bluuebunny/crossref_metadata_2025_split huggingface dataset:
MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents
Authors: Fan Weiwen , Tang Zhe , Yin Lihong , Morrison Bei , Hafez-Khayyata Said , Fu Pingfu , Huang Honglian , Bagai Rakesh , Jiang Shan , Kresak Adam , Howell Scott , Vasanji Amit , Flask Chris A. , Halmos Balazs , Koon Henry , Ma Patrick C. 
Published: May 2011

Abstract
Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epidermal growth factor receptor (EGFR) inhibitors, alone or in combination with MET-kinase inhibitors, to characterize the adaptive response that engenders drug resistance. Tumor cells displaying early resistance exhibited dependence on MET-independent activation of BCL-2/BCL-XL survival signaling. Further, such cells displayed a quiescence-like state associated with greatly retarded cell proliferation and cytoskeletal functions that were readily reversed after withdrawal of targeted inhibitors. Findings were validated in a xenograft model, showing BCL-2 induction and p-STAT3[Y705] activation within the residual tumor cells surviving the initial antitumor response to targeted therapies. Disrupting the mitochondrial BCL-2/BCL-XL antiapoptotic machinery in early survivor cells using BCL-2 Homology Domain 3 (BH3) mimetic agents such as ABT-737, or by dual RNAi-mediated knockdown of BCL-2/BCL-XL, was sufficient to eradicate the early-resistant lung-tumor-cells evading targeted inhibitors. Similarly, in a xenograft model the preemptive cotreatment of lung tumor cells with an EGFR inhibitor and a BH3 mimetic eradicated early TKI-resistant evaders and ultimately achieved a more durable response with prolonged remission. Our findings prompt prospective clinical investigations using BH3-mimetics combined with targeted receptor kinase inhibitors to optimize and improve clinical outcomes in lung-cancer treatment. Cancer Res; 71(13); 4494–505. ©2011 AACR.
Correlation of Somatic Mutation and Expression Identifies Genes Important in Human Glioblastoma Progression and Survival
Authors: Masica David L. , Karchin Rachel 
Published: May 2011

Abstract
Cooperative dysregulation of gene sequence and expression may contribute to cancer formation and progression. The Cancer Genome Atlas (TCGA) Network recently catalogued gene sequence and expression data for a collection of glioblastoma multiforme (GBM) tumors. We developed an automated, model-free method to rapidly and exhaustively examine the correlation among somatic mutation and gene expression and interrogated 149 GBM tumor samples from the TCGA. The method identified 41 genes whose mutation status is highly correlated with drastic changes in the expression (z-score ± 2.0), across tumor samples, of other genes. Some of the 41 genes have been previously implicated in GBM pathogenesis (e.g., NF1, TP53, RB1, and IDH1) and others, while implicated in cancer, had not previously been highlighted in studies using TCGA data (e.g., SYNE1, KLF6, FGFR4, and EPHB4). The method also predicted that known oncogenes and tumor suppressors participate in GBM via drastic over- and underexpression, respectively. In addition, the method identified a known synthetic lethal interaction between TP53 and PLK1, other potential synthetic lethal interactions with TP53, and correlations between IDH1 mutation status and the overexpression of known GBM survival genes. Cancer Res; 71(13); 4550–61. ©2011 AACR.
MAGE-A Inhibits Apoptosis in Proliferating Myeloma Cells through Repression of Bax and Maintenance of Survivin
Authors: Nardiello Tricia , Jungbluth Achim A. , Mei Anna , DiLiberto Maurizio , Huang Xiangao , Dabrowski Ania , Andrade Valéria C.C. , Wasserstrum Rebecca , Ely Scott , Niesvizky Ruben , Pearse Roger , Coleman Morton , Jayabalan David S. , Bhardwaj Nina , Old Lloyd J. , Chen-Kiang Selina , Cho Hearn Jay 
Published: May 2011

Abstract
Purpose: The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67+ malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells.
Experimental Design: The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis.
Results: MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms.
Conclusions: These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms. Clin Cancer Res; 17(13); 4309–19. ©2011 AACR.
SWOG Cooperative Group Biorepository Resource: Access for Scientific Research Studies
Authors: Hoban Carolyn J. , Franklin Wilbur , Kopecky Kenneth J. , Baker Laurence H. 
Published: May 2011

Abstract
SWOG (formerly the Southwest Oncology Group), a National Cancer Institute–supported cooperative group, conducts multiinstitutional, multidisciplinary clinical trials for adult patients with cancer, covering a wide range of solid tumors and hematologic cancers. The group has amassed a large set of biospecimens, collected from patients in numerous studies over many years and linked to clinical data. SWOG is now actively promoting the use of this unique scientific resource by making it available to a much wider group of researchers. This biospecimen resource offers material for research on disease mechanisms, genomic changes associated with cancer progression, markers of response and resistance to therapies, diagnosis or detection of recurrence, and more. By collecting, storing, and distributing the specimens, SWOG provides the framework for translational scientists to complete the feedback loop from “bedside to bench.” This article provides an overview of the group's biospecimen resources and guidelines for gaining access to them. Clin Cancer Res; 17(16); 5239–46. ©2011 AACR.
Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo
Authors: Yamazaki Ryuta , Nishiyama Yukiko , Furuta Tomio , Hatano Hiroshi , Igarashi Yoshiaki , Asakawa Naoyuki , Kodaira Hiroshi , Takahashi Hiroyuki , Aiyama Ritsuo , Matsuzaki Takeshi , Yagi Nao , Sugimoto Yoshikazu 
Published: May 2011

AbstractBreast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38–resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1–mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRP-transduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy. Mol Cancer Ther; 10(7); 1252–63. ©2011 AACR.
Identification and Classification of Acute Cardiac Rejection by Intragraft Transcriptional Profiling
Authors: Holweg Cécile T.J. , Potena Luciano , Luikart Helen , Yu Tianwei , Berry Gerald J. , Cooke John P. , Valantine Hannah A. , Mocarski Edward S. 
Published: May 2011

Background—
Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies according to International Society for Heart and Lung Transplantation guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation.

Methods and Results—
Transcriptional profiling was performed on 26 endomyocardial biopsies, and expression patterns were compared with the 1990 International Society for Heart and Lung Transplantation AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A profiles, and grade 3A profiles could not be distinguished from 3B profiles. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together endomyocardial biopsies with different underlying processes that are not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as 1 categorical distinction from grade 1A. Although grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings.

Conclusion—
The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studies.
Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction
Authors: Schjerning Olsen Anne-Marie , Fosbøl Emil L. , Lindhardsen Jesper , Folke Fredrik , Charlot Mette , Selmer Christian , Lamberts Morten , Bjerring Olesen Jonas , Køber Lars , Hansen Peter R. , Torp-Pedersen Christian , Gislason Gunnar H. 
Published: May 2011

Background—
Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI).

Methods and Results—
Patients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment).

Conclusions—
Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.
Putting a Name to a Face: The Role of Name Labels in the Formation of Face Memories
Authors: Gordon Iris , Tanaka James W. 
Published: May 2011

Abstract
Although previous research in ERPs has focused on the conditions under which faces are recognized, less research has focused on the process by which face representations are acquired and maintained. In Experiment 1, participants were required to monitor for a target “Joe” face that was shown among a series of nontarget “Other” faces. At the halfway point, participants were instructed to switch targets from the Joe face to a previous nontarget face that is now labeled “Bob.” The ERP analysis focused on the posterior N250 component known to index face familiarity and the P300 component associated with context updating and response decision. Results showed that, in the first half of the experiment, there was increase in N250 negativity to the target Joe face compared with the nontarget Bob and designated Other face. In the second half of the experiment, an enhanced N250 negativity was produced to the now-target Bob face compared with the Other face. Critically, the enhanced N250 negativity to the Joe face was maintained, although Joe was no longer the target. The P300 component followed a similar pattern of brain response, where the Joe face elicited a significantly larger P300 amplitude than the Other face and the Bob face. In the Bob half of the experiment, the Bob face elicited a reliably larger P300 than the Other faces, and the heightened P300 to the Joe face was sustained. In Experiment 2, we examined whether the increased N250 and P300 to Joe was because of simple naming effects. Participants were introduced to both Joe and Bob faces and names at the beginning of the experiment. In the first half of the experiment, participants monitored for the target Joe face and at the halfway point, they were instructed to switch targets to the Bob face. Findings show that N250 negativity significantly increased to the Joe face relative to the Bob and Other faces in the first half of the experiment and an enhanced N250 negativity was found for the target Bob face and the nontarget Joe face in the second half. An increased P300 amplitude was demonstrated to the target Joe and Bob faces in the first and second halves of the experiment, respectively. Importantly, the P300 amplitude elicited by the Joe face equaled the P300 amplitude to the Bob face, although it was no longer the target face. The findings from Experiments 1 and 2 suggest that the N250 component is not solely determined by name labeling, exposure, or task relevancy, but it is the combination of these factors that contribute to the acquisition of enduring face representations.
The Detection and the Neural Correlates of Behavioral (Prior) Intentions
Authors: Agosta Sara , Castiello Umberto , Rigoni Davide , Lionetti Stefano , Sartori Giuseppe 
Published: May 2011

Abstract
Prior intentions are abstract mental representations that are believed to be the prime cause of our intentional actions. To date, only a few studies have focused on the possibility that single prior intentions could be identified in people's minds. Here, for the first time, we used the autobiographical Implicit Association Test (aIAT) in order to identify a specific prior intention on the basis of a pattern of associations derived from reaction times (Experiment 1). The aIAT is based on two critical blocks: the block associating intentions with true sentences (congruent block) gave rise to faster reaction times (RTs) than the block associating intentions with false sentences (incongruent block). Furthermore, when comparing intentions with hopes, it was revealed that the reported effect was intention-specific: The pattern of associations reflected a congruency effect when intentions and the logical category “True” were paired, but not when hopes and the “True” category were paired (Experiment 2). Finally, we investigated the neural bases of the congruency effect that leads to the identification of an intention (Experiment 3). We found a reduced late positive component (LPC) for the incongruent with respect to the congruent block, suggesting that the incongruent block needs additional resources of cognitive control with respect to the congruent block.
Using Complement Coercion to Understand the Neural Basis of Semantic Composition: Evidence from an fMRI Study
Authors: Husband E. Matthew , Kelly Lisa A. , Zhu David C. 
Published: May 2011

Abstract
Previous research regarding the neural basis of semantic composition has relied heavily on violation paradigms, which often compare implausible sentences that violate world knowledge to plausible sentences that do not violate world knowledge. This comparison is problematic as it may involve extralinguistic operations such as contextual repair and processes that ultimately lead to the rejection of an anomalous sentence, and these processes may not be part of the core language system. Also, it is unclear if violations of world knowledge actually affect the linguistic operations for semantic composition. Here, we compared two types of sentences that were grammatical, plausible, and acceptable and differed only in the number of semantic operations required for comprehension without the confound of implausible sentences. Specifically, we compared complement coercion sentences (the novelist began the book), which require an extra compositional operation to arrive at their meaning, to control sentences (the novelist wrote the book), which do not have this extra compositional operation, and found that the neural response to complement coercion sentences activated Brodmann's area 45 in the left inferior frontal gyrus more than control sentences. Furthermore, the processing of complement coercion recruited different brain regions than more traditional semantic and syntactic violations (the novelist astonished/write the book, respectively), suggesting that coercion processes are a part of the core of the language faculty but do not recruit the wider network of brain regions underlying semantic and syntactic violations.
A Comprehensive Three-dimensional Cortical Map of Vowel Space
Authors: Scharinger Mathias , Idsardi William J. , Poe Samantha 
Published: May 2011

Abstract
Mammalian cortex is known to contain various kinds of spatial encoding schemes for sensory information including retinotopic, somatosensory, and tonotopic maps. Tonotopic maps are especially interesting for human speech sound processing because they encode linguistically salient acoustic properties. In this study, we mapped the entire vowel space of a language (Turkish) onto cortical locations by using the magnetic N1 (M100), an auditory-evoked component that peaks approximately 100 msec after auditory stimulus onset. We found that dipole locations could be structured into two distinct maps, one for vowels produced with the tongue positioned toward the front of the mouth (front vowels) and one for vowels produced in the back of the mouth (back vowels). Furthermore, we found spatial gradients in lateral–medial, anterior–posterior, and inferior–superior dimensions that encoded the phonetic, categorical distinctions between all the vowels of Turkish. Statistical model comparisons of the dipole locations suggest that the spatial encoding scheme is not entirely based on acoustic bottom–up information but crucially involves featural–phonetic top–down modulation. Thus, multiple areas of excitation along the unidimensional basilar membrane are mapped into higher dimensional representations in auditory cortex.
Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children
Authors: Yeatman Jason D. , Dougherty Robert F. , Rykhlevskaia Elena , Sherbondy Anthony J. , Deutsch Gayle K. , Wandell Brian A. , Ben-Shachar Michal 
Published: May 2011

Abstract
For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.