bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tetravalent Dengue Vaccine Based on a Complex Adenovirus Vector Provides Significant Protection in Rhesus Monkeys against All Four Serotypes of Dengue Virus
Authors: Raviprakash Kanakatte , Wang Danher , Ewing Dan , Holman David H. , Block Karla , Woraratanadharm Jan , Chen Lan , Hayes Curtis , Dong John Y. , Porter Kevin 
Published: May 2008

ABSTRACT
Nearly a third of the human population is at risk of infection with the four serotypes of dengue viruses, and it is estimated that more than 100 million infections occur each year. A licensed vaccine for dengue viruses has become a global health priority. A major challenge to developing a dengue vaccine is the necessity to produce fairly uniform protective immune responses to all four dengue virus serotypes. We have developed two bivalent dengue virus vaccines, using a complex adenovirus vector, by incorporating the genes expressing premembrane (prM) and envelope (E) proteins of dengue virus types 1 and 2 (dengue-1 and -2, respectively) (CAdVax-Den12) or dengue-3 and -4 (CAdVax-Den34). Rhesus macaques were vaccinated by intramuscular inoculation of a tetravalent dengue vaccine formulated by combining the two bivalent vaccine constructs. Vaccinated animals produced high-titer antibodies that neutralized all four serotypes of dengue viruses in vitro. The ability of the vaccine to induce rapid, as well as sustained, protective immune responses was examined with two separate live-virus challenges administered at 4 and 24 weeks after the final vaccination. For both of these virus challenge studies, significant protection from viremia was demonstrated for all four dengue virus serotypes in vaccinated animals. Viremia from dengue-1 and dengue-3 challenges was completely blocked, whereas viremia from dengue-2 and dengue-4 was significantly reduced, as well as delayed, compared to that of control-vaccinated animals. These results demonstrate that the tetravalent dengue vaccine formulation provides significant protection in rhesus macaques against challenge with all four dengue virus serotypes.
XML data exchange
Authors: Arenas Marcelo , Libkin Leonid 
Published: May 2008

Data exchange is the problem of finding an instance of a target schema, given an instance of a source schema and a specification of the relationship between the source and the target. Theoretical foundations of data exchange have recently been investigated for relational data.
In this article, we start looking into the basic properties of XML data exchange, that is, restructuring of XML documents that conform to a source DTD under a target DTD, and answering queries written over the target schema. We define XML data exchange settings in which source-to-target dependencies refer to the hierarchical structure of the data. Combining DTDs and dependencies makes some XML data exchange settings inconsistent. We investigate the consistency problem and determine its exact complexity.
We then move to query answering, and prove a dichotomy theorem that classifies data exchange settings into those over which query answering is tractable, and those over which it is coNP-complete, depending on classes of regular expressions used in DTDs. Furthermore, for all tractable cases we give polynomial-time algorithms that compute target XML documents over which queries can be answered.
Announcements
Authors: Lee Newton 
Published: May 2008

1. First announcement and call for papers for EuroITV 2008 --- July 3--4, 2008 --- Salzburg, Austria --- Sixth European Interactive TV Conference
2. Experimental Playground --- May 8--June 7 --- Sydney, Australia
3. GAME-ON North America 2008 --- August 13--15 , 2008 --- McGill University, Montreal, Canada
4. IADIS International Conference --- Gaming 2008: Design for engaging experience and social interaction --- Amsterdam, The Netherlands --- July 25--27, 2008
5. Immersive Virtual, Mixed, or Augmented Reality Art --- Call for Papers
6. Inclusive Interactive Television: Setting the Agenda for Innovative Research. One-Day Workshop --- In conjunction with EuroITV 2008 --- Salzburg, Austria
7. uxTV 2008 --- First International Conference on Designing Interactive User Experiences for TV and Video --- October 22--24, 2008
Activated Ca2+/Calmodulin-Dependent Protein Kinase IIγ Is a Critical Regulator of Myeloid Leukemia Cell Proliferation
Authors: Si Jutong , Collins Steven J. 
Published: May 2008

Abstract
Ca2+ signaling is an important component of signal transduction pathways regulating B and T lymphocyte proliferation, but the functional role of Ca2+ signaling in regulating myeloid leukemia cell proliferation has been largely unexplored. We observe that the activated (autophosphorylated) Ca2+/calmodulin-dependent protein kinase IIγ (CaMKIIγ) is invariably present in myeloid leukemia cell lines as well as in the majority of primary acute myelogenous leukemia patient samples. In contrast, myeloid leukemia cells induced to terminally differentiate or undergo growth arrest display a marked reduction in this CaMKIIγ autophosphorylation. In cells harboring the bcr-abl oncogene, the activation (autophosphorylation) of CaMKIIγ is regulated by this oncogene. Moreover, inhibition of CaMKIIγ activity with pharmacologic agents, dominant-negative constructs, or short hairpin RNAs inhibits the proliferation of myeloid leukemia cells, and this is associated with the inactivation/down-regulation of multiple critical signal transduction networks involving the mitogen-activated protein kinase, Janus-activated kinase/signal transducers and activators of transcription (Jak/Stat), and glycogen synthase kinase (GSK3β)/β-catenin pathways. In myeloid leukemia cells, CaMKIIγ directly phosphorylates Stat3 and enhances its transcriptional activity. Thus, CaMKIIγ is a critical regulator of multiple signaling networks regulating the proliferation of myeloid leukemia cells. Inhibiting CaMKIIγ may represent a novel approach in the targeted therapy of myeloid leukemia. [Cancer Res 2008;68(10):3733–42]
Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways
Authors: Onder Tamer T. , Gupta Piyush B. , Mani Sendurai A. , Yang Jing , Lander Eric S. , Weinberg Robert A. 
Published: May 2008

Abstract
Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts—an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner β-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss–induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes. [Cancer Res 2008;68(10):3645–53]
The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ERα Pathway in Breast Cancer
Authors: Boulay Anne , Breuleux Madlaina , Stephan Christine , Fux Caroline , Brisken Cathrin , Fiche Maryse , Wartmann Markus , Stumm Michael , Lane Heidi A. , Hynes Nancy E. 
Published: May 2008

Abstract
A limited number of receptor tyrosine kinases (e.g., ErbB and fibroblast growth factor receptor families) have been genetically linked to breast cancer development. Here, we investigated the contribution of the Ret receptor tyrosine kinase to breast tumor biology. Ret was expressed in primary breast tumors and cell lines. In estrogen receptor (ER)α-positive MCF7 and T47D lines, the ligand (glial-derived neurotrophic factor) activated signaling pathways and increased anchorage-independent proliferation in a Ret-dependent manner, showing that Ret signaling is functional in breast tumor cells. Ret expression was induced by estrogens and Ret signaling enhanced estrogen-driven proliferation, highlighting the functional interaction of Ret and ER pathways. Furthermore, Ret was detected in primary cancers, and there were higher Ret levels in ERα-positive tumors. In summary, we showed that Ret is a novel proliferative pathway interacting with ER signaling in vitro. Expression of Ret in primary breast tumors suggests that Ret might be a novel therapeutic target in breast cancer. [Cancer Res 2008;68(10):3743–51]
Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes
Authors: Ishii Hideshi , Mimori Koshi , Ishikawa Kazuhiro , Okumura Hiroshi , Pichiorri Flavia , Druck Teresa , Inoue Hiroshi , Vecchione Andrea , Saito Toshiyuki , Mori Masaki , Huebner Kay 
Published: May 2008

Abstract
The fragile FHIT gene is among the first targets of DNA damage in preneoplastic lesions, and recent studies have shown that Fhit protein is involved in surveillance of genome integrity and checkpoint response after genotoxin exposure. We now find that Fhit-deficient hematopoietic cells, exposed to the genotoxin hydroquinone, are resistant to the suppression of stem cell in vitro colony formation observed with wild-type (Wt) hematopoietic cells. In vivo–transplanted, hydroquinone-exposed, Fhit-deficient bone marrow cells also escaped the bone marrow suppression exhibited by Wt-transplanted bone marrow. Comparative immunohistochemical analyses of bone marrow transplants showed relative absence of Bax in Fhit-deficient bone marrow, suggesting insensitivity to apoptosis; assessment of DNA damage showed that occurrence of the oxidized base 8-hydroxyguanosine, a marker of DNA damage, was also reduced in Fhit-deficient bone marrow, as was production of intracellular reactive oxygen species. Treatment with the antioxidant N-acetyl-l-cysteine relieved hydroquinone-induced suppression of colony formation by Wt hematopoietic cells, suggesting that the decreased oxidative damage to Fhit-deficient cells, relative to Wt hematopoietic cells, accounts for the survival advantage of Fhit-deficient bone marrow. Homology-dependent recombination repair predominated in Fhit-deficient cells, although not error-free repair, as indicated by a higher incidence of 6-thioguanine–resistant colonies. Tissues of hydroquinone-exposed Fhit-deficient bone marrow–transplanted mice exhibited preneoplastic alterations, including accumulation of histone H2AX-positive DNA damage. The results indicate that reduced oxidative stress, coupled with efficient but not error-free DNA damage repair, allows unscheduled long-term survival of genotoxin-exposed Fhit-deficient hematopoietic stem cells carrying deleterious mutations. [Cancer Res 2008;68(10):3662–70]
Constitutive Activation of Signal Transducers and Activators of Transcription Predicts Vorinostat Resistance in Cutaneous T-Cell Lymphoma
Authors: Fantin Valeria R. , Loboda Andrey , Paweletz Cloud P. , Hendrickson Ronald C. , Pierce Jacqueline W. , Roth Jennifer A. , Li Lixia , Gooden Frank , Korenchuk Susan , Hou Xiaoli S. , Harrington Elizabeth A. , Randolph Sophia , Reilly John F. , Ware Christopher M. , Kadin Marshall E. , Frankel Stanley R. , Richon Victoria M. 
Published: May 2008

Abstract
Vorinostat is a histone deacetylase inhibitor that induces differentiation, growth arrest, and/or apoptosis of malignant cells both in vitro and in vivo and has shown clinical responses in ∼30% of patients with advanced mycosis fungoides and Sézary syndrome cutaneous T-cell lymphoma (CTCL). The purpose of this study was to identify biomarkers predictive of vorinostat response in CTCL using preclinical model systems and to assess these biomarkers in clinical samples. The signal transducer and activator of transcription (STAT) signaling pathway was evaluated. The data indicate that persistent activation of STAT1, STAT3, and STAT5 correlate with resistance to vorinostat in lymphoma cell lines. Simultaneous treatment with a pan-Janus-activated kinase inhibitor resulted in synergistic antiproliferative effect and down-regulation of the expression of several antiapoptotic genes. Immunohistochemical analysis of STAT1 and phosphorylated tyrosine STAT3 (pSTAT3) in skin biopsies obtained from CTCL patients enrolled in the vorinostat phase IIb trial showed that nuclear accumulation of STAT1 and high levels of nuclear pSTAT3 in malignant T cells correlate with a lack of clinical response. These results suggest that deregulation of STAT activity plays a role in vorinostat resistance in CTCL, and strategies that block this pathway may improve vorinostat response. Furthermore, these findings may be of prognostic value in predicting the response of CTCL patients to vorinostat. [Cancer Res 2008;68(10):3785–94]
Inflammatory Signaling and Aryl Hydrocarbon Receptor Mediate Synergistic Induction of Interleukin 6 in MCF-7 Cells
Authors: Hollingshead Brett D. , Beischlag Timothy V. , DiNatale Brett C. , Ramadoss Preeti , Perdew Gary H. 
Published: May 2008

Abstract
The pleiotropic cytokine interleukin 6 (IL-6) is involved in immune cell homeostasis. Additionally, IL-6 expression and signaling in tumor cells have been shown to elicit both protumor and antitumor properties. There is a plethora of mechanistic knowledge regarding how IL-6 signal transduction translates to biological responses. However, there is little understanding as to what factors control IL-6 expression within a tumor cell environment. The studies presented herein show that, in MCF-7 breast and ECC-1 endocervical cancer cells, the stimulation of aryl hydrocarbon receptor (AHR) activity, in combination with IL-1β or phorbol 12-myristate 13-acetate (PMA) treatment, results in a marked synergistic induction of IL-6 levels over what is seen without AHR activation. Chromatin immunoprecipitation experiments suggest that the regulation of IL-6 mRNA expression occurs at the chromatin level, as AHR presence on the IL-6 promoter was observed in response to treatment with AHR ligand. Synergistic induction of IL-6 expression was sustained for 72 hours, with accumulation of IL-6 protein reaching levels 4.8-fold above IL-1β treatment alone. In addition, transcriptional regulation of the prototypic AHR responsive gene Cyp1a1 was negatively regulated by PMA and IL-1β treatment. Silencing of RELA expression alleviated IL-1β–mediated repression of AHR transcriptional activity, whereas PMA-mediated repression was maintained. Additionally, small interfering RNA studies reveal that AHR and RELA are necessary for synergistic induction of IL-6. The findings presented here reveal the AHR as a potential therapeutic target for selective modulation of IL-6 expression in some tumor cell types. The data also suggest a possible previously unrecognized mechanism of AHR-mediated tumor promotion. [Cancer Res 2008;68(10):3609–17]
Reduced Colitis-Associated Colon Cancer inFat-1(n-3 Fatty Acid Desaturase) Transgenic Mice
Authors: Jia Qian , Lupton Joanne R. , Smith Roger , Weeks Brad R. , Callaway Evelyn , Davidson Laurie A. , Kim Wooki , Fan Yang-Yi , Yang Peiying , Newman Robert A. , Kang Jing X. , McMurray David N. , Chapkin Robert S. 
Published: May 2008

AbstractBioactive food components containing n-3 polyunsaturated fatty acids (PUFA) modulate multiple determinants that link inflammation to cancer initiation and progression. Therefore, in this study, fat-1 transgenic mice, which convert endogenous n-6 PUFA to n-3 PUFA in multiple tissues, were injected with azoxymethane followed by three cycles of dextran sodium sulfate (DSS) to induce colitis-associated cancer. Fat-1 mice exhibited a reduced number of colonic adenocarcinomas per mouse (1.05 ± 0.29 versus 2.12 ± 0.51, P = 0.033), elevated apoptosis (P = 0.03), and a decrease in n-6 PUFA–derived eicosanoids, compared with wild-type (wt) mice. To determine whether the chemoprotective effects of n-3 PUFA could be attributed to its pleiotropic anti-inflammatory properties, colonic inflammation and injury scores were evaluated 5 days after DSS exposure followed by either a 3-day or 2-week recovery period. There was no effect of n-3 PUFA at 3 days. However, following a 2-week recovery period, colonic inflammation and ulceration scores returned to pretreatment levels compared with 3-day recovery only in fat-1 mice. For the purpose of examining the specific reactivity of lymphoid elements in the intestine, CD3+ T cells, CD4+ T helper cells, and macrophages from colonic lamina propria were quantified. Comparison of 3-day versus 2-week recovery time points revealed that fat-1 mice exhibited decreased (P &lt; 0.05) CD3+, CD4+ T helper, and macrophage cell numbers per colon as compared with wt mice. These results suggest that the antitumorigenic effect of n-3 PUFA may be mediated, in part, via its anti-inflammatory properties. [Cancer Res 2008;68(10):3985–91]
Targeting AKT Signaling Sensitizes Cancer to Cellular Immunotherapy
Authors: Hähnel Patricia S. , Thaler Sonja , Antunes Edite , Huber Christoph , Theobald Matthias , Schuler Martin 
Published: May 2008

Abstract
The promise of cancer immunotherapy is long-term disease control with high specificity and low toxicity. However, many cancers fail immune interventions, and secretion of immunosuppressive factors, defective antigen presentation, and expression of death ligands or serpins are regarded as main escape mechanisms. Here, we study whether deregulation of growth and survival factor signaling, which is encountered in most human cancers, provides another level of protection against immunologic tumor eradication. We show in two models that activated cell autonomous protein kinase B (PKB)/AKT signaling mediates resistance against tumor suppression by antigen-specific CTLs in vitro and adoptively transferred cellular immune effectors in vivo. PKB/AKT-dependent immunoresistance of established tumors is reversed by genetic suppression of endogenous Mcl-1, an antiapoptotic member of the Bcl-2 family. Mechanistically, deregulated PKB/AKT stabilizes Mcl-1 expression in a mammalian target of rapamycin (mTOR)–dependent pathway. Treatment with the mTOR inhibitor rapamycin effectively sensitizes established cancers to adoptive immunotherapy in vivo. In conclusion, cancer cell–intrinsic PKB/AKT signaling regulates the susceptibility to immune-mediated cytotoxicity. Combined targeting of signal transduction pathways may be critical for improvement of cancer immunotherapies. [Cancer Res 2008;68(10):3899–906]
microRNA-7 Inhibits the Epidermal Growth Factor Receptor and the Akt Pathway and Is Down-regulated in Glioblastoma
Authors: Kefas Benjamin , Godlewski Jakub , Comeau Laurey , Li Yunqing , Abounader Roger , Hawkinson Michael , Lee Jeongwu , Fine Howard , Chiocca E. Antonio , Lawler Sean , Purow Benjamin 
Published: May 2008

Abstract
microRNAs are noncoding RNAs inhibiting expression of numerous target genes, and a few have been shown to act as oncogenes or tumor suppressors. We show that microRNA-7 (miR-7) is a potential tumor suppressor in glioblastoma targeting critical cancer pathways. miR-7 potently suppressed epidermal growth factor receptor expression, and furthermore it independently inhibited the Akt pathway via targeting upstream regulators. miR-7 expression was down-regulated in glioblastoma versus surrounding brain, with a mechanism involving impaired processing. Importantly, transfection with miR-7 decreased viability and invasiveness of primary glioblastoma lines. This study establishes miR-7 as a regulator of major cancer pathways and suggests that it has therapeutic potential for glioblastoma. [Cancer Res 2008;68(10):3566–71]
The Soluble α Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer
Authors: Badoual Cécile , Bouchaud Grégory , Agueznay Nour El Houda , Mortier Erwan , Hans Stéphane , Gey Alain , Fernani Fahima , Peyrard Séverine , -Puig Pierre Laurent , Bruneval Patrick , Sastre Xavier , Plet Ariane , Garrigue-Antar Laure , Quintin-Colonna Françoise , Fridman Wolf H. , Brasnu Daniel , Jacques Yannick , Tartour Eric 
Published: May 2008

Abstract
Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor α (TNFα), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble α chain of IL-15 receptor (sIL-15Rα), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Rα was performed with a newly developed RIA. Increased serum sIL-15Rα concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Rα was mainly produced by tumor cells via proteolytic cleavage of IL-15Rα mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Rα concentrations. Surprisingly, sIL-15Rα did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15–induced proinflammatory cytokines (IL-6, TNFα, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Rα. Overall, these results support for the first time an original protumor role of sIL-15Rα in cancer. [Cancer Res 2008;68(10):3907–14]
Radiation-Induced Gene Translation Profiles Reveal Tumor Type and Cancer-Specific Components
Authors: Kumaraswamy Sandhya , Chinnaiyan Prakash , Shankavaram Uma T. , Lü Xing , Camphausen Kevin , Tofilon Philip J. 
Published: May 2008

Abstract
The microarray analysis of total cellular RNA is a common method used in the evaluation of radiation-induced gene expression. However, profiling the cellular transcriptome does not take into account posttranscriptional processes that affect gene expression. To better define the genes whose expression is influenced by ionizing radiation, we used polysome-bound RNA to generate gene translation profiles for a series of tumor and normal cell lines. Cell lines were exposed to 2 Gy, polysome-bound RNA isolated 6 hours later, and then subjected to microarray analysis. To identify the genes whose translation was affected by radiation, the polysome-bound RNA profiles were compared with their corresponding controls using significance analysis of microarrays (&lt;1% false discovery rate). From the statistically significant genes identified for each cell line, hierarchical clustering was performed by average linkage measurement and Pearson's correlation metric. Ingenuity Pathway Analysis was used for distributing genes into biological networks and for evaluation of functional significance. Radiation-induced gene translation profiles clustered according to tissue of origin; the cell lines corresponding to each tissue type contained a significant number of commonly affected genes. Network analyses suggested that the biological functions associated with the genes whose translation was affected by radiation were tumor type–specific. There was also a set of genes/networks that were unique to tumor or normal cells. These results indicate that radiation-induced gene translation profiles provide a unique data set for the analysis of cellular radioresponse and suggest a framework for identifying and targeting differences in the regulation of tumor and normal cell radiosensitivity. [Cancer Res 2008;68(10):3819–26]