bluuebunny/crossref_metadata_2025 huggingface dataset:
Cisplatin‐induced hypomagnesemia and cardiac dysrhythmia
Authors: Bashir Hamid , Crom Debbie , Metzger Monika , Mulcahey Jean , Jones Debbie , Hudson Melissa M.
Published: April 2006

We describe a case of a patient with cisplatin‐induced hypomagnesemia who suffered brief asystole during an episode of gastroenteritis. Structural heart disease was excluded. The patient achieved complete clinical recovery after short‐term administration of intravenous magnesium supplementation. Cisplatin should be considered a cause of hypomagnesemic‐related cardiac dysrhythmia. Magnesium deficit may increase myocardial electrical instability and thus, the risk of life‐threatening arrhythmias and sudden death. Long‐term serum electrolyte measurement and appropriate replacement of magnesium are recommended. Pediatr Blood Cancer 2007;49:867–869. © 2006 Wiley‐Liss, Inc.
Endohedral carbon chains in chiral single‐wall carbon nanotubes
Authors: Vadapalli Ravi K. , Mintmire J. W.
Published: April 2006

Using a first‐principles, local density functional approach, we report the bond length optimization of endohedral linear carbon chains. In these calculations, all‐carbon nanowire structures were constructed by inserting cumulenic linear carbon chains inside the semiconducting (7,3) and metallic (7,4) single‐wall carbon nanotubes with radii of ∼0.35 nm. Our calculations show that the total energy results for the endohedral chains inside both (7,3) and (7,4) nanotubes are well described with a common total energy curve having an equilibrium bond length of ∼0.129 nm. The electronic band structures of the carbon nanowires are described in terms of a rigid‐band model, with the Fermi level for the carbon nanowire effectively pinned near the top of bands originating from the valence band of the single‐wall nanotube. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Coriolis coupling on the rotational and vibrational energy transfer in H2O+ Ar collisions: Classical trajectories simulation
Authors: Borges E. , Ferreira G. G. , Braga J. P. , Belchior J. C.
Published: April 2006

Classical trajectories studies in Cartesian coordinates are applied to analyze Coriolis coupling for the energy transfer in H2O + Ar process. Vibrational energies equal to 50 kcal/mol and 100 kcal/mol for initial rotational temperatures in the range 298–30,000 K are used as initial conditions. Initial translational temperatures for the incoming atom are selected in the same way. Effects of rotational and translational temperatures at different initial conditions are also investigated in the molecular vibrational relaxation process. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Latin America's colonial legacy: The law and its relationship to economic development
Authors: Waldron Darryl G.
Published: April 2006

This study explores the extent to which Latin America's failure to embrace a system of laws and regulations generally viewed as conducive to capital formation and the broad creation of wealth may be an important factor impairing economic development. The argument here is that the region's adherence to a legal system based on civil law is a factor contributing to Latin America's ongoing lack of economic progress. A composite measure of economic freedom served as the basis for a two‐group discriminant analysis of the civil law countries of Latin America and common law countries. The objective was to test for and explain any statistically significant between‐group differences in levels of economic freedom. © 2006 Wiley Periodicals, Inc.
Understanding Adrienne Kennedy
Authors: Fisher James
Published: April 2006

Series books do not always make for the most scintillating study of a given topic; but Philip C. Kolin's Understanding Adrienne Kennedy enlivens the format of the University of South Carolina Press's series with an elegantly written study on the interrelationships of life, work, and performance in the dramatic accomplishment of a unique African-American woman playwright. Kennedy's dark, evocative dramas emphasize the search for identity in a culture that is at once familiar and alien, real and imagined. The books in this worthy series are geared toward students and nonacademic readers, and Kolin has skillfully managed to offer a deep reading and, at the same time, an accessible survey of Kennedy's diverse plays that, under any circumstances, would provide a heady challenge to any reader or viewer.
Direct solar ultraviolet irradiance over Nainital, India, in the central Himalayas for clear‐sky day conditions during December 2004
Authors: Srivastava Manoj K , Singh Sachchidanand , Saha Auromeet , Dumka U. C. , Hegde Prashant , Singh Risal , Pant P.
Published: April 2006

From a high‐altitude station, Nainital, India (29.4°N, 79.5°E, 1958 masl), located in the central part of lower Himalayas, the observations made during December 2004 using a pair of Sun photometers (Microtops II) at wavelengths ranging from 305 to 1020 nm are reported. The observed parameters are the direct solar UV irradiance, column ozone, water vapor, and aerosol optical depths (AOD). The results are presented for the full day clear‐sky conditions that prevailed for about 16 days during the whole month. It is found that Nainital is a comparatively pristine site with average AOD at 500 nm ranging between 0.03 and 0.09 and Angstrom exponent generally close to 1. The high AOD values occurred on 2 and 25 December due to winds from populated north Indian plains as revealed by the Hybrid Single‐Particle Lagrangian Integrated Trajectory (HYSPLIT) backward trajectory model. The total column ozone varies between 251 and 308 DU during the entire period of observations. The maximum diurnal UV irradiance values in the 2.4 nm bandwidth centered at 305.5, 312.5, and 320.0 nm varied between 0.027 and 0.049, 0.15 and 0.20, and 0.29 and 0.37 W m−2, respectively. The measured UV irradiances are compared with the Tropospheric Ultraviolet Visible (TUV) radiation model and show a good agreement.
Improvements of the International Reference Ionosphere model for the topside electron density profile
Authors: Bilitza Dieter , Reinisch Bodo W. , Radicella Sandro M. , Pulinets Sergey , Gulyaeva Tamara , Triskova Lida
Published: April 2006

Shortcomings of the representation of the topside electron density profile in the International Reference Ionosphere (IRI) model have been noted in comparison with recently analyzed topside sounder data and also with total electron content (TEC) data. Various studies have proposed corrections of the IRI formulas or have introduced a new formalism. This paper reviews the different approaches, their implications for IRI, and their current status. An important challenge for topside modeling is the truthful representation of profiles in the equatorial anomaly (EA) region over the whole range of the EA fountain. This means that the latitudinal representation has to reproduce the merging of the double‐peak signature at F region heights into a single peak at the top of the fountain. In this context, special emphasis is given to the coupling between topside and plasmaspheric models.
Bell-Plesset effects for an accelerating interface with contiguous density gradients
Authors: Amendt Peter
Published: April 2006

A Plesset-type treatment [M. S. Plesset, J. Appl. Phys. 25, 96 (1954)] is used to assess the effects of contiguous density gradients at an accelerating spherical classical interface on Rayleigh-Taylor and Bell-Plesset perturbation growth. Analytic expressions are obtained that describe enhanced Rayleigh-Taylor instability growth from contiguous density gradients aligned with the acceleration and which increase the effective Atwood number of the perturbed interface. A new pathway for geometric amplification of surface perturbations on an accelerating interface with contiguous density gradients is identified. A resonance condition between the density-gradient scale length and the radius of the interface is also predicted based on a linearized analysis of Bernoulli’s equation, potentially leading to enhanced perturbation growth. Comparison of the analytic treatment with detailed two-dimensional single-mode growth-factor simulations shows good agreement for low-mode numbers where the effects of spherical geometry are most manifested.
Nonlinear propagation of modulated ion-acoustic plasma waves in the presence of an electron beam
Authors: Esfandyari-Kalejahi A. , Kourakis I. , Dasmalchi B. , Sayarizadeh M.
Published: April 2006

Theoretical and numerical studies are presented of the amplitude modulation of ion-acoustic waves (IAWs) in a plasma consisting of warm ions, Maxwellian electrons, and a cold electron beam. Perturbations parallel to the carrier IAW propagation direction have been investigated. The existence of four distinct linear ion acoustic modes is shown, each of which possesses a different behavior from the modulational stability point of view. The stability analysis, based on a nonlinear Schrödinger equation (NLSE) reveals that the IAW may become unstable. The stability criteria depend on the IAW carrier wave number, and also on the ion temperature, the beam velocity and the beam electron density. Furthermore, the occurrence of localized envelope structures (solitons) is investigated, from first principles. The numerical analysis shows that the two first modes (essentially IAWs, modified due to the beam) present a complex behavior, essentially characterized by modulational stability for large wavelengths and instability for shorter ones. Dark-type envelope excitations (voids, holes) occur in the former case, while bright-type ones (pulses) appear in the latter. The latter two modes are characterized by an intrinsic instability, as the frequency develops a finite imaginary part for small ionic temperature values. At intermediate temperatures, both bright- and dark-type excitations may exist, although the numerical landscape is intertwined between stability and instability regions.
Growing multiconfigurational potential energy surfaces with applications to X+H2 (X=C,N,O) reactions
Authors: Netzloff Heather M. , Collins Michael A. , Gordon Mark S.
Published: April 2006

A previously developed method, based on a Shepard interpolation procedure to automatically construct a quantum mechanical potential energy surface (PES), is extended to the construction of multiple potential energy surfaces using multiconfigurational wave functions. These calculations are accomplished with the interface of the PES-building program, GROW, and the GAMESS suite of electronic structure programs. The efficient computation of multiconfigurational self-consistent field surfaces is illustrated with the C+H2, N+H2, and O+H2 reactions.
Screened hybrid density functionals applied to solids
Authors: Paier J. , Marsman M. , Hummer K. , Kresse G. , Gerber I. C. , Ángyán J. G.
Published: April 2006

Hybrid Fock exchange/density functional theory functionals have shown to be very successful in describing a wide range of molecular properties. For periodic systems, however, the long-range nature of the Fock exchange interaction and the resultant large computational requirements present a major drawback. This is especially true for metallic systems, which require a dense Brillouin zone sampling. Recently, a new hybrid functional [HSE03, J. Heyd, G. E. Scuseria, and M. Ernzerhof, J. Chem. Phys. 118, 8207 (2003)] that addresses this problem within the context of methods that evaluate the Fock exchange in real space was introduced. We discuss the advantages the HSE03 functional brings to methods that rely on a reciprocal space description of the Fock exchange interaction, e.g., all methods that use plane wave basis sets. Furthermore, we present a detailed comparison of the performance of the HSE03 and PBE0 functionals for a set of archetypical solid state systems by calculating lattice parameters, bulk moduli, heats of formation, and band gaps. The results indicate that the hybrid functionals indeed often improve the description of these properties, but in several cases the results are not yet on par with standard gradient corrected functionals. This concerns in particular metallic systems for which the bandwidth and exchange splitting are seriously overestimated.
Folding thermodynamics of pseudoknotted chain conformations
Authors: Kopeikin Zoia , Chen Shi-Jie
Published: April 2006

We develop a statistical mechanical framework for the folding thermodynamics of pseudoknotted structures. As applications of the theory, we investigate the folding stability and the free energy landscapes for both the thermal and the mechanical unfolding of pseudoknotted chains. For the mechanical unfolding process, we predict the force-extension curves, from which we can obtain the information about structural transitions in the unfolding process. In general, a pseudoknotted structure unfolds through multiple structural transitions. The interplay between the helix stems and the loops plays an important role in the folding stability of pseudoknots. For instance, variations in loop sizes can lead to the destabilization of some intermediate states and change the (equilibrium) folding pathways (e.g., two helix stems unfold either cooperatively or sequentially). In both thermal and mechanical unfolding, depending on the nucleotide sequence, misfolded intermediate states can emerge in the folding process. In addition, thermal and mechanical unfoldings often have different (equilibrium) pathways. For example, for certain sequences, the misfolded intermediates, which generally have longer tails, can fold, unfold, and refold again in the pulling process, which means that these intermediates can switch between two different average end-end extensions.
Validation of the radiation hydrocode RAGE against defect-driven mix experiments in a compressible, convergent, and miscible plasma system
Authors: Lanier N. E. , Magelssen G. R. , Batha S. H. , Fincke J. R. , Horsfield C. J. , Parker K. W. , Rothman S. D.
Published: April 2006

Accurate predictive hydrodynamics codes increase the efficiency with which ignition will be achieved at the National Ignition Facility (NIF) [J. W. Hogan et al., J. Nucl. Fus. 41, 567 (2001)]. By validating these codes against well-diagnosed experiments, additional confidence in their predictive capability is attained. This work presents comparisons between the predictive simulations of the Los Alamos hydrocode RAGE [R. M. Baltrusaitus et al., Phys. Fluids 8, 2471 (1996)] and data obtained from cylindrical defect-driven mix experiments conducted on the OMEGA [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] laser. The results show that RAGE accurately captures much of the bulk hydrodynamics of the experiments. However, persistent discrepancies with respect to the small-scale fluid flows remain.
Two-dimensional modelling of blob dynamics in tokamak edge plasmas
Authors: Yu G. Q. , Krasheninnikov S. I. , Guzdar P. N.
Published: April 2006

Dynamics of blobs described by two different models for the closures of parallel plasma current is studied numerically. One of these closures describes the blob sitting on magnetic lines going in the scrape off layer through the conducting surface, while the other one describes the blob with high plasma pressure where the bending of magnetic field lines becomes important.
Diode effect in asymmetric double-tunnel barriers with single-metal nanoclusters
Authors: Iovan A. , Haviland D. B. , Korenivski V.
Published: April 2006

Asymmetric double-tunnel barriers with the center electrode being a metal cluster in the quantum regime are studied. The zero dimensionality of the clusters used and the associated quantized energy spectra are manifest in well-defined steps in the current-voltage characteristic. Record high current rectification ratios of ∼104 for tunneling through such clusters are demonstrated at room temperature. We are able to account for all of the experimentally observed features by modeling our double-barrier structures using a combination of discrete states and charging effects for tunneling through quantum dots.
Coupling effect on phonon thermal transport in a double-stub quantum wire
Authors: Tang Li-Ming , Wang Ling-Ling , Chen Ke-Qiu , Huang Wei-Qing , Zou B. S.
Published: April 2006

By using the scattering matrix method, we investigate the thermal conductance in a double-stub quantum wire at low temperatures. The coupling effects between two stubs are analyzed in detail. It is found that the quantum structures exhibit oscillatory decaying thermal conductance with the width between two stubs at low temperature. A comparison between thermal conductances is made when stress-free and hard-wall boundary conditions are applied for acoustic modes, respectively. The result indicates that the behavior of the thermal conductance versus temperature is qualitatively different for the different types of boundary conditions.
Transverse electric current induced by optically injected spin current in a cross-shaped InGaAs∕InAlAs system
Authors: Li Jian , Dai Xi , Shen Shun-Qing , Zhang Fu-Chun
Published: April 2006

We examine the electric response of a linearly polarized light normally shed on a cross-shaped quasi-two-dimensional InGaAs∕InAlAs system with structure inversion asymmetry. The photoexcited conduction electrons carry a pure spin current with in-plane spin polarization due to the Rashba spin-orbit interaction. We use the Landauer-Büttiker formalism to show that this spin current induces two inward or outward transverse charge currents, which are observable in experiments. This effect may serve as an experimental probe of certain types of spin current.
Effects of heating ramp rates on the characteristics of Al implanted 4H–SiC junctions
Authors: Poggi A. , Bergamini F. , Nipoti R. , Solmi S. , Canino M. , Carnera A.
Published: April 2006

The role of the heating rate in the postimplantation annealing process of SiC was investigated. Structural and electrical properties of an Al+ implanted junction in n-type 4H–SiC were studied for a 30min annealing at 1600°C in argon atmosphere and changing the heating rate between 7 and 40°C∕s. With the increasing of the heating rate the surface roughness increases, but the electrical performance of the devices improves. In particular, the faster ramp-up rate reduces the sheet resistance of the implanted layer of about 40% with respect to the slowest process and significantly reduces the leakage current of the diodes.
Control of Vancomycin-Resistant Enterococci in the Neonatal Intensive Care Unit
Authors: Singh Nalini , Léger Marie-Michèle , Campbell Joyce , Short Billie , Campos Joseph M.
Published: April 2006

Background and Objective:

Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants.

Methods:

Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness.

Results:

Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater.

Conclusions:

Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU. (Infect Control Hosp Epidemiol 2005;26:646-649)
Catheter-Related Vancomycin-ResistantEnterococcus FaeciumBacteremia: Clinical and Molecular Epidemiology
Authors: Raad Issam I. , Hanna Hend A. , Boktour Maha , Jabbour Noel , Hachem Ray Y. , Darouiche Rabih O.
Published: April 2006

Objective:

To study the clinical and molecular epidemiology of vancomycin-resistantEnterococcus faeciumorganisms causing catheter-related bacteremia in patients with cancer.

Design:

Retrospective case-control study.

Setting:

University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas.

Patients:

Case-patients were patients with cancer who had catheter-related vancomycin-resistantE. faeciumbacteremia and control-patients were patients with cancer and vancomycin-resistantE. faeciumgastrointestinal colonization without infection.

Results:

Ten case-patients with catheter-related vancomycin-resistantE. faeciumbacteremia were compared with 30 control-patients with gastrointestinal colonization by vancomycin-resistantE. faecium. Patients with catheter-related vancomycin-resistantE. faeciumbacteremia were more likely to have required mechanical ventilation (P< .01), received total parenteral nutrition (P< .01), and had polyurethane catheters (P< .01) inserted in the femoral vein (P= .01). With the use of pulsed-fleld gel electrophoresis, 4 of the 10 catheter-related vancomycin-resistantE. faeciumbacteremia isolates were genetically indistinguishable, whereas only 2 of the 30 control vancomycin-resistantE. faeciumisolates displayed this same DNA pattern (P= .03).

Conclusion:

This study suggests that catheter-related vancomycin-resistantE. faeciumbacteremia occurs more frequently in patients who receive total parenteral nutrition, mechanical ventilation, and femoral catheters. (Infect Control Hosp Epidemiol 2005;26:658-661)
Nosocomial Bacteremia Clinical Significance of a Single Blood Culture Positive for Coagulase-Negative Staphylococci
Authors: Favre Benoît , Hugonnet Stéphane , Correa Luci , Sax Hugo , Rohner Peter , Pittet Didier
Published: April 2006

Objectives:

To describe the epidemiology of nosocomial coagulase-negative staphylococci (CoNS) bacteremia and to evaluate the clinical significance of a single blood culture positive for CoNS.

Design:

A 3-year retrospective cohort study based on data prospectively collected through hospital-wide surveillance. Bacteremia was defined according to CDC criteria, except that a single blood culture growing CoNS was not systematically considered as a contaminant. All clinically significant blood cultures positive for CoNS nosocomial bacteremia were considered for analysis.

Setting:

A large university teaching hospital in Geneva, Switzerland.

Results:

A total of 2,660 positive blood cultures were identified. Of these, 1,108 (41.7%) were nosocomial; CoNS were recovered from 411 nosocomial episodes (37.1%). Two hundred thirty-four episodes of CoNS bacteremia in the presence of signs of sepsis were considered clinically relevant and analyzed. Crude mortality and associated mortality were 24.4% and 12.8%, respectively. Associated mortality was similar among patients with one positive blood culture and those with two or more (16.2% vs 10.8%, respectively;P= .3). Mortality rates after bacteremia for patients with a single positive blood culture and for those with two or more were 15.3% and 7.0%, respectively, at day 14 (RR, 2.2; CI%, 0.87-5.46) and 20.8% and 11.3%, respectively, at day 28 (RR, 1.9; CI95, 0.9-3.8). On multivariate analysis, only age and a rapidly fatal disease were independently associated with death.

Conclusion:

CoNS bacteremia harbor a significant mortality and a single positive blood culture in the presence of signs of sepsis should be considered as clinically relevant.
Cleaning and Sterilization Protocol for Reused Cardiac Electrophysiology Catheters Inactivates Hepatitis and Coxsackie Viruses
Authors: Druce Julian D. , Russell Jessica S. , Birch Christopher J. , Vickery Karen , Harper Richard W. , Smolich Joseph J.
Published: April 2006

Objective:

To assess the efficacy of a standard cleaning and sterilization protocol employed during reuse of cardiac electrophysiology catheters on the infectivity of duck hepatitis B virus (DHBV; a surrogate for human hepatitis B virus), bovine viral diarrhea virus (BVDV; a surrogate for human hepatitis B virus), and human Coxsackie type B3 virus (CB3).

Setting:

Public health virology laboratory.

Methods:

Studies were performed on the distal, electrode-containing segments of 120 electrophysiology catheters previously used in up to 10 clinical procedures. Catheter segments were immersed for 1 hour in blood infected with high titers of DHBV, BVDV, or CB3. After air drying for 2 hours, subgroups of 8 catheters were subjected to no treatment, washing in general-purpose detergent, washing in enzyme cleaner, sterilization in ethylene oxide, or the full protocol of sequential detergent-enzyme cleaner-ethylene oxide exposure. Presence of residual virus was assessed by nucleic acid detection and infectivity studies.

Results:

DHBV nucleic acid was detected on catheters after individual steps and the full protocol, whereas BVDV and CB3 nucleic acids were detected after individual steps but not the full protocol. These findings were associated with the presence of infectious DHBV and CB3, but not BVDV, on catheters after washing in detergent or enzyme cleaner. However, ethylene oxide alone or the full protocol reduced infectivity of all three viruses to undetectable levels.

Conclusion:

These experimental studies provide strong evidence that appropriate cleaning and sterilization of reused electrophysiology catheters inactivates blood-borne viruses such as hepatitis B and C and Coxsackie type B3.
A New Melanoma Antigen Fatty Acid–Binding Protein 7, Involved in Proliferation and Invasion, Is a Potential Target for Immunotherapy and Molecular Target Therapy
Authors: Goto Yasufumi , Matsuzaki Yuriko , Kurihara Sachiko , Shimizu Ayako , Okada Tsutomu , Yamamoto Kazuhiko , Murata Hiroshi , Takata Minoru , Aburatani Hiroyuki , Hoon Dave S.B. , Saida Toshiaki , Kawakami Yutaka
Published: April 2006

The identification of molecules that are preferentially expressed in melanoma cells and involved in their malignant phenotypes is important for understanding melanoma biology and the development of new diagnostic and therapeutic methods. By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid–binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified. Immunohistochemical examination revealed that FABP7 was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line 293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation and Matrigel invasion, indicating that FABP7 plays a role in the malignant phenotype of some melanoma cell lines. IgG antibodies specific for the phage or bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31 (26%) sera from melanoma patients, respectively, but not in sera from healthy individuals, indicating that FABP7 is an immunogenic antigen in melanoma patients. These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods. (Cancer Res 2006; 66(8): 4443-9)
High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers
Authors: Tai Amy L.S. , Mak William , Ng Phoebe K.M. , Chua Daniel T.T. , Ng Mandy Y.M. , Fu Li , Chu Kevin K.W. , Fang Yan , Qiang Song You , Chen Muhan , Zhang Minyue , Sham Pak C. , Guan Xin-Yuan
Published: April 2006

Loss of DNA copy number at the short arm of chromosome 3 is one of the most common genetic changes in human lung cancer, suggesting the existence of one or more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted regions and candidate TSGs within these regions, a recently developed single-nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was applied to investigate the loss of heterozygosity (LOH) in 30 primary non–small-cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at 3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker distance in the present study is ∼180 kb. Several frequently deleted regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several candidate TSGs within these frequently detected LOH regions have been found, including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study also showed that SMSG technology is a very useful approach to rapidly define the minimal deleted region and to identify target TSGs in a given cancer. (Cancer Res 2006; 66(8): 4133-8)
The Kinase Mirk/Dyrk1B Mediates Cell Survival in Pancreatic Ductal Adenocarcinoma
Authors: Deng Xiaobing , Ewton Daina Z. , Li Sheena , Naqvi Asghar , Mercer Stephen E. , Landas Steve , Friedman Eileen
Published: April 2006

Ductal adenocarcinoma of the pancreas is almost uniformly lethal as this cancer is invariably detected at an advanced stage and is resistant to treatment. The serine/threonine kinase Mirk/Dyrk1B has been shown to be antiapoptotic in rhabdomyosarcomas. We have now investigated whether Mirk might mediate survival in another cancer in which Mirk is widely expressed, pancreatic ductal adenocarcinoma. Mirk was an active kinase in each pancreatic cancer cell line where it was detected. Mirk knockdown by RNA interference (RNAi) reduced the clonogenicity of Panc1 pancreatic cancer cells 4-fold and decreased tumor cell number, showing that Mirk mediates survival in these cells. Mirk knockdown by synthetic duplex RNAis in Panc1, AsPc1, and SU86.86 pancreatic cancer cells induced apoptosis and enhanced the apoptosis induced by gemcitibine. Mirk knockdown did not increase the abundance or activation of Akt. However, four of five pancreatic carcinoma cell lines exhibited either elevated Mirk activity or elevated Akt activity, suggesting that pancreatic cancer cells primarily rely on Mirk or Akt for survival signaling. Mirk protein was detected by immunohistochemistry in 25 of 28 cases (89%) of pancreatic ductal adenocarcinoma, with elevated expression in 11 cases (39%). Increased expression of Mirk was seen in pancreatic carcinomas compared with primary cultures of normal ductal epithelium by serial analysis of gene expression and by immunohistochemistry. Thus, Mirk is a survival factor for pancreatic ductal adenocarcinoma. Because knockout of Mirk does not cause embryonic lethality, Mirk is not essential for normal cell growth and may represent a novel therapeutic target. (Cancer Res 2006; 66(8): 4149-58)
Suppression of Centrosome Amplification after DNA Damage Depends on p27 Accumulation
Authors: Sugihara Eiji , Kanai Masayuki , Saito Soichiro , Nitta Takayuki , Toyoshima Hideo , Nakayama Keiko , Nakayama Keiichi I. , Fukasawa Kenji , Schwab Manfred , Saya Hideyuki , Miwa Masanao
Published: April 2006

The centrosome plays a fundamental role in cell division, cell polarity, and cell cycle progression. Centrosome duplication is mainly controlled by cyclin-dependent kinase 2 (CDK2)/cyclin E and cyclin A complexes, which are inhibited by the CDK inhibitors p21Cip1 and p27Kip1. It is thought that abnormal activation of CDK2 induces centrosome amplification that is frequently observed in a wide range of aggressive tumors. We previously reported that overexpression of the oncogene MYCN leads to centrosome amplification after DNA damage in neuroblastoma cells. We here show that centrosome amplification after γ-irradiation was caused by suppression of p27 expression in MYCN-overexpressing cells. We further show that p27−/− and p27+/− mouse embryonic fibroblasts and p27-silenced human cells exhibited a significant increase in centrosome amplification after DNA damage. Moreover, abnormal mitotic cells with amplified centrosomes were frequently observed in p27-silenced cells. In response to DNA damage, the level of p27 gradually increased in normal cells independently of the ataxia telangiectasia mutated/p53 pathway, whereas Skp2, an F-box protein component of an SCF ubiquitin ligase complex that targets p27, was reduced. Additionally, p27 levels in MYCN-overexpressing cells were restored by treatment with Skp2 small interfering RNA, indicating that down-regulation of p27 by MYCN was due to high expression of Skp2. These results suggest that the accumulation of p27 after DNA damage is required for suppression of centrosome amplification, thereby preventing chromosomal instability. (Cancer Res 2006; 66(8): 4020-9)
Adeno-Associated Virus–Mediated Delivery of a Mutant Endostatin in Combination with Carboplatin Treatment Inhibits Orthotopic Growth of Ovarian Cancer and Improves Long-term Survival
Authors: Subramanian Indira V. , Bui Nguyen Tri Minh , Truskinovsky Alexander M. , Tolar Jakub , Blazar Bruce R. , Ramakrishnan Sundaram
Published: April 2006

A human ovarian cancer cell line, which migrates to mouse ovaries and establishes peritoneal carcinomatosis, was used to evaluate the cooperative effect of an antiangiogenic gene therapy combined with chemotherapy. The ovarian carcinoma cell line MA148 was genetically modified by “Sleeping Beauty” transposon-mediated delivery of DsRed2 fluorescent protein. Stable, high-level expression of DsRed protein enabled in vivo imaging of peritoneal dissemination of ovarian cancer. Both external and internal imaging, along with histopathology, showed migration of i.p. injected human ovarian cancer cell line to mouse ovaries. Using this model, we evaluated the effect of adeno-associated virus (AAV)–mediated expression of a mutant endostatin either alone or in combination with carboplatin treatment. A single i.m. injection of recombinant AAV (rAAV)-mutant human endostatin with P125A substitution (P125A-endostatin) showed sustained expression of mutant endostatin. Antiangiogenic gene therapy inhibited orthotopic growth of ovarian cancer and resulted in 33% long-term tumor-free survival. A single cycle of carboplatin treatment combined with mutant endostatin gene therapy resulted in 60% of the animals remaining tumor free for >200 days, which was significantly better than rAAV-LacZ and/or carboplatin. Combination treatment delayed tumor appearance in 40% of the animals, wherein the residual tumors were smaller in size with limited or no peritoneal metastasis. These studies suggest that AAV-mediated gene therapy of P125A-endostatin in combination with carboplatin is a useful method to inhibit peritoneal dissemination of ovarian carcinoma. (Cancer Res 2006; 66(8): 4319-28)
Chronic Exposure to Lead Chromate Causes Centrosome Abnormalities and Aneuploidy in Human Lung Cells
Authors: Holmes Amie L. , Wise Sandra S. , Sandwick Sarah J. , Lingle Wilma L. , Negron Vivian C. , Thompson W. Douglas , Wise John Pierce
Published: April 2006

Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens. The carcinogenicity of Cr(VI) is related to its solubility, with the most potent carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One possible explanation is that particulates may provide more chronic exposures to chromate over time. We found that aneuploid cells increased in a concentration- and time-dependent manner after chronic exposure to lead chromate. Specifically, a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour exposure to 0.5 and 1 μg/cm2 lead chromate induced 55% and 60% aneuploid metaphases, respectively. We also found that many of these aneuploid cells were able to continue to grow and form colonies. Centrosome defects are known to induce aneuploidy; therefore, we investigated the effects of chronic lead chromate exposure on centrosomes. We found that centrosome amplification in interphase and mitotic cells increased in a concentration- and time-dependent manner with 0.5 and 1 μg/cm2 lead chromate for 120 hours, inducing aberrant centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells, respectively; however, lead oxide did not induce centrosome amplification in interphase or mitotic cells. There was also an increase in aberrant mitosis after chronic exposure to lead chromate with the emergence of disorganized anaphase and mitotic catastrophe. These data suggest that one possible mechanism for lead chromate–induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy. (Cancer Res 2006; 66(8): 4041-8)
1-Methoxy-Canthin-6-One Induces c-Jun NH2-Terminal Kinase–Dependent Apoptosis and Synergizes with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Activity in Human Neoplastic Cells of Hematopoietic or Endodermal Origin
Authors: Ammirante Massimo , Di Giacomo Rita , De Martino Laura , Rosati Alessandra , Festa Michela , Gentilella Antonio , Pascale Maria Carmela , Belisario Maria Antonietta , Leone Arturo , Caterina Turco Maria , De Feo Vincenzo
Published: April 2006

We investigated the effects of 1-methoxy-canthin-6-one, isolated from the medicinal plant Ailanthus altissima Swingle, on apoptosis in human leukemia (Jurkat), thyroid carcinoma (ARO and NPA), and hepatocellular carcinoma (HuH7) cell lines. Cultures incubated with the compound showed >50% of sub-G1 (hypodiploid) elements in flow cytometry analysis; the apoptosis-inducing activity was evident at <10 μmol/L and half-maximal at about 40 μmol/L 1-methoxy-canthin-6-one. The appearance of hypodiploid elements was preceded by mitochondrial membrane depolarization, mitochondrial release of cytochrome c, and Smac/DIABLO and procaspase-3 cleavage. We subsequently investigated the effect of 1-methoxy-canthin-6-one in combination with human recombinant tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in the four cell lines. Suboptimal concentrations (10 μmol/L 1-methoxy-canthin-6-one and 0.25 ng/mL TRAIL, respectively) of the two agents, unable to elicit apoptosis when used alone, induced mitochondrial depolarization, activation of caspase-3, and 45% to 85% of sub-G1 elements when added together to the cells. The synergism seemed to rely partly on the enhanced expression of TRAIL receptor 1 (TRAIL-R1; DR4), analyzed by immunofluorescence, by 1-methoxy-canthin-6-one. Cell incubation with 1-methoxy-canthin-6-one resulted in activating c-Jun NH2-terminal kinase (JNK), as revealed by Western blotting; induction of apoptosis and TRAIL-R1 up-regulation by 1-methoxy-canthin-6-one were >80% prevented by the addition of the JNK inhibitor (JNKI) SP600125JNKI, indicating that both effects were almost completely mediated by JNK activity. On the other hand, synergism with TRAIL was reduced by about 50%, suggesting that besides up-regulating TRAIL-R1, 1-methoxy-canthin-6-one could influence other factor(s) that participated in TRAIL-induced apoptosis. These findings indicate that 1-methoxy-canthin-6-one can represent a candidate for in vivo studies of monotherapies or combined antineoplastic therapies. (Cancer Res 2006; 66(8): 4385-93)
Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer
Authors: Kawada Manabu , Inoue Hiroyuki , Masuda Tohru , Ikeda Daishiro
Published: April 2006

Prostate cancer shows high expression of type I insulin-like growth factor (IGF-I) receptor (IGF-IR) and prostate stromal cells (PrSC) produce IGF-I. Although high plasma level of IGF-I is a risk factor of prostate cancer, the significance of the prostate stromal IGF-I in the regulation of prostate cancer remains elusive. Here we show that the stromal IGF-I certainly regulates the development of prostate cancer. Coinoculation of PrSC increased the growth of human prostate cancer LNCaP and DU-145 tumors in severe combined immunodeficient mice. The conditioned medium of PrSC, as well as IGF-I, induced phosphorylation of IGF-IR and increased the growth of LNCaP and DU-145 cells. PrSC, but not LNCaP and DU-145 cells, secreted significant amounts of IGF-I. Coculture with PrSC increased the growth of DU-145 cells in vitro but the pretreatment of PrSC with small interfering RNA of IGF-I did not enhance it. Furthermore, various chemical inhibitors consisting of 79 compounds with ∼60 different targets led to the finding that only IGF-IR inhibitor suppressed the PrSC-induced growth enhancement of DU-145 cells. Thus, these results show that the prostate stromal IGF-I mediates tumor-stromal cell interactions of prostate cancer to accelerate tumor growth, supporting the idea that the IGF-I signaling is a valuable target for the treatment of prostate cancer. (Cancer Res 2006; 66(8): 4419-25)
Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis
Authors: Miyazaki Hiroshi , Patel Vyomesh , Wang Huixin , Edmunds Ryan K. , Gutkind J. Silvio , Yeudall W. Andrew
Published: April 2006

We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we reported transcriptional up-regulation of CXCL5 in metastatic cells. In this study, we provide biological validation of these findings and show that CXCL5 is intimately involved in tumor cell proliferation, migration, and invasion. Cells derived from a lymph node metastasis, but not from a synchronous primary tumor, secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA interference to generate cell lines (shL5) in which CXCL5 expression was greatly reduced, and tested whether this modulated the cell phenotype. shL5 cells showed decreased proliferation compared with cells harboring nontargeting control sequences. In addition, we found that the ability of shL5 cells to migrate and invade in vitro through a basement membrane substitute was greatly impaired compared with control cells. Finally, whereas control cells were highly tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was found to be ablated. Taken together, these data suggest that CXCL5 production contributes to both enhanced proliferation and invasion of squamous cell carcinomas and that targeting of chemokine pathways may represent a potential therapeutic modality for these lesions. (Cancer Res 2006; 66(8):4279-84)
Antiangiogenesis and Drug Delivery to Tumors: Bench to Bedside and Back
Authors: Duda Dan G.
Published: April 2006

After over 30 years of preclinical and clinical development, antiangiogenic agents have recently entered the clinic as attractive targeted therapeutics for the treatment of cancer. Fueled by exciting new developments in the field, the AACR Special Conference was designed to broadly survey critical scientific advances in the antiangiogenic therapy of cancer. Because these advances have come primarily with the use of combinations of antiangiogenic agents with chemotherapy, or with antiangiogenic agents that also directly target the cancer cells, the central theme included the issue of drug delivery to tumors. These two major issues were addressed in concert, from basic mechanisms of action of antiangiogenic agents to new combination approaches to cancer treatment. Nearly 300 participants from 20 countries registered for the conference, drawn both from academia and industry, with a wide range in experience and background. Dr. Rakesh Jain, along with conference co-chairs, Drs. Lee Ellis and Luisa Iruela-Arispe, assembled an outstanding lineup of speakers for this conference that included many of the pioneers in the fields of angiogenesis and drug delivery from the U.S. and abroad. This resulted in an excellent overview of the advances in our understanding of cellular and molecular aspects of tumor angiogenesis and antiangiogenic therapy of cancer in combination with conventional therapy. (Cancer Res 2006; 66(8): 3967-70)
Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression
Authors: Koster Maranke I. , Lu Shi-Long , White Lisa D. , Wang Xiao-Jing , Roop Dennis R.
Published: April 2006

Genes that are active during normal development are frequently reactivated during neoplastic transformation. We now report that developmentally expressed TAp63 isoforms are frequently reactivated in human squamous cell carcinomas. To determine the consequences of TAp63 reactivation, we induced TAp63α expression during chemically-induced skin carcinogenesis. Deregulated TAp63α expression dramatically accelerated tumor development and progression, frequently resulting in epithelial-mesenchymal transitions to spindle cell carcinomas and lung metastases. Consistent with this observation, we detected high levels of Twist and N-cadherin in tumors overexpressing TAp63α. Thus, as observed for other developmental pathways, aberrant reactivation of TAp63 predisposes to tumor development and progression. (Cancer Res 2006; 66(8): 3981-6)
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Authors: Lièvre Astrid , Bachet Jean-Baptiste , Le Corre Delphine , Boige Valérie , Landi Bruno , Emile Jean-François , Côté Jean-François , Tomasic Gorana , Penna Christophe , Ducreux Michel , Rougier Philippe , Penault-Llorca Frédérique , Laurent-Puig Pierre
Published: April 2006

The anti-epidermal growth factor receptor (anti-EGFR) cetuximab has been proven to be efficient in metastatic colorectal cancer. The molecular mechanisms underlying the clinical response to this drug remain unknown. Genetic alterations of the intracellular effectors involved in EGFR-related signaling pathways may have an effect on response to this targeted therapy. In this study, tumors from 30 metastatic colorectal cancer patients treated by cetuximab were screened for KRAS, BRAF, and PIK3CA mutation by direct sequencing and for EGFR copy number by chromogenic in situ hybridization. Eleven of the 30 patients (37%) responded to cetuximab. A KRAS mutation was found in 13 tumors (43%) and was significantly associated with the absence of response to cetuximab (KRAS mutation in 0% of the 11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003). The overall survival of patients without KRAS mutation in their tumor was significantly higher compared with those patients with a mutated tumor (P = 0.016; median, 16.3 versus 6.9 months). An increased EGFR copy number was found in 3 patients (10%) and was significantly associated with an objective tumor response to cetuximab (P = 0.04). In conclusion, in this study, KRAS mutations are a predictor of resistance to cetuximab therapy and are associated with a worse prognosis. The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment. (Cancer Res 2006; 66(8): 3992-5)