bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sports injuries and illnesses in the 2009 FINA World Championships (Aquatics)
Authors: Mountjoy Margo , Junge Astrid , Alonso Juan Manuel , Engebretsen Lars , Dragan Ioan , Gerrard David , Kouidri Mohamed , Luebs Eide , Shahpar Farhad Moradi , Dvorak Jiri 
Published: May 2010

BackgroundAnalysis of injury and illness prevalence in elite sport provides the basis for the development of prevention programmes.ObjectivesTo analyse the frequency and characteristics of injuries and illnesses occurring during the 13th Federation Internationale de Natation (FINA) World Championships 2009.DesignProspective recording of newly incurred injuries and illnesses.MethodsThe 13th FINA World Championships hosted 2592 athletes from 172 countries in the disciplines of swimming, diving, synchronised swimming water polo and open water swimming. All team physicians or physiotherapists were asked to complete daily a standardised reporting form for all newly incurred injuries and illnesses for their teams. To cover teams without medical staff, the physicians of the Local Organizing Committee also submitted daily report forms.Results171 injuries were reported resulting in an incidence of 66.0 per 1000 registered athletes. The most affected body parts were the shoulder (n=25; 14.6%), and head (n=21; 12.3%). Half of the injuries occurred during training. The most common cause of injury was overuse (n=61; 37.5%). 184 illnesses were reported resulting in an incidence of 71.0 per 1000 registered athletes. The respiratory tract was most commonly affected (n=91; 50.3%) and the most frequently classified cause was infection (n=81; 49.2%). The incidence of injuries and illnesses varied substantially among the five disciplines, with the highest incidence of injury in diving and the lowest in swimming.ConclusionsAs the risk of injury varied with the discipline, preventive measures should be discipline specific and focused on minimising the potential for overuse. As most of the illnesses were caused by infection of the respiratory and gastrointestinal tract, preventive interventions should focus on eliminating common modes of transmission.
GENERALIZED DEFORMED HARMONIC OSCILLATORS IN THE FRAMEWORK OF UNIFIED (q; α, β, γ; ν)-DEFORMATION
Authors: BURBAN I. M. 
Published: May 2010

The aim of this paper is the study of the generalized deformed quantum oscillators in the framework (q; α, β, γ; ν)-deformed of oscillator algebra. By selecting the special values of deformation parameters, we have separated a generalized deformed oscillator connected with generalized discrete Hermite II polynomials. By these means we have constructed Barut–Girardello type coherent states of this oscillator. We have found the conditions on the (q; α, β, γ; ν)-deformation parameters at which the free (q; α, β, γ; ν)-deformed oscillator approximate the usual anharmonic oscillator in the homogeneous Kerr medium.
Epigenetic Silencing of the Sulfate Transporter Gene DTDST Induces Sialyl Lewisx Expression and Accelerates Proliferation of Colon Cancer Cells
Authors: Yusa Akiko , Miyazaki Keiko , Kimura Naoko , Izawa Mineko , Kannagi Reiji 
Published: May 2010

Abstract
Colon cancer cells express the carbohydrate determinant sialyl Lewisx, while they exhibit markedly decreased the expression of its sulfated derivative, sialyl 6-sulfo Lewisx. In contrast, normal colonic epithelial cells strongly express sialyl 6-sulfo Lewisx, but they virtually do not express sialyl Lewisx. Impaired sulfation was therefore suggested to occur during the course of malignant transformation of colonic epithelial cells and was assumed to be responsible for the increased sialyl Lewisx expression in cancers. To elucidate the molecular biological background of the impaired sulfation in cancers, we studied the expression levels of mRNA for 6-O-sulfotransferase isoenzymes, PAPS synthases and transporters, and a cell membrane sulfate transporter, DTDST, in cancer tissues. The most striking decrease in cancer cells compared with nonmalignant epithelial cells was noted in the transcription of the DTDST gene (P = 0.0000014; n = 20). Most cultured colon cancer cells had a diminished DTDST transcription, which was restored when cultured with histone deacetylase inhibitors. Suppression of DTDST transcription under the control of a tet-off inducible promoter resulted in increased sialyl Lewisx expression and reduced sialyl 6-sulfo Lewisx expression. Unexpectedly, the growth rate of the cancer cells was markedly enhanced when transcription of DTDST was suppressed. These results show that the decrease in the transcription of the sulfate transporter gene is the major cause of decreased expression of sialyl 6-sulfo Lewisx and increased expression of sialyl Lewisx in colon cancers. The results also suggest that the diminished DTDST expression is closely related to enhanced proliferation of cancer cells. Cancer Res; 70(10); 4064–73. ©2010 AACR.
Androgen Receptor Requires JunD as a Coactivator to Switch on an Oxidative Stress Generation Pathway in Prostate Cancer Cells
Authors: Mehraein-Ghomi Farideh , Basu Hirak S. , Church Dawn R. , Hoffmann F. Michael , Wilding George 
Published: May 2010

Abstract
Relatively high oxidative stress levels in the prostate are postulated to be a major factor for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we showed that the transcription factor JunD is essential for androgen-induced reactive oxygen species (ROS) production in androgen-dependent human CaP cells. We also recently showed that androgen induces the first and regulatory enzyme spermidine/spermine N1-acetyltransferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present coimmunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with androgen-activated androgen receptor (AR) in situ. Our chromatin immunoprecipitation assay data show that JunD binds directly to a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD-silenced LNCaP cell line, we show that JunD is essential for androgen-induced SSAT gene expression. The elucidation of JunD-AR complex inducing SSAT expression leading to polyamine oxidation establishes the mechanistic basis of androgen-induced ROS production in CaP cells and opens up a new prostate-specific target for CaP chemopreventive/chemotherapeutic drug development. Cancer Res; 70(11); 4560–8. ©2010 AACR.
Phosphorescent Light–Emitting Iridium Complexes Serve as a Hypoxia-Sensing Probe for Tumor Imaging in Living Animals
Authors: Zhang Shaojuan , Hosaka Masahiro , Yoshihara Toshitada , Negishi Kazuya , Iida Yasuhiko , Tobita Seiji , Takeuchi Toshiyuki 
Published: May 2010

Abstract
Iridium complex is a promising organic light–emitting diode material for next generation video displays that emits phosphorescence quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light–emitting Ir(btp)2(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor-1α images. BTP was further applied to imaging five nude mouse transplanted with tumors. All tumors presented a bright BTP-emitting image even 5 minutes after injection. The minimal image recognition size was ∼2 mm in diameter. By morphologic examination and phosphorescence lifetime measurement, BTP appeared to localize to the tumor cells. Because BTP is easily modifiable, we synthesized BTP analogues with a longer excitation/emission wavelength. One of them, BTPHSA, depicted clear imaging from tumors transplanted 6 to 7 mm deep from the skin surface. We suggest that iridium complex materials have a vast potential for imaging hypoxic lesions such as tumor tissues. Cancer Res; 70(11); 4490–8. ©2010 AACR.
Carcinomas Contain a Matrix Metalloproteinase–Resistant Isoform of Type I Collagen Exerting Selective Support to Invasion
Authors: Makareeva Elena , Han Sejin , Vera Juan Carlos , Sackett Dan L. , Holmbeck Kenn , Phillips Charlotte L. , Visse Robert , Nagase Hideaki , Leikin Sergey 
Published: May 2010

Abstract
Collagen fibers affect metastasis in two opposing ways, by supporting invasive cells but also by generating a barrier to invasion. We hypothesized that these functions might be performed by different isoforms of type I collagen. Carcinomas are reported to contain α1(I)3 homotrimers, a type I collagen isoform normally not present in healthy tissues, but the role of the homotrimers in cancer pathophysiology is unclear. In this study, we found that these homotrimers were resistant to all collagenolytic matrix metalloproteinases (MMP). MMPs are massively produced and used by cancer cells and cancer-associated fibroblasts for degrading stromal collagen at the leading edge of tumor invasion. The MMP-resistant homotrimers were produced by all invasive cancer cell lines tested, both in culture and in tumor xenografts, but they were not produced by cancer-associated fibroblasts, thereby comprising a specialized fraction of tumor collagen. We observed the homotrimer fibers to be resistant to pericellular degradation, even upon stimulation of the cells with proinflammatory cytokines. Furthermore, we confirmed an enhanced proliferation and migration of invasive cancer cells on the surface of homotrimeric versus normal (heterotrimeric) type I collagen fibers. In summary, our findings suggest that invasive cancer cells may use homotrimers for building MMP-resistant invasion paths, supporting local proliferation and directed migration of the cells whereas surrounding normal stromal collagens are cleaved. Because the homotrimers are universally secreted by cancer cells and deposited as insoluble, MMP-resistant fibers, they offer an appealing target for cancer diagnostics and therapy. Cancer Res; 70(11); 4366–74. ©2010 AACR.
The Skin Cancer Chemotherapeutic Agent Ingenol-3-Angelate (PEP005) Is a Substrate for the Epidermal Multidrug Transporter (ABCB1) and Targets Tumor Vasculature
Authors: Li Luowei , Shukla Suneet , Lee Andrew , Garfield Susan H. , Maloney David J. , Ambudkar Suresh V. , Yuspa Stuart H. 
Published: May 2010

Abstract
Ingenol-3-angelate (Ing3A), extracted from Euphorbia peplus, is currently in clinical trials for eradicating basal cell carcinoma, actinic keratosis, and squamous cell carcinoma (SCC) in situ by topical application. Although structurally related to phorbol esters and a protein kinase C activator, topical Ing3A, but not phorbol 12-myristate 13-acetate (PMA), inhibited the growth of subcutaneous tumors derived from PAM212 (mouse SCC) and B16 (mouse melanoma). Ing3A and PMA both induced acute neutrophilic inflammation on mouse skin, but only Ing3A caused subcutaneous hemorrhage and vascular damage. Both Ing3A and PMA activated extracellular signal-regulated kinase 1/2 (ERK1/2) in epidermis, but Ing3A also activated ERK1/2 in skin dermal fibroblasts and endothelial cells. Pretreatment with topical cyclosporin A (CsA), verapamil, or XR9576, modulators of P-glycoprotein (P-gp), prevented Ing3A-induced hemorrhage but not neutrophil infiltration. CsA also impaired the anticancer activity of Ing3A, whereas the anti-inflammatory dexamethasone did not. Ing3A, but not PMA, blocked photoaffinity labeling of human P-gp with [125I]iodoaryazidoprazosin and inhibited P-gp–mediated drug resistance to HCT-15 cells. The intracellular levels of Ing3A were significantly lower in P-gp–expressing cells, and treatment with XR9576 increased the levels to those of cells that do not express P-gp, showing that Ing3A binds to and is transported by P-gp. Taken together, our results suggest that P-gp–mediated absorptive transport, dermal penetration, and vascular damage contribute to the anticancer activity of Ing3A in vivo. Cancer Res; 70(11); 4509–19. ©2010 AACR.
Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention
Authors: Shahani Komal , Swaminathan Suresh Kumar , Freeman Diana , Blum Angela , Ma Linan , Panyam Jayanth 
Published: May 2010

AbstractPoor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(d,l-lactide-co-glycolide), was used to fabricate curcumin microparticles. When injected s.c. in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10- to 30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared with other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished vascular endothelial growth factor expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy. Cancer Res; 70(11); 4443–52. ©2010 AACR.
Molecular Imaging of CXCR4 Receptor Expression in Human Cancer Xenografts with [64Cu]AMD3100 Positron Emission Tomography
Authors: Nimmagadda Sridhar , Pullambhatla Mrudula , Stone Kristie , Green Gilbert , Bhujwalla Zaver M. , Pomper Martin G. 
Published: May 2010

AbstractThe chemokine receptor CXCR4 and its cognate ligand CXCL12 are pivotal for establishing metastases from many tumor types. Thus, CXCR4 may offer a cell surface target for molecular imaging of metastases, assisting diagnosis, staging, and therapeutic monitoring. Furthermore, noninvasive detection of CXCR4 status of a primary tumor may provide an index of the metastatic potential of the lesion. Here, we report the development and evaluation of [64Cu]AMD3100, a positron-emitting analogue of the stem cell mobilizing agent plerixafor to image CXCR4 in human tumor xenografts preselected for graded expression of this receptor. This imaging method was evaluated in lung metastases derived from human MDA-MB-231 breast cancer cells. Ex vivo biodistribution studies, performed to validate the in vivo imaging data, confirmed the ability of [64Cu]AMD3100 to image CXCR4 expression. Our findings show the feasibility of imaging CXCR4 by positron emission tomography using a clinically approved agent as a molecular scaffold. Cancer Res; 70(10); 3935–44. ©2010 AACR.
Interaction of Integrin-Linked Kinase and Miniature Chromosome Maintenance 7–Mediating Integrin α7 Induced Cell Growth Suppression
Authors: Han Yu-Chen , Yu Yan P. , Nelson Joel , Wu Chuanyue , Wang Hui , Michalopoulos George K. , Luo Jian-Hua 
Published: May 2010

Abstract
Mutation of integrin α7 (ITGA7) was previously identified in multiple human malignancies. Restoration of ITGA7 expression in prostate cancer and leiomyosarcoma cell lines suppressed tumor growth and cell motility both in vitro and in vivo. In this study, we showed that integrin-linked kinase (ILK) binds with miniature chromosome maintenance 7 (MCM7), a DNA replication licensing protein. A 58–amino acid ILK binding motif was identified in the NH2-terminus of MCM7. The expression of ITGA7 induced the phosphorylation of MCM7. Knocking down of ILK abrogated ITGA7-induced MCM7 phosphorylation. ANK, the dominant-negative mutant of ILK, also blocked the phosphorylation of MCM7 induced by ITGA7. The phosphorylation of MCM7 reduced MCM7 chromatin association and inhibited cell growth. A MCM7 mutant that does not bind with ILK did not respond to ITGA7 stimulation, and behaved similarly to a dominant MCM7-negative mutant and neutralized the effect of ITGA7. We conclude that ILK interaction with MCM7 and MCM7 phosphorylation may be a critical event in ITGA7 signaling pathway, leading to tumor suppression. Cancer Res; 70(11); 4375–84. ©2010 AACR.
Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib
Authors: Chen Siquan , Blank Jonathan L. , Peters Theodore , Liu Xiaozhen J. , Rappoli David M. , Pickard Michael D. , Menon Saurabh , Yu Jie , Driscoll Denise L. , Lingaraj Trupti , Burkhardt Anne L. , Chen Wei , Garcia Khristofer , Sappal Darshan S. , Gray Jesse , Hales Paul , Leroy Patrick J. , Ringeling John , Rabino Claudia , Spelman James J. , Morgenstern Jay P. , Lightcap Eric S. 
Published: May 2010

Abstract
Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen to evaluate the genetic determinants that confer sensitivity to bortezomib (Velcade (R); PS-341). This screen identified 100 genes whose knockdown affected lethality to bortezomib and to a structurally diverse set of other proteasome inhibitors. A comparison of three cell lines revealed that 39 of 100 genes were commonly linked to cell death. We causally linked bortezomib-induced cell death to the accumulation of ASF1B, Myc, ODC1, Noxa, BNIP3, Gadd45α, p-SMC1A, SREBF1, and p53. Our results suggest that proteasome inhibition promotes cell death primarily by dysregulating Myc and polyamines, interfering with protein translation, and disrupting essential DNA damage repair pathways, leading to programmed cell death. Cancer Res; 70(11); 4318–26. ©2010 AACR.
Pathway Analysis of Breast Cancer Genome-Wide Association Study Highlights Three Pathways and One Canonical Signaling Cascade
Authors: Menashe Idan , Maeder Dennis , Garcia-Closas Montserrat , Figueroa Jonine D. , Bhattacharjee Samsiddhi , Rotunno Melissa , Kraft Peter , Hunter David J. , Chanock Stephen J. , Rosenberg Philip S. , Chatterjee Nilanjan 
Published: May 2010

Abstract
Genome-wide association studies (GWAS) focus on relatively few highly significant loci, whereas less attention is given to other genotyped markers. Using pathway analysis to study existing GWAS data may shed light on relevant biological processes and illuminate new candidate genes. We applied a pathway-based approach to the breast cancer GWAS data of the National Cancer Institute (NCI) Cancer Genetic Markers of Susceptibility project that includes 1,145 cases and 1,142 controls. Pathways were retrieved from three databases: KEGG, BioCarta, and NCI Protein Interaction Database. Genes were represented by their most strongly associated SNP, and an enrichment score reflecting the overrepresentation of gene-based association signals in each pathway was calculated by using a weighted Kolmogorov-Smirnov procedure. Finally, hierarchical clustering was used to identify pathways with overlapping genes, and clusters with an excess of association signals were determined by the adaptive rank-truncated product (ARTP) method. A total of 421 pathways containing 3,962 genes was included in our study. Of these, three pathways (syndecan-1–mediated signaling, signaling of hepatocyte growth factor receptor, and growth hormone signaling) were highly enriched with association signals [PES &lt; 0.001, false discovery rate (FDR) = 0.118]. Our clustering analysis revealed that pathways containing key components of the RAS/RAF/mitogen-activated protein kinase canonical signaling cascade were significantly more likely to have an excess of association signals than expected by chance (PARTP = 0.0051, FDR = 0.07). These results suggest that genetic alterations associated with these three pathways and one canonical signaling cascade may contribute to breast cancer susceptibility. Cancer Res; 70(11); 4453–9. ©2010 AACR.
C-Propeptides of Procollagens Iα1 and II that Differentially Accumulate in Enchondromas versus Chondrosarcomas Regulate Tumor Cell Survival and Migration
Authors: Vincourt Jean-Baptiste , Etienne Stéphanie , Cottet Justine , Delaunay Camille , Malanda Bantsimba , Lionneton Frédéric , Sirveaux François , Netter Patrick , Plénat François , Mainard Didier , Vignaud Jean-Michel , Magdalou Jacques 
Published: May 2010

Abstract
Chondrogenic tumors that exhibit benign or malignant behaviors synthesize variable amounts of cartilage-like extracellular matrix. To define the regulators of these phenotypes, we performed a proteomic comparison of multiple human chondrogenic tumors, which revealed differential accumulation of the C-propeptides of procollagens Iα1 and II (PC1CP and PC2CP) in malignant versus benign tumors, respectively. Expression patterns of PC1CP correlated with levels of tumor vascularization, whereas expression patterns of PC2CP suggested its susceptibility to immobilization within the extracellular matrix. Prompted by these observations, we investigated the functions of recombinant PC1CP and PC2CP in the extracellular matrix in soluble or immobilized states. Each induced β1 integrin–mediated chondrocyte adhesion by distinct domains and efficacies, suggesting that they initiated distinct signaling pathways. Indeed, immobilized PC2CP, but not PC1CP, induced apoptosis of primary chondrocytes and EAhy926 endothelial cells. In contrast, soluble PC1CP, but not PC2CP, induced the migration of EAhy926 cells and increased vascular endothelial growth factor (VEGF) and CXCR4 expression in chondrocytes. Soluble PC2CP also increased VEGF expression, but along with a more pronounced effect on CXCR4 and matrix metalloproteinase 13 expression. Our findings suggest that PC1CP favors angiogenesis and tumor progression, but that PC2CP acts in a more complex manner, exerting antitumor and antiangiogenic properties through apoptosis induction when immobilized, but progression and metastasis when soluble. In summary, the relative levels of PC1CP and PC2CP and their interactions within the extracellular matrix contribute to tumor progression, angiogenesis, and metastasis in chondrogenic tumors. Cancer Res; 70(11); 4739–48. ©2010 AACR.
Epigenetic Mechanisms of Promigratory Chemokine CXCL14 Regulation in Human Prostate Cancer Cells
Authors: Song Eun Young , Shurin Michael R. , Tourkova Irina L. , Gutkin Dmitriy W. , Shurin Galina V. 
Published: May 2010

Abstract
Chemokines play the key role in initiating immune responses by regulating the attraction and homing of immune cells to the lymphoid and nonlymphoid tissues. CXCL14 is a chemokine that in tumors may act as chemoattractant for monocytes and dendritic cells (DC), which may modulate antitumor immune responses in certain cancers. In this study, we investigated the mechanisms of loss of CXCL14 in prostate cancer cells. Cell treatment with the demethylating agent 5-aza-2-deoxycytidine resulted in the recovery of CXCL14 mRNA and protein expression. Hypermethylated CpG island sequences encompassing the CXCL14 gene promoter were identified. The restoration of CXCL14 by 5-aza-2-deoxycytidine treatment had functional impact, based on the DC chemoattractant activity of conditioned medium from drug-treated cells. Conversely, CXCL14 removal from conditioned media by affinity chromatography abolished its chemotactic properties, confirming that functionally active CXCL14 was generated in prostate cancer cells by relieving its transcriptional silencing with 5-aza-2-deoxycytidine. Our findings offer the first direct evidence for epigenetic regulation of chemokine expression in tumor cells. Cancer Res; 70(11); 4394–401. ©2010 AACR.