bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Tumor Invasiveness: The Adaptive Tumor Microenvironment Landscape Model
Authors: Lee Hyung-Ok , Silva Ariosto S. , Concilio Susanna , Li Yue-Sheng , Slifker Michael , Gatenby Robert A. , Cheng Jonathan D. 
Published: August 2011

Abstract
Interactions between cancer cells and their microenvironment are crucial for promoting tumor growth and invasiveness. In the tumor adaptive landscape model, hypoxic and acidic microenvironmental conditions reduce the fitness of cancer cells and significantly restrict their proliferation. This selects for enhanced motility as cancer cells may evolve an invasive phenotype if the consequent cell movement is rewarded by proliferation. Here, we used an integrative approach combining a mathematical tumor adaptive landscape model with experimental studies to examine the evolutionary dynamics that promote an invasive cancer phenotype. Computer simulation results hypothesized an explicit coupling of motility and proliferation in cancer cells. The mathematical modeling results were also experimentally examined by selecting Panc-1 cells with enhanced motility on a fibroblast-derived 3-dimensional matrix for cells that move away from the unfavorable metabolic constraints. After multiple rounds of selection, the cells that adapted through increased motility were characterized for their phenotypic properties compared with stationary cells. Microarray and gene depletion studies showed the role of Rho-GDI2 in regulating both cell movement and proliferation. Together, this work illustrates the partnership between evolutionary mathematical modeling and experimental validation as a potentially useful approach to study the complex dynamics of the tumor microenvironment. Cancer Res; 71(20); 6327–37. ©2011 AACR.
Eribulin Mesylate
Authors: Jain Sarika , Vahdat Linda T. 
Published: August 2011

Abstract
Eribulin mesylate, a nontaxane, completely synthetic microtubule inhibitor, has recently been approved by the U.S. Food and Drug Administration as third-line treatment of metastatic breast cancer refractory to anthracyclines and taxanes. Eribulin is a synthetic analogue of halichondrin B, which inhibits microtubule polymerization by a mechanism distinct from other available antitubulin agents. Eribulin significantly increased overall survival (OS; median OS for the eribulin-treated group was 13.1 months versus 10.6 months for the group treated by investigator's choice) in a heavily pretreated metastatic breast cancer population. Eribulin has a manageable side-effect profile, notably neutropenia and fatigue, and a relatively low incidence of peripheral neuropathy. The mechanism of action, pharmacokinetics, preclinical antitumor activity, and clinical trials of eribulin in the metastatic breast cancer setting are reviewed here. Clin Cancer Res; 17(21); 6615–22. ©2011 AACR.
NF-κB Is Required for Smac Mimetic-Mediated Sensitization of Glioblastoma Cells for γ-Irradiation–Induced Apoptosis
Authors: Berger Rebecca , Jennewein Claudia , Marschall Viola , Karl Sabine , Cristofanon Silvia , Wagner Liane , Vellanki Sri HariKrishna , Hehlgans Stephanie , Rödel Franz , Debatin Klaus-Michael , Ludolph Albert C. , Fulda Simone 
Published: August 2011

Abstract
Evasion of apoptosis contributes to radioresistance of glioblastoma, calling for novel strategies to overcome apoptosis resistance. In this study, we investigated the potential of the small molecule Smac mimetic BV6 to modulate radiosensitivity of glioblastoma cells. Here, we identify a novel proapoptotic function of NF-κB in γ-irradiation–induced apoptosis of glioblastoma cells by showing, for the first time, that NF-κB is critically required for Smac mimetic–mediated radiosensitization. BV6 significantly increases γ-irradiation–triggered apoptosis in several glioblastoma cell lines in a dose- and time-dependent manner. Calculation of combination index (CI) reveals that the interaction of BV6 and γ-irradiation is highly synergistic (CI &lt; 0.3). Molecular studies show that BV6 stimulates NF-κB activation, which is critical for radiosensitization, because genetic inhibition of NF-κB by overexpression of the dominant-negative superrepressor IκBα-SR significantly decreases BV6- and γ-irradiation–induced apoptosis. Also, the BV6-mediated enhancement of γ-irradiation–triggered caspase activation, drop of mitochondrial membrane potential, and cytochrome c release is abolished in cells overexpressing IκBα-SR. Similarly, NF-κB inhibition by ectopic expression of a kinase dead mutant of IKKβ prevents the BV6-mediated sensitization for γ-irradiation. The clinical relevance is underscored by experiments with primary tumor samples showing that BV6 sensitizes primary cultured glioma cells as well as glioblastoma-initiating cancer stem cells derived from surgical specimens for γ-irradiation. In conclusion, we identify NF-κB as a critical mediator of Smac mimetic-conferred radiosensitization of glioblastoma cells. These results have important implications for the development of Smac mimetic–based combination protocols for radiosensitization of glioblastoma. Mol Cancer Ther; 10(10); 1867–75. ©2011 AACR.
A Molecular Screening Approach to Identify and Characterize Inhibitors of Glioblastoma Stem Cells
Authors: Visnyei Koppany , Onodera Hideyuki , Damoiseaux Robert , Saigusa Kuniyasu , Petrosyan Syuzanna , De Vries David , Ferrari Denise , Saxe Jonathan , Panosyan Eduard H. , Masterman-Smith Michael , Mottahedeh Jack , Bradley Kenneth A. , Huang Jing , Sabatti Chiara , Nakano Ichiro , Kornblum Harley I. 
Published: August 2011

Abstract
Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types. Mol Cancer Ther; 10(10); 1818–28. ©2011 AACR.
Mitochondrial DNA Copy Number and Pancreatic Cancer in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study
Authors: Lynch Shannon M. , Weinstein Stephanie J. , Virtamo Jarmo , Lan Qing , Liu Chin-San , Cheng Wen-Ling , Rothman Nathaniel , Albanes Demetrius , Stolzenberg-Solomon Rachael Z. 
Published: August 2011

Abstract
Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic cancer, are sources of oxidative stress in humans that could cause mitochondrial DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA copy number is associated with increased incident pancreatic cancer, we conducted a nested case–control study in the Alpha-Tocopherol Beta Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline. Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred (follow-up: 12 years) among participants, with whole blood samples used for mtDNA extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using unconditional logistic regression, adjusting for age, smoking, and diabetes history. All statistical tests were two sided. Higher mtDNA copy number was significantly associated with increased pancreatic cancer risk (highest vs. lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01–2.67, continuous OR = 1.14, 95% CI 1.06–1.23), particularly for cases diagnosed during the first 7 years of follow-up (OR = 2.14, 95% CI = 1.16–3.96, Ptrend = 0.01, continuous OR = 1.21, 95% CI = 1.10–1.33), but not for cases occurring during follow-up of 7 years or greater (OR = 1.14, 95% CI = 0.53–2.45, continuous OR = 1.05, 95% CI = 0.93–1.18). Our results support the hypothesis that mtDNA copy number is associated with pancreatic cancer and could possibly serve as a biomarker for pancreatic cancer development. Cancer Prev Res; 4(11); 1912–9. ©2011 AACR.
Acetylcysteine for Prevention of Renal Outcomes in Patients Undergoing Coronary and Peripheral Vascular Angiography
Authors:   ACT Investigators*
Published: August 2011

Background—
It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury.

Methods and Results—

We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25;
P
=0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69;
P
=0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment.

Conclusions—
In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00736866.
The Effects of Aging on the Neural Basis of Implicit Associative Learning in a Probabilistic Triplets Learning Task
Authors: Simon Jessica R. , Vaidya Chandan J. , Howard James H. , Howard Darlene V. 
Published: August 2011

AbstractFew studies have investigated how aging influences the neural basis of implicit associative learning, and available evidence is inconclusive. One emerging behavioral pattern is that age differences increase with practice, perhaps reflecting the involvement of different brain regions with training. Many studies report hippocampal involvement early on with learning becoming increasingly dependent on the caudate with practice. We tested the hypothesis that the contribution of these regions to learning changes with age because of differential age-related declines in the striatum and hippocampi. We assessed age-related differences in brain activation during implicit associative learning using the Triplets Learning Task. Over three event-related fMRI runs, 11 younger and 12 healthy older adults responded to only the third (target) stimulus in sequences of three stimuli (“triplets”) by corresponding key press. Unbeknown to participants, the first stimulus' location predicted one target location for 80% of trials and another target location for 20% of trials. Both age groups learned associative regularities but differences in favor of the younger adults emerged with practice. The neural basis of learning (response to predictability) was examined by identifying regions that showed a greater response to triplets that occurred more frequently. Both age groups recruited the hippocampus early, but with training, the younger adults recruited their caudate whereas the older adults continued to rely on their hippocampus. This pattern enables older adults to maintain near-young levels of performance early in training, but not later, and adds to evidence that implicit associative learning is supported by different brain networks in younger and older adults.
Depth of Conceptual Knowledge Modulates Visual Processes during Word Reading
Authors: Rabovsky Milena , Sommer Werner , Abdel Rahman Rasha 
Published: August 2011

Abstract
Recent evidence suggests that conceptual knowledge modulates early visual stages of object recognition. The present study investigated whether similar modulations can be observed also for the recognition of object names, that is, for symbolic representations with only arbitrary relationships between their visual features and the corresponding conceptual knowledge. In a learning paradigm, we manipulated the amount of information provided about initially unfamiliar visual objects while controlling for perceptual stimulus properties and exposure. In a subsequent test session with electroencephalographic recordings, participants performed several tasks on either the objects or their written names. For objects as well as names, knowledge effects were observed as early as about 120 msec in the P1 component of the ERP, reflecting perceptual processing in extrastriate visual cortex. These knowledge-dependent modulations of early stages of visual word recognition suggest that information about word meanings may modulate the perception of arbitrarily related visual features surprisingly early.
Explicit and Implicit Second Language Training Differentially Affect the Achievement of Native-like Brain Activation Patterns
Authors: Morgan-Short Kara , Steinhauer Karsten , Sanz Cristina , Ullman Michael T. 
Published: August 2011

AbstractIt is widely believed that adults cannot learn a foreign language in the same way that children learn a first language. However, recent evidence suggests that adult learners of a foreign language can come to rely on native-like language brain mechanisms. Here, we show that the type of language training crucially impacts this outcome. We used an artificial language paradigm to examine longitudinally whether explicit training (that approximates traditional grammar-focused classroom settings) and implicit training (that approximates immersion settings) differentially affect neural (electrophysiological) and behavioral (performance) measures of syntactic processing. Results showed that performance of explicitly and implicitly trained groups did not differ at either low or high proficiency. In contrast, electrophysiological (ERP) measures revealed striking differences between the groups' neural activity at both proficiency levels in response to syntactic violations. Implicit training yielded an N400 at low proficiency, whereas at high proficiency, it elicited a pattern typical of native speakers: an anterior negativity followed by a P600 accompanied by a late anterior negativity. Explicit training, by contrast, yielded no significant effects at low proficiency and only an anterior positivity followed by a P600 at high proficiency. Although the P600 is reminiscent of native-like processing, this response pattern as a whole is not. Thus, only implicit training led to an electrophysiological signature typical of native speakers. Overall, the results suggest that adult foreign language learners can come to rely on native-like language brain mechanisms, but that the conditions under which the language is learned may be crucial in attaining this goal.
Distinct Contributions of the Magnocellular and Parvocellular Visual Streams to Perceptual Selection
Authors: Denison Rachel N. , Silver Michael A. 
Published: August 2011

Abstract
During binocular rivalry, conflicting images presented to the two eyes compete for perceptual dominance, but the neural basis of this competition is disputed. In interocular switch rivalry, rival images periodically exchanged between the two eyes generate one of two types of perceptual alternation: (1) a fast, regular alternation between the images that is time-locked to the stimulus switches and has been proposed to arise from competition at lower levels of the visual processing hierarchy or (2) a slow, irregular alternation spanning multiple stimulus switches that has been associated with higher levels of the visual system. The existence of these two types of perceptual alternation has been influential in establishing the view that rivalry may be resolved at multiple hierarchical levels of the visual system. We varied the spatial, temporal, and luminance properties of interocular switch rivalry gratings and found, instead, an association between fast, regular perceptual alternations and processing by the magnocellular stream and between slow, irregular alternations and processing by the parvocellular stream. The magnocellular and parvocellular streams are two early visual pathways that are specialized for the processing of motion and form, respectively. These results provide a new framework for understanding the neural substrates of binocular rivalry that emphasizes the importance of parallel visual processing streams, and not only hierarchical organization, in the perceptual resolution of ambiguities in the visual environment.
Dissociable Neural Activations of Conscious Visibility and Attention
Authors: Tsubomi Hiroyuki , Ikeda Takashi , Hanakawa Takashi , Hirose Nobuyuki , Fukuyama Hidenao , Osaka Naoyuki 
Published: August 2011

Abstract
Recent neuroimaging evidence indicates that visual consciousness of objects is reflected by the activation in the lateral occipital cortex as well as in the frontal and parietal cortex. However, most previous studies used behavioral paradigms in which attention raised or enhanced visual consciousness (visibility or recognition performance). This co-occurrence made it difficult to reveal whether an observed cortical activation is related to visual consciousness or attention. The present fMRI study investigated the dissociability of neural activations underlying these two cognitive phenomena. Toward this aim, we used a visual backward masking paradigm in which directing attention could either enhance or reduce the object visibility. The participants' task was to report the level of subjective visibility for a briefly presented target object. The target was presented in the center with four flankers, which was followed by the same number of masks. Behavioral results showed that attention to the flankers enhanced the target visibility, whereas attention to the masks attenuated it. The fMRI results showed that the occipito-temporal sulcus increased activation in the attend flankers condition compared with the attend masks condition, and occipito-temporal sulcus activation levels positively correlated with the target visibility in both attentional conditions. On the other hand, the inferior frontal gyrus and the intraparietal sulcus increased activation in both the attend flankers and attend masks compared with an attend neither condition, and these activation levels were independent of target visibility. Taken together, present results showed a clear dissociation in neural activities between conscious visibility and attention.
Early Human Visual Cortex Encodes Surface Brightness Induced by Dynamic Context
Authors: van de Ven Vincent , Jans Bert , Goebel Rainer , De Weerd Peter 
Published: August 2011

AbstractVisual scene perception owes greatly to surface features such as color and brightness. Yet, early visual cortical areas predominantly encode surface boundaries rather than surface interiors. Whether human early visual cortex may nevertheless carry a small signal relevant for surface perception is a topic of debate. We induced brightness changes in a physically constant surface by temporally modulating the luminance of surrounding surfaces in seven human participants. We found that fMRI activity in the V2 representation of the constant surface was in antiphase to luminance changes of surrounding surfaces (i.e., activity was in-phase with perceived brightness changes). Moreover, the amplitude of the antiphase fMRI activity in V2 predicted the strength of illusory brightness perception. We interpret our findings as evidence for a surface-related signal in early visual cortex and discuss the neural mechanisms that may underlie that signal in concurrence with its possible interaction with the properties of the fMRI signal.
Is Corophium Multisetosum Stock, 1952 an Exotic Invasive Species in Europe? Distribution, Habitat, and Recent Observations in the Netherlands
Authors: Wijnhoven Sander , Van Der Velde Gerard , Hummel Herman 
Published: August 2011

Abstract
Corophium multisetosum Stock, 1952 has been found in several estuaries and water bodies in Europe ranging from fresh and brackish to salt water. The species appeared to be distributed over a wide geographic range from the Iberian Peninsula to the southern Baltic region and is recently found in the Mediterranean and Gulf of Mexico, showing remarkable differences in ecology between populations. The recorded observations of the species in the Netherlands, however, remained restricted to a few smaller waters, and were published in grey literature. Recently, the species has been observed in a variety of waters in the southwestern part of the Netherlands and appears to be relatively common. The current study gives an overview of the recordings of C. multisetosum within its geographic range and its habitat preferences.
The recent observations on distribution and habitat preferences of C. multisetosum in the Netherlands are compared with the findings in other parts of Europe. Seeming discontinuities in recorded ecology of the species in the Netherlands and over Europe are discussed. C. multisetosum appears to be very flexible in its behaviour and appears to tolerate a broad range of environmental conditions. Local environmental conditions (e.g., salinity and substrate) and related communities (in the Netherlands particularly the presence of the seemingly competing species Corophium volutator (Pallas, 1766) and Chelicorophium curvispinum (G. O. Sars, 1895)) determine the presence of C. multisetosum and the local behaviour and abundance of the species in the system. As the species shows a typical distribution pattern with many recent recordings, its origin and possible dispersal routes are discussed.