bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal Events: Cell Signal Transduction and Its Inhibition in Cancer
Authors: Rowinsky Eric K. 
Published: August 2004

Abstract

Learning Objectives
After completing this course, the reader will be able to:
Recognize the importance of identifying new molecular targets for cancer therapy and how they relate to the development of novel therapeutic agents with high therapeutic indices and low toxicity. Explain the process of signal transduction (specifically the ErbB family of receptors and the mTOR pathways) and how it relates to cell growth, differentiation, and survival, and describe the effects of aberrations in signal transduction on the development of neoplasms. Describe some of the novel targeted therapies that have been developed and explain the mechanisms by which signal transduction inhibitors inhibit tumor growth and induce tumor regression in patients with cancer.
Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com
Signal transduction refers to communication processes used by regulatory molecules to mediate the essential cell processes of growth, differentiation, and survival. Signal transduction elements interact through complex biochemically related networks. Aberrations in signal transduction elements can lead to increased proliferative potential, sustained angiogenesis, tissue invasion and metastasis, and apoptosis inhibition. Most human neoplasms have aberrant signal transduction elements. Several compounds that target aberrant signal transduction elements, such as those in the ErbB family of tyrosine kinase receptors and mammalian target of rapamycin, are in development. To date, commercially available signal-transduction-targeting compounds include trastuzumab, a monoclonal antibody against the ErbB-2 receptor for the treatment of metastatic breast cancer overexpressing the ErbB-2 (HER-2) receptor, and gefitinib, an inhibitor of the ErbB-1 receptor tyrosine kinase that recently received regulatory approval for the treatment of patients with non-small cell lung cancer. In contrast to traditional cytotoxic treatments, although signal transduction inhibitors are capable of inducing tumor regression, particularly in malignancies that are principally driven by specific target aberrations, preclinical and early clinical investigations suggest that their predominant beneficial effects are growth inhibitory in nature; therefore, new clinical trial designs and evaluation end points may be required to ultimately assess their value. Prospective profiling of patients and tumors to determine treatment response is also essential to the success of these clinical trials. However, responsiveness to these novel therapies is dependent on a multitude of factors that ultimately determine the robustness and quality of the downstream response.
Use of Bronchoalveolar Lavage to Detect Lung Injury
Authors: Henderson Rogene F. , Muggenburg Bruce A. 
Published: August 2004

AbstractThis unit describes how bronchoalveolar lavage can be used in laboratory animals to sample the epithelial lining fluid of the lung for information on the degree of pulmonary inflammation induced by exposure to an airborne toxicant. The technique allows quantitative assessment of inflammatory responses and is valuable for providing dose‐response information in exposed animals. Lavage fluid samples may also be used for proteomic analyses, and the protein expression profiles may be used to address specific mechanistic questions.
Spectrophotometric Determination of Protein Concentration
Authors: Simonian Michael H. 
Published: August 2004

AbstractThis unit describes spectrophotometric and colorimetric methods for measuring the concentration of a sample protein in solution. Absorbance measured at 280 nm (A280) is used to calculate protein concentration by comparison with a standard curve or published absorptivity values for that protein (a280). Alternatively, absorbance measured at 205 nm (A205) is used to calculate the protein concentration. The A280 and A205 methods can be used to quantify total protein in crude lysates and purified or partially purified protein. A spectrofluorometer or a filter fluorometer can be used to measure the intrinsic fluorescence emission of a sample solution; this value is compared with the emissions from standard solutions to determine the sample concentration. The fluorescence emission method is used to quantify purified protein. This simple method is useful for dilute protein samples and can be completed in a short amount of time. There are two colorimetric methods: the Bradford colorimetric method, based upon binding of the dye Coomassie brilliant blue to the protein of interest, and the Lowry method, which measures colorimetric reaction of tyrosyl residues in the protein sample.
Social Transmission of Food Preference in Mice
Authors: Wrenn Craige C. 
Published: August 2004

AbstractThe social transmission of food preference (STFP) is an ethologically relevant test of olfactory memory that can be used in mice. In this test, “observer” mice interact with a “demonstrator” mouse that has recently eaten a novel food. When observer mice are presented with a choice between the food eaten by the demonstrator and some other novel food, observer mice prefer the food eaten by the demonstrator. This phenomenon depends on the observer mice detecting olfactory cues on the breath of the demonstrator mouse during their interaction. The subsequent food preference serves as a measure of memory for those olfactory cues. This unit describes a method for performing STFP in mutant mice. The method explains how to address potential confounding factors and avoid possible pitfalls.
Synthesis of 5′‐O‐Phosphoramidites with a Photolabile 3′‐O‐Protecting Group
Authors: Beier Markus , Hoheisel Jörg D. 
Published: August 2004

AbstractThis unit describes the chemical synthesis of phosphoramidite building blocks that carry a protecting group at the 3′ position. These inversely oriented synthons expose a 2‐(2‐nitrophenyl)propoxycarbonyl (NPPOC) group as the photolabile protecting group of choice. Among other applications, the building blocks can be employed for light‐controlled in situ synthesis of DNA microarrays, producing arrayed oligonucleotides that are attached to the support via their 5′ ends, leaving their 3′ termini available to act as substrates for polymerases.
Overview of mRNA Expression Profiling Using Microarrays
Authors: Katagiri Fumiaki , Glazebrook Jane 
Published: August 2004

AbstractMicroarray technology allows simultaneous measurement of the mRNA levels of thousands of genes. This powerful technology has applications in addressing many biological questions that were not approachable previously; however, the enormous size of microarray data sets leads to issues of experimental design and statistical analysis that are unfamiliar to many molecular biologists. The type of array used, design of the biological experiment, number of experimental replicates, and statistical method for data analysis should all be chosen based on the scientific goals of the investigator. This overview presents a discussion of the relative merits and limitations of various methods with respect to some common applications of microarray experiments.
Cytokine, Growth Factor, and Chemokine Ligand Database
Authors: Taub Dennis D. 
Published: August 2004

AbstractCytokines, chemokines, and growth factors are soluble proteins produced by leukocytes and other cell types, which act as chemical communicators between cells and tissues within the body. These proteins mediate a number of functions, ranging from effects on cell growth, differentiation, survival, and a number of effector activities. The main purpose of this unit is to provide an easy‐to‐use reference summarizing some of the current information on well‐established cytokine, growth factore, and chemokine ligands. The information provided is confined largely to alternative names, protein properties, genetic chracteristics, chromosomal localization, cellular expression patters, cellular‐tissue targets, stimuli regulating expression, functional properties, expression analysis, and clinical utility.
Clinical Validity and Clinical Utility of Genetic Tests
Authors: Burke Wylie 
Published: August 2004

AbstractIn considering the appropriate use of new genetic tests, clinicians and health care policymakers must consider the accuracy with which a test identifies a patient's clinical status (clinical validity) and the risks and benefits resulting from test use (clinical utility). Genetic tests in current use vary in accuracy and potential to improve health outcomes, and these test properties may be influenced by the clinical setting in which the test is used. In addition, the relative importance of clinical validity and utility varies according to the proposed use of the test. This unit defines clinical validity and clinical utility, provides examples, and considers the implications of these test properties for clinical practice.
Short Tandem Repeat Analysis for Human Identity Testing
Authors: Butler John M. 
Published: August 2004

AbstractShort tandem repeat (STR) typing has become the workhorse of modern forensic DNA analysis. The most common form of STR typing uses laser‐induced fluorescence detection of dye‐labeled polymerase chain reaction (PCR) products following capillary electrophoresis (CE) size‐based separation. This unit describes the techniques and marker systems most widely used around the world in constructing criminal DNA databases and conducting forensic casework. In addition, these same STR loci and multiplex PCR assays are commonly used for paternity testing, missing persons, and mass disaster investigations. Both autosomal and Y‐chromosome STRs are discussed in the context of their various applications. Interpretation issues surrounding degraded or mixed DNA specimens as well as tri‐allelic patterns and variant alleles are also illustrated. Finally, future technologies and DNA marker systems are briefly explored relative to the state‐of‐the‐science today.
Labeling of Bacterial Pathogens for Flow Cytometric Detection and Enumeration
Authors: Harkins Kristi R. , Harrigan Kelley 
Published: August 2004

AbstractTraditional uses of flow cytometry have been for research and diagnostic purposes, on mammalian cells. This unit focuses on using a flow cytometer for enumerating specific bacteria and parasites. Several different labeling methods are discussed, as well as how to set up a cytometer for detecting and enumerating bacteria. Labeling methods include direct detection with a primary fluorochrome‐conjugated antibody and indirect labeling with an unconjugated primary and a fluorochrome‐conjugated secondary antibody, as well as labeling with rRNA sequence‐specific peptide nucleic‐acid probes end‐labeled with a fluorochrome. Data and methods throughout this unit focus on detection of Salmonella in clean matrices; however, pertinent information is also provided on using these methods to label other pathogens. The Commentary covers critical aspects of the protocols, and also includes information and suggestions on the application of these methods for testing in the food and pharmaceutical industries, as well as in environmental water testing.
An Overview of Gene Identification: Approaches, Strategies, and Considerations
Authors: Baxevanis Andreas D. 
Published: August 2004

AbstractModern biology is on the verge of officially ushering in a new era in science with the completion of the sequencing of the human genome in April 2003. While often erroneously called the “post‐genome era”, this will actually truly mark the beginning of the “genome era,” a time in which the availability of sequence data for many genomes will have a significant effect on how science is performed in the 21st century. This unit offers an overview of many of the gene prediction methods that are currently available and offers a general assessment of how well the methods work for various problems.
An Overview of Spotfire for Gene‐Expression Studies
Authors: Kaushal Deepak , Naeve Clayton W. 
Published: August 2004

AbstractSpotfire DecisionSite for Functional Genomics (referred to here as Spotfire) is a powerful data mining and visualization application with use in many disciplines. This unit provides an overview of Spotfire's utility in analyzing gene expression data obtained from DNA microarray experiments. Analysis of microarray data requires software‐based solutions able to handle and manipulate the enormous amount of data generated. Spotfire provides a solution for accessing, analyzing and visualizing data generated from microarray experiments. Spotfire is designed to allow biologists with little or no programming or statistical skills to transform, process, and analyze microarray data.
Loading and Preparing Data for Analysis in Spotfire
Authors: Kaushal Deepak , Naeve Clayton W. 
Published: August 2004

AbstractThis unit strictly focuses on data preparation within Spotfire. Microarray data exist in a variety of formats, which often depend on the particular array technology and detection instruments used. The first protocols in this unit describe loading Affymetrix and GenePix data into Spotfire. Once the data are loaded, it is necessary to filter and preprocess the data prior to analysis. Subsequently, the data transformation and normalization techniques presented here, are critical to correctly performing powerful microarray data mining expeditions. These steps extract or enhance meaningful data characteristics and prepare the data for the application of certain analysis methods such as statistical tests to compute significance and clustering methods—which mostly require data to be normally distributed. The unit outlines several methods for normalizing the data within an experiment and between multiple experiments.
Die Mechanismen der Stille‐Reaktion
Authors: Espinet Pablo , Echavarren Antonio M. 
Published: August 2004

AbstractVor achtzehn Jahren hat John K. Stille in der Angewandten Chemie über eine neuartige Kupplung von Organostannanen mit organischen Elektrophilen berichtet, die schließlich unter seinem Namen bekannt wurde. Seither hat sich diese Methode zu einem vielseitigen und facettenreichen Gebiet voller versteckter Möglichkeiten zum Forschen, Entdecken und Genießen entwickelt. Die neuesten Modifizierungen lassen Syntheseziele in greifbare Nähe rücken, von denen man vor einigen Jahren nur zu träumen wagte. Auch beim Verständnis der mechanistischen Details der Umsetzungen wurden große Fortschritte erzielt. Daher sollte einer gezielten Anwendung dieser wichtigen Reaktion und ihrer neuen Varianten, die sich auf mehr als nur empirische Befunde stützt, nichts mehr im Wege stehen. Dieser Aufsatz legt über diese Fortschritte kritisch Rechenschaft ab.
The Mechanisms of the Stille Reaction
Authors: Espinet Pablo , Echavarren Antonio M. 
Published: August 2004

AbstractEighteen years ago in Angewandte Chemie John K. Stille reviewed a novel methodology, which eventually became known by his name, for the coupling of organostannanes with organic electrophiles. Since then that seed has blossomed into a multifaceted methodology full of hidden possibilities to explore, discover, and enjoy. Very recent modifications are making synthetic wishes come true that were only dreamed of a few years ago. Moreover, as important advances are being made in the understanding of the mechanistic details of the process, it is becoming increasingly possible to apply this essential reaction and its new variants in a less empirical way. The purpose of this Review is to give a critical account of this progress.
Analysis of mechanical, thermal, and morphological behavior of polycaprolactone/wood flour blends
Authors: Wu Chin‐San 
Published: August 2004

AbstractIn the present study, the properties of polycaprolactone (PCL) and wood flour (WF) blends were examined by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), Instron mechanical tester, and scanning electron microscopy (SEM). As for results, the mechanical properties of PCL were lowered obviously, due to the poor compatibility between the two phases, when it was blended with wood flours. A fine dispersion and homogeneity of wood flour in the polymer matrix could be obtained when the acrylic acid grafted PCL (PCL‐g‐AA) was used to replace PCL for manufacture of blends. This better dispersion is due to the formation of branched and crosslinked macromolecules since the PCL‐g‐AA copolymer had carboxyl groups to react with the hydroxyls. This is reflected in the mechanical and thermal properties of the blends. In comparison with pure PCL/WF blend, the increase in tensile strength at break was remarkable for PCL‐g‐AA/WF blend. The PCL‐g‐AA/WF blends are more easily processed than the PCL/WF ones since the former had lower melt viscosity than the latter. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1000–1006, 2004
Free‐radical bulk polymerization of styrene with a new trifunctional cyclic peroxide initiator
Authors: Sheng Wei‐Chen , Wu Jian‐Yi , Shan Guo‐Rong , Huang Zhi‐Ming , Weng Zhi‐Xue 
Published: August 2004

AbstractThe bulk free‐radical polymerization of styrene in the presence of a new cyclic trifunctional initiator, 3,6,9‐triethyl‐3,6,9‐trimethyl‐1,4,7‐triperoxonane, was studied. Full‐conversion‐range experiments were carried out to assess the effects of the temperature and initiator concentration on the polymerization kinetics, molecular weight, and polydispersity. Gel permeation chromatography was used to measure the molecular weight and the molecular weight distribution of polystyrene. When this multifunctional initiator was used for styrene polymerization at higher temperatures, it was possible to produce polymers with higher molecular weights and narrower molecular weight polydispersity at a higher rate. This showed that the molecular weight and polydispersity were influenced by the initiator concentration and the polymerization temperature in an unusual manner. Moreover, polystyrene, obtained with trifunctional peroxide, had OO bonds in the molecular chains and was investigated with differential scanning calorimetry and gel permeation chromatography. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1035–1042, 2004
Cure kinetics of epoxy resin and aromatic diamines
Authors: Ghaemy M. , Barghamadi M. , Behmadi H. 
Published: August 2004

AbstractThe kinetics of curing reaction of a diglycidyl ether of a bisphenol‐A based epoxy (DGEBA) with 4,4′‐diaminostillbene (DAS) and 4,4′‐diaminoazobenzene (DAAB) as curing agents are studied by differential scanning calorimetery (DSC) using the isothermal technique. The experimental data show that the cure reaction is autocatalytic in nature, and all kinetic parameters of the curing reaction are determined using a semiempirical equation. The reaction of DGEBA with DAS is faster than that with DAAB under the same conditions and the activation energies of both systems are higher than those reported for other aromatic diamines. With increasing isothermal temperature and concentration of curing agents the rate constants are increased by the increasing of probability collisions between epoxide and primary amine groups while the activation energies remain constant. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1049–1056, 2004
Angiographic adverse events during percutaneous coronary intervention fail to predict creatine kinase‐MB elevation
Authors: Blankenship James C. , Islam M. Ashequl , Wood G. Craig , Iliadis Elias A. 
Published: August 2004

AbstractWe attempted to determine if aggressive detection of angiographic adverse events during coronary intervention could predict subsequent creatine kinase (CK)‐MB elevations. During coronary intervention, both fluoroscopy and cine angiography were used to detect angiographic adverse events. At least one angiographic adverse event occurred in 133/251 (53%) of procedures. CK‐MB elevation occurred in 24% of procedures. Slow flow during the procedure (P = 0.002) and chest discomfort at the end of the procedure (P = 0.007) were the strongest predictors of CK‐MB elevation. Among procedures with no angiographic adverse events, CK‐MB elevation occurred in 15/121 (12%), accounting for 25% of CK‐MB elevations. We conclude that CK‐MB elevation occurs after angiographically uncomplicated coronary interventions even when angiographic adverse events are aggressively detected. Routine monitoring of cardiac enzymes is necessary to detect all patients who will experience myocardial injury after coronary intervention. Catheter Cardiovasc Interv 2004;63:31–41. © 2004 Wiley‐Liss, Inc.
Transthoracic access for cardiac catheterization
Authors: Maher Kevin O. , Murdison Kenneth A. , Norwood William I. , Murphy John D. 
Published: August 2004

AbstractPatients who have undergone Fontan palliation for congenital heart disease have limited access to the pulmonary venous atrium. We describe a transthoracic approach to the pulmonary venous atrium for diagnostic and therapeutic cardiac catheterization. A total of 22 patients ranging in age from 14 months to 25 years and weighing 7–68 kg underwent transthoracic catheterization. With the aid of fluoroscopic and angiographic markers, a 20 gauge needle was inserted into the pulmonary venous atrium. A floppy‐tipped wire was inserted, and a 4 Fr sheath was placed, upsized as needed. Access to the pulmonary venous atrium was obtained for all patients. Therapeutic procedures were completed for all patients. Transthoracic access to the pulmonary venous atrium in patients who have undergone a Fontan operation is a reliable and rapid mode of access, allowing for complex therapeutic procedures to be performed in the catheterization laboratory, obviating the need for additional open heart surgery. Catheter Cardiovasc Interv 2004;63:72–77. © 2004 Wiley‐Liss, Inc.
Catheter‐based intracardiac echocardiography in the interventional cardiac laboratory
Authors: Liu Zheng , McCormick Daniel , Dairywala Ismail , Surabhi Satish , Goldberg Sheldon , Turi Zoltan , Vannan Mani A. 
Published: August 2004

AbstractRecent advances in technology have engendered a renewed enthusiasm in the use of intracardiac echocardiography (ICE) to guide and assess cardiac interventions. AcuNav is a phased‐array sector imaging probe equipped with color and spectral Doppler capabilities. Previous‐generation imaging catheters yielded unfamiliar limited‐depth radial images with no flow information. Current imaging technology such as the AcuNav has not only consolidated the role of ICE but opened newer applications in the interventional laboratory. ICE has clear advantages over transesophageal echocardiography as the imaging modality of choice in the cardiac catheterization and electrophysiological laboratories. We review the technical evolution of ICE and describe the expanded utility of the AcuNav imaging catheter during cardiac interventions. Catheter Cardiovasc Interv 2004;63:63–71. © 2004 Wiley‐Liss, Inc.