bluuebunny/crossref_metadata_2025_split huggingface dataset:
An exploratory case study of hotel e‐marketing in Ho Chi Minh City
Authors: Bui Tung X. , Le Truc , Jones Wayne D. 
Published: April 2006

AbstractMany developing countries have made tourism their top national priority for economic development, and e‐tourism is being promoted due to its relatively low start‐up costs and its high potential to attract foreign capital. However, with a low overall level of e‐readiness, deploying e‐tourism is a rather overwhelming endeavor. This article presents a case study that uses extensive field data collection to assess the effectiveness of Web technology in promoting tourism in Ho Chi Minh City, Vietnam. This city was selected because its tourism industry has been recognized for making a concerted effort to target foreign visitors and its hotels have been among the most important adopters of e‐commerce in the country. This study assists in better understanding the opportunities, challenges, and guidance necessary for e‐tourism to be effective in developing economies. Most interestingly, e‐commerce—intended to be the enabler of a seamless, highly competitive economy—can be a key competitive advantage for those who use it effectively in a less than perfect e‐market. © 2006 Wiley Periodicals, Inc.
Banking on global success: Internationalization strategy and its limitations (the case of Allied Irish Banks)
Authors: Lawton Thomas C. , Harrington Denis G. 
Published: April 2006

AbstractThis article explores the choices and challenges facing Ireland's leading financial services corporation, Allied Irish Banks (AIB), in its strategy for international market growth. It begins with an examination of the company's internationalization strategies within the global banking context. It then considers the limitations of international market expansion and transnational management control for a company with low brand recognition outside of its home market and limited experience of international operations. Finally, it elaborates on the strategic challenges that face the organization and reflects on the lessons for other midsized international companies competing in consolidating, globalized industries.© 2006 Wiley Periodicals, Inc.
Patient-to-Patient Transmission of Hepatitis C Virus Through the Use of Multidose Vials During General Anesthesia
Authors: Germain Jeanne-Marie , Carbonne Anne , Thiers Valérie , Gros Hélène , Chastan Sylvie , Bouvet Elisabeth , Astagneau Pascal 
Published: April 2006

AbstractA duster of four patients with hepatitis C virus (HCV) infection was identified in a surgery clinic. Molecular characterization revealed close homology between viruses. This cluster was related to unsafe injection practices through multidose vials and reused materials. Among 796 patients potentially exposed to and screened for HCV, no other cluster was identified.
Id1 Transcription Inhibitor–Matrix Metalloproteinase 9 Axis Enhances Invasiveness of the Breakpoint Cluster Region/Abelson Tyrosine Kinase–Transformed Leukemia Cells
Authors: Nieborowska-Skorska Margaret , Hoser Grazyna , Rink Lori , Malecki Maciej , Kossev Plamen , Wasik Mariusz A. , Skorski Tomasz 
Published: April 2006

Abstract
Breakpoint cluster region/Abelson (BCR/ABL) tyrosine kinase enhances the ability of leukemia cells to infiltrate various organs. We show here that expression of the helix-loop-helix transcription factor Id1 is enhanced by BCR/ABL in a signal transducer and activator of transcription 5 (STAT5)–dependent manner. Enhanced expression of Id1 plays a key role in BCR/ABL–mediated cell invasion. Down-regulation of Id1 in BCR/ABL leukemia cells by the antisense cDNA significantly reduced their invasive capability through the Matrigel membrane and their ability to infiltrate hematopoietic and nonhematopoietic organs resulting in delayed leukemogenesis in mice. The Id1-promoted cell invasiveness was seemingly mediated by matrix metalloproteinase 9 (MMP9). Transactivation of MMP9 promoter in BCR/ABL cells was dependent on Id1 and abrogation of the MMP9 catalytic activity by a metalloproteinase inhibitor or blocking antibody decreased invasive capacity of leukemia cells. These data suggest that BCR/ABL-STAT5-Id1-MMP9 pathway may play a critical role in BCR/ABL–mediated leukemogenesis by enhancing invasiveness of leukemia cells. (Cancer Res 2006; 66(8): 4108-16)
Retinoic Acid Induces p27Kip1 Nuclear Accumulation by Modulating Its Phosphorylation
Authors: Borriello Adriana , Cucciolla Valeria , Criscuolo Maria , Indaco Stefania , Oliva Adriana , Giovane Alfonso , Bencivenga Debora , Iolascon Achille , Zappia Vincenzo , Della Ragione Fulvio 
Published: April 2006

Abstract
All-trans-retinoic acid (ATRA), the most biologically active metabolite of vitamin A, controls cell proliferation, apoptosis, and differentiation depending on the cellular context. These activities point to ATRA as a candidate for cancer therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin-dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which clearly precedes growth arrest. The early buildup is not due to impairment of the CDKI degradation, in contrast to previous observations. Particularly, we did not detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the CDKI nuclear export and does not cause CDK2 relocalization. The characterization of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies established that this isoform corresponds to p27Kip1 phosphorylated on S10. The buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up-regulation of the isoform. In conclusion, our data suggest a novel mechanism of ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event causes the stabilization of p27Kip1 and its accumulation in the nuclear compartment. (Cancer Res 2006; 66(8): 4240-8)
The Requirement for and Changing Composition of the Activating Protein-1 Transcription Factor during Differentiation of Human Leukemia HL60 Cells Induced by 1,25-Dihydroxyvitamin D3
Authors: Wang Xuening , Studzinski George P. 
Published: April 2006

Abstract
The activating protein-1 (AP-1) transcription factor complex is a heterogeneous entity, composed in mammalian cells of dimers chosen from a group of at least eight proteins belonging to three families: jun, fos, and activating transcription factor (ATF). The AP-1 complexes participate in diverse biological processes that include cell proliferation, survival, and differentiation. These seemingly contrasting functions have been attributed to the intensity and duration of the signals provided by AP-1, but the biological consequences of changing composition of the AP-1 complex have not been fully explored. Here, we show that functional AP-1 is required for 1,25-dihydroxyvitamin D3 (1,25D)-induced monocytic differentiation, and that the composition of the AP-1 protein complex that binds TRE, its cognate DNA element, changes as cells differentiate. In HL60 cells in an early stage of differentiation, the principal AP-1 components detected by gel shift analysis include c-jun, ATF-2, fos-B, fra-1, and fra-2. In cells with a more established monocytic phenotype, the demonstrable AP-1 components are c-jun, ATF-2, jun-B, and fos-B. Following the addition of 1 nmol/L of 1,25D, the cellular content of each of these four proteins markedly increased in a sustained manner, whereas the increases in c-fos, fra-1, fra-2, and jun-D were minimal, if any. Small increases in mRNA levels encoding all AP-1 component proteins, except c-fos, were also noted. These findings provide a basis for the previously found participation of the c-Jun N-terminal kinase pathway in 1,25D-induced differentiation of myeloid leukemia cells, and direct attention to jun-B and fos-B as new cellular therapeutic targets, that may promote replicative quiescence associated with differentiation of malignant cells. (Cancer Res 2006; 66(8): 4202-9)
Noninvasive Magnetic Resonance Imaging of Transport and Interstitial Fluid Pressure in Ectopic Human Lung Tumors
Authors: Hassid Yaron , Furman-Haran Edna , Margalit Raanan , Eilam Raya , Degani Hadassa 
Published: April 2006

AbstractTumor response to blood borne drugs is critically dependent on the efficiency of vascular delivery and transcapillary transfer. However, increased tumor interstitial fluid pressure (IFP) forms a barrier to transcapillary transfer, leading to resistance to drug delivery. We present here a new, noninvasive method which estimates IFP and its spatial distribution in vivo using contrast-enhanced magnetic resonance imaging (MRI). This method was tested in ectopic human non–small-cell lung cancer which exhibited a high IFP of ∼28 mm Hg and, for comparison, in orthotopic MCF7 human breast tumors which exhibited a lower IFP of ∼14 mm Hg, both implanted in nude mice. The MRI protocol consisted of slow infusion of the contrast agent [gadolinium-diethylenetriaminepentaacetic acid (GdDTPA)] into the blood for ∼2 hours, sequential acquisition of images before and during the infusion, and measurements of T1 relaxation rates before infusion and after blood and tumor GdDTPA concentration reached a steady state. Image analysis yielded parametric images of steady-state tissue GdDTPA concentration with high values of this concentration outside the tumor boundaries, ∼1 mmol/L, declining in the tumor periphery to ∼0.5 mmol/L, and then steeply decreasing to low or null values. The distribution of steady-state tissue GdDTPA concentration reflected the distribution of IFP, showing an increase from the rim inward, with a high IFP plateau inside the tumor. The changes outside the borders of the tumors with high IFP were indicative of convective transport through the interstitium. This work presents a noninvasive method for assessing the spatial distribution of tumor IFP and mapping barriers to drug delivery and transport. (Cancer Res 2006; 66(8): 4159-66)
Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury
Authors: Lien Yu-Chin , Noel Teresa , Liu Hua , Stromberg Arnold J. , Chen Kuey-Chu , St. Clair Daret K. 
Published: April 2006

Abstract
The clinical application of adriamycin, an exceptionally good chemotherapeutic agent, is limited by its dose-related cardiomyopathy. Our recent study showed that tumor necrosis factor-α (TNF-α) receptors mediated cytoprotective signaling against adriamycin-induced mitochondrial injury and cardiomyocyte apoptosis. In the present study, we investigated the potential targets of TNF receptor–mediated cytoprotective signaling by global genome microarray analysis using wild-type and TNF receptor–deficient mice. Microarray analysis revealed that adriamycin treatment induced the down-regulation of several mitochondrial functions and energy production–related genes in double TNF receptor–deficient mice, notably, phospholipase C-δ1, a protein involved in fatty acid metabolism and calcium regulation. The role of phospholipase C-δ1 in TNF receptor–mediated cardioprotection against adriamycin-induced injury was evaluated by measuring changes in cardiac function using high-frequency ultrasound biomicroscopy. Selective inhibition of phospholipase C activity in wild-type mice by its inhibitor, U73122, exacerbated adriamycin-induced cardiac dysfunction. Inhibition of phospholipase C-δ1 resulted in the significant decrease of left ventricular ejection fraction and fractional shortening, and the decreased levels were similar to those observed in adriamycin-treated double TNF receptor–deficient mice. The data derived from the global genome analysis identified phospholipase C-δ1 as an important target for TNF receptors and revealed the critical role of TNF receptor signaling in the protection against adriamycin-induced cardiotoxicity. (Cancer Res 2006; 66(8): 4329-38)
Hemangioblastomas Share Protein Expression with Embryonal Hemangioblast Progenitor Cell
Authors: Gläsker Sven , Li Jie , Xia John B. , Okamoto Hiroaki , Zeng Weifen , Lonser Russell R. , Zhuang Zhengping , Oldfield Edward H. , Vortmeyer Alexander O. 
Published: April 2006

Abstract
Hemangioblastomas are central nervous system (CNS) tumors of unknown histogenesis, which can occur sporadically or in von Hippel-Lindau disease. Hemangioblastomas are composed of neoplastic “stromal” cells of unknown origin, accompanied by intensive reactive angiogenesis. Failure to specify the cytologic origin of the stromal cell has precluded the development of nonsurgical therapies and limits understanding of its basic biology. We report that the stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2) that characterize embryonic progenitor cells with hemangioblastic differentiation potential and conclude that embryonic progenitors with hemangioblast potential represent a possible cytologic equivalent of the stromal cell. We also identified a new autocrine/paracrine stimulatory loop between the receptor Tie-2 and the hypoxia-inducible factor target Ang-1, which, combined with previous observations, suggests that a variety of autocrine loops may be initiated in hemangioblastomas, depending on the differentiation status of the tumor cells and the extent of HIF downstream activation. Finally, the consistent identification of Scl in the stromal cells may help explain the unique and characteristic topographical distribution of hemangioblastomas within the CNS. (Cancer Res 2006; 66(8):4167-72)
Tumor Imaging Using a Picomolar Affinity HER2 Binding Affibody Molecule
Authors: Orlova Anna , Magnusson Mikaela , Eriksson Tove L.J. , Nilsson Martin , Larsson Barbro , Höidén-Guthenberg Ingmarie , Widström Charles , Carlsson Jörgen , Tolmachev Vladimir , Ståhl Stefan , Nilsson Fredrik Y. 
Published: April 2006

Abstract
The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, ZHER2:342 showed a &gt;2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging. (Cancer Res 2006; 66(8): 4339-48)
Stat1 Deficiency in the Host Enhances Interleukin-12–Mediated Tumor Regression
Authors: Torrero Marina N. , Xia Xueqing , Henk Williams , Yu Shry , Li Shulin 
Published: April 2006

AbstractSignal transducer and activator of transcription 1 (Stat1) is considered a key transcription factor that inhibits tumorigenesis, and Stat1 activation in the host is required for interleukin-12 (IL-12)–mediated generation of CTL activity. Using syngeneic Stat1−/− C3H mice bearing SCCVII tumors in this study, we discovered opposite results. Stat1 deficiency in the host significantly enhances IL-12–mediated tumor regression, resulting in tumor eradication from 60% of SCCVII tumor–bearing mice and significant inhibition of tumor growth when compared with control treatment (P &lt; 0.01). This effect is independent of both Stat1-activating cytokine IFN-γ and Stat1-downstream effector molecule FasL because neither neutralization of IFN-γ nor knocking out of FasL enhances or inhibits IL-12–mediated tumor regression. IL-12 induces a high intensity of tumor-specific CTL activity in Stat1-deficient mice (P &lt; 0.01), increases the CD8 T-cell density in tumor bearing Stat1−/− mice, and induces a T-cell–dependent tumor regression. The increased CTL activity and the high-intensity infiltration of T cells into the tumors in IL-12–treated Stat1−/− mice are likely due to the longer survival than the same cells from wild-type mice. Together, the data show that inhibition of Stat1 expression in the host enhances tumor-local IL-12 gene therapy for regressing tumors. This conclusion provides a new concept for designing an effective treatment strategy. (Cancer Res 2006; 66(8): 4461-7)
Notch1 Signaling Promotes Primary Melanoma Progression by Activating Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase-Akt Pathways and Up-regulating N-Cadherin Expression
Authors: Liu Zhao-Jun , Xiao Min , Balint Klara , Smalley Keiran S.M. , Brafford Patricia , Qiu Ruihua , Pinnix Chelsea C. , Li Xueli , Herlyn Meenhard 
Published: April 2006

Abstract
Cellular signaling mediated by Notch receptors results in coordinated regulation of cell growth, survival, and differentiation. Aberrant Notch activation has been linked to a variety of human neoplasms. Here, we show that Notch1 signaling drives the vertical growth phase (VGP) of primary melanoma toward a more aggressive phenotype. Constitutive activation of Notch1 by ectopic expression of the Notch1 intracellular domain enables VGP primary melanoma cell lines to proliferate in a serum-independent and growth factor–independent manner in vitro and to grow more aggressively with metastatic activity in vivo. Notch1 activation also enhances tumor cell survival when cultured as three-dimensional spheroids. Such effects of Notch signaling are mediated by activation of the mitogen-activated protein kinase (MAPK) and Akt pathways. Both pathways are activated in melanoma cells following Notch1 pathway activation. Inhibition of either the MAPK or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway reverses the Notch1 signaling-induced tumor cell growth. Moreover, the growth-promoting effect of Notch1 depends on mastermind-like 1. We further showed that Notch1 activation increases tumor cell adhesion and up-regulates N-cadherin expression. Our data show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin by the Notch pathway and provide a mechanistic basis for Notch signaling in the promotion of primary melanoma progression. (Cancer Res 2006; 66(8): 4182-90)
Inactivation of Human MAD2B in Nasopharyngeal Carcinoma Cells Leads to Chemosensitization to DNA-Damaging Agents
Authors: Cheung Hiu Wing , Chun Abel C.S. , Wang Qi , Deng Wen , Hu Liang , Guan Xin-Yuan , Nicholls John M. , Ling Ming-Tat , Chuan Wong Yong , Wah Tsao Sai , Jin Dong-Yan , Wang Xianghong 
Published: April 2006

Abstract
Rev7p has been suggested to play an important role in regulating DNA damage response in yeast, and recently, the human homologue (i.e., MAD2B) has been identified, which shares significant homology to the mitotic checkpoint protein MAD2. In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and γ-irradiation. This effect was associated with reduced frequencies of spontaneous and drug-induced mutations, elevated phosphorylation of histone H2AX, and markedly increased chromosomal aberrations in response to DNA damage. In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells. These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells. Our findings reveal a novel strategy for cancer therapy, in which cancer cells are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B gene. (Cancer Res 2006; 66(8): 4357-67)
Immunoglobulin Heavy Chain Locus Events and Expression of Activation-Induced Cytidine Deaminase in Epithelial Breast Cancer Cell Lines
Authors: Babbage Gavin , Ottensmeier Christian H. , Blaydes Jeremy , Stevenson Freda K. , Sahota Surinder S. 
Published: April 2006

AbstractWhen cells transform, phenotypic and genetic profiles can be dramatically altered. Nevertheless, a recent report identifying IgG in breast cancer cells was unexpected, revealing differentiation features normally associated with B lymphocytes. To extend these findings, we focused on immunoglobulin variable (V) region gene analysis using well-defined breast cancer cell lines expressing the epithelial marker, epithelial cell adhesion molecule (EpCAM). VH gene transcripts were identifiable by nested reverse transcription-PCR either as single or dual V, diversity (D), and joining (J) rearrangements in four of six lines, most being potentially functional. V(D)J transcripts were observed in sequential cultures, indicating stable expression. To exclude coexisting lymphocytes, each cell line was shown to be EBV negative, with CD19/CD20 and cytoplasmic/surface immunoglobulin also absent by flow cytometry. Identified VH transcripts were then sought in individual tumor cells, isolated as EpCAM+ single cells by flow cytometry. Importantly, in three of three selected cell lines, VH genes were identifiable in a significant fraction (∼32%) of single cells. In five of six identified VH genes, somatic mutations were apparent with no intraclonal variation, indicating cessation of mutational activity. VH transcripts were pre- and post-isotype switch, with activation of switch events evident from expressed germ-line switch transcripts in two of six lines. Strikingly, six of six cell lines expressed activation-induced cytidine deaminase (AID) essential for mutational and switch activity. These data suggest either a de novo rearrangement and modification of VH genes in epithelial tumor cells or assimilation of lymphocyte-derived chromatin. Constitutive AID activation in malignant epithelial cells further raises a potential for inducing aberrant mutational activity. (Cancer Res 2006; 66(8): 3996-4000)