bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma
Authors: Wang Ning , Zhu Meifen , Tsao Sai-Wah , Man Kwan , Zhang Zhangjin , Feng Yibin 
Published: October 2013

Abstract

Background
microRNAs have been shown to regulate the chemosensitivity of cancer cells. The aim of this study is to investigate the role and mechanism of mir-23a in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide in human hepatocellular carcinoma (HCC).

Methods
The anti-tumor effect of chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft model. Expression of mRNA and miRNAs were determined by quantitative real-time PCR. Protein expression was analyzed by immunoblotting.

Results
Overexpression of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; however, ectopic expression of miR-23a fails to sensitize HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down-regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to 3′untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53 expression. Up-regulation of p53 induces mir-23a expression, while suppression of p53 inhibits miR-23a in HCC cells.

Conclusion
Our study sheds light on the role of miR-23a as a potential target in regulating chemosensitivity of HCC cells.
Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient’s perspective
Authors: Hirji Ishan , Gupta Shaloo , Goren Amir , Chirovsky Diana R , Moadel Alyson B , Olavarria Eduardo , Victor Timothy W , Davis Catherine C 
Published: October 2013

Abstract

Background
The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs.

Methods
Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (≥18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates.

Results
303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01).

Conclusions
Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients’ normal routine can be an important determinant of HRQoL and adherence.
New clinical application of high-intensity focused ultrasound: local control of synovial sarcoma
Authors: Hu Xiaoye , Cai Hongke , Zhou Meiqi , He Haifei , Tian Wei , Hu Yue , Chen Lirong , Deng Yongchuan 
Published: October 2013

Abstract
High-intensity focused ultrasound (HIFU) is playing an increasingly important role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely rare. We report the first case of noninvasive HIFU therapy for the control of synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on the left chest wall through lumpectomy. After four cycles of chemotherapy, local recurrence of the sarcoma was detected. Subsequent extended resection confirmed synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma relapsed again. Then the patient received five courses of HIFU; this completely ablated the sarcoma without complications. No chemotherapy, radiotherapy, or biological therapy has been applied since. Now the patient is stable and has a high quality of life.
Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China
Authors: Makhawi Abdelrafie M , Liu Xiao-Bo , Yang Shu-Ran , Liu Qi-Yong 
Published: October 2013

AbstractBackgroundAnopheles sinensisis a principal vector forPlasmodium vivaxmalaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China.MethodsThe present study investigated the genetic structure ofAn. sinensispopulations using a 729 bp fragment of mtDNAND5among 10 populations collected from seven provinces in China.ResultsND5was polymorphic by single mutations within three groups ofAn. sinensisthat were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation ofAn. sinensisvaried from low to moderate across China and with aFSTrange of 0.00065 – 0.341. Genealogy analysis clustered the populations ofAn. sinensisinto three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in theAn. sinensispopulations from China. Three clusters ofAn. sinensispopulations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations ofAn. sinensis(R2 = 0.058;P = 0.301).ConclusionsThe results indicate that theND5gene of mtDNA is highly polymorphic inAn. sinensisand has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion inAn. sinensispopulations.
Assessing the influence of the multisensory environment on the whisky drinking experience
Authors: Velasco Carlos , Jones Russell , King Scott , Spence Charles 
Published: October 2013

AbstractBackgroundFlavor perception depends not only on the multisensory integration of the sensory inputs associated with the food or drink itself, but also on the multisensory attributes (or atmosphere) of the environment in which the food/drink is tasted. We report two experiments designed to investigate whether multisensory atmospheric cues could be used to influence the perception of a glass of whisky (that is, a complex but familiar product). The pre-test (experiment 1) was conducted in the laboratory and involved a sample of 18 participants (12 females, 5 males, and 1 who did not specify gender), while the main study (experiment 2) was conducted at a large purpose-designed whisky-tasting event held in London, and enrolled a sample of 441 participants (165 female, 250 male, and 26 who failed to specify their gender). In the main experiment, participants were exposed to three different multisensory atmospheres/rooms, and rated various attributes of the whisky (specifically the nose, the taste/flavor, and the aftertaste) in each room.ResultsAnalysis of the data showed that each multisensory atmosphere/room exerted a significant effect on participants’ ratings of the attributes that the atmosphere/room had been designed to emphasize (namely grassiness, sweetness, and woodiness). Specifically, the whisky was rated as being significantly grassier in the Nose (‘grassy’) room, as being significantly sweeter in the Taste (‘sweet’) room, and as having a significantly woodier aftertaste in the Finish (‘woody’) room. Overall, the participants preferred the whisky when they tasted it in the Finish room.ConclusionsTaken together, these results further our understanding of the significant influence that a multisensory atmosphere can have on people’s experience and/or enjoyment of a drink (in this case, a glass of whisky). The implications of these results for the future design of multisensory experiences are discussed.
ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Authors: Johnson Bruce E. , Kabbinavar Fairooz , Fehrenbacher Louis , Hainsworth John , Kasubhai Saifuddin , Kressel Bruce , Lin Chin-Yu , Marsland Thomas , Patel Taral , Polikoff Jonathan , Rubin Mark , White Leonard , Yang James Chih-Hsin , Bowden Chris , Miller Vincent 
Published: October 2013

Purpose This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non–small-cell lung cancer (NSCLC). Patients and Methods One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS). Results Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms. Conclusion The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.
Dose-Dense Temozolomide for Newly Diagnosed Glioblastoma: A Randomized Phase III Clinical Trial
Authors: Gilbert Mark R. , Wang Meihua , Aldape Kenneth D. , Stupp Roger , Hegi Monika E. , Jaeckle Kurt A. , Armstrong Terri S. , Wefel Jeffrey S. , Won Minhee , Blumenthal Deborah T. , Mahajan Anita , Schultz Christopher J. , Erridge Sara , Baumert Brigitta , Hopkins Kristen I. , Tzuk-Shina Tzahala , Brown Paul D. , Chakravarti Arnab , Curran Walter J. , Mehta Minesh P. 
Published: October 2013

PurposeRadiotherapy with concomitant and adjuvant temozolomide is the standard of care for newly diagnosed glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status may be an important determinant of treatment response. Dose-dense (DD) temozolomide results in prolonged depletion of MGMT in blood mononuclear cells and possibly in tumor. This trial tested whether DD temozolomide improves overall survival (OS) or progression-free survival (PFS) in patients with newly diagnosed GBM.Patients and MethodsThis phase III trial enrolled patients older than age 18 years with a Karnofsky performance score of ≥ 60 with adequate tissue. Stratification included clinical factors and tumor MGMT methylation status. Patients were randomly assigned to standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The primary end point was OS. Secondary analyses evaluated the impact of MGMT status.ResultsA total of 833 patients were randomly assigned to either arm 1 or arm 2 (1,173 registered). No statistically significant difference was observed between arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not differ by methylation status. MGMT methylation was associated with improved OS (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P < .001), and response (P = .012). There was increased grade ≥ 3 toxicity in arm 2 (34% v 53%; P < .001), mostly lymphopenia and fatigue.ConclusionThis study did not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM, regardless of methylation status. However, it did confirm the prognostic significance of MGMT methylation. Feasibility of large-scale accrual, prospective tumor collection, and molecular stratification was demonstrated.
Prostate-Specific Antigen Changes As Surrogate for Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Second-Line Chemotherapy
Authors: Halabi Susan , Armstrong Andrew J. , Sartor Oliver , de Bono Johann , Kaplan Ellen , Lin Chen-Yen , Solomon Nicole C. , Small Eric J. 
Published: October 2013

Purpose Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy. Patients and Methods Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy. Results The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a ≥ 30% decline in PSA was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43 to 0.64; P < .001). Adjusting for treatment effect, the HR for a ≥ 30% PSA decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained statistically significant, thus failing the third Prentice criterion. The PTE for a ≥ 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of surrogacy for OS. The values of R2 were < 1, suggesting that PSA decline was not surrogate for OS. Conclusion Surrogacy for any PSA-based end point could not be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes.
Negotiating Kingship in France at the Time of the Early Crusades: Suger and the Gesta Ludovici Grossi
Authors: Naus James 
Published: October 2013

This article shows the crusading movement to be an optimal route into an understanding of Europe’s twelfth-century power structure by examining its impact on the valuation and practice of kingship in France. The article argues that Suger of Saint-Denis’s history of Louis VI, the Gesta Ludovici Grossi, can be read as one of several responses to the threat posed to kingship by the new crusade ideology and to the prestige attaching to former crusaders. Suger fuses Carolingian notions of sacred kingship with the newer crusade ideas to craft a highly selective narrative of Louis’s reign that foregrounds the motif of military actions prosecuted to vindicate justice and with ecclesiastical endorsement. Suger thereby exploits the unknown future of crusading to create a space into which the self-fashioning of Capetian kingship could insinuate itself and from which emerged the late medieval image of a “crusader king.”
Cet article présente les croisades comme le meilleur moyen de comprendre la structure du pouvoir en Europe au XIIe siècle, à travers l’examen de son impact sur l’évaluation et la pratique de la royauté en France. Plus précisément, cet article soutient que l’histoire de Louis VI par Suger de Saint-Denis, la Gesta Ludovici Grossi, peut être lue comme une réponse alternative à la menace que faisaient peser sur la royauté l’idéologie nouvelle des croisades et le prestige lié aux premiers croisés. Le texte mêle la notion carolingienne d’une royauté sacrée avec les idées nouvelles des croisades, pour rédiger un récit très sélectif du règne de Louis VI, où prédomine le thème des actions militaires engagées pour défendre la justice et obtenir l’approbation ecclésiastique. Suger exploite ainsi l’avenir inconnu des croisades pour créer un espace dans lequel se façonnerait le modèle de la royauté capétienne et d’où émergerait l’image médiévale tardive du « roi croisé ».
An Unlikely Pair: Satire and Jansenism in the Sarcelades, 1731-1764
Authors: Choudhury Mita 
Published: October 2013

Between 1731 and 1764 unknown writer Nicolas Jouin eluded arrest and published fifteen satirical verses known as the sarcelades. The poems straddled the different areas of Jansenist political culture and the world of popular opinion and clandestine literature. Written in patois, the sarcelades featured the peasant Claude Fetu, who made ultramontane bishops, the Jesuits, and even the king the objects of derision and resentment. This character embodied certain Jansenist beliefs regarding the simple believer who bore witness on behalf of individuals persecuted for resisting the anti-Jansenist bull Unigenitus. The sarcelades suggest that theological debates had a place in the world of the impoverished and underrepresented, whose views were shaped both by spiritual conviction and material needs.
Entre 1731 et 1764 un auteur inconnu, Nicolas Jouin, échappa aux arrestations et publia quinze textes satiriques versifiés, les « sarcelades ». Ces poèmes évoquent à la fois diverses sphères de la culture politique janséniste et les mondes de l’opinion populaire et de la littérature clandestine. Ecrits en patois, les « sarcelades » mettent en scène le paysan Claude Fetu, qui fait des évêques ultramontains, des Jésuites et même du roi des objets de ridicule et de reproche. Ce personnage incarne une conception janséniste particulière du simple croyant qui témoigne au nom d’individus persécutés pour avoir résisté à la bulle anti-janséniste Unigenitus. Les « sarcelades » suggèrent que les débats théologiques avaient leur place parmi les pauvres et les sous-représentés, dont l’opinion était formée à la fois par leur conviction spirituelle et leurs besoins matériels.
Regulation of CYP3A genes by glucocorticoids in human lung cells
Authors: Roberts Jessica K , Moore Chad D , Romero Erin G , Ward Robert M , Yost Garold S , Reilly Christopher A 
Published: October 2013

Inhaled glucocorticoids are the first-line treatment for patients with persistent asthma. However, approximately thirty percent of patients exhibit glucocorticoid insensitivity, which may involve excess metabolic clearance of the glucocorticoids by CYP3A enzymes in the lung. CYP3A4, 3A5, and 3A7 enzymes metabolize glucocorticoids, which in turn induce CYP3A genes. However, the mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been determined. In hepatocytes, glucocorticoids bind to the glucocorticoid receptor (GR), which induces the expression of the constitutive androstane receptor or pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading to the induction of CYP3A4, 3A5, and 3A7. There is also evidence to suggest a direct induction of CYP3A5 by GR activation in liver cells. In this study, these pathways were evaluated as the mechanism for CYP3A5 mRNA induction by glucocorticoids in freshly isolated primary tracheal epithelial, adenocarcinomic human alveolar basal epithelial (A549), immortalized bronchial epithelial (BEAS-2B), primary normal human bronchial/tracheal epithelial (NHBE), primary small airway epithelial (SAEC), and primary lobar epithelial lung cells. In A549 cells, beclomethasone 17-monopropionate ([M1]) induced CYP3A5 mRNA through the glucocorticoid receptor. CYP3A5 mRNA induction by five different glucocorticoids was attenuated by inhibiting the glucocorticoid receptor using ketoconazole, and for beclomethasone dipropionate, using siRNA-mediated knock-down of the glucocorticoid receptor. The constitutive androstane receptor was not expressed in lung cells. SAEC cells, a primary lung cell line, expressed CYP3A5, but CYP3A5 mRNA was not induced by glucocorticoid treatment despite evaluating a multitude of cell culture conditions. None of the other lung cells expressed CYP3A4, 3A5 or 3A7 mRNA. These studies demonstrate that CYP3A5 mRNA is induced by glucocorticoids in A549 cells via the glucocorticoid receptor, but that additional undefined regulatory processes exist in primary lung cells.