bluuebunny/crossref_metadata_2025_split huggingface dataset:
PU.1 Activation Relieves GATA-1–Mediated Repression of Cebpa and Cbfb during Leukemia Differentiation
Authors: Burda Pavel , Curik Nikola , Kokavec Juraj , Basova Petra , Mikulenkova Dana , Skoultchi Arthur I. , Zavadil Jiri , Stopka Tomas 
Published: October 2009

Abstract
Hematopoietic transcription factors GATA-1 and PU.1 bind each other on DNA to block transcriptional programs of undesired lineage during hematopoietic commitment. Murine erythroleukemia (MEL) cells that coexpress GATA-1 and PU.1 are blocked at the blast stage but respond to molecular removal (downregulation) of PU.1 or addition (upregulation) of GATA-1 by inducing terminal erythroid differentiation. To test whether GATA-1 blocks PU.1 in MEL cells, we have conditionally activated a transgenic PU.1 protein fused with the estrogen receptor ligand-binding domain (PUER), resulting in activation of a myeloid transcriptional program. Gene expression arrays identified components of the PU.1-dependent transcriptome negatively regulated by GATA-1 in MEL cells, including CCAAT/enhancer binding protein α (Cebpa) and core-binding factor, β subunit (Cbfb), which encode two key hematopoietic transcription factors. Inhibition of GATA-1 by small interfering RNA resulted in derepression of PU.1 target genes. Chromatin immunoprecipitation and reporter assays identified PU.1 motif sequences near Cebpa and Cbfb that are co-occupied by PU.1 and GATA-1 in the leukemic blasts. Significant derepression of Cebpa and Cbfb is achieved in MEL cells by either activation of PU.1 or knockdown of GATA-1. Furthermore, transcriptional regulation of these loci by manipulating the levels of PU.1 and GATA-1 involves quantitative increases in a transcriptionally active chromatin mark: acetylation of histone H3K9. Collectively, we show that either activation of PU.1 or inhibition of GATA-1 efficiently reverses the transcriptional block imposed by GATA-1 and leads to the activation of a myeloid transcriptional program directed by PU.1. (Mol Cancer Res 2009;7(10):1693–703)
H3 Histamine Receptor–Mediated Activation of Protein Kinase Cα Inhibits the Growth of CholangiocarcinomaIn vitroandIn vivo
Authors: Francis Heather , Onori Paolo , Gaudio Eugenio , Franchitto Antonio , DeMorrow Sharon , Venter Julie , Kopriva Shelley , Carpino Guido , Mancinelli Romina , White Mellanie , Meng Fanyin , Vetuschi Antonella , Sferra Roberta , Alpini Gianfranco 
Published: October 2009

AbstractHistamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The d-myo-inositol 1,4,5-trisphosphate (IP3)/Ca2+/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(α)-(−)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP3 and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKCα was visualized by immunofluorescence in cell smears and immunoblotting for PKCα in cytosol and membrane fractions. Following knockdown of PKCα, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal–regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKCα, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP3 levels and PKCα phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKCα expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKCα prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKCα expression was increased. RAMH inhibits cholangiocarcinoma growth by PKCα-dependent ERK1/2 dephosphorylation. Modulation of PKCα by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704–13)
Immensity and A-subjectivity
Authors: Schuback Marcia Sá Cavalcante 
Published: October 2009

AbstractThe aim of the present article is to reflect upon comparative procedures at stake in the acknowledgment of differences, following some paths of Husserl's and Heidegger's views on “comparative examination” (vergleichende Betrachtung). Although using the same expression as Husserl, Heidegger presents in this concept, rather, a phenomenology of correspondence. The encounter with otherness is described as correspondence to the immensity of the event of the world in Dasein. From out of a “destruction” of comparative examinations, it becomes possible to seize the a-subjective and ek-static structure of Dasein and claim a corresponding way of encountering otherness. In this corresponding way, the Other appears first as non-otherness, beyond a dialectics of selfhood and otherness.
The Safavids under Western Eyes: Seventeenth-Century European Travelers to Iran
Authors: Matthee Rudi 
Published: October 2009

AbstractThis essay takes a fresh look at the voluminous yet understudied Western travel writing about 17th-century Iran. It argues that, after this material is properly subjected to close scrutiny for authorial bias, interest and intertexuality, it remains exceedingly valuable for the information it provides on Safavid Iran. Early modern European travelers to Iran brought remnants of past religious and cultural prejudice with them, yet the best explored the country with an open eye, an appreciation for difference, and even a critical perspective on their own culture. They also provide remarkable, at times unique information about Iran and it inhabitants, opening up aspects of Safavid left uncovered by indigenous sources.
Monitoring the performance of the Expanded Program on Immunization: the case of Burkina Faso
Authors: Bicaba Abel , Haddad Slim , Kabore Moussa , Taminy Emile , Feletto Marta , Fournier Pierre 
Published: October 2009

Abstract

Background
The greatest challenge facing expanded programs on immunization in general, and in Burkina Faso in particular, lies in their capacity to achieve and sustain levels of immunization coverage that will ensure effective protection of children. This article aims to demonstrate that full immunization coverage of children, which is the primary indicator for monitoring national immunization programs, is sufficient neither to evaluate their performance adequately, nor to help identify the broad strategies that must be implemented to improve their performance. Other dimensions of performance, notably adherence to the vaccination schedule and the efficacy of the approaches used to reach all the children (targeting) must also be considered.

Methods
The study was carried out using data from surveys carried out in Burkina Faso: the 1993, 1998 and 2003 Demographic and Health Surveys and the 2003 national Survey of Immunization Coverage. Essentially, we described levels of immunization coverage and their trends according to the indicators considered. Performance differences are illustrated by amplitudes and maximum/minimum ratios.

Results
The health regions' performances vary according to whether they are evaluated on the basis of full immunization coverage or vaccination status of children who have not completed their vaccinations. The health regions encompass a variety of realities, and efforts of substantially different intensity would be required to reach all the target populations.

Conclusion
Decision-making can be improved by integrating a tripartite view of performance that includes full immunization coverage, adherence to the vaccination schedule (timely coverage), and the status of children who are not fully vaccinated. With such an approach, interventions can be better targeted. It provides information on the quality and timeliness of vaccination and identifies the efforts required to meet the objectives of full immunization coverage.

Abstract in French
See the full article online for a translation of this abstract in French.
IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy - a randomised controlled trial in an interdisciplinary setting
Authors: Rahbari Nuh N , Zimmermann Johannes B , Koch Moritz , Bruckner Thomas , Schmidt Thomas , Elbers Heike , Reissfelder Christoph , Weigand Markus A , Büchler Markus W , Weitz Jürgen 
Published: October 2009

Abstract

Background
Intraoperative haemorrhage is a known predictor for perioperative outcome of patients undergoing hepatic resection. While anaesthesiological lowering of central venous pressure (CVP) by fluid restriction is known to reduce bleeding during transection of the hepatic parenchyma its potential side effects remain poorly investigated. In theory it may have negative effects on kidney function and tissue perfusion and bears the risk to result in severe haemodynamic instability in case of profound intraoperative blood loss. The present randomised controlled trial evaluates efficacy and safety of infrahepatic inferior vena cava (IVC) clamping as an alternative surgical technique to reduce CVP during hepatic resection.

Methods/Design
The proposed IVC CLAMP trial is a single-centre randomised controlled trial with a two-group parallel design. Patients and outcome-assessors are blinded for the treatment intervention. Patients undergoing elective hepatic resection due to any reason are enrolled in IVC CLAMP. All patients admitted to the Department of General-, Visceral-, and Transplant Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility and written informed consent is obtained on the day before surgery. The primary objective of this trial is to assess and compare the amount of blood loss during hepatic resection in patients receiving surgical CVP reduction by clamping of the IVC as compared to anaesthesiological CVP without infrahepatic IVC clamping reduction. In addition to blood loss a set of general as well as surgical variables are analysed.

Discussion
This is a randomised controlled patient and observer blinded two-group parallel trial designed to assess efficacy and safety of infrahepatic IVC clamping during elective hepatectomy.

Trial registration
ClinicalTrials NCT00732979
HPV & head and neck cancer: a descriptive update
Authors: Goon Peter KC , Stanley Margaret A , Ebmeyer Jörg , Steinsträsser Lars , Upile Tahwinder , Jerjes Waseem , Bernal-Sprekelsen Manuel , Görner Martin , Sudhoff Holger H 
Published: October 2009

Abstract
The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers.
Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality.
Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.
Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia
Authors: Xia Xiaobo , Kung Andrew L 
Published: October 2009

Abstract
Background
Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines.

Results
We found that when cells were acutely subjected to hypoxia, HIF-1 preferentially bound to loci that were already transcriptionally active under normal growth conditions characterized by the presence of histone H3 lysine 4 methylation, the presence of RNA polymerase II, and basal production of mRNA. Cell type-specific differences in HIF-1 binding were largely attributable to differences in the basal gene expression patterns in the cells prior to the onset of hypoxia.

Conclusions
These results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors.
Costs and Cost Effectiveness of a Health Care Provider–Directed Intervention to Promote Colorectal Cancer Screening
Authors: Shankaran Veena , Luu Thanh Ha , Nonzee Narissa , Richey Elizabeth , McKoy June M. , Graff Zivin Joshua , Ashford Alfred , Lantigua Rafael , Frucht Harold , Scoppettone Marc , Bennett Charles L. , Sheinfeld Gorin Sherri 
Published: October 2009

Purpose Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention. Methods A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates. Results Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates. Conclusion A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost effective.
Prognostic Factors for Overall Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor–Targeted Agents: Results From a Large, Multicenter Study
Authors: Heng Daniel Y.C. , Xie Wanling , Regan Meredith M. , Warren Mark A. , Golshayan Ali Reza , Sahi Chakshu , Eigl Bernhard J. , Ruether J. Dean , Cheng Tina , North Scott , Venner Peter , Knox Jennifer J. , Chi Kim N. , Kollmannsberger Christian , McDermott David F. , Oh William K. , Atkins Michael B. , Bukowski Ronald M. , Rini Brian I. , Choueiri Toni K. 
Published: October 2009

Purpose There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) –targeted therapy. Methods Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy–naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. Results The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. Conclusion This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
Authors: Piekarz Richard L. , Frye Robin , Turner Maria , Wright John J. , Allen Steven L. , Kirschbaum Mark H. , Zain Jasmine , Prince H. Miles , Leonard John P. , Geskin Larisa J. , Reeder Craig , Joske David , Figg William D. , Gardner Erin R. , Steinberg Seth M. , Jaffe Elaine S. , Stetler-Stevenson Maryalice , Lade Stephen , Fojo A. Tito , Bates Susan E. 
Published: October 2009

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.
Prospective Multicenter Comparison of Models to Predict Four or More Involved Axillary Lymph Nodes in Patients With Breast Cancer With One to Three Metastatic Sentinel Lymph Nodes
Authors: Werkoff Gabrielle , Lambaudie Eric , Fondrinier Eric , Levêque Jean , Marchal Fréderic , Uzan Michele , Barranger Emmanuel , Guillemin François , Darai Emile , Uzan Serge , Houvenaeghel Gilles , Rouzier Roman , Coutant Charles 
Published: October 2009

PurposeThree models have been developed to predict four or more involved axillary lymph nodes (ALNs) in patients with breast cancer with one to three involved sentinel lymph nodes (SLNs). Two scores were developed by Chagpar et al (Louisville scores excluding or including method of detection), and a nomogram was developed by Katz et al. The purpose of our investigation was to compare these models in a prospective, multicenter study.Patients and MethodsOur study involved a cohort of 536 patients having one to three involved SLNs who underwent ALN dissection. We evaluated the area under the receiver operating characteristic curve (AUC), calibration (for the Katz nomogram only), false-negative (FN) rate, and clinical utility of the three models. Results were compared with the optimal logistic regression (OLR) model that was developed from the validation cohort.ResultsAmong the 536 patients, 57 patients (10.6%) had ≥ four involved ALNs. The AUC for the Katz nomogram was 0.84 (95% CI, 0.81 to 0.86). The Louisville score excluding method of detection was 0.75 (95% CI, 0.72 to 0.78). The Louisville score including method of detection was 0.77 (95% CI, 0.74 to 0.79). The FN rates were 2.5% (eight of 321 patients), 1.8% (two of 109 patients), and 0% (zero of 27 patients) for the Katz nomogram and the Louisville scores excluding and including method of detection, respectively. The Katz nomogram was well calibrated. Optimism-corrected bootstrap estimate AUC of the OLR model was 0.86. Using this result as a reasonable target for an external model, the performance of the Katz nomogram was remarkable.ConclusionWe validated the three models for their use in clinical practice. The Katz nomogram outperformed the two other models.
Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera
Authors: Quintás-Cardama Alfonso , Kantarjian Hagop , Manshouri Taghi , Luthra Rajyalakshmi , Estrov Zeev , Pierce Sherry , Richie Mary Ann , Borthakur Gautam , Konopleva Marina , Cortes Jorge , Verstovsek Srdan 
Published: October 2009

Purpose We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-α-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Patients and Methods Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-α-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-α-2a at 450 μg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 μg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months. Results The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2V617F mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2V617F) in 6% and 14%, respectively. The JAK2V617F mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-α-2a at 90 μg weekly was excellent. Conclusion PEG-IFN-α-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-α-2a to induce complete molecular responses suggests selective targeting of the malignant clone.