bluuebunny/crossref_metadata_2025_split huggingface dataset:
Work practices and childhood agricultural injury
Authors: Larson-Bright Muree , Gerberich Susan G , Alexander Bruce H , Gurney James G , Masten Ann S , Church Timothy R , Ryan Andrew D , Renier Colleen M 
Published: December 2007

Objective:To evaluate whether children’s agricultural work practices were associated with agricultural injury and to identify injury and work practice predictors.Design:Analyses were based on nested case–control data collected by the Regional Rural Injury Study-II (RRIS-II) surveillance study in 1999 and 2001 by computer-assisted telephone interviews.Subjects:Cases (n =  425) and controls (n =  1886) were persons younger than 20 years of age from Midwestern agricultural households. Those reporting agricultural injuries became cases; controls (no injury) were selected using incidence density sampling.Main outcome measures:Multivariate logistic regression was used to estimate the risks of injury associated with agricultural work, performing chores earlier than developmentally appropriate, hours worked per week, and number of chores performed.Results:Increased risks of injury were observed for children who performed chores 2–3 years younger than recommended, compared to being “age-appropriate” (odds ratio (OR)  =  2.6, 95% confidence interval (CI)  =  1.4–4.5); performed any agricultural work (3.9 (2.6–5.6)); performed seven to ten chores per month compared to one chore (2.2 (1.3–3.5)); and worked 11–30 or 31–40 h per week compared to 1–10 h (1.6 (1.2–2.1) and 2.2 (1.3–3.7), respectively). Decreased risks of injury were observed for non-working children compared to children performing what are commonly considered safe levels of agricultural work.Conclusions:This study demonstrated elevated risks of agricultural injury among children who perform developmentally inappropriate chores. Results suggest that the efficacy of age restrictions for preventing the occurrence of childhood agricultural injuries warrants further evaluation.
Pattern of seat belt wearing in Nanjing, China
Authors: Routley V , Ozanne-Smith J , Li D , Hu X , Wang P , Qin Y 
Published: December 2007

Objective:To describe the patterns of seat belt wearing in Nanjing, China for drivers, front seat passengers, and rear occupants of motor vehicles.Design:Roadside observational study.Setting:Four sites in central and northern Nanjing during daylight hours over 1 week in April 2005.Subjects:Drivers and passengers of 17 147 cars, taxis, goods vans, and pickups, which traveled in the inside traffic lane.Main outcome measures:Percentage seat belt wearing for each of seating position, age/sex, time of day, vehicle type, day of week.Results:The rate of seat belt wearing was significantly higher in drivers (67.3%, 95% CI 66.6 to 68.0) than front seat passengers (18.9%, 95% CI, 18.0 to 19.8). It was negligible for second front seat passengers (2.6%, 95% CI 0.3 to 4.9) and rear seat passengers (0.5%, 95% CI 0.3 to 0.7). Belt tampering, such that protection would be reduced in the event of a crash, was observed for 18.5% of taxi drivers. Drivers were most likely to wear seat belts in cars and vans and at a city roundabout; front seat passengers were most likely to wear seat belts in non-taxi vehicles, during the evening rush hour, if the driver was wearing a belt, and on the local north road. Drivers were least likely to wear a belt in the early morning, in pickups and taxis, on Tuesday (or the following week), and on the local north road; front seat passengers were least likely to wear a belt in taxis and if the driver was not wearing a belt.Conclusions:Rates of seat belt wearing by passengers were low despite national legislation and provincial regulations coming into effect several months before the survey. Combined education and enforcement are necessary accompaniments to legislation.
Association between road vehicle collisions and recent medical contact in older drivers: a case-crossover study
Authors: Leproust Sandy , Lagarde Emmanuel , Suissa Samy , Salmi L Rachid 
Published: December 2007

Objective:To estimate the association between past medical contacts and the risk of vehicle collision in a population of older drivers from the province of Quebec, Canada.Design:Case-crossover study.Setting:Quebec.Participants:111 699 older drivers involved in at least one vehicle collision between January 1988 and December 2000.Main outcome measures:For each driver, the risk of having a vehicle collision while exposed and not exposed to a medical contact was compared. Separate conditional logistic regression analyses were conducted for all drivers and in four diagnostic-specific subgroups.Results:The study found a weak but statistically significant increased risk of all collisions being associated with a medical contact within 1 month before the collision, for all drivers (OR = 1.10, 95% CI 1.08 to 1.11) and for drivers with diabetes (OR = 1.07, 95% CI 1.03 to 1.11).Conclusion:Older drivers who have a collision are more likely to have been in contact with a physician shortly before the collision. These findings suggest that there might be an opportunity to detect medical conditions that put older drivers at higher risk of collision; however, further research is needed to assess the potential effectiveness and practical modalities of screening.
Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells
Authors: Westbrook Louise , Manuvakhova Marina , Kern Francis G. , Estes Norman R. , Ramanathan Harish N. , Thottassery Jaideep V. 
Published: December 2007

Abstract
Cks1, a small protein whose expression is strongly associated with aggressive breast tumors, is a component of cyclin-cdk complexes, as well as the SCFSkp2 ubiquitin ligase. In these studies, we explored its roles in estrogen receptor–positive breast tumor cells. When exposed to the antiestrogen ICI 182780, these cells accumulate in G1 by reducing the expression of Cks1, and increasing the levels of p130/Rb2, a cdk2 inhibitor and SCFSkp2 target. Heregulin β1 or estradiol abrogate antiestrogen effects by increasing Cks1 expression, down-regulating p130/Rb2 and inducing S phase entry. Depletion of Cks1 in these cells by RNA interference concomitantly decreased Skp2 and up-regulated p130/Rb2 and another SCFSkp2 target, p27Kip1. Remarkably, however, Cks1-depleted cells not only exhibit slowed G1 progression, but also accumulate in G2-M due to blocked mitotic entry. Notably, we show that cdk1 expression, which is crucial for M phase entry, is drastically diminished by Cks1 depletion, and that restoration of cdk1 reduces G2-M accumulation in Cks1-depleted cells. cdk1 reduction in Cks1-depleted cells is a consequence of a marked decrease in its mRNA and not due to alteration in its proteolytic turnover. Both heregulin β1 and estradiol could neither restore cdk1 nor sustain cycling in Cks1-depleted cells, although classical estrogen receptor function remained unaltered. Cks1 depletion also decreased Skp2 in human mammary epithelial cells without altering cell cycle progression. Thus, the indispensability of Cks1 to the breast cancer cell cycle, versus its redundancy in normal cells, suggests that Cks1 abrogation could be an effective interventional strategy in breast cancer. [Cancer Res 2007;67(23):11393–401]
WP1066 Disrupts Janus Kinase-2 and Induces Caspase-Dependent Apoptosis in Acute Myelogenous Leukemia Cells
Authors: Ferrajoli Alessandra , Faderl Stefan , Van Quin , Koch Patricia , Harris David , Liu Zhiming , Hazan-Halevy Inbal , Wang Yongtao , Kantarjian Hagop M. , Priebe Waldemar , Estrov Zeev 
Published: December 2007

AbstractSeveral cytokines and growth factors that stimulate the proliferation of acute myelogenous leukemia (AML) cells transduce their signals by activating the transcription factor Janus-activated kinase 2 (JAK2). Accordingly, the inhibition of JAK2 or of its downstream signaling pathways suppresses the proliferation of AML cells. Because (E)-3(6-bromopyridin-2-yl)-2-cyano-N-((S0-1-phenylethyl)acrylamide) (WP1066) is a novel analogue of the JAK2 inhibitor AG490, we tested its activity in AML cells and investigated its mechanism of action. Using clonogenic assays, we found that although WP1066 had a marginal effect on normal marrow progenitors, it inhibited the proliferation of AML colony-forming cells obtained from patients with newly diagnosed AML and that of the AML cell lines OCIM2 and K562. WP1066 inhibited OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. Similar to its parent compound AG490, WP1066 inhibited the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein, thereby blocking its downstream signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase pathways. These effects resulted in the activation of the caspase pathway. Incubation of both OCIM2 and K562 cells with WP1066 activated caspase-3, induced cleavage of poly(ADP-ribose) polymerase, and caused caspase-dependent apoptotic cell death. Thus, WP1066 is a potent JAK2 inhibitor whose effects in AML and other hematologic malignancies merit further investigation. [Cancer Res 2007;67(23):11291–9]
Neuroblastoma Cells Isolated from Bone Marrow Metastases Contain a Naturally Enriched Tumor-Initiating Cell
Authors: Hansford Loen M. , McKee Amy E. , Zhang Libo , George Rani E. , Gerstle J. Ted , Thorner Paul S. , Smith Kristen M. , Look A. Thomas , Yeger Herman , Miller Freda D. , Irwin Meredith S. , Thiele Carol J. , Kaplan David R. 
Published: December 2007

Abstract
Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor. [Cancer Res 2007;67(23):11234–43]
Traf1 Induction and Protection from Tumor Necrosis Factor by Nuclear Factor-κB p65 Is Independent of Serine 536 Phosphorylation
Authors: Sasaki Carl Y. , Slemenda Colin F. , Ghosh Paritosh , Barberi Theresa J. , Longo Dan L. 
Published: December 2007

Abstract
Abnormal nuclear factor-κB (NF-κB) signaling has been attributed to the initiation and progression of cancer. Posttranslational modification of p65 facilitates optimal NF-κB signaling after activation. Here, we show that the phosphorylation of serine 536 was required for p65-mediated transcription and IκBα expression in fibroblasts. Furthermore, tumor necrosis factor (TNF) treatment slightly induced p65 phosphorylation, and both unphosphorylated and phosphorylated p65 translocated into the nucleus. The phosphorylation of serine 536 was not required for p65-mediated protection from TNF cytotoxicity and Traf1 induction in fibroblasts. Also, the corecruitment of p65 and RNA polymerase II to the Traf1 enhancer region did not require p65 phosphorylation. However, the corecruitment of p65 and RNA polymerase II to the Csf2 promoter required the phosphorylation of serine 536. These findings suggested that the requirement of serine phosphorylation at residue 536 and the distance between the NF-κB response element and the start of transcription may influence which genes will be transcribed. [Cancer Res 2007;67(23):11218–25]
Delta-like 4 Notch Ligand Regulates Tumor Angiogenesis, Improves Tumor Vascular Function, and Promotes Tumor Growth In vivo
Authors: Li Ji-Liang , Sainson Richard C.A. , Shi Wen , Leek Russell , Harrington Laura S. , Preusser Matthias , Biswas Swethajit , Turley Helen , Heikamp Emily , Hainfellner Johannes A. , Harris Adrian L. 
Published: December 2007

Abstract
The vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. However, clinical trials targeting the VEGF pathway are often ineffective, suggesting that other factors/pathways are also important in tumor angiogenesis. We have previously shown that the Notch ligand Delta-like 4 (DLL4) is up-regulated in tumor vasculature. Here, we show that DLL4, when expressed in tumor cells, functions as a negative regulator of tumor angiogenesis by reducing the number of blood vessels in all five types of xenografts, but acts as a positive driver for tumor growth in two of them (human glioblastoma and prostate cancer). The growth of in vivo models was not related to the effects on growth in vitro. DLL4 expressed in the tumor cells activated Notch signaling in host stromal/endothelial cells, increased blood vessel size, and improved vascular function within tumors. The promotion of tumor growth was, to some extent, due to a reduction of tumor hypoxia and apoptosis. DLL4-expressing tumor cells responded to anti-VEGF therapy with bevacizumab. A soluble form of DLL4 (D4ECD-Fc) blocked tumor growth in both bevacizumab-sensitive and bevacizumab-resistant tumors by disrupting vascular function despite increased tumor vessel density. In addition, we show that DLL4 is up-regulated in tumor cells and tumor endothelial cells of human glioblastoma. Our findings provide a rational basis for the development of novel antiangiogenic strategies via blockade of DLL4/Notch signaling and suggest that combined approaches for interrupting both DLL4 and VEGF pathways may improve antiangiogenic therapy. [Cancer Res 2007;67(23):11244–53]
Drug Sensitivity Prediction by CpG Island Methylation Profile in the NCI-60 Cancer Cell Line Panel
Authors: Shen Lanlan , Kondo Yutaka , Ahmed Saira , Boumber Yanis , Konishi Kazuo , Guo Yi , Chen Xinli , Vilaythong Jill N. , Issa Jean-Pierre J. 
Published: December 2007

Abstract
Aberrant promoter hypermethylation and associated gene silencing are epigenetic hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation can affect the sensitivity of cancers to antineoplastic agents by altering expression of genes critical to drug response. To study this issue, we used bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in human cancer cell lines from the National Cancer Institute (NCI) drug-screening panel (NCI-60 panel). The frequency of aberrant hypermethylation of these islands ranged from 2% to 81% in NCI-60 cancer cells, and provided a database that can be analyzed for the sensitivity to ≈30,000 drugs tested in this panel. By correlating drug activity with DNA methylation, we identified a list of methylation markers that predict sensitivity to chemotherapeutic drugs. Among them, hypermethylation of the p53 homologue p73 and associated gene silencing was strongly correlated with sensitivity to alkylating agents. We used small interfering RNA to down-regulate p73 expression in multiple cell lines, including the resistant cell lines TK10 (renal cancer) and SKMEL28 (melanoma). Down-regulating p73 substantially increased sensitivity to commonly used alkylating agents, including cisplatin, indicating that epigenetic silencing of p73 directly modulates drug sensitivity. Our results confirm that epigenetic profiles are useful in identifying molecular mediators for cancer drug sensitivity (pharmaco-epigenomics). [Cancer Res 2007;67(23):11335–43]
Novel Quinazoline-Based Compounds Impair Prostate Tumorigenesis by Targeting Tumor Vascularity
Authors: Garrison Jason B. , Shaw Yeng-Jeng , Chen Ching-Shih , Kyprianou Natasha 
Published: December 2007

Abstract
Previous evidence showed the ability of the quinazoline-based α1-adrenoreceptor antagonist doxazosin to suppress prostate tumor growth via apoptosis. In this study, we carried out structural optimization of the chemical nucleus of doxazosin and a subsequent structure-function analysis toward the development of a novel class of apoptosis-inducing and angiogenesis-targeting agents. Our lead compound, DZ-50, was effective at reducing endothelial cell viability via a nonapoptotic mechanism. Treatment with DZ-50 effectively prevented in vitro tube formation and in vivo chorioallantoic membrane vessel development. Confocal microscopy revealed a significantly reduced ability of tumor cells to attach to extracellular matrix and migrate through endothelial cells in the presence of DZ-50. In vivo tumorigenicty studies using two androgen-independent human prostate cancer xenografts, PC-3 and DU-145, showed that DZ-50 treatment leads to significant suppression of tumorigenic growth. Exposure to the drug at the time of tumor cell inoculation led to prevention of prostate cancer initiation. Furthermore, DZ-50 resulted in a reduced formation of prostate-tumor derived metastatic lesions to the lungs in an in vivo spontaneous metastasis assay. Thus, our drug discovery approach led to the development of a class of lead (quinazoline-based) compounds with higher potency than doxazosin in suppressing prostate growth by targeting tissue vascularity. This new class of quinazoline-based compounds provides considerable promise as antitumor drugs for the treatment of advanced prostate cancer. [Cancer Res 2007;67(23):11344–52]
Novel NBS1 Heterozygous Germ Line Mutation Causing MRE11-Binding Domain Loss Predisposes to Common Types of Cancer
Authors: Ebi Hiromichi , Matsuo Keitaro , Sugito Nobuyoshi , Suzuki Motoshi , Osada Hirotaka , Tajima Kazuo , Ueda Ryuzo , Takahashi Takashi 
Published: December 2007

Abstract
DNA damage response (DDR) pathways maintain genomic stability. A 657del5 mutation of NBS1, a key DDR component, causing the rare cancer-predisposing Nijmegen breakage syndrome has been reported nearly exclusively in Slavic populations. In this study, we describe the first identification in a Japanese population of an unprecedented type of heterozygous NBS1 mutant, termed IVS11+2insT, lacking the MRE11- and ATM-binding site at the COOH terminus. Profoundly defective in crucial binding to MRE11, MDC1, BRCA1, and wild-type NBS1, the mutant caused impaired ATM phosphorylation in response to low-dose irradiation in a heterozygous state. Importantly, whereas IVS11+2insT was found in only 2 (0.09%) of 2,348 control subjects, it was identified in 2% (2 of 96) of heterozygotes with gastric cancer, 0.8% (3 of 376) of those with colorectal cancer, and 0.4% (2 of 532) of those with lung cancer, which were comparable to frequencies reported for other DDR-related genes known to confer cancer susceptibility. The presence of the heterozygous IVS11+2insT mutation seemed to be associated with an increased risk for gastrointestinal cancers, with an odds ratio of 12.6 and 95% confidence interval (95% CI) of 2.05 to 132.1 (P = 0.0001). The odds ratios separately calculated for gastric and colorectal cancers were 25.0 (95% CI, 1.78–346.0) and 9.43 (95% CI, 1.08–113.1), respectively. These findings suggest that IVS11+2insT is associated with an increased risk for the development of certain types of common cancers, warranting future investigation including detailed phenotypic characterization of age of onset and penetrance in heterozygotes, as well as screening in other ethnic groups. [Cancer Res 2007;67(23):11158–65]
Sigma-1 Receptors Bind Cholesterol and Remodel Lipid Rafts in Breast Cancer Cell Lines
Authors: Palmer Christopher P. , Mahen Robert , Schnell Eva , Djamgoz Mustafa B.A. , Aydar Ebru 
Published: December 2007

AbstractLipid rafts are membrane platforms that spatially organize molecules for specific signaling pathways that regulate various cellular functions. Cholesterol is critical for liquid-ordered raft formation by serving as a spacer between the hydrocarbon chains of sphingolipids, and alterations in the cholesterol contents of the plasma membrane causes disruption of rafts. The role that σ receptors play in cancer is not clear, although it is frequently up-regulated in human cancer cells and tissues and σ receptors inhibit proliferation in carcinoma and melanoma cell lines, induce apoptosis in colon and mammary carcinoma cell lines, and reduce cellular adhesion in mammary carcinoma cell lines. In this study, we provide molecular and functional evidence for the involvement of the enigmatic σ1 receptors in lipid raft modeling by σ1 receptor–mediated cholesterol alteration of lipid rafts in breast cancer cell lines. Cholesterol binds to cholesterol recognition domains in the COOH terminus of the σ1 receptor. This binding is blocked by σ receptor drugs because the cholesterol-binding domains form part of the σ receptor drug-binding site, mutations of which abolish cholesterol binding. Furthermore, we outline a hypothetical functional model to explain the myriad of biological processes, including cancer, in which these mysterious receptors are involved. The findings of this study provide a biological basis for the potential therapeutic applications of lipid raft cholesterol regulation in cancer therapy using σ receptor drugs. [Cancer Res 2007;67(23):11166–75]
Epithelial-Mesenchymal Transition Events during Human Embryonic Stem Cell Differentiation
Authors: Eastham Angela M. , Spencer Helen , Soncin Francesca , Ritson Sarah , Merry Catherine L.R. , Stern Peter L. , Ward Christopher M. 
Published: December 2007

Abstract
Epithelial-mesenchymal transition (EMT) occurs during embryonic development and may also be associated with the metastatic spread of epithelial tumors. During EMT, E-cadherin is down-regulated and this correlates with increased motility and invasion of cells. We show that differentiation of human embryonic stem (ES) cells in monolayer culture is associated with an E- to N-cadherin switch, increased vimentin expression, up-regulation of E-cadherin repressor molecules (Snail and Slug proteins), and increased gelatinase (matrix metalloproteinases; MMP-2 and MMP-9) activity and cellular motility, all characteristic EMT events. The 5T4 oncofetal antigen, previously shown to be associated with early human ES cell differentiation, is also part of this process. Abrogation of E-cadherin–mediated cell-cell contact in undifferentiated ES cells using neutralizing antibody (nAb) SHE78.7 resulted in increased cellular motility, altered actin cytoskeleton arrangement and a mesenchymal phenotype together with presentation of the 5T4 antigen at the cell surface. nAb-treated ES cells remained in an undifferentiated state, as assessed by OCT-4 protein expression, and did not express EMT-associated transcripts. Removal of nAb from ES cells resulted in the restoration of cell-cell contact, absence of cell surface 5T4, decreased mesenchymal cellular morphology and motility, and enabled the differentiation of the cells to the three germ layers upon their removal from the fibroblast feeder layer. We conclude that E-cadherin functions in human ES cells to stabilize the cortical actin cyoskeletal arrangement and this prevents cell surface localization of the 5T4 antigen. Furthermore, human ES cells represent a useful model system with which to study EMT events relevant to embryonic development and tumor cell metastasis. [Cancer Res 2007;67(23):11254–62]