bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth
Authors: DeRosier Leo Christopher , Vickers Selwyn M. , Zinn Kurt R. , Huang Zhi , Wang Wenquan , Grizzle William E. , Sellers Jeffrey , Stockard Cecil R. , Zhou Tong , Oliver Patsy G. , Arnoletti Pablo , LoBuglio Albert F. , Buchsbaum Donald J. 
Published: December 2007

Abstract
Purpose: To evaluate agonistic TRA-8 monoclonal antibody to human death receptor 5 (DR5) and gemcitabine in vitro and in an orthotopic pancreatic cancer model. Experimental Design: Pancreatic cancer cell lines were screened for DR5 expression, cytotoxicity, and apoptosis induced by TRA-8, gemcitabine, or gemcitabine and TRA-8. An orthotopic model of pancreatic cancer was established in severe combined immunodeficient mice. Mice were treated with TRA-8, gemcitabine, or a combination for one or two cycles of therapy. Tumor growth (ultrasound) and survival were analyzed. Results: All five pancreatic cancer cell lines showed DR5 protein expression and varying sensitivity to TRA-8–mediated cytotoxicity. MIA PaCa-2 cells were very sensitive to TRA-8, moderately resistant to gemcitabine, with additive cytotoxicity to the combination. S2-VP10 cells were resistant to TRA-8 and sensitive to gemcitabine with synergistic sensitivity to the combination. Combination treatment in vitro produced enhanced caspase-3 and caspase-8 activation. A single cycle of therapy produced comparable efficacy for single-agent TRA-8 and the combination of TRA-8 and gemcitabine, with significant reduction in tumor size and prolonged survival compared with gemcitabine alone or control animals. With two cycles of therapy, TRA-8 and combination therapy produced enhanced inhibition of tumor growth compared with single-agent gemcitabine or untreated animals. However, the combination regimen showed enhanced survival as compared with single-agent TRA-8. Conclusions: Pancreatic cancer cell lines express varying levels of DR5 and differ in their sensitivity to TRA-8 and gemcitabine-induced cytotoxicity. TRA-8 with two cycles of gemcitabine therapy produced the best overall survival. [Mol Cancer Ther 2007;6(12):3198–207]
Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent substrate of the multidrug resistance–linked ABCG2 transporter
Authors: Wu Chung-Pu , Shukla Suneet , Calcagno Anna Maria , Hall Matthew D. , Gottesman Michael M. , Ambudkar Suresh V. 
Published: December 2007

Abstract
Multidrug resistance due to reduced drug accumulation is a phenomenon predominantly caused by the overexpression of members of the ATP-binding cassette (ABC) transporters, including ABCB1 (P-glycoprotein), ABCG2, and several ABCC family members [multidrug resistance–associated protein (MRP)]. We previously reported that a thiosemicarbazone derivative, NSC73306, is cytotoxic to carcinoma cells that overexpress functional P-glycoprotein, and it resensitizes these cells to chemotherapeutics. In this study, we investigated the effect of NSC73306 on cells overexpressing other ABC drug transporters, including ABCG2, MRP1, MRP4, and MRP5. Our findings showed that NSC73306 is not more toxic to cells that overexpress these transporters compared with their respective parental cells, and these transporters do not confer resistance to NSC73306 either. In spite of this, we observed that NSC73306 is a transport substrate for ABCG2 that can effectively inhibit ABCG2-mediated drug transport and reverse resistance to both mitoxantrone and topotecan in ABCG2-expressing cells. Interactions between NSC73306 and the ABCG2 drug-binding site(s) were confirmed by its stimulatory effect on ATPase activity (140–150 nmol/L concentration required for 50% stimulation) and by inhibition of [125I]iodoarylazidoprazosin photolabeling (50% inhibition at 250–400 nmol/L) of the substrate-binding site(s). Overall, NSC73306 seems to be a potent modulator of ABCG2 that does not interact with MRP1, MRP4, or MRP5. Collectively, these data suggest that NSC73306 can potentially be used, due to its dual mode of action, as an effective agent to overcome drug resistance by eliminating P-glycoprotein–overexpressing cells and by acting as a potent modulator that resensitizes ABCG2-expressing cancer cells to chemotherapeutics. [Mol Cancer Ther 2007;6(12):3287–96]
Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity
Authors: Chan Florence , Sun Chongbo , Perumal Meg , Nguyen Quang-De , Bavetsias Vassilios , McDonald Edward , Martins Vanessa , Wilsher Nicola E. , Raynaud Florence I. , Valenti Melanie , Eccles Sue , te Poele Robert , Workman Paul , Aboagye Eric O. , Linardopoulos Spiros 
Published: December 2007

Abstract
The Aurora family of serine/threonine kinases is important for the regulation of centrosome maturation, chromosome segregation, and cytokinesis during mitosis. Overexpression of Aurora kinases in mammalian cells leads to genetic instability and transformation. Increased levels of Aurora kinases have also been linked to a broad range of human tumors. Here, we describe the properties of CCT129202, a representative of a structurally novel series of imidazopyridine small-molecule inhibitors of Aurora kinase activity. This compound showed high selectivity for the Aurora kinases over a panel of other kinases tested and inhibits proliferation in multiple cultured human tumor cell lines. CCT129202 causes the accumulation of human tumor cells with ≥4N DNA content, leading to apoptosis. CCT120202-treated human tumor cells showed a delay in mitosis, abrogation of nocodazole-induced mitotic arrest, and spindle defects. Growth of HCT116 xenografts in nude mice was inhibited after i.p. administration of CCT129202. We show that p21, the cyclin-dependent kinase inhibitor, is induced by CCT129202. Up-regulation of p21 by CCT129202 in HCT116 cells led to Rb hypophosphorylation and E2F inhibition, contributing to a decrease in thymidine kinase 1 transcription. This has facilitated the use of 3′-deoxy-3′[18F]fluorothymidine-positron emission tomography to measure noninvasively the biological activity of the Aurora kinase inhibitor CCT129202 in vivo. [Mol Cancer Ther 2007;6(12):3147–57]
Identification of a human immunodominant B-cell epitope within the immunoglobulin A1 protease of Streptococcus pneumoniae
Authors: De Paolis Francesca , Beghetto Elisa , Spadoni Andrea , Montagnani Francesca , Felici Franco , Oggioni Marco R , Gargano Nicola 
Published: December 2007

AbstractBackgroundThe IgA1 protease ofStreptococcus pneumoniaeis a proteolytic enzyme that specifically cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a major role in pathogen's resistance to the host immune response. The present work was focused at identifying the immunodominant regions of pneumococcal IgA1 protease recognized by the human antibody response.ResultsAn antigenic sequence corresponding to amino acids 420–457 (epiA) of theigagene product was identified by screening a pneumococcal phage display library with patients' sera. The epiA peptide is conserved in all pneumococci and in two out of threeS. mitisstrains, while it is not present in other oral streptococci so far sequenced. This epitope was specifically recognized by antibodies present in sera from 90% of healthy adults, thus representing an important target of the humoral response toS. pneumoniaeandS. mitisinfection. Moreover, sera from 68% of children less than 4 years old reacted with the epiA peptide, indicating that the human immune response against streptococcal antigens occurs during childhood.ConclusionThe broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope. The use of phage display libraries to identify microbe or disease-specific antigens recognized by human sera is a valuable approach to epitope discovery.
The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice
Authors: Biketov Sergey , Potapov Vasilii , Ganina Elena , Downing Katrina , Kana Bavesh D , Kaprelyants Arseny 
Published: December 2007

AbstractBackgroundMycobacterium tuberculosiscan enter into a dormant state which has resulted in one third of the world's population being infected with latent tuberculosis making the study of latency and reactivation of utmost importance.M. tuberculosisencodes five resuscitation promoting factors (Rpfs) that bear strong similarity to a lysozyme-like enzyme previously implicated in reactivation of dormant bacteriain vitro.We have developed an intraperitoneal infection model in mice, with immune modulation, that models chronic infection with similar properties in mouse lungs as those observed in the murine aerosol infection model. We have assessed the behavior of mutants that lack two or threerpfgenes in different combinations in our intraperitoneal model.MethodsC57Bl/6 mice were intraperitonealy infected with H37Rv wild typeM. tuberculosisor mutant strains that lacked two or threerpfgenes in different combinations. After 90 days of infection aminoguanidine (AG) or anti-TNFα antibodies were administrated. Organ bacillary loads were determined at various intervals post infection by plating serial dilutions of organ homogenates and enumerating bacteria.ResultsWe found that therpftriple and double mutants tested were attenuated in their ability to disseminate to mouse lungs after intraperitoneal administration and were defective in their ability to re-grow after immunosuppression induced by administration of aminoguanidine and anti-TNFα antibodies.ConclusionRpf proteins may have a significant physiological role for development of chronic TB infection and its reactivationin vivo.
Application of the comprehensive set of heterozygous yeast deletion mutants to elucidate the molecular basis of cellular chromium toxicity
Authors: Holland Sara , Lodwig Emma , Sideri Theodora , Reader Tom , Clarke Ian , Gkargkas Konstantinos , Hoyle David C , Delneri Daniela , Oliver Stephen G , Avery Simon V 
Published: December 2007

Abstract
Background
The serious biological consequences of metal toxicity are well documented, but the key modes of action of most metals are unknown. To help unravel molecular mechanisms underlying the action of chromium, a metal of major toxicological importance, we grew over 6,000 heterozygous yeast mutants in competition in the presence of chromium. Microarray-based screens of these heterozygotes are truly genome-wide as they include both essential and non-essential genes.

Results
The screening data indicated that proteasomal (protein degradation) activity is crucial for cellular chromium (Cr) resistance. Further investigations showed that Cr causes the accumulation of insoluble and toxic protein aggregates, which predominantly arise from proteins synthesised during Cr exposure. A protein-synthesis defect provoked by Cr was identified as mRNA mistranslation, which was oxygen-dependent. Moreover, Cr exhibited synergistic toxicity with a ribosome-targeting drug (paromomycin) that is known to act via mistranslation, while manipulation of translational accuracy modulated Cr toxicity.

Conclusion
The datasets from the heterozygote screen represent an important public resource that may be exploited to discover the toxic mechanisms of chromium. That potential was validated here with the demonstration that mRNA mistranslation is a primary cause of cellular Cr toxicity.
Reduced-Intensity Conditioning Compared With Conventional Allogeneic Stem-Cell Transplantation in Relapsed or Refractory Hodgkin's Lymphoma: An Analysis From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Sureda Anna , Robinson Stephen , Canals Carmen , Carella Angelo M. , Boogaerts Marc A. , Caballero Dolores , Hunter Ann E. , Kanz Lothar , Slavin Shimon , Cornelissen Jan J. , Gramatzki Martin , Niederwieser Dietger , Russell Nigel H. , Schmitz Norbert 
Published: December 2007

Purpose To compare the clinical outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell transplantation (alloSCT). Patients and Methods A total of 168 patients with HL undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79) between January 1997 and December 2001 and registered in the European Group for Blood and Marrow Transplantation database were analyzed. Results NRM was significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62 to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to 3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53; 95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but not in multivariate analysis. The development of chronic graft-versus-host disease (GVHD) significantly decreased the incidence of relapse, which translated into a trend for a better PFS. Conclusion The lower incidence of NRM in the RIC group is encouraging, particularly because these patients experienced adverse pretransplantation characteristics more frequently. This analysis also indicates the existence of a graft-versus-HL effect correlated to the development of GVHD. Additional efforts to reduce the high RR seen in both groups of patients will be necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients prepared with RIC or myeloablative conditioning.
Microbial Spectrum and Antibiotic Susceptibility Profile of Gram-Positive Aerobic Bacteria Isolated From Cancer Patients
Authors: Ashour Hossam M. , El-Sharif Amany 
Published: December 2007

Purpose Cancer patients are particularly susceptible to nosocomial infections because of their compromised immune system, and because of the nature of treatment practices they experience. Recently, a shift of the microbial spectrum of cancer patients from Gram-negative to Gram-positive has been demonstrated. This study analyzed the distribution and the antimicrobial resistance of Gram-positive bacteria isolated from cancer patients in Egypt. Patients and Methods We examined the microbial spectrum of Gram-positive bacteria in patients with hematologic malignancies and solid tumors. In addition, we also studied the antimicrobial resistance of pathogens accounting for the majority of Gram-positive infections in these cancer patients. Results Most of Gram-positive isolates from urinary tract (100%), respiratory tract (89.7%), and bloodstream infections (BSIs; 65.5%) were obtained from leukemic patients. All Gram-positive isolates from skin infections were isolated from solid-tumor patients. In both leukemic and solid-tumor patients, Gram-positive bacteria causing nosocomial BSI were mainly Coagulase-negative staphylococcus (CNS) and S aureus, whereas Gram-positive bacteria causing nosocomial RTI were mainly α-hemolytic streptococci and CNS. Gram-positive bacteria were not isolated from GI tract infections. S aureus, CNS, and α-hemolytic streptococci demonstrated methicillin resistance (81.5%, 92.3%, and 90% resistance, respectively). S aureus and CNS were susceptible to linezolid (15.4% and 0% resistance, respectively), and vancomycin (15.5% and 11% resistance, respectively). Conclusion This is the first study to report the emergence of vancomycin- and linezolid-resistant S aureus in Egypt. Newer generation quinolones (moxifloxacin and gatifloxacin) were more active than older quinolones (ciprofloxacin and ofloxacin) against S aureus and CNS, suggesting the use of newer generation quinolones in the prophylaxis of cancer patients.
Hydrolase-catalyzed Kinetic Resolution of 5-[4-(1-Hydroxyethyl)phenyl]-10,15,20-tris(pentafluorophenyl)porphyrin in Ionic Liquids
Authors: Ema Tadashi , Doi Tokuhiro , Sakai Takashi 
Published: December 2007

Abstract
Bulky alcohol, 5-[4-(1-hydroxyethyl)phenyl]-10,15,20-tris(pentafluorophenyl)porphyrin (1b), was synthesized, and enantiomerically pure alcohol 1b and ester 2b were obtained by a single kinetic resolution catalyzed by Candida antarctica lipase in i-Pr2O and in [bdmim][PF6].
Text messaging in Kuwait. Is the medium the message?
Authors: Haggan Madeline 
Published: December 2007

Abstract
In Kuwait the use of the mobile phone has spread rapidly and universally and the use of text messaging has become popular among the younger members of society. One aim of the paper was (by means of a questionnaire) to elicit some basic information about users' attitudes and practices with regard to the medium in their culture. Until comparatively recently it was not technically possible to send Arabic text messages using the Arabic alphabet and they had to be sent using the English alphabet. Another aim, therefore, was to ascertain whether Kuwaitis still use the English alphabet for Arabic text messages or whether they make use of the Arabic keypad now available. It was found that while Arabic messages are sent, a substantial percentage of messages use English and a mixture of Arabic and English. Of particular interest is how users use English characters to transcribe their Arabic texts. This raises linguistic and cultural questions which are explored in the paper.
The differentiation of the Romani dialects
Authors: Boretzky Norbert 
Published: December 2007

Abstract
Romani is split up in a great number of dialects and dialect groups, but it is not clear when and under what circumstances linguistic diversification took place. It is controversial whether innovations mainly spread by “diffusion” over a once homogeneous continuum or were transported to other places mainly by the split-up of groups of speakers and subsequent migration. The diffusion model explains diversification in general, but it cannot explain how mere diffusion would bring about the emergence of well-delimited dialect groups or families. Most probably, differentiation began very early accumulating during the European history of the language, effected both by linguistic (innovations and diffusion of innovations) and extralinguistic (split and migration) processes.
The phonological basis of linguistic rhythm: cross-linguistic data and diachronic interpretation
Authors: Schiering René 
Published: December 2007

AbstractSeveral research traditions have hypothesized that rhythmic differences between mora-, syllable- and stress-timed languages are rooted in the different phonological profiles of the languages in question. In this paper, ten of the proposed prosodic, phonotactic and morphophonological parameters are tested against data from a twenty-language sample. The evidence suggests that rhythmic differences across languages are gradual rather than discrete. Linguistic rhythm should therefore be conceived as a continuum with mora- and stress-based rhythm as focal points. Since evolutionary processes on stress- and mora-related parameters are in principle independent from each other, diachrony casts doubt on holistic typologies of linguistic rhythm.
Retinal Arteriolar Narrowing Predicts Incidence of Diabetes
Authors: Nguyen Thanh T. , Wang Jie Jin , Islam F.M. Amirul , Mitchell Paul , Tapp Robyn J. , Zimmet Paul Z. , Simpson Richard , Shaw Jonathan , Wong Tien Y. 
Published: December 2007

OBJECTIVE—To examine the relationship of retinal vascular caliber to incident diabetes in a population-based cohort.
RESEARCH DESIGN AND METHODS—The Australian Diabetes, Obesity and Lifestyle (AusDiab) Study recruited adults aged 25+ years across Australia in 1999–2000, with a follow-up 5 years later in 2004–2005. Participants' glycemic status was classified using fasting plasma glucose (FPG) and 2-h oral glucose tolerance (2-h plasma glucose [2hPG]) tests. Diabetes was diagnosed if FPG was ≥7.0 mmol/l or 2hPG was ≥11.1 mmol/l. Retinal vascular caliber was measured from baseline retinal photographs using a computer-assisted program.
RESULTS—Of the 803 participants without diabetes at baseline, 108 (13.4%) developed diabetes at follow-up: 7 (2.8%) of 246 participants with normal glucose tolerance, 9 (13.6%) of 66 participants with impaired fasting glucose, and 92 (18.7%) of 491 participants with impaired glucose tolerance. After multivariate analysis, participants with narrower retinal arteriolar caliber had a higher risk of diabetes (odds ratio 2.21 [95% CI 1.02–4.80], comparing smallest versus highest arteriolar caliber tertiles, P = 0.04 for trend). There was no association between retinal venular caliber and incident diabetes.
CONCLUSIONS—Narrower retinal arteriolar caliber predicted risk of diabetes. These data provide further evidence that microvascular changes may contribute to the pathogenesis of diabetes.
The effect of bottom boundary conditions in the ice-sheet to ice-shelf transition zone problem
Authors: Wilchinsky Alexander V. 
Published: December 2007

AbstractUniqueness of the transition zone solution is discussed. It is argued that when it is assumed that the stresses are continuous at the grounding line, the ice-shelf solution at the grounding line should possess a zero slope. In order to avoid issues caused by the mathematical singularity of the solution, the same technique as that used to study the transition zone is applied to a similar problem of lifting an elastic sheet from a rigid substrate, which allows a better physical understanding. This exemplifies the effect of the bottom boundary condition of no vertical motion imposed up to a fixed grounding line position, while the forcing parameters, such as the flow rate, vary. Its effect is to produce multiple solutions due to suppression of the separation mechanism.