bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic Profiling Identifies Afamin as a Potential Biomarker for Ovarian Cancer
Authors: Jackson David , Craven Rachel A. , Hutson Richard C. , Graze Ina , Lueth Paul , Tonge Robert P. , Hartley Joanne L. , Nickson Janice A. , Rayner Steve J. , Johnston Colin , Dieplinger Benjamin , Hubalek Michael , Wilkinson Nafisa , Perren Timothy J. , Kehoe Sean , Hall Geoffrey D. , Daxenbichler Guenter , Dieplinger Hans , Selby Peter J. , Banks Rosamonde E. 
Published: December 2007

Abstract
Purpose: To discover and validate serum glycoprotein biomarkers in ovarian cancer using proteomic-based approaches.
Experimental Design: Serum samples from a “discovery set” of 20 patients with ovarian cancer or benign ovarian cysts or healthy volunteers were compared by fluorescence two-dimensional differential in-gel electrophoresis and parallel lectin-based two-dimensional profiling. Validation of a candidate biomarker was carried out with Western blotting and immunoassay (n = 424).
Results: Twenty-six proteins that changed significantly were identified by mass spectrometric sequencing. One of these, confirmed by Western blotting, was afamin, a vitamin E binding protein, with two isoforms decreasing in patients with ovarian cancer. Validation using cross-sectional samples from 303 individuals (healthy controls and patients with benign, borderline, or malignant ovarian conditions and other cancers) assayed by ELISA showed significantly decreased total afamin concentrations in patients with ovarian cancer compared with healthy controls (P = 0.002) and patients with benign disease (P = 0.046). However, the receiver operating characteristic areas for total afamin for the comparison of ovarian cancer with healthy controls or benign controls were only 0.67 and 0.60, respectively, with comparable figures for CA-125 being 0.92 and 0.88 although corresponding figures for a subgroup of samples analyzed by isoelectric focusing for afamin isoform 2 were 0.85 and 0.79. Analysis of a further 121 samples collected prospectively from 9 patients pretreatment through to relapse indicated complementarity of afamin with CA-125, including two cases in whom CA-125 was noninformative.
Conclusions: Afamin shows potential complementarity with CA-125 in longitudinal monitoring of patients with ovarian cancer, justifying prospective larger-scale investigation. Changes in specific isoforms may provide further information.
Modulation of Reactive Oxygen Species in Pancreatic Cancer
Authors: Teoh Melissa L.T. , Sun Wenqing , Smith Brian J. , Oberley Larry W. , Cullen Joseph J. 
Published: December 2007

Abstract
Purpose: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer.
Experimental Design: Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts.
Results: Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct.
Conclusions: Scavenging plasma membrane–generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
HLA Tetramer–Based Artificial Antigen-Presenting Cells Efficiently Stimulate CTLs Specific for Malignant Glioma
Authors: Jiang Xiaobing , Lu Xiaoling , Liu Ruen , Zhang Fangcheng , Zhao Hongyang 
Published: December 2007

AbstractPurpose: The interleukin-13 receptor α2 (IL-13Rα2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we report a novel approach for targeting malignant glioma with IL-13Rα2–specific CTLs.Experimental Design: Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13Rα2345-354 tetrameric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads, and used to stimulate IL-13Rα2–specific CTLs from the peripheral blood mononuclear cells of HLA-A2+ healthy donors. After multiple stimulations, the induced CTLs were analyzed for tetramer staining, IFN-γ production, and CTL reactivity.Results: Tetramer staining assay showed that the induced CTLs specifically bound HLA-A2/pIL-13Rα2345-354 tetramers. The CTLs specifically produced IFN-γ in response to the HLA-A2/pIL-13Rα2345-354-aAPCs and exhibited specific lysis against T2 cells pulsed with the peptide pIL-13Rα2345-354 and HLA-A2+ glioma cells expressing IL-13Rα2345-354, whereas HLA-A2− glioma cell lines that express IL-13Rα2345-354 could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti–HLA class I monoclonal antibody.Conclusion: The induced CTLs specific for IL-13Rα2345-354 peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.
The Roles of Therapy-Induced Autophagy and Necrosis in Cancer Treatment
Authors: Amaravadi Ravi K. , Thompson Craig B. 
Published: December 2007

Abstract
Metabolic and therapeutic stresses activate several signal transduction pathways that regulate cell death and cell survival in cancer cells. Although decades of research unraveled the pathways that regulate apoptosis and allowed the development of novel diagnostic and therapeutic modalities in cancer treatment, only recently has the regulation and significance of tumor cell autophagy and necrosis become the focus of investigations. Necrosis is an irreversible inflammatory form of cell death. In contrast, autophagy is a reversible process that can contribute both to tumor cell death and survival. This review describes recent advances in understanding the regulation of autophagy and necrosis and their implications for cancer therapy. Currently available methods to measure autophagy and necrosis are highlighted. The effect of tumor cell autophagy and necrosis on host immunity is explored. Finally, therapeutic approaches that target autophagy and necrosis in cancer are described.
BCL-2 Family Proteins: Critical Checkpoints of Apoptotic Cell Death
Authors: Danial Nika N. 
Published: December 2007

Abstract
Apoptosis is a morphologically distinct form of programmed cell death essential for normal development and tissue homeostasis. Aberrant regulation of this pathway is linked to multiple human diseases, including cancer, autoimmunity, neurodegenerative disorders, and diabetes. The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. Since this original discovery, remarkable efforts marshaled by many investigators around the world have advanced our knowledge of the basic biology, molecular mechanisms, and therapeutic targets in the apoptotic pathway. This review highlights findings from many laboratories that have helped uncover some of the critical control points in apoptosis. The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death.
EWSR1-CREB1 and EWSR1-ATF1 Fusion Genes in Angiomatoid Fibrous Histiocytoma
Authors: Rossi Sabrina , Szuhai Kàroly , Ijszenga Marije , Tanke Hans J. , Zanatta Lucia , Sciot Raf , Fletcher Christopher D.M. , Dei Tos Angelo P. , Hogendoorn Pancras C.W. 
Published: December 2007

Abstract
Purpose: Angiomatoid fibrous histiocytoma (AFH) is a low-grade mesenchymal neoplasm which usually occurs in children and adolescents. Either FUS-ATF1 or EWSR1-ATF1 have been detected in the few cases published, pointing to the interchangeable role of FUS and EWSR1 in this entity. EWSR1-ATF1 also represents the most frequent genetic alteration in clear cell sarcoma, suggesting the existence of a molecular homology between these two histotypes. We investigated the presence of EWSR1-CREB1, recently found in gastrointestinal clear cell sarcoma, and FUS-CREB1, as well as the already reported FUS-ATF1 and EWSR1-ATF1 in a series of AFH.
Experimental Design: Fourteen cases were analyzed by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections, using a commercial EWSR1 probe and custom-designed probes for FUS, ATF1, and CREB1. In two cases, four-color FISH was also done. Reverse transcription-PCR for the four hypothetical fusion genes was done in one case, for which frozen material was available.
Results: Thirteen cases showed rearrangements of both EWSR1 and CREB1, whereas one case showed the rearrangement of both EWSR1 and ATF1. Four-color FISH confirmed the results in two selected cases. Reverse transcription-PCR showed EWSR1-CREB1 transcript in the case analyzed.
Conclusion: We identified the presence of either EWSR1-CREB1 or EWSR1-ATF1 in all the cases, strengthening the concept of chromosomal promiscuity between AFH and clear cell sarcoma. Either the occurrence of a second unknown tumor-specific molecular event or, perhaps more likely, divergent differentiation programs of the putatively distinct precursor cells of AFH and clear cell sarcoma might be invoked in order to explain the two different phenotypes.
From the Field: A Proposal for Educating Leaders for Social Justice
Authors: McKenzie Kathryn Bell , Christman Dana E. , Hernandez Frank , Fierro Elsy , Capper Colleen A. , Dantley Michael , González María Luisa , Cambron-McCabe Nelda , Scheurich James Joseph 
Published: December 2007

Purpose: The purpose of this article is to suggest the structure and content of an educational leadership program whose aim is to prepare principals for social justice work. Research Design: The authors have conceptualized foundational components for a comprehensive principalship program focused on social justice. They assert that educational leaders for social justice must have three goals at the forefront of their efforts: (a) They must raise the academic achievement of all the students in their school, that is, high test scores do matter; (b) they must prepare their students to live as critical citizens in society; and (c) both of these goals can only be achieved when leaders assign students to inclusive, heterogeneous classrooms that provide all students access to a rich and engaging curriculum. The components addressed for this social justice—oriented principalship preparation program include (a) how students should be selected for such a program and (b) an outline of the knowledge and content for educating social justice leaders. The importance of induction/praxis after students graduate from these programs is discussed. Conclusions: The aim of this article is to provoke a discussion in the field and spark faculty to engage in ongoing conversations and thinking about their own programs and to imagine new avenues for future research in this area. Faculty also can use these suggestions as a guide to assess their efforts and to bolster program quality, sensitive to the unique needs and schooling contexts of their particular students.
Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis
Authors: Moro-Sibilot D. , Lantuejoul S. , Diab S. , Moulai N. , Aubert A. , Timsit J. F. , Brambilla C. , Brichon P. Y. , Brambilla E. 
Published: December 2007

Lung carcinoma with a basaloid pattern (BC) is classified as either a basaloid variant of squamous cell carcinoma (SCC) or as variant of large cell carcinoma (LCC) depending on the presence of a squamous component. In a previous study of 37 cases, the present authors showed that BC presented with a shorter median and overall survival.In order to confirm its clinical significance in a larger series, 90 BC, including 46 basaloid variants of LCC and 44 basaloid variants of SCC, were compared with 1,328 other nonsmall cell lung carcinoma (NSCLC) with regard to clinical features and survival.The survival of basaloid variants of LCC and SCC was comparable. Median and overall survival were significantly lower for BC than for NSCLC in stage I–II patients, with a median survival of 29 and 49 months, respectively, and 5-yr survival rates of 27 and 44% for BC and NSCLC. When disease-specific survival was considered, BC had a shorter survival than both NSCLC and SCC.Basaloid pattern confers a poor prognosis in nonsmall cell lung carcinoma, especially in stage I–II patients, suggesting that lung carcinoma with a basaloid pattern is not only a variant of squamous cell carcinoma or large cell carcinoma, but is a unique entity with a significantly poor prognosis.
Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients
Authors: Grasemann C. , Ratjen F. , Schnabel D. , Reutershahn E. , Vester U. , Grasemann H. 
Published: December 2007

Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone therapy has been shown to increase nitric oxide production in growth hormone-deficient patients, it may also affect nitric oxide production in patients with cystic fibrosis. The objective of the present study was to investigate the effect of growth hormone therapy on systemic and airway nitric oxide formation in patients with cystic fibrosis.Nitric oxide metabolites in serum and urine, amino acid concentrations in serum and sputum, as well as exhaled nitric oxide, were measured in children with cystic fibrosis before, during and after 1 yr of treatment with human growth hormone.Nitric oxide metabolite concentrations increased significantly in serum and urine during the treatment period. Serum amino acid concentrations (includingl-arginine, the substrate for nitric oxide synthases) also increased during treatment. The systemic bioavailability ofl-arginine for nitric oxide synthases, expressed as ratio ofl-arginine/l-ornithine+lysine, remained unchanged. In contrast,l-arginine concentrations in sputum decreased significantly during growth hormone treatment, as did exhaled nitric oxide levels.Treatment with growth hormone in children with cystic fibrosis decreases exhaled nitric oxide by reducing the concentration ofl-arginine in the airways.
A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation
Authors: Suzaki Y. , Hamada K. , Nomi T. , Ito T. , Sho M. , Kai Y. , Nakajima Y. , Kimura H. 
Published: December 2007

Asthma is associated with increased numbers of T-cells in the lung. CC chemokine receptor (CCR)5 and CXC chemokine receptor (CXCR)3 have been reported to play important roles in the lung T-cell homing pathway, and may be potential targets for asthma therapy. The aim of the present study was to investigate the role of CCR5 and CXCR3 in allergen-induced acute asthma and to determine whether a novel small-molecule compound, TAK-779, targeting CCR5 and CXCR3 can attenuate allergic airway responses.Mice were sensitised with ovalbumin (OVA). mRNA expression of chemokine receptors in the lung were measured after the challenge with either aerosolised phosphate-buffered saline or OVA. OVA-sensitised mice were also treated with TAK-779. Respiratory function was measured, bronchoalveolar lavage was performed, and blood and lung samples were obtained.OVA challenge increased CCR3, CCR5 and CXCR3 expression in the lung. Treatment with TAK-779 significantly attenuated altered respiratory function and pulmonary allergic inflammation. The beneficial effect was associated with reduced expression of CCR5 and CXCR3 in the lung.These data demonstrate that blockade of CC chemokine receptor 5 and CXC chemokine receptor 3 using TAK-779, a synthetic nonpeptide compound, can prevent the development of asthma features in a mouse model. Thus, CC chemokine receptor 5 and CXC chemokine receptor 3 may be potential targets for asthma therapy.
Troponin I and risk stratification of patients with acute nonmassive pulmonary embolism
Authors: Jiménez D. , Díaz G. , Molina J. , Martí D. , Del Rey J. , García-Rull S. , Escobar C. , Vidal R. , Sueiro A. , Yusen R. D. 
Published: December 2007

The assessment of risk and appropriate treatment of patients with acute pulmonary embolism (PE) remains a challenge.The prognostic performance of cardiac troponin I (cTnI) in predicting 30-day all-cause mortality was prospectively assessed in consecutive haemodynamically stable patients with PE.The present study included 318 haemodynamically stable patients with PE. During the 30-day study period, 23 (7%) patients died. cTnI was elevated (≥0.1 ng·mL−1) in 102 (32%) patients. An age >65 yrs, systolic blood pressure <120 mmHg and severity of illness assessed using the PE severity index (PESI) were significantly associated with an increased risk for mortality, but no significant association was found between elevation of cTnI and 30-day mortality in a logistic regression analysis. When only fatal PE was considered, multivariate analysis showed that severity of illness using the PESI and an elevated cTnI (odds ratio 3.7, 95% confidence interval (CI) 1.1–12.8) were associated with a significant increase in the risk for death. The negative predictive value (95% CI) of a negative cTnI for mortality was 93 (90–97)%.In conclusion, in haemodynamically stable patients with acute pulmonary embolism, cardiac troponin I was not an independent predictor of 30-day all-cause mortality, although it did predict fatal pulmonary embolism.
Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma
Authors: Ueda Ryo , Low Keri L , Zhu Xinmei , Fujita Mitsugu , Sasaki Kotaro , Whiteside Theresa L , Butterfield Lisa H , Okada Hideho 
Published: December 2007

Abstract

Background
In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs). In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence.

Methods
Peripheral blood mononuclear cells (PBMCs) derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL) activity and differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2) by immunohistochemistry.

Results
The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2883–891 and IL-13Rα2345–353-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2883–891-reactive CD8+ T cells contained high numbers of CD45RA-/CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found.

Conclusion
To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8+ T cells dictates survival of patients and/or response to therapeutic vaccines.
Quality of Anticoagulation Monitoring in Nonvalvular Atrial Fibrillation Patients: Comparison of Anticoagulation Clinic versus Usual Care
Authors: Nichol Michael B , Knight Tara K , Dow Tom , Wygant Gail , Borok Gerald , Hauch Ole , O'Connor Richard 
Published: December 2007

Background: Prior research suggests that receiving specialized anticoagulation services enables patients to achieve better clinical outcomes. Objective: To assess the quality of anticoagulation therapy in patents with atrial fibrillation who were enrolled in an anticoagulation clinic (ACC) versus usual care (UC). Methods: Using Sharp Rees-Stealy physician group claims data, we estimated time spent in therapeutic range and time to first major bleeding episode or stroke for ACC and UC patients. t-Tests were used to compare time h therapeutic range proportions, and Kaplan-Meier survival analysis was performed to compare rates of bleeding and stroke between groups. Results: We identified 1107 patients (351 ACC, 756 UC) treated with anticoagulation therapy for atrial fibrillation with more than one international normalized ratio (INR) reported between March 2001 and March 2004. ACC patients spent a greater proportion (68.14%) of time in therapeutic range compared with UC patients (42.07%; p < 0.001). There was a significant difference between groups in average time between INR tests (ACC = 14.31 days, UC = 18.39 days; p < 0.001). ACC patients were 59% less likely to experience a bleed following the index date than were UC patients (HR = 0.41; 95% CI 0.2444 to 0.6999; p = 0.001), but type of care was not a significant predictor for stroke (HR = 0.95; 95% CI 0.5125 to 1.7777; p value NS). Conclusions: Results from this observational study reinforce the positive impact that anticoagulation services have on anticoagulation therapy outcomes, emphasizing the importance of providing such services for patients undergoing treatment with warfarin.