bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frizzled 4 Regulates Stemness and Invasiveness of Migrating Glioma Cells Established by Serial Intracranial Transplantation
Authors: Jin Xun , Jeon Hee-Young , Joo Kyeung Min , Kim Jun-Kyum , Jin Juyoun , Kim Sung Hak , Kang Bong Gu , Beck Samuel , Lee Se Jeong , Kim Joong Kyu , Park Ae-Kyung , Park Woong-Yang , Choi Yun-Jaie , Nam Do-Hyun , Kim Hyunggee 
Published: March 2011

Abstract
One of the most detrimental hallmarks of glioblastoma multiforme (GBM) is cellular invasiveness, which is considered a potential cause of tumor recurrence. Infiltrated GBM cells are difficult to completely eradicate surgically and with local therapeutic modalities. Although much effort has focused on understanding the various mechanisms controlling GBM invasiveness, its nature remains poorly understood. In this study, we established highly serial intracranial transplantation. U87R4 cells were highly invasive and displayed stem cell-like properties, as compared to noninvasive but proliferative U87L4 cells. Microarray analysis during serial transplantation revealed that apoptosis-inducing genes (caspase3 and PDCD4) were downregulated whereas several cancer stem cell–relevant genes [Frizzled 4 (FZD4) and CD44] were upregulated in more invasive cells. U87R4 cells were resistant to anticancer drug–induced cell death, partly due to downregulation of caspase3 and PDCD4, and they retained activated Wnt/β-catenin signaling due to upregulation of Frizzled 4, which was sufficient to control neurosphere formation. We also found that FZD4 promoted expression of the epithelial to mesenchymal transition regulator SNAI1, along with acquisition of a mesenchymal phenotype. Taken together, our results argue that Frizzled 4 is a member of the Wnt signaling family that governs both stemness and invasiveness of glioma stem cells, and that it may be a major cause of GBM recurrence and poor prognosis. Cancer Res; 71(8); 3066–75. ©2011 AACR.
EMT and Stem Cell–Like Properties Associated with miR-205 and miR-200 Epigenetic Silencing Are Early Manifestations during Carcinogen-Induced Transformation of Human Lung Epithelial Cells
Authors: Tellez Carmen S. , Juri Daniel E. , Do Kieu , Bernauer Amanda M. , Thomas Cindy L. , Damiani Leah A. , Tessema Mathewos , Leng Shuguang , Belinsky Steven A. 
Published: March 2011

AbstractEpithelial-to-mesenchymal transition (EMT) is strongly associated with cancer progression, but its potential role during premalignant development has not been studied. Here, we show that a 4-week exposure of immortalized human bronchial epithelial cells (HBEC) to tobacco carcinogens can induce a persistent, irreversible, and multifaceted dedifferentiation program marked by EMT and the emergence of stem cell–like properties. EMT induction was epigenetically driven, initially by chromatin remodeling through H3K27me3 enrichment and later by ensuing DNA methylation to sustain silencing of tumor-suppressive microRNAs (miRNA), miR-200b, miR-200c, and miR-205, which were implicated in the dedifferentiation program in HBECs and also in primary lung tumors. Carcinogen-treated HBECs acquired stem cell–like features characterized by their ability to form spheroids with branching tubules and enrichment of the CD44high/CD24low, CD133, and ALDH1 stem cell–like markers. miRNA overexpression studies indicated that regulation of the EMT, stem-like, and transformed phenotypes in HBECs were distinct events. Our findings extend present concepts of how EMT participates in cancer pathophysiology by showing that EMT induction can participate in cancer initiation to promote the clonal expansion of premalignant lung epithelial cells. Cancer Res; 71(8); 3087–97. ©2011 AACR.
High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation
Authors: Nassar Taher , Attili-Qadri Suha , Harush-Frenkel Oshrat , Farber Shimon , Lecht Shimon , Lazarovici Philip , Benita Simon 
Published: March 2011

Abstract
Docetaxel, an efficient chemotherapeutic drug, exhibits low and variable oral bioavailability due to the active efflux by P-glycoprotein (P-gp) and more so to CYP3A4 gut metabolism. Using a spray-drying technique, docetaxel was incorporated in PLGA [poly(lactic-co-glycolic acid)] nanocapsules (NC) which were embedded in entero-coated microparticles. An oral administration of the NC formulation elicited a higher absolute bioavailability than both a docetaxel solution (276%) and a free docetaxel NC formulation (400%) injected intravenously, a 5-mg/kg dose. The batches (B) I and II NC formulations elicited Cmax values that were 1,735% and 2,254%, respectively; higher than the Cmax value of the oral docetaxel solution combined with blank microparticles, a 10-mg/kg dose. No significant difference in AUC (area under curve) was observed between the batches. These unexpected results can be explained only if the pharmacokinetics of docetaxel had been modified. It was shown that NCs released from the microparticles penetrated the enterocytes, bypassing P-gp; apparently circumventing gut metabolism and accumulating within the lymphatic system from where both intact or biodegraded NCs and free docetaxel were progressively released into the circulation as plausibly supported by the fluorescent imaging results. Furthermore, the circulating docetaxel in plasma was unencapsulated and circulated either in free form or bound to albumin. Both free docetaxel NCs and microparticles exhibited in vitro efficacy on WRC 256 cells suggesting that the activity of docetaxel was not altered. This delivery concept has potential for clinical translation, perhaps allowing docetaxel chemotherapy to be switched from intravenous to oral delivery. Cancer Res; 71(8); 3018–28. ©2011 AACR.
Genome-Wide DNA Methylation Profiling of CpG Islands in Breast Cancer Identifies Novel Genes Associated with Tumorigenicity
Authors: Hill Victoria K. , Ricketts Christopher , Bieche Ivan , Vacher Sophie , Gentle Dean , Lewis Cheryl , Maher Eamonn R. , Latif Farida 
Published: March 2011

Abstract
Epigenetic profiling of tumor DNAs may reveal important new theranostic targets to improve prognosis and treatment of advanced cancer patients. In this study, we performed a genome-wide profile of DNA methylation patterns in sporadic breast tumors by using the HumanMethylation27 BeadChips to assess relationships between DNA methylation changes and patient tumor characteristics. The arrays identified 264 hypermethylated loci/genes present in genomic CpG islands. Hierarchical clustering based on methylation levels divided the specimens into three distinct groups, within which certain clinical features also clustered. Statistically significant differences were determined between overall methylation levels of these clusters and estrogen receptor and progesterone receptor (ER/PR) status (P = 0.001), tumor relapse (P = 0.035), and lymph node metastasis (P = 0.042). We identified several individual methylated genes associated with clinical features, including six genes (RECK, SFRP2, UAP1L1, ACADL, ITR, and UGT3A1) that showed statistical significance between methylation and relapse-free survival. Notably, the RECK gene in this group has been associated in other cancers with poorest prognosis. Among the leading relapse-associated genes and the genes associated with ER/PR status, we sequenced an independent set of paired normal/tumor breast DNA samples to confirm tumor specificity of methylation. Further, we carried out quantitative real-time reverse transcriptase PCR to confirm reduced expression in methylated tumors. Our findings suggest the utility for the DNA methylation patterns in these genes as clinically useful surrogate markers in breast cancer, as well as new molecular pathways for further investigation as therapeutic targets. Cancer Res; 71(8); 2988–99. ©2011 AACR.
Accurate Classification of Diffuse Large B-Cell Lymphoma into Germinal Center and Activated B-Cell Subtypes Using a Nuclease Protection Assay on Formalin-Fixed, Paraffin-Embedded Tissues
Authors: Rimsza Lisa M. , Wright George , Schwartz Mark , Chan Wing C. , Jaffe Elaine S. , Gascoyne Randy D. , Campo Elias , Rosenwald Andreas , Ott German , Cook James R. , Tubbs Raymond R. , Braziel Rita M. , Delabie Jan , Miller Tom P. , Staudt Louis M. 
Published: March 2011

AbstractClassification of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes based on gene expression profiles has well-established prognostic value. These subtypes, termed germinal center B cell (GCB) and activated B cell (ABC) also have different genetic alterations and overexpression of different pathways that may serve as therapeutic targets. Thus, accurate classification is essential for analysis of clinical trial results and planning new trials by using targeted agents. The current standard for COO classification uses gene expression profiling (GEP) of snap frozen tissues, and a Bayesian predictor algorithm. However, this is generally not feasible. In this study, we investigated whether the qNPA technique could be used for accurate classification of COO by using formalin-fixed, paraffin-embedded (FFPE) tissues. We analyzed expression levels of 14 genes in 121 cases of R-CHOP-treated DLBCL that had previously undergone GEP by using the Affymetrix U133 Plus 2.0 microarray and had matching FFPE blocks. Results were evaluated by using the previously published algorithm with a leave-one-out cross-validation approach. These results were compared with COO classification based on frozen tissue GEP profiles. For each case, a probability statistic was generated indicating the likelihood that the classification by using qNPA was accurate. When data were dichotomized into GCB or non-GCB, overall accuracy was 92%. The qNPA technique accurately categorized DLBCL into GCB and ABC subtypes, as defined by GEP. This approach is quantifiable, applicable to FFPE tissues with no technical failures, and has potential for significant impact on DLBCL research and clinical trial development. Clin Cancer Res; 17(11); 3727–32. ©2011 AACR.
PET Tumor Metabolism in Locally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy: Value of Static versus Kinetic Measures of Fluorodeoxyglucose Uptake
Authors: Dunnwald Lisa K. , Doot Robert K. , Specht Jennifer M. , Gralow Julie R. , Ellis Georgiana K. , Livingston Robert B. , Linden Hannah M. , Gadi Vijayakrishna K. , Kurland Brenda F. , Schubert Erin K. , Muzi Mark , Mankoff David A. 
Published: March 2011

Abstract
Purpose: Changes in tumor metabolism from positron emission tomography (PET) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NC) are predictive of pathologic response. Serial dynamic [18F]-FDG (fluorodeoxyglucose) PET scans were used to compare kinetic parameters with the standardized uptake value (SUV) as predictors of pathologic response, disease-free survival (DFS), and overall survival (OS).
Experimental Design: Seventy-five LABC patients underwent FDG PET prior to and at midpoint of NC. FDG delivery (K1), FDG flux (Ki), and SUV measures were calculated and compared by clinical and pathologic tumor characteristics using regression methods and area under the receiver operating characteristic curve (AUC). Associations between K1, Ki, and SUV and DFS and OS were evaluated using the Cox proportional hazards model.
Results: Tumors that were hormone receptor negative, high grade, highly proliferative, or of ductal histology had higher FDG Ki and SUV values; on an average, FDG K1 did not differ systematically by tumor features. Predicting pathologic response in conjunction with estrogen receptor (ER) and axillary lymph node positivity, kinetic measures (AUC = 0.97) were more robust predictors than SUV (AUC = 0.84, P = 0.005). Changes in K1 and Ki predicted both DFS and OS, whereas changes in SUV predicted OS only. In multivariate modeling, only changes in K1 remained an independent prognosticator of DFS and OS.
Conclusion: Kinetic measures of FDG PET for LABC patients treated with NC accurately measured treatment response and predicted outcome compared with static SUV measures, suggesting that kinetic analysis may hold advantage of static uptake measures for response assessment. Clin Cancer Res; 17(8); 2400–9. ©2011 AACR.
In Vitro and Human Studies of a 4F Double-Coaxial Technique (“Mother-Child” Configuration) to Facilitate Stent Implantation in Resistant Coronary Vessels
Authors: Takeshita Satoshi , Shishido Koki , Sugitatsu Kazuya , Okamura Nobuhiro , Mizuno Shingo , Yaginuma Kenji , Suenaga Hidetaka , Tanaka Yutaka , Matsumi Junya , Takahashi Saeko , Saito Shigeru 
Published: March 2011

Background—
We recently developed a 4F child catheter that can be inserted into 6F or larger conventional guiding catheters. The use of 4F mother-child technique may improve the delivery of coronary stents to complex lesions. Accordingly, we sought to determine the potential of using a 4F mother-child technique to treat complex coronary lesions.

Methods and Results—

The support power and the trackability of the mother-child technique of 4-in-6 were evaluated using a coronary artery tree model. In addition, the results of 51 lesions treated by using a 4F child catheter were retrospectively analyzed. The in vitro experiment demonstrated that backup support of the 4-in-6 system was increased when the child catheter was advanced into the coronary tree ≥5 cm (
P
≤0.01); further, the 4F child catheter was associated with superior trackability as compared with a 5F child catheter (15.0 cm [15.0 to 15.0] versus 13.0 cm [12.8 to 13.0],
P
<0.005). A total of 51 lesions, in which conventional techniques had been unsuccessful, were treated using the 4F mother-child technique. Lesion success was achieved in 48 (94%) lesions. Stent deployment was attempted in 44 (86%) and was successful in 40 of 44 (91%). There were 2 instances of stent dislodgment.

Conclusions—
With the superior trackability of the 4F child catheter and with increased backup support of the mother-child system, the 4F mother-child system provided >90% success rate for lesions in which conventional techniques had failed. The 4F mother-child system may become a viable alternative to conventional techniques in treating complex coronary lesions.
Bivalirudin Is a Dual Inhibitor of Thrombin and Collagen-Dependent Platelet Activation in Patients Undergoing Percutaneous Coronary Intervention
Authors: Kimmelstiel Carey , Zhang Ping , Kapur Navin K. , Weintraub Andrew , Krishnamurthy Barath , Castaneda Vilma , Covic Lidija , Kuliopulos Athan 
Published: March 2011

Background—
Bivalirudin, a direct thrombin inhibitor, is a widely used adjunctive therapy in patients undergoing percutaneous intervention (PCI). Thrombin is a highly potent agonist of platelets and activates the protease-activated receptors, PAR1 and PAR4, but it is not known whether bivalirudin exerts antiplatelet effects in PCI patients. We tested the hypothesis that bivalirudin acts as an antiplatelet agent in PCI patients by preventing activation of PARs on the platelet surface.

Methods and Results—
The effect of bivalirudin on platelet function and systemic thrombin levels was assessed in patients undergoing elective PCI. Mean plasma levels of bivalirudin were 2.7±0.5 μmol/L during PCI, which correlated with marked inhibition of thrombin-induced platelet aggregation and significantly inhibited cleavage of PAR1. Unexpectedly, bivalirudin also significantly inhibited collagen-platelet aggregation during PCI. Collagen induced a conversion of the platelet surface to a procoagulant state in a thrombin-dependent manner that was blocked by bivalirudin. Consistent with this result, bivalirudin reduced systemic thrombin levels by >50% during PCI. Termination of the bivalirudin infusion resulted in rapid clearance of the drug with a half-life of 29.3 minutes.

Conclusions—
Bivalirudin effectively suppresses thrombin-dependent platelet activation via inhibition of PAR1 cleavage and inhibits collagen-induced platelet procoagulant activity as well as systemic thrombin levels in patients undergoing PCI.
Novel Approaches for Preventing or Limiting Events in Diabetic Patients (Naples-Diabetes) Trial
Authors: Briguori Carlo , Airoldi Flavio , Visconti Gabriella , Focaccio Amelia , Caiazzo Gianluca , Golia Bruno , Biondi-Zoccai Giuseppe , Ricciardelli Bruno , Condorelli Gerolama 
Published: March 2011

Background—
To expand the paucity of data on the efficacy of various drug-eluting stents in diabetic patients.

Methods and Results—

Type 2 diabetic patients treated in our institution from October 2005 to January 2007 presenting with of de novo lesions in native coronary arteries were randomly assigned to sirolimus-eluting stents (Cypher group; n=76); paclitaxel-eluting stents (Taxus group; n=75); and everolimus-eluting stents (Endeavor group; n=75). Poor metabolic control (HbA1c >7% and low-density lipoprotein cholesterol >100 mg/dL) and microvascular complications (retinopathy and/or nephropathy) were assessed. The primary end point was the 3-year composite of major adverse cardiac events (MACE), including death of any cause, myocardial infarction, and clinically driven target vessel revascularization. MACE-free survival was 86.8% in the Cypher group, 82.5% in the Taxus group, and 64.4% in the Endeavor group (
P
=0.006 by log-rank test). The post hoc comparisons showed no significant difference between Cypher versus Taxus groups (adjusted
P
=1.0) but a higher MACE rate in the Endeavor group versus both the Cypher group (adjusted
P
=0.012) and the Taxus group (adjusted
P
=0.075). Independent predictors of 3-year MACE at Cox analysis were treatment by Endeavor versus Cypher stent (2.35 [95% confidence interval, 1.07 to 5.41];
P
=0.030), multivessel disease (hazard ratio, 1.78 [95% confidence interval, 1.06 to 2.66];
P
=0.031), diabetic retinopathy (hazard ratio, 1.60; [95% confidence interval, 1.03 to 2.76];
P
=0.038), and poor metabolic control (hazard ratio, 1.60; [95% confidence interval, 1.02 to 2.52];
P
=0.048).

Conclusions—
The present pilot study suggests that in diabetic patients, the Endeavor stent is associated with a higher 3-year MACE rate when compared with Cypher and Taxus stents.
On the Separability of Various Classes from the GOES Visible and Infrared Data
Authors: Tsonis A. A. 
Published: March 2011

Abstract
The spatial and spectral characteristics of the GOES visible and infrared images are examined. From that analysis, a scheme is developed which identifies and separates the following classes: clear skies/no snow cover, clear skies/snow cover and clouds. Clouds are then classified as high or low broken clouds and overcast. The scheme is tested for various weather situations. Comparison of the classification results with reports from ground synoptic stations and maps reflect an average accuracy of approximately 72%, and a higher accuracy (∼87%) when high or low broken clouds and overcast are considered as one class (i.e., clouds). The differentiation between clouds and snow, or no snow-covered ground has been found to be very satisfactory, even in cases of temperature inversions.
Icing Conditions Encountered by a Research Aircraft
Authors: Sand Wayne R. , Cooper William A. , Politovich Marcia K. , Veal Donald L. 
Published: March 2011

Abstract
The characteristics of clouds which have led to airframe icing on an instrumented Beechcraft Super King Air are summarized. The icing encounters occurred at altitudes from 0–8000 m MSL, in summer and winter, in stratiform and cumuliform clouds, and at temperatures from 0 to −30°C. The characteristics of icing encounters in different areas and in different seasons are compared. The fraction of measurements exceeding various threshold values of liquid water content, average liquid water content over a given distance, volume-median droplet diameter, droplet concentration, ice crystal concentration, and potential ice accumulation are given. The effects of these cloud characteristics on aircraft performance were measured by comparing the rate of climb of the aircraft with ice to the rate of climb for the clean aircraft under the same conditions. Most icing encounters led to a reduction in the rate of climb that increased linearly with the path integral of the supercooled liquid water content. The volume-median diameter had little correlation with changes in performance. Some potentially hazardous conditions, which decreased the rate of climb capability of this aircraft by 7–9 m s−1, are also discussed.
Numerical Simulation of Slope and Mountain Flows
Authors: McNider Richard T. , Pielke Roger A. 
Published: March 2011

Abstract
Early descriptive models of mountain-valley circulations indicated that the mountain flow (i.e., the along-valley axis component out of the valley) is a true three-dimensional phenomenon. According to these descriptions, at night shallow-down slope flows on the valley sidewalls directly driven by temperature deficits near the surface produce a pooling of cool air in the valley. This deep pool of cool air in the valley compared with a much shallower surface inversion over the plains (to which the valley opens) produces a secondary flow (the mountain flow) out of the valley driven by a deep hydrostatic pressure gradient. It is this deep secondary flow which is most important to pollutant transport in deep valleys and which has not been previously investigated in a numerical model.
It is the purpose of this investigation to numerically simulate the above-mentioned secondary circulation using a three-dimensional numerical model. The Colorado State University Hydrostatic Mesoscale Model-a hydrostatic, primitive equation model, forced by a surface energy budget-was utilized for the simulations. Both idealized topography and an actual Colorado valley were used in the investigation to emulate the classic mountain-plain configuration discussed above. Special attention was given to the development of the sidewall slope flows which produce the pooling of air in the valley. Results of the simulations indicated shallow slope flows less than 100 m deep started almost immediately after cooling began and reached their maximum velocity after approximately one hour and then slowly decreased through the night. A high level of turbulence was noted near the top of the slope flows. The turbulence was not only due to shear in the slope flow, but to destabilization of the temperature profile because of thermal advection. Definite pooling of cool air occurred in the valley with cooling occurring at all heights to near ridge tops. The secondary flow out of the valley lagged the development of the slope flows by approximately one hour, but was very deep, filling the whole valley to near ridge height.
Evidence of Arctic-wide Atmospheric Aerosols from DMSP Visible Imagery
Authors: Shine Keith P. , Robinson David A. , Henderson-Sellers Ann , Kukla George 
Published: March 2011

Abstract
Recent work has emphasized the potential importance of atmospheric aerosols in the Arctic. This paper presents results indicating the large-scale presence of arctic aerosols during late spring. Their screening effect may be sufficient to alter significantly the shortwave radiation budget. The ratios of brightness over sea and snow covered ice surfaces are shown to be considerably lower, using DMSP shortwave imagery, than those calculated for clear skies using a radiative transfer scheme. Our analysis shows that aerosols are the most likely cause of the discrepancy. With additional calibration the method offers the potential for remote sensing of the aerosol distribution and concentration over the Arctic.