bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of GD2 Peptide Mimotope DNA Vaccines Effective against Spontaneous Neuroblastoma Metastases
Authors: Fest Stefan , Huebener Nicole , Weixler Silke , Bleeke Matthias , Zeng Yan , Strandsby Anne , Volkmer-Engert Rudolf , Landgraf Christiane , Gaedicke Gerhard , Riemer Angelika B. , Michalsky Elke , Jaeger Ines S. , Preissner Robert , Förster-Wald Elisabeth , Jensen-Jarolim Erika , Lode Holger N. 
Published: November 2006

Abstract
Disialoganglioside GD2 is an established target for immunotherapy in neuroblastoma. We tested the hypothesis that active immunization against the glycolipid GD2 using DNA vaccines encoding for cyclic GD2-mimicking decapeptides (i.e., GD2 mimotopes) is effective against neuroblastoma. For this purpose, two GD2 peptide mimotopes (MA and MD) were selected based on docking experiments to anti-GD2 antibody ch14.18 (binding free energy: −41.23 kJ/mol for MA and −48.06 kJ/mol for MD) and Biacore analysis (Kd = 12.3 × 10−5 mol/L for MA and 5.3 × 10−5 mol/L for MD), showing a higher affinity of MD over MA. These sequences were selected for DNA vaccine design based on pSecTag2-A (pSA) also including a T-cell helper epitope. GD2 mimicry was shown following transfection of CHO-1 cells with pSA-MA and pSA-MD DNA vaccines, with twice-higher signal intensity for cells expressing MD over MA. Finally, these DNA vaccines were tested for induction of tumor protective immunity in a syngeneic neuroblastoma model following oral DNA vaccine delivery with attenuated Salmonella typhimurium (SL 7207). Only mice receiving the DNA vaccines revealed a reduction of spontaneous liver metastases. The highest anti-GD2 humoral immune response and natural killer cell activation was observed in mice immunized with the pSA-MD, a finding consistent with superior calculated binding free energy, dissociation constant, and GD2 mimicry potential for GD2 mimotope MD over MA. In summary, we show that DNA immunization with pSA-MD may provide a useful strategy for active immunization against neuroblastoma. (Cancer Res 2006; 66(21): 10567-75)
Neurospheres Enriched in Cancer Stem–Like Cells Are Highly Effective in Eliciting a Dendritic Cell–Mediated Immune Response against Malignant Gliomas
Authors: Pellegatta Serena , Poliani Pietro Luigi , Corno Daniela , Menghi Francesca , Ghielmetti Francesco , Suarez-Merino Blanca , Caldera Valentina , Nava Sara , Ravanini Maria , Facchetti Fabio , Bruzzone Maria Grazia , Finocchiaro Gaetano 
Published: November 2006

AbstractCancer stem–like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P &lt; 0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P &lt; 0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination. (Cancer Res 2006; 66(21): 10247-52)
Interleukin-6 Contributes to Growth in Cholangiocarcinoma Cells by Aberrant Promoter Methylation and Gene Expression
Authors: Wehbe Hania , Henson Roger , Meng Fanyin , Mize-Berge Janna , Patel Tushar 
Published: November 2006

Abstract
The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. IL-6 can regulate the activity of DNA methyltransferases, and moreover, aberrant DNA methylation can contribute to carcinogenesis. We therefore investigated the effect of chronic exposure to IL-6 on methylation-dependent gene expression and transformed cell growth in human cholangiocarcinoma. The relationship between autocrine IL-6 pathways, DNA methylation, and transformed cell growth was assessed using malignant cholangiocytes stably transfected to overexpress IL-6. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine decreased cell proliferation, growth in soft agar, and methylcytosine content of malignant cholangiocytes. However, this effect was not observed in IL-6-overexpressing cells. IL-6 overexpression resulted in the altered expression and promoter methylation of several genes, including the epidermal growth factor receptor (EGFR). EGFR promoter methylation was decreased and gene and protein expression was increased by IL-6. Thus, epigenetic regulation of gene expression by IL-6 can contribute to tumor progression by altering promoter methylation and gene expression of growth-regulatory pathways, such as those involving EGFR. Moreover, enhanced IL-6 expression may decrease the sensitivity of tumor cells to therapeutic treatments using methylation inhibitors. These observations have important implications for cancer treatment and provide a mechanism by which persistent cytokine stimulation can promote tumor growth. (Cancer Res 2006; 66(21): 10517-24)
Increased Expression of Tissue Transglutaminase in Pancreatic Ductal Adenocarcinoma and Its Implications in Drug Resistance and Metastasis
Authors: Verma Amit , Wang Huamin , Manavathi Bramanandam , Fok Jansina Y. , Mann Aman P. , Kumar Rakesh , Mehta Kapil 
Published: November 2006

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases and is virtually incurable. The molecular mechanisms that contribute to the intrinsic resistance of PDAC to various anticancer therapies are not well understood. Recently, we have observed that several drug-resistant and metastatic tumors and tumor cell lines expressed elevated levels of tissue transglutaminase (TG2). Because PDAC exhibits inherent resistance to various drugs, we determined the constitutive expression of TG2 in 75 PDAC and 12 PDAC cell lines. Our results showed that 42 of 75 (56%) PDAC tumor samples expressed higher basal levels of TG2 compared with the normal pancreatic ducts [odds ratio (OR), 2.439; P = 0.012]. The increased expression of TG2 in PDAC was strongly associated with nodal metastasis (OR, 3.400; P = 0.017) and lymphovascular invasion (OR, 3.055; P = 0.045). Increased expression of TG2 was also evident in all 12 cell lines examined. The elevated expression of TG2 in PDAC cell lines was associated with gemcitabine resistance and increased invasive potential. Overexpression of catalytically active or inactive (C277S mutant) TG2 induced focal adhesion kinase (FAK) activation and augmented invasive functions in the BxPC-3 cell line. Conversely, down-regulation of TG2 by small interfering RNA attenuated FAK phosphorylation. Immunoprecipitation and confocal microscopy data revealed that TG2 was associated with FAK protein in PDAC cells. The activated FAK colocalized with TG2 at focal adhesion points. These results show for the first time that elevated expression of TG2 can induce constitutive activation of FAK and thus may contribute to the development of drug resistance and invasive phenotypes in PDAC. (Cancer Res 2006; 66(21): 10525-33)
Mechanisms for Diurnal Variability of Global Tropical Rainfall Observed from TRMM
Authors: Yang Song , Smith Eric A. 
Published: October 2006

AbstractThe behavior and various controls of diurnal variability in tropical–subtropical rainfall are investigated using Tropical Rainfall Measuring Mission (TRMM) precipitation measurements retrieved from the three level-2 TRMM standard profile algorithms for the 1998 annual cycle. Results show that diurnal variability characteristics of precipitation are consistent for all three algorithms, providing assurance that TRMM retrievals are producing consistent estimates of rainfall variability. As anticipated, most ocean areas exhibit more rainfall at night, while over most land areas, rainfall peaks during daytime; however, important exceptions are noted.The dominant feature of the oceanic diurnal cycle is a rainfall maximum in late-evening–early-morning (LE–EM) hours, while over land the dominant maximum occurs in the mid- to late afternoon (MLA). In conjunction with these maxima are pronounced seasonal variations of the diurnal amplitudes. Amplitude analysis shows that the diurnal pattern and its seasonal evolution are closely related to the rainfall accumulation pattern and its seasonal evolution. In addition, the horizontal distribution of diurnal variability indicates that for oceanic rainfall, there is a secondary MLA maximum coexisting with the LE–EM maximum at latitudes dominated by large-scale convergence and deep convection. Analogously, there is a preponderancy for an LE–EM maximum over land coexisting with the stronger MLA maximum, although it is not evident that this secondary continental feature is closely associated with the large-scale circulation. Neither of the secondary maxima exhibit phase behavior that can be considered semidiurnal in nature. Diurnal rainfall variability over the ocean associated with large-scale convection is clearly an integral component of the general circulation.Phase analysis reveals differences in regional and seasonal features of the diurnal cycle, indicating that underlying forcing mechanisms differ from place to place. This is underscored by the appearance of secondary ocean maxima in the presence of large-scale convection, along with other important features. Among these, there are clear-cut differences between the diurnal variability of seasonal rainfall over the mid-Pacific and Indian Ocean Basins. The mid-Pacific exhibits double maxima in spring and winter but only LE–EM maxima in summer and autumn, while the Indian Ocean exhibits double maxima in spring and summer and only an LE–EM maximum in autumn and winter. There are also evident daytime maxima within the major large-scale marine stratocumulus regions off the west coasts of continents. The study concludes with a discussion concerning how the observational evidence either supports or repudiates possible forcing mechanisms that have been suggested to explain diurnal rainfall variability.
Diagnosing the Annual Cycle Modes in the Tropical Atlantic Ocean Using a Directly Coupled Atmosphere–Ocean GCM
Authors: DeWitt David G. , Schneider Edwin K. 
Published: October 2006

Abstract
The annual cycle of sea surface temperature (SST) in the tropical Atlantic of a directly coupled atmosphere–ocean general circulation model (CGCM) is decomposed into the parts forced by different surface fluxes (denoted as modes) for the two extreme months of March and August using forced ocean experiments. Almost all previous diagnostic work of the forcing of the SST annual cycle in the Atlantic has concentrated on the near-equatorial region. Here, the annual cycle is examined within the latitude range of 25°S–25°N to facilitate comparison with the interannual variability. The structure of the response to the different surface flux forcings bears some resemblance to the interannual SST modes in the tropical Atlantic, which are diagnosed using rotated empirical orthogonal function (REOF) analysis. Diagnosis of the forcing of the annual cycle modes and the interannual modes shows that they do not always have a common cause. Hence, the simple interpretation that the leading interannual modes are perturbations to the annual cycle is not always valid.
In particular, the equatorial SST annual cycle mode is primarily driven by variations in vertical velocity while the equatorial interannual mode is associated with eastward-propagating thermocline anomalies and is forced by both thermocline anomalies and vertical velocity anomalies. As for the interannual modes, there exist off-equatorial annual cycle modes in both the Northern and Southern Hemispheres. The annual cycle off-equatorial mode in both hemispheres is shown to be primarily driven by heat flux variations. The Southern Hemisphere interannual mode is primarily driven by heat flux variations while the Northern Hemisphere interannual mode shows a strong influence of thermocline depth anomalies. In addition, the Southern Hemisphere interannual mode is centered about 10° south of the annual cycle mode. An interannual mode that has maximum variability along the South American coast south of the equator is shown to be associated with thermocline depth anomalies. This interannual mode has no analog in the annual cycle modes.
The coupled model simulation of the annual cycle is found to be fairly realistic so that the results presented here could have applicability to the observed Atlantic.
Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus
Authors: De Leeuw K , Freire B , Smit A J , Bootsma H , Kallenberg C G , Bijl M 
Published: November 2006

To determine risk factors of accelerated atherosclerosis in patients with systemic lupus erythematosus (SLE), 72 patients with inactive disease and 36 ageand sex-matched controls were included. The intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. Traditional risk factors and disease-related factors were recorded. Cardiovascular risk was estimated using SCORE (systematic coronary risk evaluation). Markers of inflammation, endothelial activation and vascular remodelling (matrix metalloproteinases (MMP-3, MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1)) were determined. IMT was increased in patients (0.67 mm 0.13 versus 0.61 mm 0.11, P 0.05). Prevalence of hypertension (33% versus 6%, P 0.001), SCORE (2.2 (1.7–4.2) versus 1.7 (1.3–2.1), P 0.001), as well as parameters of inflammation (CRP 1.8 (0.6–5.8) mg/L versus 0.6 (0.2–1.0) mg/L, P 0.001) and endothelial activation (VCAM-1 505 (389–683) ng/mL versus 374 (322–427) ng/mL, P 0.001) and von Willebrand factor (138 (59–208)% versus 48 (24–92)%, P 0.001), were increased in patients. Vascular remodelling was altered: MMP-3 and TIMP-1 were increased (18 (10–29) ng/mL versus 8 (5–11) ng/mL, P 0.001, and 275 (216–352) ng/mL versus 230 (197–268) ng/mL, P 0.001, respectively), and MMP-9 was decreased in SLE (266 (147–412) ng/mL versus 348 (226–530) ng/mL, P 0.05). Univariate analyses revealed that in patients IMT was associated with age, systolic blood pressure, SCORE and disease duration. In multivariate analysis, age and SCORE were independent predictors of IMT. In conclusion, SLE patients have an increased IMT, which is associated with traditional risk factors. Non-traditional risk factors, such as endothelial activation, altered vascular remodelling and disease duration, might play an additional role.
Trauma injuries sustained by cyclists
Authors: Kloss F R , Tuli T , Haechl O , Gassner R 
Published: October 2006

The aim of this article is to review the pertinent literature and to analyse our own data on facial trauma related to bicycling and mountain-biking. This article focuses on the mechanisms and the variety of bicycle related injuries and addresses the advantages of wearing protection clothes. Within the world of bicycling, the popularity of mountain-biking has increased the most dramatically. The main risk factors for the growing number of bicycle-related injuries are not wearing a helmet, age, male sex, unsafe riding techniques and intoxication. Bikers most commonly collide or fall in daily traffic whereas mountain-bikers get hurt whilst descending. The most common types of injury apart from superficial lesions are dentoalveolar trauma and facial fractures. Wearing protective clothing such as a helmet is demonstrably beneficial and so we suggest that the obligatory use of protective wear should be introduced. For a better insight into overall cycling-related trauma further research will be required.
Monitoring the injured patient
Authors: Hulme Jonathan 
Published: October 2006

Monitoring of the injured patient is important. It includes clinical assessment, following the ABCDE approach, and the use of instruments found from the prehospital to critical care setting. Correctly used, these provide important information about the patient's current physiological state and response to treatment plus diagnostic and prognostic implications that are useful to the clinician involved in the care of injured patients.
Predictive Value of Ischemic Lesion Volume Assessed With Magnetic Resonance Imaging for Neurological Deficits and Functional Outcome Poststroke: A Critical Review of the Literature
Authors: Schiemanck S. K. , Kwakkel G. , Post M. W. M. , Prevo A. J. H. 
Published: November 2006

Objective. Ischemic lesion volume is assumed to be an important predictor of poststroke neurological deficits and functional outcome. This critical review examines the methodological quality of MRI studies and the predictive value of hemispheric infarct volume for neurological deficits (at body function level) and functional outcome (at activities level). Methods. Using Medline, PiCarta, and Embase to identify studies, 13 of the 747 identified studies met the authors’ inclusion criteria. Subsequently, studies were tested for adherence to the key methodological criteria for internal, statistical, and external validity. Each criterion was weighted binary, and studies with 6 points or more were judged to be valid for assessing the predictive value of MRI for outcome. Results. The 13 included studies had several methodological weaknesses with respect to internal validity, and none of them took lesion location into account. Only a few used outcome measures according to the International Classification of Functioning, Disability and Health and followed patients beyond 6 months. Correlation coefficients between MRI lesion volume and outcomes were higher for outcomes defined at body function level (National Institutes of Health Stroke Scale; median 0.67; range: 0.57-0.91) than for those defined at the level of activities (Barthel Index; median -0.49; range: -0.33 to -0.74). Conclusions. Methodological shortcomings of most studies confound the prognostic value of MRI in predicting stroke outcome, and few studies have focused on functional outcome. Future studies should investigate the added value of MRI volume over clinical neurological variables in predicting functional outcome beyond 6 months poststroke.
The Scale for Contraversive Pushing: A Reliability and Validity Study
Authors: Baccini Marco , Paci Matteo , Rinaldi Lucio A. 
Published: November 2006

Objective. Pushing toward the hemiplegic side can interfere with mobility training after stroke. This study estimated the internal consistency, interrater reliability, and validity of the Scale for Contraversive Pushing (SCP). Methods. Twenty-six patients with recent stroke were diagnosed with pusher behavior (PB). Two testers, randomly selected from 3 other examiners, independently assessed each patient using the SCP on the same day within 3 days of admission for rehabilitation. Cohen kappa coefficient was used to determine the agreement between the clinical and SCP diagnosis. The interrater reliability of the scale was estimated by calculation of the intraclass correlation coefficient. Cronbach’s alpha coefficient and Pearson’s coefficients were used to estimate the internal consistency of the scale and correlations between the subscores and the total score. Results. The agreement between SCP and clinical diagnosis was very low when the original cutoff criterion for SCP diagnosis was used but was almost perfect with a modified criterion. The interrater reliability was good to excellent with regard both to each sub-score and to the total score. The internal consistency was very high, along with correlations between subscores and total score of the scale. Conclusions. The results provide support for use of the SCP based on its reliability and validity using a modified cutoff criterion to make a diagnosis of PB.
Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials
Authors: Bossard Céline , Belhadj Karim , Reyes Felix , Martin-Garcia Nadine , Berger Françoise , Kummer Jean Alain , Brière Josette , Baglin Anne-Catherine , Cheze Stéphane , Bosq Jacques , Ribrag Vincent , Gisselbrecht Christian , Mounier Nicolas , Gaulard Philippe 
Published: November 2006

AbstractNasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5−/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression.