emotional overheat, generating a “liminal hotspot.” This paper addresses the possibility of ending such entrapment. Reasoning cannot guide out of permanent liminality, as—in the absence of stability necessary to apprehend ratio, or harmonious proportionality—it is also liable to short-circuit, being closely associated under liminal conditions with imitativity. A solution is offered, through Pascal rather than Kant, by the heart. Such an idea also receives support from the Palaeolithic Age, maternal heartbeat in the womb, and long-distance walking pilgrimage.
Online adaptation for humanoids walking on uncertain surfaces
Authors: Khadiv Majid , Moosavian S Ali A , Yousefi-Koma Aghil , Maleki Hessam , Sadedel Majid
Published: April 2017

In this article, an online adaptation algorithm for bipedal walking on uneven surfaces with height uncertainty is proposed. To generate walking patterns on flat terrains, the trajectories in the task space are planned to satisfy the dynamic balance and slippage avoidance constraints and also to guarantee smooth landing of the swing foot. To ensure smooth landing of the swing foot on surfaces with height uncertainty, the preplanned trajectories in the task space should be adapted. The proposed adaptation algorithm consists of two stages. In the first stage, once the swing foot reaches its maximum height, the supervisory control is initiated until the touch is detected. After the detection, the trajectories in the task space are modified to guarantee smooth landing. In the second stage, this modification is preserved during the double support phase and released in the next single support phase. Effectiveness of the proposed online adaptation algorithm is experimentally verified through realization of the walking patterns on the SURENA III humanoid robot, designed and fabricated at Center of Advanced Systems and Technologies. The walking is tested on a surface with various flat obstacles, where the swing foot is prone to land on the ground either soon or late.
The Electronically Activated Recorder (EAR)
Authors: Mehl Matthias R.
Published: April 2017

This article reviews the Electronically Activated Recorder (EAR) as an ambulatory ecological momentary assessment tool for the real-world observation of daily behavior. Technically, the EAR is an audio recorder that intermittently records snippets of ambient sounds while participants go about their lives. Conceptually, it is a naturalistic observation method that yields an acoustic log of a person’s day as it unfolds. The power of the EAR lies in unobtrusively collecting authentic real-life observational data. In preserving a high degree of naturalism at the level of the raw recordings, it resembles ethnographic methods; through its sampling and coding, it enables larger empirical studies. This article provides an overview of the EAR method; reviews its validity, utility, and limitations; and discusses it in the context of current developments in ambulatory assessment, specifically the emerging field of mobile sensing.
An Emotion Divided
Authors: Cohen-Charash Yochi , Larson Elliott C.
Published: April 2017

The recent surge in envy research has brought with it a line of inquiry differentiating between “benign” and “malicious” envy. “Benign” envy involves the motivation to improve the self, leading to socially desirable reactions. “Malicious” envy involves the motivation to harm the envied other, leading to socially undesirable reactions. We suggest that studying “benign” and “malicious” envy involves confounding envy with its outcomes, which causes confusion and impairs the understanding of envy. We discuss the roots of this differentiation, the theoretical and methodological challenges it involves, and its negative ramifications for envy research. We provide theory and findings showing that envy, conceptualized and measured as a unitary construct, can lead to a wide range of reactions, both socially desirable and undesirable, depending on personal and situational moderators. Therefore, we believe the distinction between “benign” and “malicious” envy is unwarranted and advocate for the use of envy as a unitary construct.
Video Games and Hippocampus-Dependent Learning
Authors: West Greg L. , Konishi Kyoko , Bohbot Veronique D.
Published: April 2017

Research examining the impact of video games on neural systems has largely focused on visual attention and motor control. Recent evidence now shows that video games can also impact the hippocampal memory system. Further, action and 3D-platform video-game genres are thought to have differential impacts on this system. In this review, we examine the specific design elements unique to either action or 3D-platform video games and break down how they could either favor or discourage use of the hippocampal memory system during gameplay. Analysis is based on well-established principles of hippocampus-dependent and non-hippocampus-dependent forms of learning from the human and rodent literature.
Mood and the Regulation of Mental Abstraction
Authors: Bless Herbert , Burger Axel M.
Published: April 2017

Individuals can apply different processing strategies to deal with situations they encounter. One central question in social-cognition research refers to the factors that determine reliance on different processing strategies. Parting from a functional perspective, which holds that processing strategies need to be adjusted to the requirements of the situation, we argue that individuals’ mood carries information about the benign versus problematic nature of the situation and thus that mood can regulate cognitive processing. Focusing on mental abstraction, we propose that positive mood contributes to a processing style characterized by reliance on prior knowledge in the form of general knowledge structures, whereas negative mood elicits a processing style characterized by attention to details and consideration of new situation-specific information.
Periostin promotes migration and invasion of renal cell carcinoma through the integrin/focal adhesion kinase/c-Jun N-terminal kinase pathway
Authors: Chuanyu Sun , Yuqing Zhu , Chong Xu , Guowei Xia , Xiaojun Zhao
Published: April 2017

Periostin (POSTN) is an extracellular matrix protein which is overexpressed in a variety of cancers and has been related to tumorigenesis of renal cell carcinoma. However, the involvement of POSTN in renal cell carcinoma migration, invasion, and their underlying mechanisms has not been established. In this study, renal cell carcinoma cell lines stably overexpressing POSTN were established using a lentiviral vector, and the effects of POSTN on renal cell carcinoma cell migration and invasion were investigated. POSTN overexpression increased the migration and invasion capabilities of renal cell carcinoma cell lines as well as activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. Integrin αvβ3 and αvβ5 antibodies inhibited POSTN overexpression or recombinant POSTN-induced focal adhesion kinase activation, cell migration, and invasion. Furthermore, lentivirus-mediated focal adhesion kinase knockdown and c-Jun N-terminal kinase inhibitor reduced POSTN-enhanced phosphorylation of c-Jun N-terminal kinase, matrix metalloproteinase-9 and matrix metalloproteinase-2 expressions, cell migration, and invasion. Our research thus indicates that POSTN promotes renal cell carcinoma cell migration and invasion through interaction with integrins αvβ3 and αvβ5 and subsequent activation of the focal adhesion kinase/c-Jun N-terminal kinase pathway. These results suggest that POSTN plays a critical role in renal cell carcinoma metastasis and may represent a potential target for novel therapeutic approaches against renal cell carcinoma.
The apoptotic and genomic studies on A549 cell line induced by silver nitrate
Authors: Kaplan Ayse , Akalin Ciftci Gulsen , Kutlu Hatice Mehtap
Published: April 2017

Lung cancer is the leading cause of male cancer deaths worldwide. Metal-based anticancer drugs have evolved significantly during the past decades. Recently, silver ions have been investigated for their anticancer effects. We aimed to study the time-course cytotoxic effects of silver nitrate on A549 adenocarcinomic human alveolar basal epithelial cells to provide insights into the molecular-level understanding of growth suppression mechanism involved in apoptosis. The influences of silver nitrate were studied via MTT assay, flow cytometry, immunocytochemical, confocal and transmission electron microscopy, and microarray assays. Silver nitrate showed inhibitory effects against A549 cells in a dose- and time-dependent manner for 24, 48, and 72 h and induced apoptosis. The early and late apoptotic cells and depolarized mitochondrial membrane potential were determined by the half-maximal inhibitory concentration (IC50) value of silver nitrate treated for 72 h. But cysteinyl aspartate proteinase-3 was not activated for 72 h. Furthermore, IC50 value of silver nitrate also induced apoptosis according to immunocytochemical assays for 72 h. The downregulated CCNY, HNRNPL, ASF1B, PIAS4, HNRNPH1, EIF2C2, TAF15, FOXC1, LEP, and PCB2 genes administered with silver nitrate IC50 were identified as apoptosis-leading genes. Silver nitrate may be a suitable therapeutic agent against lung cancer.
Repressor activator protein 1–promoted colorectal cell migration is associated with the regulation of Vimentin
Authors: Yang Yongyong , Ye Chunxiang , Wang Lixin , An Guo , Tian Zhihua , Meng Lin , Qu Like , Lian Shenyi , Shou Chengchao
Published: April 2017

Repressor activator protein 1 plays important roles in telomere protection, while repressor activator protein 1 binds to extra-telomeric DNA and exerts the function as a transcriptional regulator. Previous study showed that repressor activator protein 1 regulates the transcriptional activity of nuclear factor-κB, and it was highly expressed in breast cancer tissues; however, the clinical significance of repressor activator protein 1 expression in cancer remains to be elucidated. In this study, we discovered that repressor activator protein 1 was highly expressed in colorectal cancer tissues. High expression of repressor activator protein 1 was significantly correlated with poor prognosis and distant metastasis. Knockdown of repressor activator protein 1 in colorectal cancer cells did not affect cell proliferation or colony formation, but dramatically decreased cell migration and F-actin-enriched membrane protrusions. Microarray screening revealed that Vimentin was downregulated after repressor activator protein 1 knockdown, which was validated by analysis of a colorectal cancer dataset. Furthermore, knockdown of Vimentin attenuated repressor activator protein 1–enhanced cell migration. Thus, our study suggests that repressor activator protein 1 is a prognostic marker and a potential target for colorectal cancer therapy.
Ectopic overexpression of CD133 in HNSCC makes it resistant to commonly used chemotherapeutics
Authors: Lee Junyoung , Park Mineon , Ko Youngjong , Kim Bora , Kim Okjoon , Hyun Hoon , Kim DongHwi , Sohn HongMoon , Moon Young Lae , Lim Wonbong
Published: April 2017

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Resistance to cytotoxic chemotherapy is a major cause of mortality in patients with HNSCC. A small subset of cancer cells called cancer stem cells (CSCs) may be key contributors to drug resistance and tumor recurrence in HNSCC. The aim of this study was to determine whether CD133, which maintains properties of CSCs, promotes chemoresistance by arresting cell cycle transition and reducing apoptosis in HNSCC cells. CD133 overexpression was examined in KB cells, and colony forming and aldehyde dehydrogenase activity assays were performed. To investigate the role of CD133 in chemoresistance, cell death was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Diff-Quick, flow cytometry, and western blot of apoptosis-related protein expression in fluorouracil (5-FU)- or cisplatin-treated cells. In addition, microarray and related protein expression assessments were performed to investigate the mechanism of chemoresistance against 5-FU and cisplatin in KB cells. Moreover, chemoresistance against 5-FU or cisplatin in a KB-inoculated mouse model was analyzed by hematoxylin and eosin staining, immunohistochemical study of CD133, and immunofluorescence of tumor tissue. In this study, we demonstrate that ectopic overexpression of CD133 significantly promotes properties of stemness in KB cell lines. Furthermore, CD133 promotes chemoresistance by arresting transition of the cell cycle and reducing apoptosis, which results in inhibition of tumor growth in 5-FU- or cisplatin-injected mouse tumor model. Taken together, our findings show that elevated levels of CD133 lead to HNSCC chemoresistance through increased stemness and cell cycle arrest.
Elevated expression of protein arginine methyltransferase 5 predicts the poor prognosis of breast cancer
Authors: Wu Ying , Wang Zhe , Zhang Jian , Ling Rui
Published: April 2017

Protein arginine methyltransferase 5 is one of the type II protein arginine methyltransferase family members that can symmetrically dimethylate arginine residues on target proteins in both the cytoplasm and the nucleus. Protein arginine methyltransferase 5 was reported to be an oncoprotein that participates in tumor progression through both epigenetic silencing and organelle biogenesis. So far, it has been implicated in various cancers, but its expression pattern in breast cancer has not been elucidated thoroughly. We analyzed the protein arginine methyltransferase 5 expression patterns in several breast cancer samples and tissue arrays to better characterize its contribution to breast cancer. Primary breast tumors showed increased protein arginine methyltransferase 5 expression compared with adjacent normal tissues in both the fresh tissue samples and tissue arrays. Also, there was a tendency that metastatic lymph nodes demonstrated enhanced protein arginine methyltransferase 5 expression compared to primary sites. Moreover, we found a significant correlation between protein arginine methyltransferase 5 and Ki-67, with higher Ki-67 and protein arginine methyltransferase 5 expressions in primary breast tumors compared with normal breast tissues. Moreover, the Cancer Genome Atlas cohort analysis revealed that high protein arginine methyltransferase 5 messenger RNA expression was associated with an unfavorable prognosis in human epidermal growth factor receptor 2 (HER-2) positive and triple negative breast cancer patients. Finally, the roles and mechanisms of protein arginine methyltransferase 5 in the proliferation, cell cycle progression, and apoptosis of MDA-MB-231 cells were assessed using protein arginine methyltransferase 5 and shPRMT5 transfection. In conclusion, we proposed that protein arginine methyltransferase 5 is an independent prognostic biomarker for breast cancer, and targeting protein arginine methyltransferase 5 might be a promising strategy for breast cancer treatment.
Distinct prognostic values of YAP1 in gastric cancer
Authors: Yu Lan , Gao Chun , Feng Bei , Wang Liming , Tian Xun , Wang Hui , Ma Ding
Published: April 2017

The Hippo pathway regulates intrinsic organ sizes by regulating apoptosis and cell proliferation. YAP1 (yes-associated protein 1) is a transcriptional effector of the Hippo pathway. YAP1 expression is reported to be associated with gastric cancer carcinogenesis and malignancy. In this study, we compared the expression of YAP1 in gastric cancer and normal stomach tissues. Tissue microarray analysis was performed in 156 gastric cancer samples, 8 adjacent normal stomach tissues, and 4 normal stomach tissues. We also analyzed the association between YAP1 protein expression and clinicopathological features, such as age, gender, histological differentiation, and clinical stages. We used the ONCOMINE database and the Kaplan–Meier plotter to analyze YAP1 expression status in different clinicopathological parameters of gastric cancer. We also used the Kaplan–Meier plotter to summarize the survival information of YAP1 from a total of 631 gastric cancer patients. YAP1 expression was found to be elevated in gastric cancer tissues compared to normal stomach tissues. YAP1 messenger RNA was found to be upregulated in gastric intestinal-type adenocarcinoma and gastric mixed adenocarcinoma compared to gastric mucosa. YAP1 high expression was found to be correlated to worse overall survival for all gastric cancer patients followed for 20 years. These results indicate that YAP1 can be used to predict the prognosis of gastric cancer. And YAP1 maybe a potential drug target for gastric cancer patients.
Expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins in non–small cell lung cancer
Authors: Shi Run , Yu Xinnian , Wang Yajing , Sun Jing , Sun Qi , Xia Wenjie , Dong Gaochao , Wang Anpeng , Gao Zhaojia , Jiang Feng , Xu Lin
Published: April 2017

Insulin-like growth factor 2 messenger RNA-binding proteins have been described to associate with malignant process in many cancers. However, the role of insulin-like growth factor 2 messenger RNA-binding protein family has not been thoroughly elucidated in non–small cell lung cancer. This study was to investigate the expression profile, clinical significance, and biological function of insulin-like growth factor 2 messenger RNA-binding proteins family in non–small cell lung cancer. The expression levels of IGF2BP1–IGF2BP3 in tumor and adjacent normal tissues were determined, and association with clinicopathological features and overall survival was investigated by analyzing The Cancer Genome Atlas lung cancer database. Proliferation, migration, invasion assays, and flow-cytometry analysis were used to investigate the biological function in vitro. Insulin-like growth factor 2 messenger RNA-binding protein expression levels were significantly increased in non–small cell lung cancer compared to adjacent normal lung tissues. Chi-square test indicated that IGF2BP1 and IGF2BP3 expressions correlated with some meaningful clinical characteristics in non–small cell lung cancer. Kaplan–Meier analysis showed that high-level expression of IGF2BP1 or IGF2BP3 predicted poor overall survival in lung adenocarcinoma patients. Multivariate regression analysis showed that high level of IGF2BP3 was an independent risk factor for poor prognosis in lung adenocarcinoma patients (hazard ratio = 1.616, p = 0.017). In vitro, knockdown of IGF2BP3 inhibited lung adenocarcinoma cell proliferation by inducing cell cycle arrest and apoptosis, and undermined abilities of migration and invasion, and overexpression of IGF2BP3 could promote malignant phenotypes in lung adenocarcinoma cells. Our study revealed that expression of insulin-like growth factor 2 messenger RNA-binding proteins was widely upregulated and correlated with some certain clinicopathological features in non–small cell lung cancer. Especially, in insulin-like growth factor 2 messenger RNA-binding protein family, IGF2BP3 might play the most important role in tumor aggressiveness and prognosis in lung adenocarcinoma, and IGF2BP3 might serve as a potential therapeutic target and a novel prognostic biomarker in lung adenocarcinoma patients.
Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma
Authors: Wu Tian-Fu , Li Yi-Cun , Ma Si-Rui , Bing-Liu  , Zhang Wen-Feng , Sun Zhi-Jun
Published: April 2017

Tumor necrosis factor receptor–associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor–associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor–associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor–associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor–associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor–associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r2 = 0.109; p < 0.0001, r2 = 0.64; and p < 0.001, r2 = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor–associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor–associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest that tumor necrosis factor receptor–associated factor 1 has potential direct/indirect regulations with the cancer stem cell markers in oral squamous cell carcinoma, which may help in further analysis of the cancer stem cell characteristics.
Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats
Authors: Cervantes-Anaya Nancy , Ponciano-Gómez Alberto , López-Álvarez Guadalupe Soledad , Gonzalez-Reyes Christian , Hernández-Garcia Sergio , Cabañas-Cortes María Asunción , Garrido-Guerrero José Efraín , Villa-Treviño Saúl
Published: April 2017

As of 2012, liver cancer was the second leading cause of death worldwide, and hepatocellular carcinoma is the most common primary cancer of the liver. The identification of molecules that might be molecular markers or therapeutic targets is urgently needed to improve clinical management. Based on a microarray analysis performed in our laboratory, we selected six genes—namely, ANXA2, DYNLT1, PFKP, PLA2G7, KRT19, and SNX10—as candidates for validation as tumor markers of liver cancer in a rat model. Their patterns of overexpression in preneoplastic lesions and established tumors at 10 different time points between 24 h and 18 months were analyzed to identify putative tumor markers for further studies. We validated the microarray results by quantitative reverse transcription polymerase chain reaction, which revealed high transcriptional expression for five of the genes, consistent with their high protein expression during cancer progression reported in the literature. However, studies of the association of sorting nexin 10 with different types of cancer are limited, prompting further study. The characterization of sorting nexin 10 in preneoplastic lesions and established tumors revealed messenger RNA overexpression and a simultaneous decrease in sorting nexin 10 protein expression. A group of microRNAs related to sorting nexin 10 messenger RNA were selected based on a data analysis conducted using miRDB and microrna.org . An analysis of the expression of these microRNAs revealed an increase in the transcription of microRNA-30d whenever the sorting nexin 10 protein was downregulated. These results suggest that sorting nexin 10 is a potential liver cancer marker exhibiting characteristics of a putative suppressor protein that is likely regulated by microRNA-30d.
Mesothelin-targeting chimeric antigen receptor–modified T cells by piggyBac transposon system suppress the growth of bile duct carcinoma
Authors: Xu Jie-Ying , Ye Zhen-Long , Jiang Du-Qing , He Jiang-Chuan , Ding Yong-Mei , Li Lin-Fang , Lv Sai-Qun , Wang Ying , Jin Hua-Jun , Qian Qi-Jun
Published: April 2017

Chimeric antigen receptor modified T cell–based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor–modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor–modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor–modified T cells than control T cells (CD107α: 71.9% vs 48.6%; CD27: 92.1% vs 61.8%; CD137: 55.5% vs 8.4%; CD28: 98.0% vs 82.1%; CD134: 37.5% vs 10.4%). Furthermore, mesothelin-targeting chimeric antigen receptor–modified T cells exerted cytotoxicity toward mesothelin-expressing EH-CA1b and EH-CA1a cells in an effector-to-target ratio-dependent manner, while leaving mesothelin-negative GSC-SD and EH-GB1 cells and normal liver L02 cells almost unharmed. Mesothelin-targeting chimeric antigen receptor–modified T cells secreted cytokines at higher levels when co-cultured with mesothelin-positive EH-CA1a and EH-CA1b cells than with mesothelin-negative GSC-SD and EH-GB1 cells. Enhanced cytotoxicity and cytokine secretion of mesothelin-targeting chimeric antigen receptor–modified T cells compared to control T cells were also observed when co-cultured with 293-meso cells (interferon γ: 85.1% ± 1.47% vs 8.3% ± 2.50%, p = 0.000; tumor necrosis factor α: 90.9% ± 4.67% vs 18.5% ± 3.62%, p = 0.0004; interleukin 2: 60.8% ± 2.00% vs 15.6% ± 2.06%, p = 0.002; interleukin 6: 6.4% ± 2.95% vs 1.7% ± 0.63%, p = 0.055). In addition, mesothelin-targeting chimeric antigen receptor–modified T cells showed greater inhibitory and proliferative capability than control T cells within EH-CA1a cell xenografts. This study shows the potential of mesothelin-targeting chimeric antigen receptor–modified T cells in treating bile duct carcinoma.
Involvement of miR-125a in resistance to daunorubicin by inhibiting apoptosis in leukemia cell lines
Authors: Bai Haitao , Zhou Lili , Wang Chun , Xu Xiaowei , Jiang Jieling , Qin Youwen , Wang Xiaorui , Zhao Chuxian , Shao Shan
Published: April 2017

In this study, we investigated whether miR-125a participated in the resistance of the leukemia cell lines to the chemotherapeutic agent daunorubicin. Higher expression of miR-125a is correlated with lower treatment response and shorter overall survival in acute leukemia patients. Overexpression of miR-125a induced drug resistance in HL-60, K562, and THP-1cell lines through reducing apoptosis. We also showed that miR-125a mediated daunorubicin resistance in leukemia cell lines through the decrease of GRK2 and Puma which were proved to be direct targets of miR-125a. This study may provide novel therapeutic targets for therapy and improve predictions of therapeutic responses in leukemia to daunorubicin.
Effect of histone modifications on hMLH1 alternative splicing in gastric cancer
Authors: Zhao Jin-Xuan , Li Xiao-Wei , Shi Bing-Yu , Wang Fang , Xu Zheng-Rong , Meng Hai-Lan , Su Yun-Yan , Wang Jing-Mei , Xiao Nong , He Qiong , Wang Ya-Ping , Fan Yi-Mei
Published: April 2017

hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10–11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines. Lower level of H4K16ac and H3ac was detected in hMLH1 exon 10–11 region in gastric cancer cell lines when compared with human gastric mucosal epithelial cell line GES-1. A significant decrease of hMLH1 delEx11 and delEx10–11 was observed in gastric cancer cell lines after trichostatin A treatment. H3K36me3 and H3K4me2 levels were lower in hMLH1 exon 10–11 and exon 16–17 regions in gastric cancer lines when compared with GES-1. Aberrant transcripts such as hMLH1 delEx11 and delEx10–11 were significantly higher in gastric cancer cell lines after small interfering RNA–mediated knockdown of SETD2 (the specific methyltransferase of H3K36). The hMLH1 delEx10 and delEx10–11 transcripts were increased after interference of SRSF2. Taken together, our study demonstrates that lower level of histone acetylation and specific histone methylation such as H3K36me3 correlate with aberrant transcripts in hMLH1 exon 10–11 region. SRSF2 may be involved in these specific exons skipping as well.
Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences
Authors: Hromadnikova Ilona , Kotlabova Katerina , Krofta Ladislav , Hron Filip
Published: April 2017

The aim of the study was to evaluate the effectiveness of placental-specific markers, extracellular fetal DNA (sex-determining region Y and hypermethylated RASSF1A sequences) and circulating C19MC microRNAs (miR-516-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, miR-525, and miR-526a) for the diagnosis and consecutive follow-up of gestational trophoblastic disease/neoplasia. Increased levels of extracellular fetal DNA and C19MC microRNAs were detected in patients with active disease when compared with the period when the patients reached remission of the disease. The positive correlation between plasma levels of hypermethylated RASSF1A sequence, C19MC microRNAs, and human chorionic gonadotropin serum levels was found. MiR-520a-5p had the best performance to detect patients with active disease (a positive predictive value of 100% at a null false positive ratio (FPR)). MiR-516-5p and miR-525 were able to diagnose 100% of women with active disease at the FPR 3.9%/7.7%. The overall predictive capacity of single miR-526a (81.8% at null FPR), miR-517-5p (90.9% at 15.4% FPR), miR-518b (100% at 38.5% FPR), and miR-520h (90.9% at 26.9% FPR) biomarkers to detect active disease cases was slightly lower. Transient increase in C19MC microRNA plasma levels after the first cycle of chemotherapy indicated the decay of placental trophoblast residual tissue. The increased levels of extracellular fetal DNA and placental-specific C19MC microRNAs are associated with gestational trophoblastic disease/neoplasia. Screening of extracellular placental-specific biomarkers may represent an additional option to identify a significant proportion of women with active disease and to monitor the therapy response. Non-invasive follow-up of the decomposing residual tissue in the form of extracellular nucleic acids of placental origin packed into apoptotic bodies derived from placental trophoblasts is available.
Insights into the involvement of noncoding RNAs in 5-fluorouracil drug resistance
Authors: Deng Jun , Wang Yi , Lei Jun , Lei Wan , Xiong Jian Ping
Published: April 2017

5-Fluorouracil is a classic chemotherapeutic drug that is widely used to treat various cancers. However, patients often exhibit primary or acquired drug resistance during treatment with 5-fluorouracil chemotherapy. 5-Fluorouracil resistance is a multifactorial event that involves abnormal enzyme metabolism, transport deregulation, cell cycle disorders, apoptosis resistance, and mismatch repair deficiency. Despite advancements in bioresearch technologies in the past several decades, the molecular mechanisms of 5-fluorouracil resistance have not been completely clarified. Recently, microarray analyses have shown that noncoding RNAs (i.e. microRNAs and long noncoding RNAs) play a vital role in 5-fluorouracil resistance in multiple cancer cell lines. These noncoding RNAs can function as oncogenes or tumor suppressors, contributing to 5-fluorouracil drug resistance. In this review, we discuss the effects of microRNAs on 5-fluorouracil sensitivity via targeting of metabolic enzymes, the cell cycle, apoptosis, autophagy, the epithelial–mesenchymal transition, and cancer stem cells. In particular, we focus on summarizing current knowledge on the molecular mechanisms through which long noncoding RNAs mediate 5-fluorouracil drug resistance. Moreover, we describe the specific microRNAs that may function as markers for prediction of chemotherapeutic response to 5-fluorouracil. This review will help to improve the current understanding of how to reverse 5-fluorouracil resistance and may facilitate the establishment of new strategies for alleviating drug resistance in the future.
Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer
Authors: Panagopoulou Maria , Lambropoulou Maria , Balgkouranidou Ioanna , Nena Evangelia , Karaglani Makrina , Nicolaidou Christina , Asimaki Anthi , Konstantinidis Theocharis , Constantinidis Theodoros C , Kolios George , Kakolyris Stylianos , Agorastos Theodoros , Chatzaki Ekaterini
Published: April 2017

Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus–infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerous lesions, and normal cervices. Methylation of BRMS1 promoter was detected in 37.5% of women with no high-risk types of human papilloma virus infection and was less frequent in smears with high-risk types of human papilloma virus (11.4%) and in women with pathological histology (cervical intraepithelial neoplasia) (11.9%). Methylation was detected also in HeLa cervical cancer cells. Immunohistochemistry revealed nuclear BRMS1 protein staining in normal high-risk types of human papilloma virus–free cervix, in cervical intraepithelial neoplasias, and in malignant tissues, where staining was occasionally also cytoplasmic. In cancer, expression was stronger in the more differentiated cancer blasts. In conclusion, BRMS1 promoter methylation and aberrant protein expression seem to be related to high-risk types of human papilloma virus–induced carcinogenesis in uterine cervix and is worthy of further investigation.