bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of Australian men diagnosed with advanced prostate cancer: a qualitative study
Authors: Chambers Suzanne K , Hyde Melissa K , Laurie Kirstyn , Legg Melissa , Frydenberg Mark , Davis Ian D , Lowe Anthony , Dunn Jeff 
Published: February 2018

ObjectiveTo explore men’s lived experience of advanced prostate cancer (PCa) and preferences for support.DesignCross-sectional qualitative study applying open-ended surveys and interviews conducted between June and November 2016. Interviews audio-recorded and transcribed verbatim and analysed from an interpretive phenomenological perspective.SettingAustralia, nation-wide.Participants39 men diagnosed with advanced PCa (metastatic or castration-resistant biochemical progression) were surveyed with 28 men subsequently completing a semistructured in depth telephone interview.ResultsThematic analysis of interviews identified two organising themes: lived experience and supportive care. Lived experience included six superordinate themes: regret about late diagnosis and treatment decisions, being discounted in the health system, fear/uncertainty about the future, acceptance of their situation, masculinity and treatment effects. Supportive care included five superordinate themes: communication, care coordination, accessible care, shared experience/peer support and involvement of their partner/family.ConclusionsLife course and the health and social context of PCa influence men’s experiences of advanced disease. Multimodal interventions integrating peer support and specialist nurses are needed that more closely articulate with men’s expressed needs.
Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements—identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland
Authors: Stadler Tanja , Meinel Dominik , Aguilar-Bultet Lisandra , Huisman Jana S , Schindler Ruth , Egli Adrian , Seth-Smith Helena M B , Eichenberger Lucas , Brodmann Peter , Hübner Philipp , Bagutti Claudia , Tschudin-Sutter Sarah 
Published: February 2018

IntroductionExtended-spectrum beta-lactamases (ESBL)-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-producingEscherichia coliwas increasingly described as an important cause of community-acquired infections, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different bacterial species. The aim of this research project is to quantify hospital-wide transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial species and the mobile genetic elements and to determine if hospital-acquired infections caused by ESBL producers are related to strains and mobile genetic elements predominantly circulating in the community or in the healthcare setting. This distinction is critical in prevention since the former emphasises the urgent need to establish or reinforce antibiotic stewardship programmes, and the latter would call for more rigorous infection control.Methods and analysisThis protocol presents an observational study that will be performed at the University Hospital Basel and in the city of Basel, Switzerland. ESBL-producing Enterobacteriaceae will be collected from any specimens obtained by routine clinical practice or by active screening in both inpatient and outpatient settings, as well as from wastewater samples and foodstuffs, both collected monthly over a 12-month period for analyses by whole genome sequencing. Bacterial chromosomal, plasmid and ESBL-gene sequences will be compared within the cohort to determine genetic relatedness and migration between humans and their environment.Ethics and disseminationThis study has been approved by the local ethics committee (Ethikkommission Nordwest-und Zentralschweiz) as a quality control project (Project-ID 2017–00100). The results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders.
Acceptability and use of glaucoma virtual clinics in the UK: a national survey of clinical leads
Authors: Gunn Patrick J G , Marks Joanne R , Au Leon , Waterman Heather , Spry Paul G D , Harper Robert A 
Published: February 2018

ObjectiveThe purpose of this paper is to describe the findings of a national survey that aimed to estimate the proportion of Hospital Eye Service (HES) units using glaucoma virtual clinics, to determine how these services differ and to gauge clinicians’ views and opinions on the safety and acceptability of this model of care compared with usual care.Methods and analysisThis 12-question survey was disseminated nationally to 92 clinical lead consultant ophthalmologists using SurveyMonkey.ResultsThe response rate was 45.7%. There were 21 out of the total 42 respondents (50.0%) who were based at an NHS Trust where glaucoma virtual clinics were already being used and a further 9 (21.4%) were planning to establish one. Clinical leads largely rated efficiency and patient safety to be at least equivalent to usual care (92.9%) and 81.0% perceived glaucoma virtual clinics to be acceptable to patients. The main reasons for not running glaucoma virtual clinics were insufficient staff (71.4%) and inadequate space (47.6%). The majority of those running virtual clinics used this model of care for ‘lower risk’ patients such as ocular hypertensives (90.5%) and glaucoma suspects.ConclusionGlaucoma virtual clinics are employed by a large proportion of HES units, with many seeking to develop such services. Clinical leads largely rate efficiency, patient safety and the perception of patient acceptability to be at least equivalent to usual care.
Histone H3.3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric Glioma
Authors: Deng Houliang , Zeng Jianming , Zhang Ting , Gong Longcai , Zhang Hongjie , Cheung Edwin , Jones Chris , Li Gang 
Published: February 2018

Abstract
Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drives the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3.3K27M and performed microarray analysis. H3.3K27M caused the upregulation of multiple cancer/testis (CT) antigens, such as ADAMTS1, ADAM23, SPANXA1, SPANXB1/2, IL13RA2, VCY, and VCX3A, in pediatric glioma cells. Chromatin immunoprecipitation analysis from H3.3K27M cells revealed decreased H3K27me3 levels and increased H3K4me3 levels on the VCX3A promoter. Knockdown of VCX3A by siRNA significantly inhibited the growth of pediatric glioma cells harboring H3.3K27M. Overexpression of VCX3A/B genes stimulated the expression of several HLA genes, including HLA-A, HLA-B, HLA-E, HLA-F, and HLA-G. The expression of VCX3A in pediatric HGG was confirmed using a tissue microarray. Gene set enrichment analysis revealed that CT antigens are enriched in pediatric HGG clinical specimens with H3.3K27M, with the upregulation of IL13RA2 contributing to the enrichment significantly. These results indicate that the upregulation of CT antigens, such as VCX3A and IL13RA2, correlates with pediatric gliomagenesis. Mol Cancer Res; 16(4); 623–33. ©2018 AACR.
AR Expression in Breast Cancer CTCs Associates with Bone Metastases
Authors: Aceto Nicola , Bardia Aditya , Wittner Ben S. , Donaldson Maria C. , O'Keefe Ryan , Engstrom Amanda , Bersani Francesca , Zheng Yu , Comaills Valentine , Niederhoffer Kira , Zhu Huili , Mackenzie Olivia , Shioda Toshi , Sgroi Dennis , Kapur Ravi , Ting David T. , Moy Beverly , Ramaswamy Sridhar , Toner Mehmet , Haber Daniel A. , Maheswaran Shyamala 
Published: February 2018

Abstract
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER+ breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.
Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720–7. ©2018 AACR.
Leptin Signaling Mediates Obesity-Associated CSC Enrichment and EMT in Preclinical TNBC Models
Authors: Bowers Laura W. , Rossi Emily L. , McDonell Shannon B. , Doerstling Steven S. , Khatib Subreen A. , Lineberger Claire G. , Albright Jody E. , Tang Xiaohu , deGraffenried Linda A. , Hursting Stephen D. 
Published: February 2018

Abstract
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks (n = 15/group). Mice were monitored for tumor development and euthanized when tumor diameter reached 1.5 cm. Tumoral gene expression was assessed via RNA sequencing (RNA-seq). DIO mice had greater body weight and percent body fat at termination than controls. DIO mice, versus controls, demonstrated reduced survival, increased systemic metabolic and inflammatory perturbations, upregulated tumoral CSC/EMT gene signature, elevated tumoral aldehyde dehydrogenase activity (a CSC marker), and greater leptin signaling. In cell culture experiments using TNBC cells (murine: E-Wnt and M-Wnt; human: MDA-MB-231), leptin enhanced mammosphere formation, and media supplemented with serum from DIO versus control mice increased cell viability, migration, invasion, and CSC- and EMT-related gene expression, including Foxc2, Twist2, Vim, Akt3, and Sox2. In E-Wnt cells, knockdown of leptin receptor ablated these procancer effects induced by DIO mouse serum. These findings indicate that increased leptin signaling is causally linked to obesity-associated TNBC development by promoting CSC enrichment and EMT.
Implications: Leptin-associated signals impacting CSC and EMT may provide new targets and intervention strategies for decreasing TNBC burden in obese women. Mol Cancer Res; 16(5); 869–79. ©2018 AACR.
BRD1-Mediated Acetylation Promotes Integrin αV Gene Expression Via Interaction with Sulfatide
Authors: Cai Qian Qian , Dong Yi Wei , Qi Bing , Shao Xiao-Ting , Wang Rong , Chen Zhong Yi , He Bao Mei , Wu Xing Zhong 
Published: February 2018

Abstract
Integrin αV gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and bromodomain containing protein 1 (BRD1) was identified as an interacting protein that also colocalized with sulfatide in HCC cells. BRD1 was also formed a complex with Sp1, which was recruited to the integrin αV gene promoter. Sulfatide was also found to induce BRD1, monocytic leukemia zinc finger (MOZ) and histone acetyltransferase binding to ORC1 (HBO1) acetyltransferase multiprotein complex recruitment to the integrin αV promoter, which is responsible for histone H3K9/14 acetylation. Finally, knockdown of BRD1 limited sulfatide-induced H3K9/14 acetylation and occupancy of MOZ or HBO1 on integrin αV gene promoter.
Implications: This study demonstrates that sulfatide interaction with BRD1 mediates acetylation and is important for regulation of integrin αV gene expression. Mol Cancer Res; 16(4); 610–22. ©2018 AACR.
Multigene Profiling of CTCs in mCRPC Identifies a Clinically Relevant Prognostic Signature
Authors: Singhal Udit , Wang Yugang , Henderson James , Niknafs Yashar S. , Qiao Yuanyuan , Gursky Amy , Zaslavsky Alexander , Chung Jae-Seung , Smith David C. , Karnes R. Jeffrey , Chang S. Laura , Feng Felix Y. , Palapattu Ganesh S. , Taichman Russell S. , Chinnaiyan Arul M. , Tomlins Scott A. , Morgan Todd M. 
Published: February 2018

AbstractThe trend toward precision-based therapeutic approaches dictated by molecular alterations offers substantial promise for men with metastatic castration-resistant prostate cancer (mCRPC). However, current approaches for molecular characterization are primarily tissue based, necessitating serial biopsies to understand changes over time and are limited by the challenges inherent to extracting genomic material from predominantly bone metastases. Therefore, a circulating tumor cell (CTC)-based assay was developed to determine gene expression across a panel of clinically relevant and potentially actionable prostate cancer–related genes. CTCs were isolated from the whole blood of mCRPC patients (n = 41) and multiplex qPCR was performed to evaluate expression of prostate cancer–related target genes (n = 78). A large fraction of patients (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression (70% of samples) and evidence of Wnt signaling (67% of samples) were observed. The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive prostate cancer–associated long noncoding RNA SChLAP1 was upregulated in 70%. WNT5a [HR 3.62, 95% confidence interval (CI), 1.63–8.05, P = 0.002], AURKA (HR 5.56, 95% CI, 1.79–17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60–9.32, P = 0.003) were independently predictive of overall survival (FDR &lt; 10%) after adjusting for a panel of previously established prognostic variables in mCRPC (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC = 0.70). Understanding the molecular landscape of CTCs has utility in predicting clinical outcomes in patients with aggressive prostate cancer and provides an additional tool in the arsenal of precision-based therapeutic approaches in oncology.Implications: Analysis of CTC gene expression reveals a clinically prognostic “liquid biopsy” signature in patients with metastatic castrate-resistance prostate cancer. Mol Cancer Res; 16(4); 643–54. ©2018 AACR.
Inhibition of CD95/CD95L (FAS/FASLG) Signaling with APG101 Prevents Invasion and Enhances Radiation Therapy for Glioblastoma
Authors: Blaes Jonas , Thomé Carina M. , Pfenning Philipp-Niclas , Rübmann Petra , Sahm Felix , Wick Antje , Bunse Theresa , Schmenger Torsten , Sykora Jaromir , von Deimling Andreas , Wiestler Benedikt , Merz Christian , Jugold Manfred , Haberkorn Uwe , Abdollahi Amir , Debus Jürgen , Gieffers Christian , Kunz Claudia , Bendszus Martin , Kluge Michael , Platten Michael , Fricke Harald , Wick Wolfgang , Lemke Dieter 
Published: February 2018

Abstract
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. Although CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear. APG101 action was examined by in vitro proliferation, apoptosis, and invasion assays with human and murine glioma and human microglial cells, as well as in vivo therapy studies with orthotopic gliomas and clinical data. APG101 inhibits CD95L-mediated invasion of glioma cells. APG101 treatment was effective in glioma-bearing mice, independently of the presence or absence of CD4 and CD8 T lymphocytes, which should be sensitive to CD95L. Combined with radiotherapy, APG101 demonstrated a reduction of tumor growth, fewer tumor satellites, reduced activity of matrix metalloproteinases (MMP) as well as prolonged survival of tumor-bearing mice compared with radiotherapy alone. Inhibiting rather than inducing CD95 activity is a break-of-paradigm therapeutic approach for malignant gliomas. Evidence, both in vitro and in vivo, is provided that CD95L-binding fusion protein treatment enhanced the efficacy of radiotherapy and reduced unwanted proinfiltrative effects by reducing metalloproteinase activity by directly affecting the tumor cells.
Implications: APG101 (asunercept) successfully used in a controlled phase II glioblastoma trial (NCT01071837) acts anti-invasively by inhibiting matrix metalloproteinase signaling, resulting in additive effects together with radiotherapy and helping to further develop a treatment for this devastating disease. Mol Cancer Res; 16(5); 767–76. ©2018 AACR.
Distinct Chemopreventive Effects of Aspirin in Diffuse and Intestinal-Type Gastric Cancer
Authors: Niikura Ryota , Hayakawa Yoku , Hirata Yoshihiro , Konishi Mitsuru , Suzuki Nobumi , Ihara Sozaburo , Yamada Atsuo , Ushiku Tetsuo , Fujishiro Mitsuhiro , Fukayama Masashi , Koike Kazuhiko 
Published: February 2018

Abstract
Introduction: Although aspirin/NSAIDs may have potential preventive effects on several cancers, it remains unclear on gastric cancer. The purpose of this study is to compare the risk of developing gastric cancer and the histologic changes of intestinal metaplasia and neutrophil infiltration, between aspirin/NSAID users and nonusers.
Methods: Using an electronic endoscopy database in two hospitals from 1996 to 2017, we analyzed the data from patients with chronic gastritis who received aspirin or NSAIDs prior to upper gastrointestinal endoscopy. One-to-one propensity score matching was performed to compare the proportion of gastric cancer, intestinal metaplasia, and neutrophil infiltration between these drug users and nonusers.
Results: We analyzed 2,082 aspirin users and 2,082 nonusers as well as 898 NSAID users and 898 nonusers. Six diffuse-type and 19 intestinal-type gastric cancer, 1,243 intestinal metaplasia, and 1,503 neutrophil infiltration patients were identified. The proportion of diffuse-type gastric cancer (0.05%) was 80% lower in aspirin users compared with the nonusers (0.24%), and there was no case of diffuse-type cancer in patients who took aspirin for more than 2 years. In contrast, intestinal-type gastric cancer incidence was significantly higher in aspirin users (0.72%) compared with nonusers (0.14%). No significant differences in the incidence of gastric cancer were found between NSAID use and nonusers. NSAID use was significantly associated with decreased proportion of neutrophil infiltration compared with nonusers.
Conclusion: Aspirin may have distinct effects between intestinal-type and diffuse-type gastric cancer development. Cancer Prev Res; 11(5); 279–86. ©2018 AACR.
A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease
Authors: Gucalp Ayca , Zhou Xi K. , Cook Elise D. , Garber Judy E. , Crew Katherine D. , Nangia Julie R. , Bhardwaj Priya , Giri Dilip D. , Elemento Olivier , Verma Akanksha , Wang Hanhan , Lee J. Jack , Vornik Lana A. , Mays Carrie , Weber Diane , Sepeda Valerie , O'Kane Holly , Krasne Margaret , Williams Samantha , Morris Patrick G. , Heckman-Stoddard Brandy M. , Dunn Barbara K. , Hudis Clifford A. , Brown Powel H. , Dannenberg Andrew J. 
Published: February 2018

AbstractObesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I–III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1β, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P &lt; 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203–14. ©2018 AACR.See related editorial by Fabian and Kimler, p. 187