bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-148a Suppresses Tumor Cell Invasion and Metastasis by Downregulating ROCK1 in Gastric Cancer
Authors: Zheng Biqiang , Liang Linhui , Wang Chunmeng , Huang Shenglin , Cao Xi , Zha Ruopeng , Liu Li , Jia Deshui , Tian Qi , Wu Jianghong , Ye Yanwei , Wang Qifeng , Long Ziwen , Zhou Ye , Du Chunyan , He Xianghuo , Shi Yingqiang 
Published: October 2011

Abstract
Purpose: MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis.
Experimental Design: We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored.
Results: We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3′ untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a–induced suppression of gastric cancer cell migration and invasion.
Conclusions: miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis. Clin Cancer Res; 17(24); 7574–83. ©2011 AACR.
Targeting Radiation-Induced G2 Checkpoint Activation with the Wee-1 Inhibitor MK-1775 in Glioblastoma Cell Lines
Authors: Sarcar Bhaswati , Kahali Soumen , Prabhu Antony H. , Shumway Stuart D. , Xu Yang , Demuth Tim , Chinnaiyan Prakash 
Published: October 2011

AbstractThe purpose of this study was to determine the capacity of MK-1775, a potent Wee-1 inhibitor, to abrogate the radiation-induced G2 checkpoint arrest and modulate radiosensitivity in glioblastoma cell models and normal human astrocytes. The radiation-induced checkpoint response of established glioblastoma cell lines, glioblastoma neural stem (GNS) cells, and astrocytes were determined in vitro by flow cytometry and in vivo by mitosis-specific staining using immunohistochemistry. Mechanisms underlying MK-1775 radiosensitization were determined by mitotic catastrophe and γH2AX expression. Radiosensitivity was determined in vitro by the clonogenic assay and in vivo by tumor growth delay. MK-1775 abrogated the radiation-induced G2 checkpoint and enhanced radiosensitivity in established glioblastoma cell lines in vitro and in vivo, without modulating radiation response in normal human astrocytes. MK-1775 appeared to attenuate the early-phase of the G2 checkpoint arrest in GNS cell lines, although the arrest was not sustained and did not lead to increased radiosensitivity. These results show that MK-1775 can selectively enhance radiosensitivity in established glioblastoma cell lines. Further work is required to determine the role Wee-1 plays in checkpoint activation of GNS cells. Mol Cancer Ther; 10(12); 2405–14. ©2011 AACR.
Dual Inhibition of Tumor Energy Pathway by 2-Deoxyglucose and Metformin Is Effective against a Broad Spectrum of Preclinical Cancer Models
Authors: Cheong Jae-Ho , Park Eun Sung , Liang Jiyong , Dennison Jennifer B. , Tsavachidou Dimitra , Nguyen-Charles Catherine , Wa Cheng Kwai , Hall Hassan , Zhang Dong , Lu Yiling , Ravoori Murali , Kundra Vikas , Ajani Jaffer , Lee Ju-Seog , Ki Hong Waun , Mills Gordon B. 
Published: October 2011

Abstract
Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and metformin. We evaluated the in vitro antitumor activity of 2DG, metformin or AICAR alone, and 2DG in combination either with metformin or AICAR. We examined in vivo efficacy using xenograft mouse models. 2DG alone was not sufficient to promote tumor cell death, reflecting the limited efficacy showed in clinical trials. A combined use of 2DG and AICAR also failed to induce cell death. However, 2DG and metformin led to significant cell death associated with decrease in cellular ATP, prolonged activation of AMPK, and sustained autophagy. Gene expression analysis and functional assays revealed that the selective AMPK agonist AICAR augments mitochondrial energy transduction (OXPHOS) whereas metformin compromises OXPHOS. Importantly, forced energy restoration with methyl pyruvate reversed the cell death induced by 2DG and metformin, suggesting a critical role of energetic deprivation in the underlying mechanism of cell death. The combination of 2DG and metformin inhibited tumor growth in mouse xenograft models. Deprivation of tumor bioenergetics by dual inhibition of energy pathways might be an effective novel therapeutic approach for a broad spectrum of human tumors. Mol Cancer Ther; 10(12); 2350–62. ©2011 AACR.
Cytokine Induction of Tumor Necrosis Factor Receptor 2 Is Mediated by STAT3 in Colon Cancer Cells
Authors: Hamilton Kathryn E. , Simmons James G. , Ding Shengli , Van Landeghem Laurianne , Lund P. Kay 
Published: October 2011

AbstractThe IL-6/STAT3 and TNFα/NFκB pathways are emerging as critical mediators of inflammation-associated colon cancer. TNF receptor (TNFR) 2 expression is increased in inflammatory bowel diseases, the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated cancer, and by combined interleukin (IL) 6 and TNFα. The molecular mechanisms that regulate TNFR2 remain undefined. This study used colon cancer cell lines to test the hypothesis that IL-6 and TNFα induce TNFR2 via STAT3 and/or NFκB. Basal and IL-6 + TNFα–induced TNFR2 were decreased by pharmacologic STAT3 inhibition. NFκB inhibition had little effect on IL-6 + TNFα–induced TNFR2, but did inhibit induction of endogenous IL-6 and TNFR2 in cells treated with TNFα alone. Chromatin immunoprecipitation (ChIP) revealed cooperative effects of IL-6 + TNFα to induce STAT3 binding to a −1,578 STAT response element in the TNFR2 promoter but no effect on NFκB binding to consensus sites. Constitutively active STAT3 was sufficient to induce TNFR2 expression. Overexpression of SOCS3, a cytokine-inducible STAT3 inhibitor, which reduces tumorigenesis in preclinical models of colitis-associated cancer, decreased cytokine-induced TNFR2 expression and STAT3 binding to the −1,578 STAT response element. SOCS3 overexpression also decreased proliferation of colon cancer cells and dramatically decreased anchorage-independent growth of colon cancer cells, even cells overexpressing TNFR2. Collectively, these studies show that IL-6- and TNFα-induced TNFR2 expression in colon cancer cells is mediated primarily by STAT3 and provide evidence that TNFR2 may contribute to the tumor-promoting roles of STAT3. Mol Cancer Res; 9(12); 1718–31. ©2011 AACR.
A note on the nonlinear mechanical behavior of planar random network structures subjected to in-plane compression
Authors: Åslund Pär E. , Isaksson Per 
Published: October 2011

The microstructural effect on the mechanical behavior of idealized two-dimensional random fiber networks subjected to in-plane compression is studied. A finite element model utilizing nonlinear beam elements assuming a linearly elastic material is developed. On a macroscopic level, random fiber networks often display an asymmetric material behavior when loaded in tension and compression. In mechanical models, this nonlinearity is traditionally described using continuum elastic-inelastic and/or damage models even though using a continuum approach risks overlooking microstructural effects. It is found that even though a linear elastic material model is used for the individual fibers, the network gives a nonlinear response in compression. The nonlinearity is found to be caused by buckling of individual fibers. This reversible nonlinear mechanism is limited in tensile loading and hence offers an alternative explanation to the global asymmetry of random fibernetworks.
The randomized fast-track trial in palliative care: Role, utility and ethics in the evaluation of interventions in palliative care?
Authors: Higginson Irene J , Booth Sara 
Published: October 2011

Background: Randomized trials are the gold standard method for evaluating treatments and services in health care. However, they are often difficult to complete in palliative care, and suffer from poor recruitment. Aim: To introduce the randomized fast-track trial and its potential use in palliative care. Method: The randomized fast-track trial is a form of randomized trial with two periods. In the first, the trial runs as a normal randomized trial. In the second period, the standard (control) group also are offered the intervention. The design is adapted from a ‘wait list’ design (sometimes called a deferred entry or delayed intervention trial) but is both less confusing for patients, who are not on waiting lists, and more appropriate to the nature of services offered. The methodology has the advantage of being more acceptable to many patients, clinicians and ethics committees than standard randomized trials, because all patients will eventually be offered the intervention. Yet it has the rigour of a traditional randomized trial. However, care is needed to ensure the correct timing for the first period, before the standard group receive the intervention. The analysis of data in the second period is complex. Conclusion: The fast-track trial has been used successfully in palliative care among patients severely affected by multiple sclerosis, chronic obstructive pulmonary disease and cancer. It is best suited to evaluations of palliative care services among patients who have longer prognoses, for example of several months or more although it has been used in people with prognoses of weeks.
Management of chronic cough in patients receiving palliative care: Review of evidence and recommendations by a task group of the Association for Palliative Medicine of Great Britain and Ireland
Authors: Wee Bee , Browning Juliet , Adams Astrid , Benson Debbie , Howard Paul , Klepping Gwen , Molassiotis Alex , Taylor David 
Published: October 2011

Background: Chronic cough is a disruptive and exhausting symptom, reported as very distressing in a quarter of those in their last year of life. Existing guidelines for management of chronic cough primarily deal with the commonest benign causes of cough: asthma; eosinophilic bronchitis; gastro-oesophageal reflux disease; rhinosinusitis. Aim/design: to examine what literature evidence exists and formulate recommendations for managing chronic cough in patients with advanced, progressive, life-limiting illnesses. Data sources: Electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Library, Google Scholar); hand-search; grey literature. Results: Of 11 initially eligible studies, 5 provided evidence at level 2 or better. The small size of these studies, heterogeneity of study population and diversity of interventions and outcome measures used meant that comparison across studies and compilation of guidelines based on high-quality evidence was not possible. Pragmatic recommendations based on available evidence were formulated, drawing on the included studies and, in addition, extrapolating from two other well-designed studies involving patients with chronic cough. They also took into consideration convenience, toxicity and minimizing burden and harm of intervention, as well as considering the potential for disease-directed treatment and the possibility of pharmacological and co-existing benign causes of chronic cough. Conclusions: These recommendations (Grade D) include simple linctus, therapeutic trial of sodium cromoglycate and then prescription of an opioid or opioid derivative (dextromethorphan, morphine or codeine). Further research is clearly and urgently required in this area for more effective approaches to managing cough, tested in trials that have sufficient size, power and validity.
Establishing hospice care for prison populations: An integrative review assessing the UK and USA perspective
Authors: Stone Katie , Papadopoulos Irena , Kelly Daniel 
Published: October 2011

Background: models of care based on the hospice model have delivered effective support to dying people since their inception. Over the last 20 years this form of care has also been introduced into the prison system (mainly in the United States) to afford terminally ill inmates the right to die with dignity. Aim: the aim of this review is to examine the evidence from the United States and the United Kingdom on the promotion of palliative care in the prison sector, summarizing examples of good practice and identifying barriers for the provision of end-of-life care within the prison environment both in the USA and UK. Design: an integrative review design was adopted using the Green et al. model incorporating theoretical and scientific lines of enquiry. Data sources: literature was sourced from six electronic databases between the years 2000 and 2011; the search rendered both qualitative and quantitative papers, discussion papers, ‘grey literature’ and other review articles. Results: the results highlight a number of issues surrounding the implementation of palliative care services within the prison setting and emphasize the disparity between the USA model of care (which emphasizes the in-prison hospice) and the UK model of care (which emphasizes palliative care in-reach) for dying prisoners. Conclusion: the provision of palliative care for the increasing prison population remains under-researched globally, with a notable lack of evidence from the United Kingdom.
Reliability and validity of the Thai translation (Thai PPS Adult Suandok) of the Palliative Performance Scale (PPSv2)
Authors: Chewaskulyong Busyamas , Sapinun Ladarat , Downing G Michael , Intaratat Prapai , Lesperance Mary , Leautrakul Suntree , Somwangprasert Areewan , Leerapun Thaninit 
Published: October 2011

Purpose: the Thai PPS Adult Suandok tool was translated from the Palliative Performance Scale (PPSv2) and had been used in Chiang Mai, Thailand for several years. Aim: to test the reliability and validity of the Thai translation of PPSv2. Design: a set of 22 palliative cases were used to determine a PPS score on Time-1, and repeated two weeks later as Time-2. A survey questionnaire was also completed for qualitative analysis. Participants: a total of 70 nurses and physicians from Maharaj Nakorn Hospital in Chiang Mai participated. Results: The Time-1 intraclass correlation coefficient (ICC) for absolute agreement is 0.911 (95% CI 0.86–0.96) and for consistency is 0.92 (95% CI 0.87–0.96). The Time-2 ICC for agreement is 0.905 (95% CI 0.85–0.95) and for consistency is 0.912 (95% CI 0.86–0.96). These findings indicate good agreement among participants and also were somewhat higher in the Time-2 re-test phase. Cohen’s kappa score is 0.55, demonstrating a moderate agreement. Thematic analysis from the surveys showed that 91% felt PPS to be a valuable clinical tool overall, with it being ‘very useful’ or ‘useful’ in several areas, including care planning (78% and 20%), disease monitoring (69% and 27%) and prognostication (61% and 31%), respectively. Some respondents noted difficulty in determining appropriate scores in paraplegic patients or those with feeding tubes, while others found the instructions long or difficult. Conclusion: the Thai PPS Adult Suandok translated tool has good inter- and intra-rater reliability and can be used regularly for clinical care.
Zebrafish (Danio rerio) as a Screen for Attenuation of Lancefield Group C Streptococci and a Model for Streptococcal Pathogenesis
Authors: Borst L. B. , Patterson S. K. , Lanka S. , Suyemoto M. M. , Maddox C. W. 
Published: October 2011

Group C streptococci are highly contagious pyogenic bacteria responsible for respiratory tract, lymph node, urogenital tract, and wound infections. Wild-type strains of Streptococcus equi ssp equi ( S. equi) and Streptococcus equi ssp zooepidemicus ( S. zoo) as well as a commercially available modified live vaccine strain of S. equi were evaluated for virulence in zebrafish. Survival times, histologic lesions, and relative gene expression were compared among groups. Based on the intramuscular route of infection, significantly shorter survival times were observed in fish infected with wild-type strain when compared to modified live vaccine and S. zoo strains. Histologically, S. zoo–infected fish demonstrated a marked increase in inflammatory infiltrates (predominantly macrophages) at the site of infection, as well as increased cellularity in the spleen and renal interstitium. In contrast, minimal cellular immune response was observed in S. equi–injected fish with local tissue necrosis and edema predominating. Based on whole comparative genomic hybridization, increased transcription of positive acute-phase proteins, coagulation factors, and antimicrobial peptides were observed in S. equi–injected fish relative to S. zoo–injected fish, while mediators of cellular inflammation, including CXC chemokines and granulin, were upregulated in S. zoo–injected fish relative to S. equi–injected fish. In a screen of 11 clinical isolates, S. equi strains with a single nucleotide deletion in the upstream region of szp, a known virulence factor of streptococci, were found to be significantly attenuated in zebrafish. These collective findings underscore the value of the zebrafish as a model of streptococcal pathogenesis.
Headaches during war: Analysis of presentation, treatment, and factors associated with outcome
Authors: Cohen Steven P , Plunkett Anthony R , Wilkinson Indy , Nguyen Conner , Kurihara Connie , Flagg Artemus , Morlando Benny , Stone Christina , White Ronald L , Anderson-Barnes Victoria C , Galvagno Samuel M 
Published: October 2011

Background: Headache is often associated with physical trauma and psychological stress. The aim of this study is to evaluate the impact of headache on personnel deployed in war zones and to identify factors associated with return to duty (RTD). Methods: Outcome data were prospectively collected on 985 personnel medically evacuated out of Operations Iraqi and Enduring Freedom for a primary diagnosis of headache between 2004 and 2009. Electronic medical records were reviewed to examine clinical and treatment patterns and the effect that myriad factors had on RTD. Results: 33.6% of evacuees returned to duty. The most common headaches were post-concussion (34.1%) and migraine (30.0%). Headaches typically associated with trauma such as post-concussion (18.7%), occipital neuralgia (23.1%), and cervicogenic headache (29.7%) had the lowest RTD rates, whereas tension headache (49.6%) was associated with the best outcome. Other variables associated with negative outcome included presence of aura (OR 0.51, 95% CI 0.30–0.88; p = 0.02), traumatic brain injury (OR 0.50, 95% CI 0.29–0.87; p = 0.01), opioid (OR 0.41, 95% CI 0.26–0.63; p < 0.001), and beta-blocker (OR 0.26, 95% CI 0.12–0.61; p = 0.002) use, and co-existing psychopathology ( p < 0.001 in univariable analysis). Conclusion: Headaches represent a significant cause of unit attrition in personnel deployed in military operations, with physical trauma and co-existing psychopathology associated with poorer outcomes.
Treatment costs and indirect costs of cluster headache: A health economics analysis
Authors: Gaul Charly , Finken Julia , Biermann Janine , Mostardt Sarah , Diener Hans-Christoph , Müller Oliver , Wasem Jürgen , Neumann Anja 
Published: October 2011

Background: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (eCH) or chronic cluster headache (cCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. Methods: Treatment costs (direct costs) due to healthcare utilisation, as well as costs caused by disability and reduction in earning capacity (indirect costs), were obtained using a questionnaire in CH patients treated in a tertiary headache centre based at the University Duisburg-Essen over a 6-month period. Results: A total 179 patients (72 cCH, 107 eCH) were included. Mean attack frequency was 3.5 ± 2.5 per day. Mean direct and indirect costs for one person were €5963 in the 6-month period. Direct costs were positively correlated with attack frequency ( r = 0.467, p < 0.001). Burden of disease measured with HIT-6 showed a significant correlation with attack frequency ( r = 0.467, p < 0.001). Twenty-four (13.4%) of the participants were disabled and not able to work. Conclusion: CH leads to major socioeconomic impact on patients as well as society due to direct healthcare costs and indirect costs caused by loss of working capacity.
Sports Activity After Short-Stem Hip Arthroplasty
Authors: Schmidutz Florian , Grote Stefan , Pietschmann Matthias , Weber Patrick , Mazoochian Farhad , Fottner Andreas , Jansson Volkmar 
Published: October 2011

Background: No data are available about the sports activity of patients with bone-conserving short-stem hip implants. Hypothesis: Patients can return to a good level of sports activity after implantation of a short-stem hip implant. Study Design: Case series; Level of evidence, 4. Methods: The sports activity level of 68 patients (76 hips) after short-stem hip arthroplasty was assessed for a minimum of 2 years after implantation. In addition to the clinical examination, a detailed evaluation of the patients’ sports pattern was obtained. Furthermore, the results were analyzed with regard to gender (female and male) and age (≤55 and >55 years). Results: After a mean of 2.7 years, patients showed a Harris Hip Score (HHS) of 93.6, a Western Ontario and McMaster Universities Arthritis Index (WOMAC) score of 9.5, and a University of California, Los Angeles (UCLA) activity score of 7.6, with each individual participating on average in 3.5 different disciplines after surgery compared with 3.9 before surgery. High-impact activities decreased significantly postoperatively, whereas low-impact activities increased significantly. The duration of the sports activities remained stable, while the frequency actually increased. In contrast, men participated preoperatively in more sports than women (4.3 men vs 3.3 women). However, because of a pronounced decrease in high-impact activities by men, both genders participated in an equal number of sports postoperatively (3.5 men vs 3.5 women). Finally, 45% (n = 31) reported at least one activity that they missed. Most of them were disciplines with an intermediate- or high-impact level. Conclusion: Patients with a short-stem hip implant can return to a good level of activity postoperatively. Participation in sports almost reached similar levels as preoperatively but with a shift from high- to low-impact activities. This seems desirable from a surgeon’s point of view but should also be communicated to the patient before hip replacement.