bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultivating a school-university partnership for teacher learning
Authors: Reischl Catherine H. , Khasnabis Debi , Karr Kevin
Published: May 2017

The Mitchell Scarlett Teaching and Learning Collaborative (MSTLC) is a vigorous, six-year-old partnership between two Title I schools — Mitchell Elementary School and Scarlett Middle School in Ann Arbor, Mich. — and the teacher education program at the University of Michigan. MSTLC was formed between educators who had related but quite different problems to solve: As the schools began to collaborate in 2010, the Ann Arbor Public Schools needed to address the achievement gap in its two lowest SES and lowest-achieving schools relative to other district schools, and the University of Michigan needed a school site where teaching interns could learn to teach diverse students and where it could implement and refine its newly reformed, practice-based elementary teacher education curriculum.
Making teaching visible through learning opportunities
Authors: Ermeling Bradley A. , Gallimore Ronald , Hiebert James
Published: May 2017

Observing teaching with a practiced, professional eye can yield valuable insights into the specific learning opportunities that students are (or are not) provided. However, recent policy initiatives have emphasized using formulaic rubrics and checklists to rate teacher behaviors and evaluate their use of particular instructional moves. Rather than investing so much time and money in such an approach, which is designed to evaluate teachers’ performance, school systems should focus on helping educators observe teaching in more sophisticated ways and make such focused observation a regular part of their professional routines.
Madam Secretary, help us improve social-emotional learning
Authors: Elias Maurice J. , Nayman Samuel J. , Duffell Joan C. , Kim Sarah A.
Published: May 2017

Considering the key role of social-emotional and character development (SECD) competencies in college, career, and life success — and considering that many of those competencies are teachable — there is no excuse for failing to incorporate them systematically into our education system. That would be the equivalent of depriving children of oxygen. This article is addressed to the U.S. Secretary of Education and other education policymakers and offers them specific recommendations to guide policy that would yield high-quality programs of support for SECD in all schools.
The Editor’s Note
Authors: Richardson Joan
Published: May 2017

Kappan’s editor tells the story of one young woman’s journey from working with autistic peers while in high school, to spending a decade in special education classrooms as a paraprofessional, to finishing her college degree with the hope of becoming a certified teacher of elementary and special education.
Washington View
Authors: Ferguson Maria
Published: May 2017

In the first few months of the new administration, President Donald Trump and Secretary of Education Betsy DeVos have made a number of dramatic statements about their plans for K-12 education, including their intention to change certain education laws and promote specific kinds of school choice. Not only have those statements prompted a great deal of concern among many Americans, they have also invited a great deal of confusion about who has the power to make what sorts of decisions about education policy. This article offers a primer on some of the ground rules.
Daily Symptom Variability in Patients With Stable COPD: A Narrative Review
Authors: Wu Maochun , Wang Zequan , Li Manman , Li Kun
Published: May 2017

Daily symptom variability refers to the fluctuation of chronic obstructive pulmonary disease (COPD) symptoms over the day. Although most clinicians can describe the day-to-day variation in symptoms experienced by patients with COPD, little has been done to quantify the variability. This review aims to synthesize evidence of daily symptom variability among patients with stable COPD. Of the 325 potentially relevant articles that were retrieved, 11 observational articles were finally included in the review. Patients with stable COPD commonly experience daily symptom variability, with morning being the most troublesome time of day, followed by night. Morning symptoms had a significant effect on morning routines or daily activities, and night-time symptoms affected the sleep quality of patients. In comparison with patients without symptom variability, patients with morning/night-time symptoms or symptom variability exhibited poorer health status as well as greater disease severity and incidence of exacerbation.
Assessing Cognitive Representations of Antidepressants: Development and Validation of the Attitudes Toward Medication–Depression Inventory
Authors: Hagerty Bonnie M. , Williams Reg A. , Aikens James , Bathish Melissa A. , West Brady T. , Fuller Douglas S. , Kazemi Joe
Published: May 2017

Antidepressant drugs represent the mainstay of treatment for depression; however, nonadherence is a major problem. Attitudes are predictors of long-term adherence and drive medication use. The Attitudes Toward Medication–Depression (ATM-D) Inventory was developed and tested with 131 patients in primary care settings who reported a diagnosis of depression. Content validity was assessed by experts with a 94.4% agreement on item relevancy. Exploratory factor analysis showed three factors (course of medication treatment, identity, and control) that accounted for 57% of the total variance in the final 17-item scale. The instrument demonstrated good internal consistency reliability (α = .76-.84) and test–retest reliability (α = .74-.83). Results support the construct validity and reliability of the instrument and revealed unique insights into patients’ cognitive representations of their antidepressants. This study supported that patients have cognitive representations related to depression and antidepressants that go beyond simple concerns about the effects of the medication.
Embedding an enriched environment in an acute stroke unit increases activity in people with stroke: a controlled before–after pilot study
Authors: Rosbergen Ingrid CM , Grimley Rohan S , Hayward Kathryn S , Walker Katrina C , Rowley Donna , Campbell Alana M , McGufficke Suzanne , Robertson Samantha T , Trinder Janelle , Janssen Heidi , Brauer Sandra G
Published: May 2017

Objectives:

To determine whether an enriched environment embedded in an acute stroke unit could increase activity levels in acute stroke patients and reduce adverse events.

Design:

Controlled before–after pilot study.

Setting:

An acute stroke unit in a regional Australian hospital.

Participants:

Acute stroke patients admitted during (a) initial usual care control period, (b) an enriched environment period and (c) a sustainability period.

Intervention:

Usual care participants received usual one-on-one allied health intervention and nursing care. The enriched environment participants were provided stimulating resources, communal areas for eating and socializing and daily group activities. Change management strategies were used to implement an enriched environment within existing staffing levels.

Main Measures:

Behavioural mapping was used to estimate patient activity levels across groups. Participants were observed every 10 minutes between 7.30 am and 7.30 pm within the first 10 days after stroke. Adverse and serious adverse events were recorded using a clinical registry.

Results:

The enriched environment group ( n = 30, mean age 76.7 ± 12.1) spent a significantly higher proportion of their day engaged in ‘any’ activity (71% vs. 58%, P = 0.005) compared to the usual care group ( n = 30, mean age 76.0 ± 12.8). They were more active in physical (33% vs. 22%, P < 0.001), social (40% vs. 29%, P = 0.007) and cognitive domains (59% vs. 45%, P = 0.002) and changes were sustained six months post implementation. The enriched group experienced significantly fewer adverse events (0.4 ± 0.7 vs.1.3 ± 1.6, P = 0.001), with no differences found in serious adverse events (0.5 ± 1.6 vs.1.0 ± 2.0, P = 0.309).

Conclusions:

Embedding an enriched environment in an acute stroke unit increased activity in stroke patients.
Role of coagulopathy in glucocorticoid-induced osteonecrosis of the femoral head
Authors: Zhang Qiankun , L v Jin , Jin Lie
Published: May 2017

The two major theories of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) are apoptosis and ischaemia. The traditional theory implicates ischaemia as the main aetiological factor because the final common pathway of ONFH is interruption of blood supply to the bone. The most common causes of interruption of blood supply include fat embolism and coagulation disorders. GCs can directly or indirectly lead to coagulation disorders, producing a hypercoagulable state, followed by poor blood flow, ischaemia, and eventually ONFH. This review summarizes the existing knowledge on coagulation disorders in the context of GC-induced ONFH, including hypofibrinolysis and thrombophilia, endothelial cell dysfunction and damage, endothelial cell apoptosis, lipid metabolism, platelet activation, and the effect of anticoagulant treatment.
Manipulation of Foot Strike and Footwear Increases Achilles Tendon Loading During Running
Authors: Rice Hannah , Patel Mubarak
Published: May 2017

Background:

The Achilles tendon is the most common site of tendon overuse injury in humans. Running with a forefoot strike pattern and in minimal shoes is a topic of recent interest, yet evidence is currently limited regarding the combined influence of foot strike and footwear on Achilles tendon loading.

Purpose:

To investigate the influence of both foot strike and footwear on Achilles tendon loading in habitual rearfoot strike runners.

Study Design:

Controlled laboratory study.

Methods:

Synchronized kinematic and force data were collected from 22 habitual rearfoot strikers (11 male), who habitually ran in nonminimal running shoes, during overground running at 3.6 m·s-1. Participants ran in 3 different footwear conditions (standard running shoe, minimal running shoe, and barefoot) with both a rearfoot strike (RFS) and an imposed forefoot strike (FFS) in each footwear condition. Achilles tendon loading was estimated by use of inverse dynamics, where the Achilles tendon moment arm was determined with a regression equation. A 2-way, repeated-measures analysis of variance was used to compare conditions.

Results:

Achilles tendon impulse was greater when subjects ran with an FFS rather than an RFS in minimal shoes. Achilles tendon loading rates were higher when subjects ran either in minimal shoes or barefoot than in standard shoes, regardless of foot strike.

Conclusion:

In runners who habitually rearfoot strike in standard running shoes, running in minimal shoes or barefoot increased the rate of tendon loading, and running with a forefoot strike in minimal shoes increased the magnitude of tendon loading.

Clinical Relevance:

Transitioning to these running conditions may increase the risk of tendinopathy.
Clinical Features and Neurologic Complications of Children Hospitalized With Chikungunya Virus in Honduras
Authors: Samra José A. , Hagood Nancy L. , Summer Andrea , Medina Marco T. , Holden Kenton R.
Published: May 2017

The first case of Chikungunya virus in Honduras was identified in 2014. The virus has spread widely across Honduras via the Aedes aegypti mosquito, leading to an outbreak of Chikungunya virus (CHIKV) in 2015 that significantly impacted children. A retrospective chart review of 235 children diagnosed with CHIKV and admitted to the National Autonomous University of Honduras Hospital Escuela (Hospital Escuela) in Tegucigalpa, Honduras, was accomplished with patients who were assessed for clinical features and neurologic complications. Of 235 children admitted to Hospital Escuela with CHIKV, the majority had symptoms of fever, generalized erythematous rash, and irritability. Fourteen percent had clinical arthritis. Ten percent of patients had seizures. Six percent had meningoencephalitis. There were 2 childhood deaths during the course of this study, one from meningoencephalitis and another from myocarditis. Chikungunya virus can cause severe complications in children, the majority of which impact the central nervous system.
Victim Motivations for Disclosing Unwanted Sexual Experiences and Partner Abuse
Authors: Demers Jennifer M. , Roberts Alexa P. , Bennett Sidney , Banyard Victoria L.
Published: May 2017

Sexual assault and partner abuse are major problems on college campuses. While the majority of victims will tell a friend or other informal support about their experience, formal disclosures to authorities are still infrequent. Past research has examined barriers to choosing to disclose; however, little research has explored victims’ motivational goals behind their decision to disclose to various people. In the present study, 13 semistructured interviews were conducted with survivors of partner abuse and/or sexual violence at northeastern universities in the United States and the resulting data were content coded for motivations associated with disclosing. Four major themes emerged: (1) improving emotional or psychological well-being; (2) fulfilling perceived social obligations or responsibilities; (3) seeking information or assessment; and (4) seeking action in the form of advocacy, accommodations, or criminal prosecution. Results from this study suggest that there is not a “one-size-fits-all” model for responding to informal and formal reports of victimization on campuses. Implications of these results for designing survivor-centered college community responses will be discussed.
Improvement in the vehicle stability of distributed-drive electric vehicles based on integrated model-matching control
Authors: Zhang Xudong , Göhlich Dietmar
Published: May 2017

This paper presents a vehicle dynamic stability controller for distributed-drive electric vehicles. A hierarchical control structure is adopted for the proposed controller. An upper controller is designed on the basis of integrated model-matching control. It consists of a feedforward component plus a feedback component to calculate the desired external yaw moment to achieve the desired vehicle motion. The feedforward control aims at compensating the effect caused by the variation in the linear cornering stiffnesses of the tyres during the life cycle of the tyres. It provides a rapid response under common driving conditions. The linear cornering stiffnesses of the tyres are estimated in real time by the adaptive forgetting-factor recursive least-squares method. Since many vehicle parameters have strongly non-linear and time-varying characteristics, adaptive sliding mode control is used as the feedback component to make the controller robust against systematic uncertainties. To combine the outputs of feedforward and feedback together and to avoid probable conflict, a weight gain coefficient is obtained. Additionally, a conventional sliding-mode controller is introduced as a comparative upper control strategy. The lower controller is utilized to allocate the required yaw moment and traction to the four independent motors, taking into account the tyre grip margins. Simulations for a low- g manoeuvre and a high- g manoeuvre are carried out to evaluate the proposed control algorithm. The results show that the proposed vehicle stability controller can significantly stabilize the vehicle motion and greatly reduce the driver’s workload in comparison with with the conventional sliding-mode controller.
Atmospheric vehicle trajectory optimization with minimum dynamic pressure constraint
Authors: Kumar G Naresh , Sarkar AK , Mangrulkar KK , Talole SE
Published: May 2017

In this work, a trajectory optimization formulation for hypersonic boost–glide class vehicles to achieve maximum range under various in-flight and terminal constraints is proposed. While most of the published literature has considered maximum dynamic pressure as a constraint, the requirement of a certain minimum dynamic pressure has been addressed in this formulation to ensure aerodynamic controllability throughout the flight envelope for various ranges. The minimum dynamic pressure constraint is imposed as an in-flight inequality constraint and is achieved through a penalty function approach by casting it as a differential equation. Simulations are carried out, and the results are analyzed and presented to demonstrate the efficacy of the proposed formulation.
Application and analysis of an improved multiconic method in trajectory design of the lunar south pole return mission
Authors: Feng Fei , Zhang Ya-Sheng
Published: May 2017

The multiconic method is a fast and accurate method for trajectory propagation, which fills the gap between the patched conic and numerical integration. However, this method has been rarely applied in the Moon–Earth trajectory design, and Lunar oblateness perturbation is a necessary term that cannot be ignored. In Lunar exploration, the south polar region of the Moon has been highlighted as an attractive destination by European Space Agency and Russia because of technical and scientific factors. First, according to the illumination and communication conditions, this paper presents analysis of the trajectory injection window. An improved multiconic method that combines the Lunar oblateness correction in the propagation of Moon–Earth trajectories is then proposed. In additional, the elliptical B-plane parameters are introduced to improve the rate of convergence during the correction of initial values. Compared with the traditional multiconic method, significantly, the proposed methods improve the accuracy of propagation of the Moon–Earth trajectory.
Experimental and theoretical study on a dual-thrust rocket motor with subsonic intermediate nozzle
Authors: El-Nady AM , Ahmed MYM , El-Senbawy MA , Sarhan AM
Published: May 2017

Dual-thrust rocket motors, with proper designs, can yield the desired boost-sustain thrust profiles for a variety of applications. Of the various designs that a dual-thrust rocket motor can have, the one with an intermediate nozzle provides a high boost-to-sustain thrust ratio as well as a stable operation. Depending on the internal conditions, the flow through the intermediate nozzle in the boost phase can be sonic, subsonic, or initially reversed. The present paper discusses the operation and performance of Dual-thrust rocket motors with subsonic intermediate nozzle. A mathematical model describing the internal ballistics of these dual-thrust rocket motors is derived from the basic governing equation. In addition, a set of experiments is conducted using a developed test motor to explore the physics of dual-thrust rocket motors with subsonic intermediate nozzle and assess the mathematical model validity. Results of the theoretical and experimental investigations explain most of the internal ballistics characteristics that were not discussed before in the open literature.
Modeling the motion of small unmanned aerial system (sUAS) due to ground collision
Authors: Du Xianping , Dori Alex , Divo Eduardo , Huayamave Victor , Zhu Feng
Published: May 2017

The aim of this paper is to develop a modeling method in order to predict the rebounce distance of a small size unmanned aerial system (sUAS) after collision with the ground. This distance would be useful to determine the safe range on the ground when operating the UAS. A two-step strategy is developed to model this procedure. In step one, numerical simulations are performed to model the first impact and predict the rebounce angle and impact velocity. Based on the information obtained, in step two, an analytical model is employed to calculate the rebounce distance without running numerical simulations, to save the computational time. Based on the model predictions, a non-linear function (known as a Meta model) is established to describe the rebounce behavior as a function of impact parameters, i.e. impact velocity, angle, and friction coefficient between the vehicle and ground. A correlation analysis is further performed to analyze the effect of these parameters on the response. The results show that the maximum rebounce range could be greater than 10 m. Compared to impact angle and friction coefficient, impact velocity is the most significant factor influencing the rebounce range. The larger velocity, smaller impact angle, and smaller ground friction coefficient would lead to the large rebounce range. The established Meta model would be useful to estimate safety range when operating sUAS platforms.
Effect of ambient temperature on piston-type synthetic jet actuator
Authors: Eri Qitai , Hong Liang , Li Ting , Wang Qiang
Published: May 2017

The effect of the ambient temperature on the piston-type synthetic jet actuator performance is investigated numerically. And the effects of the actuation frequency and orifice diameter on mass flow, cylinder pressure and jet momentum are also analysed under high and normal temperatures as well as the effect of the auxiliary air inlet on synthetic jet actuator performance under high temperature. The results indicated that ambient temperature has a significant effect on synthetic jet actuator performance. As the ambient temperature rises, the mass flow, cylinder pressure and jet maximum momentum decrease significantly. Compared with that at normal temperature, the synthetic jet actuator performance with high actuation frequency or large orifice diameter has large degradation under high ambient temperature. In addition, auxiliary air inlet can significantly improve the suction capability and performance of the synthetic jet actuator.
Risk politics and the pro-nuclear growth coalition in Japan in relation to the Fukushima
Authors: Shin HaeRan
Published: May 2017

This paper focuses on the development of the pro-nuclear growth coalition in Japan. It also describes how, after the Fukushima disaster, the coalition was challenged by an increasing number of anti-nuclear movements and scientific discussions of nuclear energy policies. By analyzing the risk politics associated with nuclear power, the study helps explain the development of pro-nuclear narratives and the pro-nuclear coalition. Based on archival analysis of accounts from the media, governments, and experts, it argues that governmental and nongovernmental actors in Japan and the United States formed a pro-nuclear growth coalition to pursue economic growth and then cooperated to promote pro-nuclear energy policies. The research also illustrates that post-Fukushima risk narratives challenged pro-nuclear energy policies and the dominance of the pro-nuclear growth coalition with fear. Although anti-nuclear sentiment has increased after Fukushima, it has not coalesced enough to be considered a consensus.
A change-point model for detecting heterogeneity in ordered survival responses
Authors: Bouaziz Olivier , Nuel Grégory
Published: May 2017

In this article, we suggest a new statistical approach considering survival heterogeneity as a breakpoint model in an ordered sequence of time-to-event variables. The survival responses need to be ordered according to a numerical covariate. Our estimation method will aim at detecting heterogeneity that could arise through the ordering covariate. We formally introduce our model as a constrained Hidden Markov Model, where the hidden states are the unknown segmentation (breakpoint locations) and the observed states are the survival responses. We derive an efficient Expectation-Maximization framework for maximizing the likelihood of this model for a wide range of baseline hazard forms (parametrics or nonparametric). The posterior distribution of the breakpoints is also derived, and the selection of the number of segments using penalized likelihood criterion is discussed. The performance of our survival breakpoint model is finally illustrated on a diabetes dataset where the observed survival times are ordered according to the calendar time of disease onset.
Long noncoding nature brain-derived neurotrophic factor antisense is associated with poor prognosis and functional regulation in non–small cell lung caner
Authors: Shen MingJing , Xu Zhonghua , Jiang Kanqiu , Xu Weihua , Chen Yongbin , Xu ZhongHeng
Published: May 2017

In this study, we evaluated the prognostic potential and functional regulation of human nature antisense, brain-derived neurotrophic factor antisense, in non–small cell lung cancer. Non–small cell lung cancer carcinoma and adjacent non-carcinoma lung tissues were extracted from 151 patients. Their endogenous brain-derived neurotrophic factor antisense expression levels were compared by quantitative reverse transcription polymerase chain reaction. Clinical relevance between endogenous brain-derived neurotrophic factor antisense expression level and patients’ clinicopathological variances or overall survival was analyzed. The potential of brain-derived neurotrophic factor antisense being an independent prognostic factor in non–small cell lung cancer was also evaluated. In in vitro non–small cell lung cancer cell lines, brain-derived neurotrophic factor antisense was upregulated through forced overexpression. The effects of brain-derived neurotrophic factor antisense upregulation on non–small cell lung cancer in vitro survival, proliferation, and migration were evaluated by viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and transwell assays. Brain-derived neurotrophic factor antisense is lowly expressed in non–small cell lung cancer carcinoma tissues and further downregulated in late-stage carcinomas. Brain-derived neurotrophic factor antisense downregulation was closely associated with non–small cell lung cancer patients’ advanced tumor, lymph node, metastasis stage, and positive status of lymph node metastasis, and confirmed to be an independent prognostic factor for patients’ poor overall survival. In non–small cell lung cancer A549 and H226 cell lines, forced overexpression of brain-derived neurotrophic factor antisense did not alter cancer cell viability but had significantly tumor suppressive effect in inhibiting in vitro non–small cell lung cancer proliferation and migration. Endogenous brain-derived neurotrophic factor antisense in non–small cell lung cancer carcinoma could be a potential biomarker for predicting patients’ prognosis. Overexpressing brain-derived neurotrophic factor antisense may also have a therapeutic potential in inhibiting non–small cell lung cancer tumor growth.
Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway
Authors: Zhong Jia-Teng , Yu Jian , Wang Hai-Jun , Shi Yu , Zhao Tie-Suo , He Bao-Xia , Qiao Bin , Feng Zhi-Wei
Published: May 2017

Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway–related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V–fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V–fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.
Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway
Authors: Shi Hui , Pu Jin , Zhou Xiao-Li , Ning Yun-Ye , Bai Chong
Published: May 2017

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.
Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway
Authors: Zhang Mingdi , Cai Shizhong , Zuo Bin , Gong Wei , Tang Zhaohui , Zhou Di , Weng Mingzhe , Qin Yiyu , Wang Shouhua , Liu Jun , Ma Fei , Quan Zhiwei
Published: May 2017

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA–epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.
Predictive and prognostic value of serum periostin in advanced non–small cell lung cancer patients receiving chemotherapy
Authors: Zhang Yan , Yuan Dongmei , Yao Yanwen , Sun Wenkui , Shi Yi , Su Xin
Published: May 2017

Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. However, the role of serum periostin as a surrogate marker for treatment efficacy is still unknown. In 122 advanced non–small cell lung cancer cases, 37 patients with benign lung disease and 40 healthy controls, serum periostin was measured by enzyme-linked immunosorbent assays. The associations of serum periostin levels with the clinic-pathological parameters, chemotherapy response, and clinical outcomes of non–small cell lung cancer patients were analyzed. Serum periostin levels were significantly higher in non–small cell lung cancer patients, and it was related significantly to bone metastasis ( p = 0.021). Serum periostin of 65 non–small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy ( p = 0.001). For the 122 non–small cell lung cancer patients, the median progression-free survival was 5 months. In a multivariate analysis, performance status (hazard ratio, 1.71; 95% confidence interval, 1.10–2.67), baseline periostin (hazard ratio, 1.01; 95% confidence interval, 1.00–1.01), and periostin response (hazard ratio, 0.50; 95% confidence interval, 0.29–0.86) were significantly correlated with prognosis. In conclusion, serum periostin was elevated in advanced non–small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non–small cell lung cancer.
Epithelial–mesenchymal transition and gastric cancer stem cell
Authors: Xia Pu , Xu Xiao-Yan
Published: May 2017

Gastric cancer remains a big health problem in China. Gastric cancer cells contain a small subpopulation of cells that exhibit capabilities of differentiation and tumorigenicity. A putative explanation for ineffective therapy is the presence of cancer stem-like cells. Side population cells, which have cancer stem-like cells’ property, are characterized by the high efflux ability of Hoechst 33342 dye. Side population cells have been isolated from gastric cancer cell lines in previous studies. The epithelial–mesenchymal transition is very important in the invasion and metastasis of epithelial-derived cancers. More and more studies showed that gastric cancer stem-like cells possess high invasive ability and epithelial–mesenchymal transition property. A brief overview of the recent advancements in gastric cancer stem-like cells and epithelial–mesenchymal transition will be helpful for providing novel insight into gastric cancer treatment.
Organochlorine pesticides accumulation and breast cancer: A hospital-based case–control study
Authors: He Ting-Ting , Zuo An-Jun , Wang Ji-Gang , Zhao Peng
Published: May 2017

The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case–control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp′-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp′-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp′-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp′-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.
Interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats
Authors: Yang Ke-Ke , Sui Yi , Zhou Hui-Rong , Zhao Hai-Lu
Published: May 2017

Renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin–angiotensin system and adenosine monophosphate–activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate–activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate–activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate–activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate–activated protein kinase signaling pathway resulted in hyperlipidemia and carcinogenesis in tubular epithelial cells, which may be largely attenuated by renin–angiotensin system blockade, implying the interaction of renin–angiotensin system and adenosine monophosphate–activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.
Abrus agglutinin targets cancer stem-like cells by eliminating self-renewal capacity accompanied with apoptosis in oral squamous cell carcinoma
Authors: Sinha Niharika , Panda Prashanta Kumar , Naik Prajna Paramita , Maiti Tapas K , Bhutia Sujit K
Published: May 2017

The accumulating evidences show that Abrus agglutinin, a plant lectin, displays a broad range of anticancer activity including cancer-specific induction of apoptosis; however, the underlying molecular mechanism of Abrus agglutinin–induced oral cancer stem cell elimination remains elusive. Our data documented that Abrus agglutinin effectively downregulated the CD44+ expression with the increased CD44− population in different oral cancer cells. After 24-h Abrus agglutinin treatment, FaDu cells were quantified for orosphere formation in ultra-low attachment plates and data showed that Abrus agglutinin inhibited the number and size of orosphere in a dose-dependent manner in FaDu cells. Furthermore, Abrus agglutinin hindered the plasticity of FaDu orospheres as supported by reduced sphere formation and downregulated the self-renewal property via inhibition of Wnt-β-catenin signaling pathway. Introduction of LiCl, a glycogen synthase kinase 3β inhibitor, rescued the Abrus agglutinin–stimulated inhibition of β-catenin and phosphorylated glycogen synthase kinase 3β in FaDu cell–derived orospheres confirming importance of Wnt signaling in Abrus agglutinin–mediated inhibition of stemness. In this connection, our data showed that Abrus agglutinin restrained proliferation and induced apoptosis in FaDu-derived cancer stem cells in dose-dependent manner. Moreover, western blot data demonstrated that Abrus agglutinin increased the Bax/Bcl-2 ratio with activation of poly(adenosine diphosphate–ribose) polymerase and caspase-3 favoring apoptosis induction in orospheres. Abrus agglutinin induced reactive oxygen species accumulation in orospheres and pretreatment of N-acetyl cysteine, and a reactive oxygen species scavenger inhibited Abrus agglutinin–mediated caspase-3 activity and β-catenin expression indicating reactive oxygen species as a principal regulator of Wnt signaling and apoptosis. In conclusion, Abrus agglutinin has a potential role as an integrative therapeutic approach for combating oral cancer through targeting self-renewability of orospheres via reactive oxygen species–mediated apoptosis.
The expression of RNA-binding protein RBM38 decreased in renal cell carcinoma and represses renal cancer cell proliferation, migration, and invasion
Authors: Huang Wen , Wei Xiao-Long , Ni WeiWei , Cao Mengda , Meng Ling , Yang Haiwei
Published: May 2017

RBM38, a member of RNA recognition motif family of RNA-binding proteins, can regulate the expression of diverse targets by influencing their messenger RNA stability and play a vital role in cancer development. RBM38 may act as an oncogene or suppressor gene in several human tumors. However, its role in human renal cell carcinoma remains unclear. In this study, we found that the expression of RBM38 was lower in renal cell carcinoma tissues and cell lines. Moreover, overexpression of RBM38 could reduce, whereas knockdown of RBM38 could accelerate renal cell carcinoma cell lines growth rate and number of colonies formation of renal cell carcinoma cell lines. Furthermore, RBM38 inhibited renal cell carcinoma cell lines migration and invasion through epithelial–mesenchymal transition suppression by up-regulating E-cadherin and down-regulating β-catenin and vimentin. For in vivo assays, we found that the RBM38-positive group CAKI-1-RBM38 formed smaller tumors in nude mice compared with the control group. Kaplan–Meier analysis showed that renal cell carcinoma patients with lower expression of RBM38 had a significantly shorter survival time than those with higher expression of RBM38 ( p = 0.028). All these suggested that RBM38 acts as a tumor suppressor in renal cell carcinoma, which has the potential value for the prediction of renal cell carcinoma prognosis.
Estradiol via estrogen receptor beta influences ROS levels through the transcriptional regulation of SIRT3 in human seminoma TCam-2 cells
Authors: Panza Salvatore , Santoro Marta , De Amicis Francesca , Morelli Catia , Passarelli Valentina , D’Aquila Patrizia , Giordano Francesca , Cione Erika , Passarino Giuseppe , Bellizzi Dina , Aquila Saveria
Published: May 2017

Human testis, gonocytes, and adult germ cells mainly express estrogen receptor beta, and estrogen receptor beta loss is associated with advanced tumor stage; however, the molecular mechanisms of estrogen receptor beta–protective effects are still to be defined. Herein, we provide evidence that in human seminoma TCam-2 cells, E2 through estrogen receptor beta upregulates the mitochondrial deacetylase sirtuin-3 at protein and messenger RNA levels. Specifically, E2 increases sirtuin-3 expression through a transcriptional mechanism due to the occupancy of sirtuin-3 promoter by estrogen receptor beta, together with the transcription factor Sp1 as evidenced by Chip reChIp assay. This complex binds to a GC cluster located between −128 bp/+1 bp and is fundamental for E2 effects, as demonstrated by Sp1 small interfering RNA studies. Beside, after 24 h, E2 stimulus significantly increased activities of superoxide dismutase and catalase to scavenge reactive oxygen species produced by 30 min of E2 stimulus. In summary, this article indicates a novel functional interplay between estrogen receptor beta and sirtuin-3 counteracting reactive oxygen species production in TCam-2 cells. Our findings thus show that an important tumor-suppressive pathway through estrogen receptor beta is target of E2, actually proposing a distinctive protecting action against seminoma. Future studies may lead to additional strategies for the current therapy of seminoma.
MicroRNA-409-5p is upregulated in breast cancer and its downregulation inhibits cancer development through downstream target of RSU1
Authors: Yu Hong , Xing Hua , Han Wei , Wang Yali , Qi Tianyang , Song Changlong , Xu Zheli , Li Hongjun , Huang Yinghui
Published: May 2017

We investigated the expression and function of miR-409-5p in human breast cancer. Quantitative real-time polymerase chain reaction was conducted to evaluate endogenous miR-409-5p expression in breast cancer tumors and breast cancer cell lines. Lentiviral transduction was performed to stably downregulate miR-409-5p in breast cancer cell lines MDA-MB-231 and MCF-7 and cells. The effects of miR-409-5p downregulation on breast cancer proliferation, migration, and xenograft development were then evaluated. Downstream target gene of miR-409-5p, Ras suppressor protein 1, was examined by dual-luciferase activity assay, quantitative real-time polymerase chain reaction, and western blot in lentiviral-transduced breast cancer cells. Ras suppressor protein 1 was also inhibited in miR-409-5p-downregulated breast cancer cells to examine its functional effect on breast cancer proliferation and migration. MiR-409-5p was aberrantly upregulated in both breast cancer tumors and cell lines. Lentiviral transduction successfully downregulated endogenous miR-409-5p expression as well as suppressed proliferation, migration, and xenograft development in MDA-MB-231 and MCF-7 cells. Ras suppressor protein 1 was confirmed to be directly targeted by miR-409-5p in breast cancer cells. Small interfering RNA–mediated Ras suppressor protein 1 inhibition reversely promoted cancer proliferation and migration in miR-409-5p-downregualted breast cancer cells. MiR-409-5p is downregulated in breast cancer and its inhibition has anti-cancer effect on breast cancer development both in vitro and in vivo. The regulatory effect of miR-409-5p inhibition is likely through the inverse upregulation of Ras suppressor protein 1 in breast cancer.