bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic Evaluation of the Novel HSP90 Inhibitor NVP-AUY922 in Adult and Pediatric Glioblastoma
Authors: Gaspar Nathalie , Sharp Swee Y. , Eccles Suzanne A. , Gowan Sharon , Popov Sergey , Jones Chris , Pearson Andrew , Vassal Gilles , Workman Paul 
Published: May 2010

Abstract
The dismal prognosis of glioblastoma (GB) indicates the urgent need for new therapies for these tumors. Heat shock protein 90 (HSP90) inhibitors induce the proteasome-mediated degradation of many oncogenic client proteins involved in all of the hallmark characteristics of cancer. Here, we explored the mechanistic potential of the potent synthetic diarylisoxazole amide resorcinol HSP90 inhibitor, NVP-AUY922, in adult and pediatric GB. In vitro antiproliferative potency (nanomolar range) was seen in both adult and pediatric human GB cell lines with different molecular pathologies. A cytostatic effect was observed in all GB lines; more apoptosis was observed at lower concentrations in the SF188 pediatric GB line and at 144 hours in the slower growing KNS42 pediatric GB line, as compared with the adult GB lines U87MG and SF268. In vitro combination studies with inhibitors of phosphoinositide 3-kinase/mammalian target of rapamycin (PI-103) or mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (PD-0325901) supported the hypothesis that sustained inhibition of ERK up to 72 hours and at least temporary inhibition of AKT were necessary to induce apoptosis in GB lines. In athymic mice bearing established s.c U87MG GB xenografts, NVP-AUY922 (50 mg/kg i.p × 3 days) caused the inhibition of ERK1/2 and AKT phosphorylation and induced apoptosis, whereas 17-AAG used at maximum tolerated dose was less effective. NVP-AUY922 antitumor activity with objective tumor regression resulted from antiproliferative, proapoptotic, and antiangiogenic effects, the latter shown by decreased microvessel density and HIF1α levels. Our results have established a mechanistic proof of concept for the potential of novel synthetic HSP90 inhibitors in adult and pediatric GB, alone or in combination with phosphoinositide 3-kinase/mammalian target of rapamycin and mitogen-activated protein/ERK kinase inhibitors. Mol Cancer Ther; 9(5); 1219–33. ©2010 AACR.
Sunitinib Malate and Figitumumab in Solitary Fibrous Tumor: Patterns and Molecular Bases of Tumor Response
Authors: Stacchiotti Silvia , Negri Tiziana , Palassini Elena , Conca Elena , Gronchi Alessandro , Morosi Carlo , Messina Antonella , Pastorino Ugo , Pierotti Marco A. , Casali Paolo G. , Pilotti Silvana 
Published: May 2010

Abstract
Antiangiogenic treatment activity has been reported in solitary fibrous tumor (SFT), a rare and little chemosensitive sarcoma. We explored the activity of sunitinib malate (SM) in SFT and studied receptor tyrosine kinase (RTK) activation profile. Eleven patients with progressive metastatic SFT resistant to chemotherapy were treated with continuous-dosing 37.5 mg/d SM on a named-use basis. One of them also received the insulin-like growth factor I receptor (IGFIR) inhibitor figitumumab after developing secondary resistance to SM. Besides, biochemical, molecular, and fluorescence in situ hybridization analyses were done in eight naïve SFTs whose cryopreserved material was available to clarify RTK upstream and downstream signaling. In two cases treated with SM and belonging to the naïve series, both pretreatment and posttreatment samples were available. Ten patients were evaluable for response to SM. The best response according to the Choi criteria was six partial response (all with Response Evaluation Criteria in Solid Tumors stable disease), one stable disease, and three progressive disease. Responses lasted &gt;6 months in five patients. The eight naïve samples showed high expression/phosphorylation of PDGFRB, epidermal growth factor receptor, and IGFIR/IR, in the presence of their cognate ligands. Downstream pathways revealed expression/activation of Akt, extracellular signal-regulated kinase 1-2 and, closely related to SFT subtypes, of S6 and 4E-BP1. In two patients, whose pretreatment and posttreatment clinical and molecular status were available, biochemical data confirmed the activity of SM, although they also suggested a possible time-dependent shift of dominant RTK from PDGFRB to IGFIR/insulin receptor. A Response Evaluation Criteria in Solid Tumors partial response to figitumumab corroborated these findings. SM has antitumor activity in SFT, possibly through a PDGFRB-mediated mechanism, but treatments with IGFIR/insulin receptor and possibly epidermal growth factor receptor inhibitors are worth testing. Mol Cancer Ther; 9(5); 1286–97. ©2010 AACR.
Sons and Lovers and the Mirage: Recognition, Melodrama and Psychoanalysis in Mahfūz’s al-Sarāb
Authors: Kennedy Philip F. 
Published: May 2010

AbstractThis essay provides a commentary on one of the less celebrated novels of Najīb Mahfū z,al-Sarāb (The Mirage), one of a series of tragic melodramas he wrote in the 1940s. Uniquely in Mahfūz’s oeuvre, this novel explores an “Oedipal” relationship between the narrator/protagonist and his mother; it is a relationship that blights the man’s married life. What Aristotle identified as anagnorisis—a movement towards startling disclosure—is a common feature of Oedipal narratives; the anagnorisis in Sophocles’s Oedipus Rex being the most famous example (and Aristotle’s favorite instance of tragic disclosure). In general, and across genres, anagnorisis provides narratives with familiar, sometimes comforting, shape; it can also provide an interpretive portal onto the meaning and values revealed by a narrative. It tends to provide closure, especially in melodrama, and often purveys a sense of certainty (though in contemporary or experimental fiction that complacency is often misplaced: incertitude, ambiguity and difficult knowledge are just as often revealed). The commentary below concentrates on three aspects of al-Sarāb alluded to and the relationship between them: recognition, psychoanalysis and melodrama.
Nile Crossings: Hospitality and Revenge in Egyptian Rural Narratives
Authors: Granara William 
Published: May 2010

AbstractThis essay looks at acts of hospitality and revenge as constituent elements of a broad social code in rural Egyptian narratives. By looking at five stories in particular, I argue that hospitality and revenge work in complementarity, and that they often trespass and blur each other’s social and literary borders, creating ambiguity and complexity in the stories. The traditional rules that govern hospitality are at times challenged or inverted by hostile intentions, and revenge may be exacted for common or personal well-being. Also, the Nile River, richly symbolic of Egyptian history and identity, plays a vital role in situating the self, in all its pristine, bifurcated, and sullied forms.
Beyond Univocal Baklava: Deconstructing Food-as-Ethnicity and the Ideology of Homeland in Diana Abu Jaber’s The Language of Baklava
Authors: Bardenstein Carol 
Published: May 2010

AbstractIn this article I examine and analyze the complex configuration of diasporic/homeland relations as represented in Arab American author Diana Abu Jaber’s most recent “cookbook-memoir” The Language of Baklava. Abu Jaber’s work resists prevalent conventions of most nostalgic/ ethnic cookbook memoirs, by both diasporic authors from the Arab world who have taken up residence in the U.S., and by some Arab American authors as well. The Language of Baklava neither portrays a simplistic or reductive binary between homeland and hostland, constructing the “old country” as a locus of unambiguous authenticity and familiarity, nor the hostland as a watered-down, assimilated, or inauthentic version of “the real thing” back home, with nostalgia and alienation as the prevalent respective tropes. Instead, Abu Jaber’s work presents a far more complex and ambivalent configuration of both the hyphenated existence of Arab Americans in the contemporary U.S., and of “back home” and, very central to her work, a nuanced portrayal of interactions between the two spheres and their inhabitants as complex and inter-penetrating.<xref ref-type="fn" rid="FN1">1</xref>
Determination of a Consistent Time for the Extratropical Transition of Tropical Cyclones. Part II: Potential Vorticity Metrics
Authors: Kofron David E. , Ritchie Elizabeth A. , Tyo J. Scott 
Published: May 2010

Abstract
As a tropical cyclone moves poleward and interacts with the midlatitude circulation, the question of whether it will undergo extratropical transition (ET) and, if it does, whether it will reintensify or dissipate, is a complex problem. Uncertainties include the tropical cyclone, the midlatitude circulation, the subtropical anticyclone, and the nonlinear interactions among these systems. A large part of the uncertainty is due to a lack of an understanding of when extratropical transition begins and how it progresses. In this study, absolute potential vorticity and isentropic, or Ertel’s, potential vorticity is examined for its ability to more consistently determine significant times (i.e., beginning or end) of the ET life cycle using the Navy Operational Global Assimilation and Prediction System gridded analyses.
It is found that isentropic potential vorticity on the 330-K potential temperature isentropic level is a good discriminator for examining the extratropical transition of tropical cyclones. At this level, a consistent “ET time” is defined as when the TC-centered circular average of isentropic potential vorticity reaches a minimum value. All 82 tropical cyclones moving into the midlatitudes meet this criterion. The completion of extratropical transition for the reintensifying cases is defined as when the storm exceeds an isentropic potential vorticity threshold value of 1.6 PVU at the 330-K potential temperature isentropic level. The success rate of this threshold value for the completion of extratropical transition for the reintensification cases is found to be 94.3% with a 27.6% false-alarm rate.
CFS Prediction of Winter Persistent Inversions in the Intermountain Region
Authors: Gillies Robert R. , Wang Shih-Yu , Yoon Jin-Ho , Weaver Scott 
Published: May 2010

Abstract
A recent study by Gillies and others of persistent inversion events in the Intermountain West of the United States found a substantive linkage between the intraseasonal oscillation (ISO) and the development of persistent inversion events. Given that NCEP’s Climate Forecast System (CFS) has demonstrated skill in the prediction of the ISO as far out as 1 month, it was decided to examine the CFS forecast’s capability in the prediction of such winter persistent inversions. After initial analysis, a simple regression scheme is proposed that is coupled to the CFS output of geopotential height as a way to predict the occurrence of persistent inversion events for Salt Lake City, Utah. Analysis of the CFS hindcasts through the period 1981–2008 indicates that the regression coupled with the CFS can predict persistent inversion events with lead times of up to 4 weeks. The adoption of this coupled regression–CFS prediction may improve the forecasting of persistent inversion events in the Intermountain West, which is currently restricted to the more limited time span (∼10 days) of medium-range weather forecast models.
Comparison of healthcare resource use between patients receiving ondansetron or palonosetron as prophylaxis for chemotherapy-induced nausea and vomiting
Authors: Yeh Yu-Chen , McDonnell Anne , Klinger Elissa , Fowler Bridget , Matta Lina , Voit Daniel , Reddy Prabashni 
Published: May 2010

Objective: To analyze the differences between ondansetron and palonosetron in healthcare resource use (i.e., inpatient/ outpatient encounters) among patients receiving intraperitoneal cisplatin. Method: A medical record review was performed. Intraperitoneal cisplatin administrations for gynecological cancers from January through June 2006 and from October 2007 through June 2008 were divided into two groups based on the serotonin-receptor antagonist used. The occurrence of chemotherapy-induced nausea and vomiting (CINV)-related hospital readmissions, emergency department visits, and outpatient encounters occurring within 7 days after cisplatin administration was compared. CINV-related resource use was defined as events associated with dehydration, hypovolemia, nausea/vomiting, hypokalemia, constipation, shortness of breath, or syncope/collapse. Results: Ondansetron or palonosetron was used in 39 and 89 cisplatin administrations, respectively. The baseline characteristics were similar between the groups with mean age of 59 years and ovarian cancer being the most common cancer. Length of stay was approximately 2 days. Palonosetron was always administered as a single-day therapy while one- or multi-day ondansetron therapy was administered in 27% and 73% of cycles, respectively. A trend towards more CINV-related hospitalizations with ondansetron versus palonosetron was observed (5.1% vs. 0%, p = 0.09) with no significant difference in other CINV-related encounters. Conclusion: Palonosetron was associated with a trend to a lower risk of CINV-related hospital readmission than ondansetron in patients receiving intraperitoneal cisplatin for gynecological cancers, although not statistically significant. The duration of ondansetron therapy might be suboptimal with 27% of patients receiving only 1 day of therapy during hospital stay. These findings need to be confirmed in future studies.
Efficacy of Guided Imagery With Theta Music for Advanced Cancer Patients With Dyspnea: A Pilot Study
Authors: Lai Wei-Shu , Chao Co-Shi Chantal , Yang Wan-Ping , Chen Ching-Huey 
Published: May 2010

Background: Dyspnea is a frequent and devastating symptom among advanced cancer patients for which improved and low-cost palliative techniques are needed. Methods: A one-group repeated measures research design investigated the efficacy of guided imagery (GI) with theta music (θM) on dyspnea in advanced cancer patients. The intervention consisted of four periods: (a) pretest; (b) intervention with peaceful non-θM; (c) intervention with 10 min of GI with θM (GI/θM), with the first and last 3 min being θM only (i.e., the middle 4 min was GI/θM); and (d) posttest. Dyspnea outcome was measured with the Modified Borg Scale (MBS) for self-reported evaluation of dyspneic symptoms. Physiological parameters measured were pulse oxygen saturation (SpO2), end-tidal CO 2 (EtCO2), heart rate (HR), and respiratory rate (RR). Posttest qualitative data were obtained via interview for subjective patient experience. Results: Participants included 53 patients, 33% with lung cancer. GI/θM produced a significant decrease in MBS scores; 90% of the subjects gave positive qualitative reviews of GI/θM. SpO2 did not change significantly over time. GI/θM significantly increased EtCO2, decreased RR, and decreased HR. Discussion: This study demonstrates that GI/θM is a useful intervention for palliative care of patients with dyspnea. θM alone was demonstrated to be effective, while soothing non-θM was not effective. GI/θM was more effective than θM alone. GI/θM should be considered low-cost end-of-life palliative care for dyspnea.
Repression of Id2 expression by Gfi-1 is required for B-cell and myeloid development
Authors: Li Huajie , Ji Ming , Klarmann Kimberly D. , Keller Jonathan R. 
Published: May 2010

AbstractThe development of mature blood cells from hematopoietic stem cells requires coordinated activities of transcriptional networks. Transcriptional repressor growth factor independence 1 (Gfi-1) is required for the development of B cells, T cells, neutrophils, and for the maintenance of hematopoietic stem cell function. However, the mechanisms by which Gfi-1 regulates hematopoiesis and how Gfi-1 integrates into transcriptional networks remain unclear. Here, we provide evidence that Id2 is a transcriptional target of Gfi-1, and repression of Id2 by Gfi-1 is required for B-cell and myeloid development. Gfi-1 binds to 3 conserved regions in the Id2 promoter and represses Id2 promoter activity in transient reporter assays. Increased Id2 expression was observed in multipotent progenitors, myeloid progenitors, T-cell progenitors, and B-cell progenitors in Gfi-1−/− mice. Knockdown of Id2 expression or heterozygosity at the Id2 locus partially rescues the B-cell and myeloid development but not the T-cell development in Gfi-1−/− mice. These studies demonstrate a role of Id2 in mediating Gfi-1 functions in B-cell and myeloid development and provide a direct link between Gfi-1 and the B-cell transcriptional network by its ability to repress Id2 expression.
Death induction by CD99 ligation in TEL/AML1-positive acute lymphoblastic leukemia and normal B cell precursors
Authors: Husak Zvenyslava , Printz Dieter , Schumich Angela , Pötschger Ulrike , Dworzak Michael N 
Published: May 2010

Abstract
Results suggest that CD99 may play a physiologic role in the clonal deletion processes necessary for B-lymphoid selection.
Our study was performed to examine the role of CD99 in normal and leukemia BCPs. CD99 is strongly expressed by certain pediatric cancers including BCP-ALL. Modulation of the antigen in ETs and T cells induces apoptosis, hence implicating CD99 as a potential target for anti-cancer therapy. However, nothing is known about these aspects in BCPs. We investigated BCP-ALL cases and normal BCP cells from pediatric BM for CD99 protein and RNA expression as well as for effects of CD99 modulation by mAb. Immunophenotypes, recovery, apoptosis, and aggregation were assessed. Flow cytometry, light microscopy, and qRT-PCR were used in our experiments. An association of CD99 expression levels with the cytogenetic background of pediatric BCP-ALLs was found. Highest CD99 levels were observed in hyperdiploid, followed by TEL/AML1 and random karyotype leukemias. CD99 ligation moderately induced cell death only in TEL/AML1 cases. Stroma cell contact mitigated this effect. Very immature normal BCPs were the most sensitive to CD99-mediated death induction. Type I CD99 mRNA was the main isoform in ALLs and was expressed differentially during BCP maturation. Our data suggest that clinical targeting of CD99 may be effective in BCP-ALL-bearing TEL/AML1 but also may elicit negative effects on normal B-lymphopoiesis. We consider our results as an indication that CD99 may play a physiologic role in the clonal deletion processes necessary for B-lymphoid selection.
Role of STK in mouse liver macrophage and endothelial cell responsiveness during acute endotoxemia
Authors: Laskin Debra L , Chen Li , Hankey Pamela A , Laskin Jeffrey D 
Published: May 2010

AbstractHepatic macrophages and endothelial cells express STK which may function to down-regulate endotoxin-induced inflammatory responses in the liver.Acute endotoxemia is associated with excessive production of proinflammatory mediators by hepatic macrophages and endothelial cells, which have been implicated in liver injury and sepsis. In these studies, we analyzed the role of MSP and its receptor STK in regulating the activity of these cells. Acute endotoxemia, induced by administration of LPS (3 mg/kg) to mice, resulted in increased expression of STK mRNA and protein in liver macrophages and endothelial cells, an effect that was dependent on TLR-4. This was correlated with decreased MSP and increased pro-MSP in serum. In Kupffer cells, but not endothelial cells, MSP suppressed LPS-induced NOS-2 expression, with no effect on COX-2. LPS treatment of mice caused a rapid (within 3 h) increase in the proinflammatory proteins NOS-2, IL-1β, and TNF-α, as well as TREM-1 and TREM-3 and the anti-inflammatory cytokine IL-10 in liver macropahges and endothelial cells. Whereas LPS-induced expression of proinflammatory proteins was unchanged in STK−/− mice, IL-10 expression was reduced significantly. Enzymes mediating eicosanoid biosynthesis including COX-2 and mPGES-1 also increased in macrophages and endothelial cells after LPS administration. In STK−/− mice treated with LPS, mPGES-1 expression increased, although COX-2 expression was reduced. LPS-induced up-regulation of SOD was also reduced in STK−/− mice in liver macrophages and endothelial cells. These data suggest that MSP/STK signaling plays a role in up-regulating macrophage and endothelial cell anti-inflammatory activity during hepatic inflammatory responses. This may be important in protecting the liver from tissue injury.
Can a health forecasting service offer COPD patients a novel way to manage their condition?
Authors: Marno Penny , Chalder Melanie , Laing-Morton Tish , Levy Mark , Sachon Patrick , Halpin David 
Published: May 2010

Objectives: The UK Meteorological Office (Met Office) has developed a health forecasting service for chronic obstructive pulmonary disease (COPD) patients, combining a rule-based model predicting risk based on environmental conditions with an anticipatory care intervention providing information on self-management and warnings via an interactive telephone call. Our aim was to explore the acceptability and utility of such a service to patients with COPD and its perceived impact on their behaviour and disease management. Methods: A cross-sectional questionnaire survey of service users drawn from 189 general practices in England, Scotland and Wales at the end of the winter of 2007/8. Results: Completed questionnaires were received from 3288 COPD patients, representing a response rate of 40%. Eighty-five percent of those returning a questionnaire reported at least one exacerbation during the study period and 8% had been admitted to hospital on one occasion or more. The majority of respondents deemed the information pack (comprising a booklet and thermometers) useful while the automated calls were generally said to be convenient, easy to understand and reassuring. Those less satisfied with the service felt they were already sufficiently aware of the prevailing weather conditions or felt more detailed information was needed. Most benefit was reported by those patients who were willing to be pro-active in the management of their condition, with the service encouraging 36% of respondents to seek a repeat prescription, 28% to reread their information pack and 12% to consult their GP for worsening of symptoms. Conclusions: Patients found the automated interactive calling, combined with a health risk forecast, both viable and useful, welcoming the information and tools it offered. In many cases, it added to patients’ understanding of their illness and promoted better self-management. Future research should focus on the potential impact of the service in terms of health outcomes and cost-effectiveness.
Patient opinion
Authors: Wright Kath , Light Kate , Stirk Lisa 
Published: May 2010

A number of websites now offer patients the opportunity to give their opinion on the quality of the health services they have received. These comments and criticisms can offer a valuable alternative source of information to that provided by quantitative websites. Patient views and experiences can also provide the impetus for providers to improve the quality of their services. This edition of ‘What's on the web’ collects together and compares some of these websites. If you would like to alert readers to useful web pages or suggest topics for this column, please send details to: