bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMPRSS2–ERG-Mediated Feed-Forward Regulation of Wild-Type ERG in Human Prostate Cancers
Authors: Mani Ram-Shankar , Iyer Matthew K. , Cao Qi , Brenner J. Chad , Wang Lei , Ghosh Aparna , Cao Xuhong , Lonigro Robert J. , Tomlins Scott A. , Varambally Sooryanarayana , Chinnaiyan Arul M. 
Published: June 2011

Abstract
Recurrent gene fusions involving ETS family genes are a distinguishing feature of human prostate cancers, with TMPRSS2–ERG fusions representing the most common subtype. The TMPRSS2–ERG fusion transcript and its splice variants are well characterized in prostate cancers; however, not much is known about the levels and regulation of wild-type ERG. By employing an integrative approach, we show that the TMPRSS2–ERG gene fusion product binds to the ERG locus and drives the overexpression of wild-type ERG in prostate cancers. Knockdown of TMPRSS2–ERG in VCaP cells resulted in the downregulation of wild-type ERG transcription, whereas stable overexpression of TMPRSS2–ERG in the gene fusion-negative PC3 cells was associated with the upregulation of wild-type ERG transcript. Further, androgen signaling-mediated upregulation of TMPRSS2–ERG resulted in the concomitant upregulation of wild-type ERG transcription in VCaP cells. The loss of wild-type ERG expression was associated with a decrease in the invasive potential of VCaP cells. Importantly, 38% of clinically localized prostate cancers and 27% of metastatic prostate cancers harboring the TMPRSS2–ERG gene fusions exhibited overexpression of wild-type ERG. Taken together, these results provide novel insights into the regulation of ERG in human prostate cancers. Cancer Res; 71(16); 5387–92. ©2011 AACR.
Hematopoietic Stem Cell Niche Is a Potential Therapeutic Target for Bone Metastatic Tumors
Authors: Shiozawa Yusuke , Pienta Kenneth J. , Taichman Russell S. 
Published: June 2011

Abstract
Despite significant improvements in therapy, the prognosis for cancer with bone metastasis is generally poor. Therefore, there is a great need for new therapeutic approaches for metastatic disease. It has been appreciated that tumor cells metastasize to bone using mechanisms similar to those of hematopoietic stem cells (HSC) homing to bone marrow (e.g., CXCL12/CXCR4). It was recently found that prostate cancer cells target the bone marrow microenvironment for HSCs, or the HSC niche, during metastasis. Of importance, these disseminated prostate cancer cells can be mobilized out of the niche with the use of HSC mobilizing agents. These findings suggest that the bone marrow HSC niche is a potential therapeutic target for metastatic disease. Therefore, a hypothesis worth considering is that agents that can disrupt the interactions between tumor cells and the HSC niche may be efficacious when used in conjunction with standard chemotherapeutic agents. Although further understanding of the tumor-niche interactions is needed, the concept of targeting the niche in conjunction with chemotherapy could open up new possibilities to eradicate incurable metastatic diseases. Clin Cancer Res; 17(17); 5553–8. ©2011 AACR.
Targeting the Mitochondria Activates Two Independent Cell Death Pathways in Ovarian Cancer Stem Cells
Authors: Alvero Ayesha B. , Montagna Michele K. , Holmberg Jennie C. , Craveiro Vinicius , Brown David , Mor Gil 
Published: June 2011

Abstract
Cancer stem cells are responsible for tumor initiation and chemoresistance. In ovarian cancer, the CD44+/MyD88+ ovarian cancer stem cells are also able to repair the tumor and serve as tumor vascular progenitors. Targeting these cells is therefore necessary to improve treatment outcome and patient survival. The previous demonstration that the ovarian cancer stem cells are resistant to apoptotic cell death induced by conventional chemotherapy agents suggests that other forms of targeted therapy should be explored. We show in this study that targeting mitochondrial bioenergetics is a potent stimulus to induce caspase-independent cell death in a panel of ovarian cancer stem cells. Treatment of these cells with the novel isoflavone derivative, NV-128, significantly depressed mitochondrial function exhibited by decrease in ATP, Cox-I, and Cox-IV levels, and by increase in mitochondrial superoxide and hydrogen peroxide. This promotes a state of cellular starvation that activates two independent pathways: (i) AMPKα1 pathway leading to mTOR inhibition; and (ii) mitochondrial MAP/ERK kinase/extracellular signal-regulated kinase pathway leading to loss of mitochondrial membrane potential. The demonstration that a compound can specifically target the mitochondria to induce cell death in this otherwise chemoresistant cell population opens a new venue for treating ovarian cancer patients. Mol Cancer Ther; 10(8); 1385–93. ©2011 AACR.
Comparative study of experienced and anticipated stigma in Serbia and the world
Authors: Vidojević Ivona Milačić , Jočić Dragana Ðurić , Tošković Oliver 
Published: June 2011

Aim: The presented study is part of the International Study of Discrimination and Stigma Outcomes (INDIGO) conducted in 28 countries. The aim of this study was to compare the degree of experienced and anticipated stigma of patients with schizophrenia in Serbia with world results. Method: The Discrimination and Stigma Scale (DISC) was applied in individual interviews. The sample comprised 732 subjects of the main study and 50 subjects from Serbia. Results: The amount of negative experienced discrimination in Serbia is the same as in other participating countries. The Serbian sample shows more negative discrimination in intimate relationships, personal safety and general harm due to the diagnosis, but more positive discrimination within the family, privileges during treatment of somatic illnesses, and benefits enjoyed in social and retirement insurance. The Serbian sample shows less anticipated discrimination in looking for a close relationship and in stopping self from applying for work. The results show that socio-demographic variables could not predict negative experienced and anticipated discrimination, while those same variables enable the prediction of 34% of positive discrimination. Conclusion: Compared to other investigated countries, stigmatization processes for persons with schizophrenia do not differ considerably in Serbia, which justifies the implementation of unique anti-stigma programmes and joint upgrading of legal regulations.
Estimation of the surface energy of chemically and oxygen plasma-treated regenerated cellulosic fabrics using various calculation models
Authors: Peršin Zdenka , Stenius Per , Stana-Kleinschek Karin 
Published: June 2011

The aim of this work was to evaluate and compare the surface energies (SFEs) of regenerated cellulose fabrics modified by washing, bleaching, conventional chemical treatment (slack-mercerization), and plasma treatment. Three commonly used methods of estimating apolar, polar, and acid/base contributions were applied: geometric mean (GM), using diiodomethane (MI) and water as probes; van Oss—Good—Chaudhury (vOGC), using MI, tetrahydrofuran (THF), and chloroform (CF); and Owens—Wendt—Rabel—Kaelble (OW), using water, MI, THF, CF, ethanol and ethylene glycol. All treatments gave rise to more hydrophilic materials, as indicated by a decrease in the water contact angle. The GM and OW methods both showed that the polar component of the SFE increased after bleaching or conventional chemical treatment and, in particular, after plasma treatment. The vOGC method showed much smaller effects and indicated decreasing polarity after plasma treatment. This was probably due to the use of acid and base probes that did not contain hydroxyl groups in the determination of vOGC parameters, that is, the effect of the treatments was to introduce acid functionalities that could interact strongly with hydroxyls (hydrogen bonding) but not with the Lewis base THF or Lewis acid CF.
Variability in the Management of Idiopathic Sudden Sensorineural Hearing Loss
Authors: Coelho Daniel H. , Thacker Leroy R. , Hsu David W. 
Published: June 2011

ObjectivesTo evaluate current trends in the management of idiopathic sudden sensorineural hearing loss (ISSNHL), determine if variance in diagnostic and treatment protocols exists, and compare diagnostic and treatment strategies of ISSNHL between nonotologists/neurotologists (NONs) and otologists/neurotologists (ONs).Study DesignCross‐sectional survey of practicing otolaryngologists.SettingOtolaryngology practices within the United States.Subjects and MethodsIn January 2010, a survey was mailed to 500 NONs and 500 ONs. Data were collected and analyzed using χ2, standard deviations, and variance.ResultsA variety and distribution of responses were seen in the definition of ISSNHL, including dB loss necessary for diagnosis, number of consecutive frequencies involved, and maximum duration of hearing loss. Differences in diagnostic tools were also seen, with 50.4% of respondents (NON 34.2%, ON 66.7%;P=. 0001) always using magnetic resonance imaging in their workup. Of the total respondents, 26.7% (NON 35.0%, ON 18.3%;P<. 0001) preferred oral steroids alone; 22.1% (NON 11.7%, ON 32.5%;P<. 0001) preferred a combination of oral and intratympanic steroids. Of the respondents, 68.6% (NON 57.5%, ON 80.0%;P=. 0003) would continue with additional treatment after partial response; 20.8% (NON 33.3%, ON 8.3%;P<. 005) would retreat with oral steroids alone and 46.6% (NON 35.8%, ON 57.3%;P<. 05) with intratympanic injections. Overall, 69.2% (NON 45.8%, ON 92.5%;P=. 0001) were very comfortable managing ISSNHL.ConclusionSignificant differences exist in the diagnosis and treatment of ISSNHL. Such lack of uniformity highlights the need for strong evidence‐based research—ultimately leading to formalized practice guidelines and educational outreach.
‘That’s part of everybody’s job’: the perspectives of health care staff in England and New Zealand on the meaning and remit of palliative care
Authors: Gott Merryn , Seymour Jane , Ingleton Christine , Gardiner Clare , Bellamy Gary 
Published: June 2011

Background: the right for patients of all diagnoses to be in receipt of palliative care from an early point in the diagnosis of a life-limiting condition is now enshrined in policy in a number of countries and increased emphasis is placed upon the role of generalist palliative care. However, little is known as to how this policy is enacted on the ground. Aim: to explore understandings of, and perceived roles in relation to, palliative care provision amongst generalist and specialist health care providers in England and New Zealand. Design: qualitative data were collected via individual interviews and focus groups. Setting/participants: participants comprised generalist and specialist palliative care providers working in a variety of settings in England ( n = 58) and New Zealand ( n = 80). Results: the following issues with significant implications for this new phase of development for palliative care were identified: (1) difficulties with terminology and perceived roles/responsibilities; (2) problems of integrating palliative care into a generalist workload; (3) challenges in generalist/specialist partnership working; and (4) the potential negative consequences of specialization. Conclusions: these data indicate that, within England and New Zealand, the policy rhetoric of universal palliative care provision is not being straightforwardly translated into service delivery and individual clinical practice. Further research is required to explore and evaluate different models of organization and service provision that empower ‘generalists’ to provide palliative care, without resulting in deskilling. Finally, definitional clarity at an academic/policy level is also needed.
Experimental analysis of unsteady flow performance in an automotive turbocharger turbine fitted with a waste-gate valve
Authors: Capobianco M , Marelli S 
Published: June 2011

Downsizing and turbocharging is today an effective way of enhancing fuel economy in automotive engines. However, more information on compressor and turbine behaviour when working under unsteady flow conditions typically occurring in automotive turbocharged engines is still required to improve simulation models. The results of an experimental investigation into a small turbocharger turbine fitted with a waste-gate valve are presented in this paper. Turbine performance was measured under both steady and unsteady flow operation. Particular attention was given to pulsating flow performance, evaluated starting from the measurement of instantaneous parameters (inlet and outlet static pressure, mass flowrate, and turbocharger rotational speed). The effect of flow unsteadiness on turbine behaviour is analysed, referring to different pulse frequencies and waste-gate settings. The paper highlights that steady and unsteady turbine performance when the waste-gate valve is partially or totally open should be known in order to improve engine-turbocharger matching calculations.
Cognitive dysfunction in SLE: development of a screening tool
Authors: Adhikari T , Piatti A , Luggen M 
Published: June 2011

Background. Cognitive dysfunction (CD) is among the most common neuropsychiatric manifestations of systemic lupus erythematosus (SLE). There are two methods which have been used to detect CD in patients with SLE: traditional neuropsychological tests (NPT) and the Automated Neuropsychological Assessment Metrics (ANAM). Both are time-consuming and neither is readily available for screening purposes. Purpose. The aim of our study was to evaluate the Montreal Cognitive Assessment (MoCA) test as a screening tool for detection of CD in SLE. Methods. SLE patients fulfilling ACR criteria were administered the ANAM, a computerized test battery which measures various cognitive domains and the MoCA, a one-page, performance-based screening test designed to detect mild cognitive impairment in the elderly. With the ANAM as the gold standard, the performance characteristics of the MoCA were assessed. Results. In total, 44 patients were evaluated. Of these, 11 (25%) were identified by the ANAM as being impaired in comparison with 13 (29.5%) by the MoCA. The scores were significantly correlated ( r = 0.57, p < 0.001). Using the standard cutoff of 26, the sensitivity of MoCA was 83% and specificity 73%. Conclusion. The MoCA appears to be a promising screening tool for the detection of CD in SLE both for epidemiologic studies and for routine clinical care.
Clinical Outcomes and Hospitalizations among Children Perinatally Infected with HIV-1 in Baja California, Mexico
Authors: Viani Rolando M. , Araneta Maria Rosario G. , Lopez Graciano , Chacón-Cruz Enrique , Spector Stephen A. 
Published: June 2011

This study characterizes temporal trends in HIV disease progression among perinatally infected children at a clinic in Baja California, Mexico. A total of 73 children were followed, 52% were categorized under US Centers for Disease Control and Prevention (CDC) classification group C with a mean age of 2.3 years (SD ± 3.16) at HIV diagnosis. For the years 1998 to 2001, 2002 to 2003, 2004 to 2005, and 2006 to 2007, highly active antiretroviral therapy (HAART) use increased to 60%, 75%, 83%, and 94% ( P < .001) as did mean CD4 percentage of 23.4%, 23.2%, 26.9%, and 29.0%, respectively ( P = .009), while HIV plasma RNA log10 decreased significantly (4.49, 4.23, 4.00, and 3.79, respectively; P = .019). Overall mortality was 31% (23 of 73), with pneumonia being the most common cause of death (43% of all deaths) followed by tuberculosis (22%). Mortality rates declined from 30.4% to 25%, 8.9%, and 9.3% ( p = 0.035) for the years 1998 to 2001, 2002 to 2003, 2004 to 2005, and 2006 to 2007, respectively. Kaplan-Meier survival analysis showed that median survival was 11.2 years; 1-, 2-, and 5-year survival was 87%, 83%, and 67%, respectively. These findings document a high but improving trend in morbidity and mortality of children perinatally infected with HIV in Tijuana, Baja California, Mexico.
Experience of first- and subsequent-line systemic therapy in the treatment of non-small cell lung cancer
Authors: Eccles B. K. , Geldart T. R. , Laurence V. M. , Bradley K. L. , Lwin M. T. 
Published: June 2011

Introduction: The treatment of advanced non-small cell cancer (NSCLC) has changed with multiple new treatment algorithms proposed based on histological and molecular subtyping but low mutation rates will ensure the dominance of cytotoxic chemotherapy. Accordingly, we undertook a detailed review of our practice delivering multiple lines of systemic therapy. Method: We undertook a retrospective review of consecutive patients presenting with advanced (stage IIIb/IV) NSCLC treated with systemic therapy at two UK hospitals during a 2-year period, January 2007 to December 2008. Results: A total of 130 patients were identified, treated with predominantly carboplatin/gemcitabine (20 initially radically). Fifty of 110 patients (45%) treated with first-line systemic therapy subsequently received second-line therapy, of which 10 patients received third-line and two patients fourth-line therapy. Sixty three of 110 first-line patients (58%) achieved clinical benefit, 19 out of 50 (38%) in the second-line, 6 out of 10 (60%) in third-line but both patients progressed at fourth-line. Median overall survival for 110 patients was 10 months (95% confidence interval [CI] 8.6–11.4); but 16 months (95% CI 14-17.9) in those receiving multiple lines. Median survival from the first cycle of last-line treatment to death in the multiple therapy lines was 5 months (95% CI 2.6-7.3) and the majority of patients spent more time off treatment. Conclusion: Overall our outcomes are consistent with published data and show good survival times can be achieved. The future of advanced NSCLC is in selecting the best treatment approach on a histological and genotypic basis.
Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion
Authors: Steger Guenther G. , Bartsch Rupert 
Published: June 2011

Introduction: Denosumab, a fully human monoclonal antibody, targets the receptor activator of nuclear factor-kappaB (RANK) ligand, a protein essential for osteoclast differentiation, activity and survival. Loss of osteoclasts from the bone surface reduces bone turnover and bone loss in malignant and benign diseases. In breast cancer, bone metastases are frequently observed; cancer treatment-induced bone loss (CTIBL) may result as a consequence of endocrine treatment or chemotherapy. Furthermore, preclinical studies suggest a direct role of the RANK/RANK-ligand pathway in breast tumorigenesis. This paper reviews preclinical and clinical data on denosumab in breast cancer. Materials and methods: Studies were identified through the Medline database. Key search terms included: AMG-162, bisphosphonates, denosumab, RANK-ligand and zoledronic acid. Information available in abstract form only was retrieved from major oncology meetings, such as the American Society of Clinical Oncology (ASCO) annual meeting, ASCO breast meeting, European Cancer Organization, European Society of Medical Oncology and the San Antonio Breast Cancer Symposium. Results: Denosumab was consistently well tolerated throughout clinical trials, although the observed incidence of osteonecrosis of the jaw was comparable to that with bisphosphonates. Efficacy as determined by a reduction of skeletal-related events was at least equal to zoledronic acid, and superior in one phase III study conducted in patients with metastatic breast cancer. Clinical trials investigating the role of denosumab for the prevention of CTIBL and breast cancer recurrences are currently ongoing. Conclusion: In conclusion, denosumab appears to be an effective and safe treatment option in patients with bone metastases from breast cancer with the potential of also preventing CTIBL.
CD81 is essential for the formation of membrane protrusions and regulates Rac1-activation in adhesion-dependent immune cell migration
Authors: Quast Thomas , Eppler Felix , Semmling Verena , Schild Cora , Homsi Yahya , Levy Shoshana , Lang Thorsten , Kurts Christian , Kolanus Waldemar 
Published: June 2011

AbstractCD81 (TAPA-1) is a member of the widely expressed and evolutionary conserved tetraspanin family that forms complexes with a variety of other cell surface receptors and facilitates hepatitis C virus entry. Here, we show that CD81 is specifically required for the formation of lamellipodia in migrating dendritic cells (DCs). Mouse CD81−/− DCs, or murine and human CD81 RNA interference knockdown DCs lacked the ability to form actin protrusions, thereby impairing their motility dramatically. Moreover, we observed a selective loss of Rac1 activity in the absence of CD81, the latter of which is exclusively required for integrin-dependent migration on 2-dimensional substrates. Neither integrin affinity for substrate nor the size of basal integrin clusters was affected by CD81 deficiency in adherent DCs. However, the use of total internal reflection fluorescence microscopy revealed an accumulation of integrin clusters above the basal layer in CD81 knockdown cells. Furthermore, β1- or β2-integrins, actin, and Rac are strongly colocalized at the leading edge of DCs, but the very fronts of these cells protrude CD81-containing membranes that project outward from the actin–integrin area. Taken together, these data suggest a thus far unappreciated role for CD81 in the mobilization of preformed integrin clusters into the leading edge of migratory DCs on 2-dimensional surfaces.
Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia
Authors: Eapen Mary , Le Rademacher Jennifer , Antin Joseph H. , Champlin Richard E. , Carreras Jeanette , Fay Joseph , Passweg Jakob R. , Tolar Jakub , Horowitz Mary M. , Marsh Judith C. W. , Deeg H. Joachim 
Published: June 2011

Abstract
Outcome after unrelated donor bone marrow (BM) transplantation for severe aplastic anemia (SAA) has improved, with survival rates now approximately 75%. Increasing use of peripheral blood stem and progenitor cells (PBPCs) instead of BM as a graft source prompted us to compare outcomes of PBPC and BM transplantation for SAA. We studied 296 patients receiving either BM (n = 225) or PBPC (n = 71) from unrelated donors matched at human leukocyte antigen-A, -B, -C, -DRB1. Hematopoietic recovery was similar after PBPC and BM transplantation. Grade 2 to 4 acute graft-versus-host disease risks were higher after transplantation of PBPC compared with BM (hazard ratio = 1.68, P = .02; 48% vs 31%). Chronic graft-versus-host disease risks were not significantly different after adjusting for age at transplantation (hazard ratio = 1.39, P = .14). Mortality risks, independent of age, were higher after PBPC compared with BM transplantation (hazard ratio = 1.62, P = .04; 76% vs 61%). These data indicate that BM is the preferred graft source for unrelated donor transplantation in SAA.