bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ability of Biomarkers to Predict Systemic Progression in Men with High-Risk Prostate Cancer Treated Surgically Is Dependent on ERG Status
Authors: Karnes R. Jeffrey , Cheville John C. , Ida Cristiane M. , Sebo Thomas J. , Nair Asha A. , Tang Hui , Munz Jan-Marie , Kosari Farhad , Vasmatzis George 
Published: November 2010

Abstract
The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP). A 150-pair case-control study was designed from RP patients who developed systemic progression (SP) within 6 years of RP (cases) and men who were free of disease at least 8 years after RP (controls). The cases and controls were matched on conventional prognostic clinical parameters. TOP2A and MIB-1 levels were assessed by immunohistochemical methods, and ERG status was assessed by quantitative reverse transcription-PCR. The prognostic abilities of TOP2A and MIB-1 were significantly better in ERG(−) patients, and TOP2A was superior to MIB-1. In receiver operating characteristic analysis, the TOP2A and MIB-1 scores exhibited AUCs of 0.81 and 0.78 for ERG(−) patients, versus 0.67 and 0.68 for ERG(+) patients, respectively. Clinical parameters attained an AUC of 0.65 in ERG(−) patients and 0.54 in ERG(+) patients. When both markers were incorporated into a model for ERG(−) patients, the AUC increased to 0.83, with TOP2A showing a stronger association with SP than MIB-1. The time to SP was significantly associated with TOP2A; higher 5-year SP rates were observed in patients with higher TOP2A protein levels. In addition, although patient numbers are small, the response to adjuvant androgen deprivation therapy is associated with ERG status, showing more significant treatment effect in ERG(+) patients. Cancer Res; 70(22); 8994–9002. ©2010 AACR.
Eradication of Medullary Multiple Myeloma by CD4+ Cytotoxic Human T Lymphocytes Directed at a Single Minor Histocompatibility Antigen
Authors: Spaapen Robbert M. , Groen Richard W.J. , van den Oudenalder Kelly , Guichelaar Teun , van Elk Maureen , Aarts-Riemens Tineke , Bloem Andries C. , Storm Gert , Martens Anton C. , Lokhorst Henk M. , Mutis Tuna 
Published: November 2010

AbstractPurpose: The essential role of CD4+ T cells as helpers of anticancer immunity is indisputable. Little is known, however, about their capacity to serve as effector cells in cancer treatment. Therefore, we explored the efficacy of immunotherapy with sole CD4+ cytotoxic human T cells directed at a hematopoietic-restricted minor histocompatibility antigen (mHag).Experimental Design: In macrophage-depleted Rag2−/−γc−/− mice, which were also devoid of T, B, and natural killer cells, mHag-specific native T cells or tetanus toxoid (TT)-specific T cells transduced with the mHag-specific T-cell receptor (TCR) were injected to treat full-blown mHag+ human multiple myeloma tumors.Results: mHag-specific antitumor responses were achieved after injection of native or mHag-TCR-transduced T cells. Although the therapy completely eradicated the primary tumors in the bone marrow, it failed to control extramedullary relapses, even after repeated T-cell injections. Detailed analyses ruled out mHag or MHC downregulation as mechanisms of extramedullary tumor escape. Impaired T-cell survival in vivo or defective homing to the tumor site were also ruled out as mechanisms behind extramedullary relapses, because injections of TT-loaded antigen presenting cells could facilitate homing of long-term surviving T cells to s.c. tumor sites. Moreover, intratumoral treatment of extramedullary tumors with 3AB11 was also ineffective.Conclusions: Taken together, these results for the first time show the feasibility of immunotherapy of primary bone marrow tumors with sole CD4+ human T cells directed to a tumor-associated mHag. Extramedullary relapses, probably due to microenvironment-dependent inhibitory mechanisms, remain a challenging issue towards effective cellular immunotherapy of hematologic malignancies. Clin Cancer Res; 16(22); 5481–8. ©2010 AACR.
Expression and Silencing of the Microtubule-Associated Protein Tau in Breast Cancer Cells
Authors: Spicakova Tatiana , O'Brien Maureen M. , Duran George E. , Sweet-Cordero Alejandro , Sikic Branimir I. 
Published: November 2010

Abstract
The microtubule-associated protein Tau has been reported to be a predictive factor for clinical response to taxanes in metastatic breast cancer. We generated a panel of eight taxane-resistant variants from four human breast cancer cell lines (MCF-7, T-47D, MDA-MB-231, and BT-549). Four variants had higher levels of Tau compared with their T-47D and MDA-MB-231 parental cells. Using isoform-specific primers, we found that Tau 0N, 1N, 2N, 3R, and 4R isoforms are overexpressed in the resistant variants, as is Tau exon 6 but not exons 4A or 8. To determine whether Tau overexpression produces resistance to taxanes, we derived three independent T-47D clones stably overexpressing Tau 3R and 4R isoforms. Tau overexpression did not result in taxane resistance compared with parental cells transfected with vector alone. We then knocked down Tau expression in three cell lines that expressed Tau constitutively (MCF-7 and ZR-75-1 breast cancer cells, and OVCAR-3 ovarian cancer cells). Lentivirus-mediated silencing of Tau expression in MCF-7 and OVCAR-3 cells did not result in increased taxane sensitivity compared with luciferase short hairpin RNA–infected cells and uninfected parental cells. Transient silencing using Tau-specific small interfering RNAs also did not alter taxane sensitivity relative to nontargeting controls in both MCF-7 and ZR-75-1 cells. These results show that neither overexpression nor depletion of Tau modulates cellular sensitivity to taxanes. Although Tau overexpression has been reported to be a predictive marker of taxane resistance, it is not likely to be a direct mechanism of taxane resistance in breast cancer. Mol Cancer Ther; 9(11); 2970–81. ©2010 AACR.
Luteinizing Hormone-Releasing Hormone (LHRH)-I Antagonist Cetrorelix Inhibits Myeloma Cell Growth In vitro and In vivo
Authors: Wen Jianguo , Feng Yongdong , Bjorklund Chad C. , Wang Michael , Orlowski Robert Z. , Shi Zheng-Zheng , Liao Bing , O'Hare Jacqueline , Zu Youli , Schally Andrew V. , Chang Chung-Che 
Published: November 2010

Abstract
The objective of this study was to determine the effects of an luteinizing hormone-releasing hormone (LHRH)-I antagonist, Cetrorelix, on human multiple myeloma (MM) cells and to elucidate the mechanisms of action. We showed that LHRH-I and LHRHR-I genes were expressed in MM cell lines and primary MM cells. Treatment with Cetrorelix inhibited growth and colony-forming ability of myeloma cells, including cell lines resistant to arsenic trioxide, bortezomib, or lenalidomide. Cetrorelix induced apoptosis in myeloma cells including primary myeloma cells. In addition, Cetrorelix inhibited the growth of human myeloma cells xenografted into mice without any apparent side effects. Cetrorelix downregulated the nuclear factor-kappa B (NF-κB) pathway activity and the expression of cytokines, including interleukin 6, insulin-like growth factor 1, VEGF-A, and stromal-derived factor 1, important for myeloma cell growth and survival in myeloma cells and/or marrow stromal cells from myeloma patients. Cetrorelix decreased the phosphorylation of extracellular signal regulated kinase 1/2 and STAT3 in myeloma cells, two crucial pathways for myeloma cells growth and survival. Moreover, the expression of p21 and p53 was increased, whereas that of antiapoptotic proteins Bcl-2 and Bcl-xL was reduced by Cetrorelix. Our findings indicate that Cetrorelix induces cytotoxicity in myeloma cells through various mechanisms and provide a rationale for investigating Cetrorelix for the treatment of MM. Mol Cancer Ther; 10(1); 148–58. ©2010 AACR.
Incidence and Management of CoreValve Dislocation During Transcatheter Aortic Valve Implantation
Authors: Geisbüsch Sarah , Bleiziffer Sabine , Mazzitelli Domenico , Ruge Hendrik , Bauernschmitt Robert , Lange Rüdiger 
Published: November 2010

Background—
Transcatheter aortic valve implantation is a highly specialized technique offering a new therapeutic option to patients at high risk for conventional surgery. Complications associated with this catheter procedure differ from complications after surgical aortic valve replacement. This is to report incidence, management, and impact on morbidity and mortality of CoreValve dislocation during catheter valve implantation.

Methods and Results—

Between June 2007 and September 2009, the self-expandable CoreValve prosthesis (Medtronic Inc, Minneapolis, Minn) was implanted in 212 patients through a transarterial (femoral or subclavian) access. Patients with severe aortic stenosis who were at high risk for conventional surgery were included. We observed dislocation of the prosthesis during CoreValve implantation in 21 patients. In 16 cases, the CoreValve could be implanted in the correct annular position after retrieving it and reloading the catheter. In 4 patients, the completely deployed prosthesis had to be placed in the ascending or abdominal aorta before implanting a second one. One patient underwent open surgery. Overall 30-day mortality was 11.0%, 21.5% in the dislocation group and 9.9% in patients without dislocation (
P
=0.024). Coronary ischemia, stroke, and renal failure occurred more frequently in patients with dislocation, whereas pacemaker dependency did not differ significantly between the groups.

Conclusions—
CoreValve dislocation during transcatheter aortic valve implantation occurred in 10% of the cases and significantly increases perioperative risk for severe complications or death. It requires individual specific management and can be managed either interventionally or, rarely, results in open surgery.
Reference and Accessibility from a Givenness Hierarchy Perspective
Authors: Gundel Jeanette 
Published: November 2010

AbstractMost work on reference and discourse structure appeals, in some sense, to the notion of accessibility. While the term "accessibility" itself is rarely mentioned in research within Gundel, Hedberg and Zacharski's Givenness Hierarchy (GH) framework, the GH has often been interpreted by others as an accessibility hierarchy. This paper aims to clarify the major claims and predictions of the GH theory, showing how it is fundamentally diff erent from other referential hierarchies in a number of ways, most importantly because cognitive statuses on the hierarchy are assumed to encode manner of accessibility, not degree of accessibility. The GH thus differs from the other referential hierarchies, not only in the kinds of facts it aims to predict and explain, but in the specific empirical predictions that can plausibly be derived from it regarding degree of accessibility, as measured by ease of processing.
An Experimental Study on the Scope of (Un)modified Indefinites
Authors: Ionin Tania 
Published: November 2010

AbstractThis paper reports on three experiments which investigate the availability of long-distance scope for different types of indefinite expressions, in order to test the predictions of different semantic theories of indefinite scope. The main findings of the experiments are: (i) local, narrow-scope readings are preferred for a indefinites, whereas long-distance scope is preferred for a certain indefinites; and (ii) long-distance scope is more readily available to bare one indefinites than to modified at least/exactly one indefinites, but modified numeral indefinites nevertheless allow long-distance scope more readily than universal quantifiers. While the first finding is consistent with theories that link scope and epistemic specificity (since a certain indefinites are often analyzed as markers of specificity), the second finding suggests that long-distance scope is also available to non-specific, quantificational indefinites. It is shown that the findings are problematic for choice-function theories of indefinite scope, and are more consistent with long-distance scopeshifting, or with accounts that link scope and topicality.
Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia
Authors: Fiedler Katja , Sindrilaru Anca , Terszowski Grzegorz , Kokai Enikö , Feyerabend Thorsten B. , Bullinger Lars , Rodewald Hans-Reimer , Brunner Cornelia 
Published: November 2010

AbstractBruton tyrosine kinase (Btk) is essential for B cell development and function and also appears to be important for myeloid cells. The bone marrow of Btk-deficient mice shows enhanced granulopoiesis compared with that of wild-type mice. In purified granulocyte-monocyte-progenitors (GMP) from Btk-deficient mice, the development of granulocytes is favored at the expense of monocytes. However, Btk-deficient neutrophils are impaired in maturation and function. Using bone marrow chimeras, we show that this defect is cell-intrinsic to neutrophils. In GMP and neutrophils, Btk plays a role in GM-CSF– and Toll-like receptor–induced differentiation. Molecular analyses revealed that expression of the lineage-determining transcription factors C/EBPα, C/EBPβ, and PU.1, depends on Btk. In addition, expression of several granule proteins, including myeloperoxidase, neutrophilic granule protein, gelatinase and neutrophil elastase, is Btk-dependent. In the Arthus reaction, an acute inflammatory response, neutrophil migration into tissues, edema formation, and hemorrhage are significantly reduced in Btk-deficient animals. Together, our findings implicate Btk as an important regulator of neutrophilic granulocyte maturation and function in vivo.
Origin and evolution of a placental-specific microRNA family in the human genome
Authors: Yuan Zhidong , Sun Xiao , Jiang Dongke , Ding Yan , Lu Zhiyuan , Gong Lejun , Liu Hongde , Xie Jianming 
Published: November 2010

Abstract

Background
MicroRNAs (miRNAs) are a class of short regulatory RNAs encoded in the genome of DNA viruses, some single cell organisms, plants and animals. With the rapid development of technology, more and more miRNAs are being discovered. However, the origin and evolution of most miRNAs remain obscure. Here we report the origin and evolution dynamics of a human miRNA family.

Results
We have shown that all members of the miR-1302 family are derived from MER53 elements. Although the conservation scores of the MER53-derived pre-miRNA sequences are low, we have identified 36 potential paralogs of MER53-derived miR-1302 genes in the human genome and 58 potential orthologs of the human miR-1302 family in placental mammals. We suggest that in placental species, this miRNA family has evolved following the birth-and-death model of evolution. Three possible mechanisms that can mediate miRNA duplication in evolutionary history have been proposed: the transposition of the MER53 element, segmental duplications and Alu-mediated recombination. Finally, we have found that the target genes of miR-1302 are over-represented in transportation, localization, and system development processes and in the positive regulation of cellular processes. Many of them are predicted to function in binding and transcription regulation.

Conclusions
The members of miR-1302 family that are derived from MER53 elements are placental-specific miRNAs. They emerged at the early stage of the recent 180 million years since eutherian mammals diverged from marsupials. Under the birth-and-death model, the miR-1302 genes have experienced a complex expansion with some members evolving by segmental duplications and some by Alu-mediated recombination events.
SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in african-americans of the GENOA study
Authors: Meyers Kristin J , Chu Jian , Mosley Thomas H , Kardia Sharon LR 
Published: November 2010

Abstract

Background
Left ventricular mass (LVM) is a strong, independent predictor of heart disease incidence and mortality. LVM is a complex, quantitative trait with genetic and environmental risk factors. This research characterizes the genetic architecture of LVM in an African-American population by examining the main and interactive effects of individual candidate gene single nucleotide polymorphisms (SNPs) and conventional risk factors for increased LVM.

Methods
We used least-squares linear regression to investigate 1,878 SNPs from 234 candidate genes for SNP main effects, SNP-risk factor interactions, or SNP-SNP interactions associated with LVM in 1,328 African-Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We reduced the probability of false positive results by implementing three analytic criteria: 1) the false discovery rate, 2) cross-validation, and 3) testing for internal replication of results.

Results
We identified 409 SNP-SNP interactions passing all three criteria, while no SNP main effects or SNP-risk factor interactions passed all three. A multivariable model including four SNP-SNP interactions explained 11.3% of the variation in LVM in the full GENOA sample and 5.6% of LVM variation in independent test sets.

Conclusions
The results of this research underscore that context dependent effects, specifically SNP-SNP interactions, may dominate genetic contributions to variation in complex traits such as LVM.
Hospitalisation for rotavirus gastroenteritis in the paediatric population in the Veneto Region, Italy
Authors: Saia Mario , Giliberti Aurore , Callegaro Giampietro , Baldovin Tatjana , Busana Marta Cecilia , Pietrobon Francesco , Bertoncello Chiara , Baldo Vincenzo 
Published: November 2010

Abstract

Background
This study evaluates the epidemiological impact of RVGE hospitalisation in the Veneto Region during the period spanning from 2000-2007 along with the associated costs. The analysis was conducted in an area where rotavirus vaccination is not included into immunization programmes and is an attempt to assess the potential benefits of such introduction.

Methods
To update the estimates of acute RVGE hospitalisation rates in children ≤5 years in the Veneto Region, we conducted an 8 year retrospective observational population-based analysis (2000-2007).

Results
Over the study period, a total of 4,119 admissions for RVGE were reported, with a mean hospital stay of 3.5 days. The population-based hospitalisation RVGE incidence rate was 195.8 per 100,000 children aged ≤5 years (lower than other European countries).

Conclusions
RVGE is an important cause of paediatric hospitalisation in the Veneto Region. The data reaffirm the substantial burden of rotavirus hospitalisations in children and the potential health benefits of the vaccination as well as the possibility of adding rotavirus vaccination to the current schedule.
Identification of a stem-like cell population by exposing metastatic breast cancer cell lines to repetitive cycles of hypoxia and reoxygenation
Authors: Louie Elizabeth , Nik Sara , Chen Juei-suei , Schmidt Marlies , Song Bo , Pacson Christine , Chen Xiu Fang , Park Seonhye , Ju Jingfang , Chen Emily I 
Published: November 2010

Abstract
Introduction
The irregular vasculature of solid tumors creates hypoxic regions, which are characterized by cyclic periods of hypoxia and reoxygenation. Accumulated evidence suggests that chronic and repetitive exposure to hypoxia and reoxygenation seem to provide an advantage to tumor growth. Although the development of hypoxia tolerance in tumors predicts poor prognosis, mechanisms contributing to hypoxia tolerance remain to be elucidated. Recent studies have described a subpopulation of cancer stem cells (CSC) within tumors, which have stem-like properties such as self-renewal and the ability to differentiate into multiple cell types. The cancer stem cell theory suggests CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Since hypoxia is considered to be one of the critical niche factors to promote invasive growth of tumors, we hypothesize that repetitive cycles of hypoxia/reoxygenation also play a role in the enrichment of breast CSCs.

Methods
Two metastatic human breast cancer cell lines (MDA-MB 231 and BCM2) were used to optimize the conditions of hypoxia and reoxygenation cycles. The percentage of CSCs in the cycling hypoxia selected subpopulation was analyzed based on the CD44, CD24, ESA, and E-cadherin expression by three-color flow cytometry. Colony formation assays were used to assess the ability of this subpopulation to self-renew. Limiting dilution assays were performed to evaluate the tumor-initiating and metastatic ability of this subpopulation. Induction of EMT was examined by the expression of EMT-associated markers and EMT-associated microRNAs.

Results
Using an optimized hypoxia and reoxygenation regimen, we identified a novel cycling hypoxia-selected subpopulation from human breast cancer cell lines and demonstrated that a stem-like breast cancer cell subpopulation could be expanded through repetitive hypoxia/reoxygenation cycles without genetic manipulation. We also found that cells derived from this novel subpopulation form colonies readily, are highly tumorigenic in immune-deficient mice, and exhibit both stem-like and EMT phenotypes.

Conclusions
These results provide the validity to the newly developed hypoxia/reoxygenation culture system for examining the regulation of CSCs in breast cancer cell lines by niche factors in the tumor microenvironment and developing differential targeting strategies to eradicate breast CSCs.
Shifts in subjectivity during the therapy for psychosis
Authors: Karatza Harikleia , Avdi Evrinomy 
Published: November 2010

Objectives. This paper examines the process of therapy with families in which a member has a diagnosis of psychosis. On a methodological level, the study aims to demonstrate the usefulness of discourse analysis as a method for analysing texts produced in therapy in the context of process research. On a clinical and theoretical level, it aims to contribute to the literature that approaches psychosis and its treatment from the viewpoint of narrative and discourse. Design. Several contemporary conceptualizations emphasize the role of discursive processes, such as a collapse of meaning and narrative and an alienation from shared communicative practices, in psychosis. Drawing from this perspective, discourse analysis was used on family therapy session transcripts to empirically examine these processes. Moreover, given that in different conceptualizations psychosis is seen to entail a profound disturbance to the person's sense of self, the analysis focuses more specifically on the identified patients' subjectivity. Methods. Seven sessions were analysed, drawn from the beginning, middle, and end phases of two therapies with families with a member with a diagnosis of psychosis. Discourse analysis was used and the analysis focused on the transformation of meaning and more specifically on shifts in the subject positions occupied by the identified patient in the clinical dialogue. Results. With regards to the identified patients' subjectivity, the analysis suggests that (a) psychosis was associated with the ‘patient’ being rigidly positioned exclusively through the psychiatric discourse in the first case and the lack of a voice in the second, and (b) that therapeutic change was associated with increased flexibility in the subject positions that the identified patient occupied in the first case and with the emergence of a personal and reflective voice in the second. Conclusions. The findings in this study suggest that an important aspect in clinical work with families with a member with a diagnosis of psychosis relates to de‐centring the dominant, pathology maintaining accounts and to the emergence of a wider range of less problematic explanatory frames.