bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-86: Metabolic presentation of bladder cancer in urine
Authors: McDunn Jonathan , Perichon Regis , Goodison Steve , Rosser Charles J. 
Published: August 2012

Abstract
Introduction and Objective Recently it has been shown that many oncogenes regulate metabolism, revitalizing interest in Warburg's observation of aerobic glycolysis by tumors. We and others have demonstrated the utility of metabolic signatures for the diagnosis of cancer in minimally invasive clinical samples and the differential diagnosis of cancer by stage and grade using biopsy samples. Here we apply state of the art metabolomic analysis to the diagnosis of bladder cancer from urine samples. Methods A case controlled study of ten transitional cell carcinoma (TCC) patients and matched non-TCC controls was performed. Briefly, clarified urine was extracted into aqueous methanol and characterized using three analytical platforms (gas chromatography mass spectrometry (MS) and ultrahigh performance liquid chromatography tandem MS). Spectral data were compared against an in-house library of over 2500 authentic standards and the relative abundance of each compound within the data set was calculated. Two-group statistics (R) and multivariate analysis (Array Studio, OmicSoft) were performed to identify differentially abundant metabolites. Results Three hundred and sixty-seven compounds were identified in this study and polypharmacy did not compromise the quality of the signal obtained for endogenous metabolites. Thirteen compounds, arising from diverse metabolic pathways, including: energetics, oxidative stress and amino acid catabolism, exhibited statistically significant differences between TCC and non-TCC cases. Principal component (PC) analysis demonstrated that the majority of the information in these metabolites (PC 1) separated TCC from non-TCC cases. Conclusions These data indicate the feasibility of a novel, non-invasive, urine-based diagnostic test to detect the presence of bladder tumors. Such a test could be positioned for use in conjunction with the current standard of care to improve patient management.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-86. doi:1538-7445.AM2012-LB-86
Abstract LB-90: Essential kinases for human metastatic cells pertaining to c-Met signaling
Authors: Ai Nanping , Harlow Ed , Li Wenliang 
Published: August 2012

Abstract
Kinases play key roles in the regulation of many cellular processes and are postulated to participate in the development of metastatic capability. To test the role of kinases in tumor progression, we compared pairs of non-metastatic and metastatic tumor cells, a commonly used model, to study the cellular changes that accompany metastasis. As such, we performed arrayed shRNA screens to determine how kinase requirements for survival and proliferation varied between the matched cell lines. These screens revealed patterns of kinase requirements among 4 pairs of cell lines. Of particular interest, we identified a set of kinases that were essential predominately for metastatic cells, including c-Met. In vivo metastasis experiments are underway to evaluate which kinases can promote metastasis when ectopically expressed in otherwise non-metastatic cells. Since inhibition of these kinases phenocopied c-Met inhibition, we also sought to test if any of these kinases are functionally linked to c-Met signaling. Indeed, several of the identified kinases, including PRKCZ, became essential when immortalized melanocytes were made tumorigenic and metastatic by introduction of activated c-Met. Biochemical and genetic rescue experiments are currently ongoing to further examine the links between these genes and c-Met. These studies offer new insights into the cellular signaling pathways operating in metastatic cancer cells and also suggest potential targets to treat metastatic cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-90. doi:1538-7445.AM2012-LB-90
Abstract LB-94: Highly specific and sensitive detection of BRAF and KRAS mutations in tumor samples
Authors: Mishra Anjali , Chupreta Sergey , Beaubien Ron , Kurihara Laurie , Kelchner Vanessa , LaLiberte Julie , Mikheykin Andrey , Makarov Vladimir 
Published: August 2012

Abstract
The development of highly sensitive and specific mutation detection assays that are suitable for clinical and laboratory research opens up new opportunities in the fields of cancer diagnostics and therapeutics. Swift Biosciences has developed myT™ Primer technology which has unique structural and thermodynamic properties that enable highly sensitive mismatch discrimination. Real-time PCR assays using myT Primers are able to detect 1% mutant BRAF V600E/K or mutant KRAS (codons 12A, 12R, 12C, 12V, 12S, 12D and 13D) present in a background of 103 wild-type genomic DNA copies. Notably there is no non-specific amplification from wild-type. The extreme selectivity and reproducibility of such assays results in a definitive Yes/No answer and eliminates the need to use a delta Ct method to call positives. myT Primer specific reagents are well suited for genotyping and have been tested on FFPE samples derived from melanoma, colorectal and lung tumors and their corresponding normal adjacent samples, and are also effective on fresh frozen tissues. A separate ultrasensitive version of myT Primers has also been developed. The ultrasensitive myT Primers format enables the detection of a single mutant copy of BRAF or KRAS in &gt; 104 wild-type genomic DNA copies, representing 0.01% detection; again, non-specific amplification from wild-type was not observed. The myT Primer ultrasensitive reagents are ideal for use when sample sizes are limiting such as in needle biopsies, CTCs, and serum. myT Primers are compatible with Roche LC480, ABI 7500 and Bio-Rad CFX96 real-time PCR instruments as well as different PCR master mixes. Thus the use of myT Primer reagents will allow for better detection, evaluation and monitoring of cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-94. doi:1538-7445.AM2012-LB-94
Abstract PL04-03: Cell signaling by receptor tyrosine kinases: From basic principles to cancer therapy
Authors: Schlessinger Joseph 
Published: August 2012

Abstract
Receptor tyrosine kinases (RTKs) comprise a family of cell surface receptors that control many critical cellular processes. Various human diseases are caused by dysfunction in RTKs or in their intracellular signaling pathways. Stem Cell Factor (SCF) initiates its multiple cellular responses by binding to the extracellular region of the RTK KIT resulting in receptor dimerization and tyrosine kinase activation. We have determined the crystal structure of the entire extracellular region of KIT before and after SCF stimulation. The structures show that KIT dimerization is driven by SCF binding whose sole role is to bring two KIT molecules together. We have used X-ray crystallography, electron microscopy (EM) and biochemical experiments to determine the three dimensional structure of intact, SCF-stimulated KIT dimers. Several forms of dimeric KIT molecules with different asymmetric arrangements of the two tyrosine kinase domains were identified. These asymmetric contacts may represent specific interactions occurring between two KIT tyrosine kinase domains poised towards trans autophosphorylation. We propose that cooperative interactions mediated by multiple weak homotypic contacts between the extracellular, transmembrane and cytoplasmic regions of KIT are responsible for tyrosine kinase activation and cell signaling in normal and transformed cells. Sutent is a drug that blocks the tyrosine kinase activities of several RTKs including KIT and VEGFR2. Sutent has been approved by the FDA for the treatment of advanced kidney cancers, gastrointestinal tumors and for endocrine pancreatic cancers. A scaffold-based drug discovery approach was developed enabling the development of new families of inhibitors for protein kinases and other enzymes that play a role in cell signaling. V600E B-RAF mutant is an oncogenic mutation identified in approximately 50% of melanomas and in 4% of all solid tumors. By using a scaffold-based drug discovery approach, a potent inhibitor of V600E B-RAF mutant has been discovered designated PLX 4032 (Vemurafenib). Phase-I and-II clinical trials in multiple medical centers revealed 80% responses such as tumor shrinkage, delay in tumor progression and survival of melanoma patients harboring the B-RAF mutation. Primary endpoints of phase-III clinical trials in multiple medical centers were achieved to support Vemurafenib registration.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr PL04-03. doi:1538-7445.AM2012-PL04-03
Abstract SY04-02: Reaching escape velocity: Using lineage tracing to study EMT and dissemination in pancreatic cancer
Authors: Stanger Ben Z. 
Published: August 2012

Abstract
Metastastic spread has been difficult to study because it involves a series of rare events that are difficult to observe in vivo. To capture such events, we have employed lineage tracing - a technique which allows cells to be tagged and tracked - and applied it to an autochthonous mouse model of pancreatic cancer. Using this approach, found that pancreas-derived cells entered the circulation at the PanIN-stage, prior to the presence of a histologically recognizable tumor. Moreover, invasive behavior was almost universally associated with epithelial-to-mesenchymal transition (EMT), and bloodstream entry was associated with a “cancer stem cell” phenotype. These observations demonstrate that cellular dissemination in pancreatic cancer can occur at a very early stage of tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY04-02. doi:1538-7445.AM2012-SY04-02
Abstract SY05-01: microRNAs: Micromanagers of human cancers
Authors: Calin George A. 
Published: August 2012

Abstract
The newly discovered differential expression in numerous tissues, key cellular processes and multiple diseases for several families of long and short non-codingRNAs (ncRNAs, RNAs that do not codify for proteins but for RNAs with regulatory functions), including the already famous class of microRNAs (miRNAs) strongly suggest that the scientific and medical communities have significantly underestimated the spectrum of ncRNAs whose altered expression has significant consequences in diseases. MicroRNA and other short or long non-codingRNAs alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of non-codingRNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long non-codingRNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-codingRNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the malignant phenotype. Last, but not least, the shown expression correlations of these new ncRNAs with cancer metastatic potential and overall survival rates suggest that at least some member of these novel classes of molecules could potentially find use as biomarkers or novel therapeutics in cancers and other diseases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY05-01. doi:1538-7445.AM2012-SY05-01
Abstract SY36-01: Mechanisms of autophagy addiction in cancer
Authors: White Eileen P. 
Published: August 2012

Abstract
Autophagy is a catabolic pathway utilized by cells to eat themselves and recycle cellular components to support metabolism and survival in response to starvation. Autophagy also functions to clear damaged proteins and organelles. Autophagy can thereby maintain tissue health and suppress tissue degeneration and cancer initiation in liver, and in this context autophagy is a tumor suppressor. Autophagy, however, is also a survival pathway used by both normal cells and established cancers to sustain metabolism and tolerate stress, and in this context autophagy is a tumor promoter. Activation of a powerful oncogene such as Ras, for example, up-regulates basal autophagy required for tumor cell survival in stress and in tumorigenesis. In Ras-driven cancer cells, defective autophagy causes accumulation of abnormal mitochondria, reduces oxygen consumption, and impairs metabolism causing energy depletion. Thus, without autophagy, tumor cells have impaired stress tolerance that reduces tumorigenesis. As cancers with Ras mutations have a poor prognosis, this “autophagy addiction” suggests that targeting autophagy is valuable new approaches to treat these aggressive cancers. Recent findings demonstrating roles for autophagy in genetically engineered mouse models for cancer and the regulation of nutrient sensing and autophagy regulation by mTOR will be presented. New developments in the approach to and effectiveness of autophagy modulation in cancer therapy and the mechanism of cancer cell death induction will be discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY36-01. doi:1538-7445.AM2012-SY36-01
Abstract SY36-02: Autophagy in cell death and cancer
Authors: Ryan Kevin 
Published: August 2012

Abstract
Macroautophagy (autophagy) is a catabolic membrane-trafficking process that serves to deliver cytoplasmic constituents to lysosomes for degradation. The process functions in the majority, if not all, cells as a means to turnover damaged proteins and organelles. Autophagy therefore functions as a cellular homeostatic mechanism which when perturbed leads to accumulation of misfolded proteins and non-functional organelles and loss of cellular integrity. The levels and cargoes of autophagy can respond to various extracellular and intracellular cues to bring about selective and sometimes contrasting effects. For example, in relation to cell death, autophagy has, depending on context, been reported to have both positive and negative effects on cell viability. Due the multiple roles of autophagy in regulating cellular homeostasis, it is not a surprise that changes in autophagy can have effects on tumour development. It is not yet clear, however, when autophagy is tumour-promoting or tumour-suppressive in any given context. We have therefore been addressing this issue by studying the role of autophagy at different stages of tumour development in vivo. Data from these studies will be presented alongside our in vitro studies to understand the role of autophagy in tumour suppression.
Work in our laboratory is supported by Cancer Research UK and The Association for International Cancer Research.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY36-02. doi:1538-7445.AM2012-SY36-02
Selecting Representative Days for More Efficient Dynamical Climate Downscaling: Application to Wind Energy
Authors: Rife Daran L. , Vanvyve Emilie , Pinto James O. , Monaghan Andrew J. , Davis Christopher A. , Poulos Gregory S. 
Published: August 2012

AbstractThis paper describes a new computationally efficient and statistically robust sampling method for generating dynamically downscaled climatologies. It is based on a Monte Carlo method coupled with stratified sampling. A small yet representative set of “case days” is selected with guidance from a large-scale reanalysis. When downscaled, the sample closely approximates the long-term meteorological record at a location, in terms of the probability density function. The method is demonstrated for the creation of wind maps to help determine the suitability of potential sites for wind energy farms. Turbine hub-height measurements at five U.S. and European tall tower sites are used as a proxy for regional climate model (RCM) downscaled winds to validate the technique. The tower-measured winds provide an independent test of the technique, since RCM-based downscaled winds exhibit an inherent dependence upon the large-scale reanalysis fields from which the case days are sampled; these same reanalysis fields would provide the boundary conditions to the RCM. The new sampling method is compared with the current approach widely used within the wind energy industry for creating wind resource maps, which is to randomly select 365 case days for downscaling, with each day in the calendar year being represented. The new method provides a more accurate and repeatable estimate of the long-term record of winds at each tower location. Additionally, the new method can closely approximate the accuracy of the current (365 day) industry approach using only a 180-day sample, which may render climate downscaling more tractable for those with limited computing resources.
Large-Eddy Simulations of Air Flow and Turbulence within and around Low-Aspect-Ratio Cylindrical Open-Top Chambers
Authors: Cunningham Philip , Linn Rodman R. , Koo Eunmo , Wilson Cathy J. 
Published: August 2012

AbstractThe flow around cylindrical open-top chambers (OTCs) with aspect ratios (i.e., height-to-diameter ratios) much less than unity is investigated using a large-eddy simulation (LES) model. The solid structures are represented using the immersed boundary method, and the ambient flow in which the OTCs are embedded is representative of a turbulent atmospheric boundary layer. Results from the LES model show that the flow inside OTCs depends strongly on the height of the chamber wall. In particular, as chamber height increases the flow impinging on the upstream wall is deflected more in the vertical direction, a stronger recirculation flow develops inside the chamber, turbulence intensities are greater, and there is stronger vertical transport and mixing within the OTC, even at or near the ground. For low wall heights (i.e., very low aspect ratios), however, the flow impinging on the OTC is only diverted weakly in the vertical direction; aside from a small recirculation zone inside the OTC near the upstream wall and a small region near the downstream wall as the flow separates from the ground, there is minimal vertical mixing and the turbulence intensities are small. The results of these simulations, while general in nature, are particularly relevant to design considerations for manipulative field experiments in highly heterogeneous, low-stature ecosystems such as Arctic shrubs and grasses.
Quantifying the Non-Gaussianity of Wintertime Daily Maximum and Minimum Temperatures in the Southeast
Authors: Stefanova Lydia , Sura Philip , Griffin Melissa 
Published: August 2012

Abstract
In this paper the statistics of daily maximum and minimum surface air temperature at weather stations in the southeast United States are examined as a function of the El Niño–Southern Oscillation (ENSO) and Arctic Oscillation (AO) phase. A limited number of studies address how the ENSO and/or AO affect U.S. daily—as opposed to monthly or seasonal—temperature averages. The details of the effect of the ENSO or AO on the higher-order statistics for wintertime daily minimum and maximum temperatures have not been clearly documented.
Quality-controlled daily observations collected from 1960 to 2009 from 272 National Weather Service Cooperative Observing Network stations throughout Florida, Georgia, Alabama, and South and North Carolina are used to calculate the first four statistical moments of minimum and maximum daily temperature distributions. It is found that, over the U.S. Southeast, winter minimum temperatures have higher variability than maximum temperatures and La Niña winters have greater variability of both minimum and maximum temperatures. With the exception of the Florida peninsula, minimum temperatures are positively skewed, while maximum temperatures are negatively skewed. Stations in peninsular Florida exhibit negative skewness for both maximum and minimum temperatures. During the relatively warmer winters associated with either a La Niña or AO+, negative skewnesses are exacerbated and positive skewnesses are reduced. To a lesser extent, the converse is true of the El Niño and AO−. The ENSO and AO are also shown to have a statistically significant effect on the change in kurtosis of daily maximum and minimum temperatures throughout the domain.
Mitigating an undesirable immune response of inherent susceptibility to cutaneous leishmaniosis in a mouse model: the role of the pathoantigenic HISA70 DNA vaccine
Authors: Domínguez-Bernal Gustavo , Horcajo Pilar , Orden José A , De La Fuente Ricardo , Herrero-Gil Aldara , Ordóñez-Gutiérrez Lara , Carrión Javier 
Published: August 2012

AbstractLeishmania majoris the major cause of cutaneous leishmaniosis (CL) outside of the Americas. In the present study we have cloned sixLeishmaniagenes (H2A, H2B, H3, H4, A2 and HSP70) into the eukaryotic expression vector pCMVβ-m2a, resulting in pCMV-HISA70m2A, which encodes all six pathoantigenic proteins as a single polyprotein. This expression plasmid has been evaluated as a novel vaccine candidate in the BALB/c mouse model of CL. The DNA vaccine shifted the immune response normally induced byL. majorinfection away from a Th2-specific pathway to one of basal susceptibility. Immunization with pCMV-HISA70m2A dramatically reduced footpad lesions and lymph node parasite burdens relative to infected control mice. Complete absence of visceral parasite burden was observed in all 12 immunized animals but not in any of the 24 control mice. Moreover, vaccinated mice produced large amounts of IFN-γ, IL-17 and NO at 7 weeks post-infection (pi), and they showed lower arginase activity at the site of infection, lower IL-4 production and a weaker humoral immune response than infected control mice. Taken together, these results demonstrate the ability of the HISA70 vaccine to shift the murine immune response toL. majorinfection away from an undesirable, Th2-specific pathway to a less susceptible-like pathway involving Th1 and Th17 cytokine profiles.