bluuebunny/crossref_metadata_2025_split huggingface dataset:
15-Hydroxyprostaglandin Dehydrogenase Is a Tumor Suppressor of Human Breast Cancer
Authors: Wolf Ido , O'Kelly James , Rubinek Tamar , Tong Min , Nguyen Anh , Lin Bryan T. , Tai Hsin-Hsiung , Karlan Beth Y. , Koeffler H. Phillip 
Published: August 2006

Abstract
Prostaglandin E2 plays a growth-stimulatory role in breast cancer, and the rate-limiting enzyme in its synthesis, cyclooxygenase-2, is often overexpressed in these cancers. Little is known about the role of the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in breast cancer pathogenesis. Using a pharmacologically based screen for epigenetically silenced genes, we found low levels of 15-PGDH in MDA-MB-231 cells [estrogen receptor (ER) negative] but high levels in MCF-7 cells (ER positive) and observed its up-regulation following demethylation treatment. Further analysis revealed methylation of the 15-PGDH promoter in one breast cancer cell line and 30% of primary tumors. Analysis of 15-PGDH expression revealed low levels in 40% of primary breast tumors and identified a correlation between 15-PGDH and ER expression. Transfection assays showed that transient up-regulation of 15-PGDH levels in MDA-MB-231 cells resulted in a decreased clonal growth, and stable up-regulation significantly decreased the ability of these cells to form tumors in athymic mice. In contrast, transient silencing of 15-PGDH in MCF-7 cells resulted in their enhanced proliferation, and a stable silencing in these cells enhanced cell cycle entry in vitro and tumorigenicity in vivo. Forced expression of 15-PGDH inhibited the ER pathway and silencing of 15-PGDH up-regulated expression of aromatase. In addition, 15-PGDH levels were down-regulated by estrogen but up-regulated by the tumor suppressor gene CAAT/enhancer binding protein α. Our results indicate for the first time that 15-PGDH may be a novel tumor suppressor gene in breast cancer, and suggest that this enzyme can modulate the ER pathway. (Cancer Res 2006; 66(15): 7818-23)
Selection of Tumor-binding Ligands in Cancer Patients with Phage Display Libraries
Authors: Krag David N. , Shukla Girja S. , Shen Guang-Ping , Pero Stephanie , Ashikaga Taka , Fuller Susan , Weaver Donald L. , Burdette-Radoux Susan , Thomas Christian 
Published: August 2006

AbstractPhage display has been used extensively in vitro and in animal models to generate ligands and to identify cancer-relevant targets. We report here the use of phage-display libraries in cancer patients to identify tumor-targeting ligands. Eight patients with stage IV cancer, including breast, melanoma, and pancreas, had phage-displayed random peptide or scFv library (1.6 × 108-1 × 1011 transducing units/kg) administered i.v.; tumors were excised after 30 minutes; and tumor-homing phage were recovered. In three patients, repeat panning was possible using phage recovered and amplified from that same patient's tumor. No serious side effects, including allergic reactions, were observed with up to three infusions. Patients developed antiphage antibodies that reached a submaximal level within the 10-day protocol window for serial phage administration. Tumor phage were recoverable from all the patients. Using a filter-based ELISA, several clones from a subset of the patients were identified that bound to a tumor from the same patient in which clones were recovered. The clone-binding to tumor was confirmed by immunostaining, bioassay, and real-time PCR–based methods. Binding studies with noncancer and cancer cell lines of the same histology showed specificity of the tumor-binding clones. Analysis of insert sequences of tumor-homing peptide clones showed several motifs, indicating nonrandom accumulation of clones in human tumors. This is the first reported series of cancer patients to receive phage library for serial panning of tumor targeting ligands. The lack of toxicity and the ability to recover clones with favorable characteristics are a first step for further research with this technology in cancer patients. (Cancer Res 2006; 66(15): 7724-33)
Targeted Therapy with aSalmonella TyphimuriumLeucine-Arginine Auxotroph Cures Orthotopic Human Breast Tumors in Nude Mice
Authors: Zhao Ming , Yang Meng , Ma Huaiyu , Li Xiaoming , Tan Xiuying , Li Shukuan , Yang Zhijian , Hoffman Robert M. 
Published: August 2006

AbstractWe report here a modified auxotrophic strain of Salmonella typhimurium that can target and cure breast tumors in orthotopic mouse models. We have previously reported development of a genetically modified strain of S. typhimurium, selected for prostate tumor targeting and therapy in vivo. The strain, termed S. typhimurium A1, selectively grew in prostate tumors in xenograft models causing tumor regression. In contrast, normal tissue was cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. A1 is auxotrophic (leucine-arginine dependent) but apparently receives sufficient nutritional support only from tumor tissue. The ability to grow in viable tumor tissue may account, in part, for the unique antitumor efficacy of the strain. In the present report, to increase tumor-targeting capability of A1, the strain was reisolated after infection of a human colon tumor growing in nude mice. The tumor-isolated strain, termed A1-R, had increased targeting for tumor cells in vivo as well as in vitro compared with A1. Treatment with A1-R resulted in highly effective tumor targeting, including viable tumor tissue and significant tumor shrinkage in mice with s.c. or orthotopic human breast cancer xerographs. Survival of the treated animals was significantly prolonged. Forty percent of treated mice were cured completely and survived as long as non–tumor-bearing mice. These results suggest that amino acid auxotrophic virulent bacteria, which selectively infect and attack viable tumor tissue, are a promising approach to cancer therapy. (Cancer Res 2006; 66(15): 7647-52)
Impaired Notch Signaling Promotes De novo Squamous Cell Carcinoma Formation
Authors: Proweller Aaron , Tu Lili , Lepore John J. , Cheng Lan , Lu Min Min , Seykora John , Millar Sarah E. , Pear Warren S. , Parmacek Michael S. 
Published: August 2006

Abstract
Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor–mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1), to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)–dependent] Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice display hyperplastic epidermis and spontaneously develop cutaneous squamous cell carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice expressing epidermal DNMAML1 display enhanced accumulation of nuclear β-catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from SCCs, which was also observed in human cutaneous SCC. These results suggest a model wherein CSL-dependent Notch signaling confers protection against cutaneous SCC. The demonstration that inhibition of canonical Notch signaling in mice leads to spontaneous formation of SCC and recapitulates the disease in humans yields fundamental insights into the pathogenesis of SCC and provides a unique in vivo animal model to examine the pathobiology of cutaneous SCC and for evaluating novel therapies. (Cancer Res 2006; 66(15): 7438-44)
Ifosfamide-Induced Nephrotoxicity: Mechanism and Prevention
Authors: Nissim Itzhak , Horyn Oksana , Daikhin Yevgeny , Nissim Ilana , Luhovyy Bohdan , Phillips Peter C. , Yudkoff Marc 
Published: August 2006

AbstractThe efficacy of ifosfamide (IFO), an antineoplastic drug, is severely limited by a high incidence of nephrotoxicity of unknown etiology. We hypothesized that inhibition of complex I (C-I) by chloroacetaldehyde (CAA), a metabolite of IFO, is the chief cause of nephrotoxicity, and that agmatine (AGM), which we found to augment mitochondrial oxidative phosphorylation and β-oxidation, would prevent nephrotoxicity. Our model system was isolated mitochondria obtained from the kidney cortex of rats treated with IFO or IFO + AGM. Oxidative phosphorylation was determined with electron donors specific to complexes I, II, III, or IV (C-I, C-II, C-III, or C-IV, respectively). A parallel study was done with 13C-labeled pyruvate to assess metabolic dysfunction. Ifosfamide treatment significantly inhibited oxidative phosphorylation with only C-I substrates. Inhibition of C-I was associated with a significant elevation of [NADH], depletion of [NAD], and decreased flux through pyruvate dehydrogenase and the TCA cycle. However, administration of AGM with IFO increased [cyclic AMP (cAMP)] and prevented IFO-induced inhibition of C-I. In vitro studies with various metabolites of IFO showed that only CAA inhibited C-I, even with supplementation with 2-mercaptoethane sulfonic acid. Following IFO treatment daily for 5 days with 50 mg/kg, the level of CAA in the renal cortex was ∼15 μmol/L. Taken together, these observations support the hypothesis that CAA is accumulated in renal cortex and is responsible for nephrotoxicity. AGM may be protective by increasing tissue [cAMP], which phosphorylates NADH:oxidoreductase. The current findings may have an important implication for the prevention of IFO-induced nephrotoxicity and/or mitochondrial diseases secondary to defective C-I. (Cancer Res 2006; 66(15): 7824-31)
Real-time Evaluation of p53 Oscillatory Behavior In vivo Using Bioluminescent Imaging
Authors: Hamstra Daniel A. , Bhojani Mahaveer S. , Griffin Laura B. , Laxman Bharathi , Ross Brian D. , Rehemtulla Alnawaz 
Published: August 2006

Abstract
p53 is a key mediator of cellular response to stress, and, although its function has been carefully evaluated in vitro, noninvasive evaluation of the transcriptional activity of p53 in live animals has not been reported. To this end, we developed a transgenic mouse model wherein the firefly luciferase gene expression was dependent on the p53-responsive P2 promoter from the murine double minute 2 (MDM2) gene. Bioluminescence activity following ionizing radiation was shown to be dose, time, and p53 dependent. In addition, expression of both p53 and its activated form as well as the expression of p53 target genes (MDM2 and p21) correlated with bioluminescence activity. Temporal evaluation of p53 activity following ionizing radiation showed a distinct oscillatory pattern, which confirmed the oscillations observed previously in cultured cells. In addition, the kinetics of oscillations were altered by pretreatment with radiation-modifying agents. These results show the use of this mouse model in enhancing our understanding of the transcriptional role of p53 in vivo. (Cancer Res 2006; 66(15): 7482-9)
Notes on the Vocabulary of Abyāne'ī
Authors: Joneidi-Ja'fari Mahmud 
Published: August 2006

AbstractIn his article, the author maintains the view that within the Central Iranian linguistic continuum, there is a separate dialect area including ten small villages, which he calls the Abyāne group, after the name of its most typical member. He supports his argument by discussing two characteristic isoglosses for this group—the terms for "mouth" and "dog".
On Measuring the Terms of the Turbulent Kinetic Energy Budget from an AUV
Authors: Goodman Louis , Levine Edward R. , Lueck Rolf G. 
Published: August 2006

AbstractThe terms of the steady-state, homogeneous turbulent kinetic energy budgets are obtained from measurements of turbulence and fine structure from the small autonomous underwater vehicle (AUV) Remote Environmental Measuring Units (REMUS). The transverse component of Reynolds stress and the vertical flux of heat are obtained from the correlation of vertical and transverse horizontal velocity, and the correlation of vertical velocity and temperature fluctuations, respectively. The data were obtained using a turbulence package, with two shear probes, a fast-response thermistor, and three accelerometers. To obtain the vector horizontal Reynolds stress, a generalized eddy viscosity formulation is invoked. This allows the downstream component of the Reynolds stress to be related to the transverse component by the direction of the finescale vector vertical shear. The Reynolds stress and the vector vertical shear then allow an estimate of the rate of production of turbulent kinetic energy (TKE). Heat flux is obtained by correlating the vertical velocity with temperature fluctuations obtained from the FP-07 thermistor. The buoyancy flux term is estimated from the vertical flux of heat with the assumption of a constant temperature–salinity (T–S) relationship. Turbulent dissipation is obtained directly from the usage of shear probes.A multivariate correction procedure is developed to remove vehicle motion and vibration contamination from the estimates of the TKE terms. A technique is also developed to estimate the statistical uncertainty of using this estimation technique for the TKE budget terms. Within the statistical uncertainty of the estimates herein, the TKE budget on average closes for measurements taken in the weakly stratified waters at the entrance to Long Island Sound. In the strongly stratified waters of Narragansett Bay, the TKE budget closes when the buoyancy Reynolds number exceeds 20, an indicator and threshold for the initiation of turbulence in stratified conditions. A discussion is made regarding the role of the turbulent kinetic energy length scale relative to the length of the AUV in obtaining these estimates, and in the TKE budget closure.
The Autoimmune Disease Database: a dynamically compiled literature-derived database
Authors: Karopka Thomas , Fluck Juliane , Mevissen Heinz-Theodor , Glass Änne 
Published: August 2006

Abstract

Background
Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an overview of these related diseases it is not feasible to do a literary review but it requires methods of automated analyses of the more than 500,000 Medline documents related to autoimmune disorders.

Results
In this paper we present the first version of the Autoimmune Disease Database which to our knowledge is the first comprehensive literature-based database covering all known or suspected autoimmune diseases. This dynamically compiled database allows researchers to link autoimmune diseases to the candidate genes or proteins through the use of named entity recognition which identifies genes/proteins in the corresponding Medline abstracts. The Autoimmune Disease Database covers 103 autoimmune disease concepts. This list was expanded to include synonyms and spelling variants yielding a list of over 1,200 disease names. The current version of the database provides links to 541,690 abstracts and over 5,000 unique genes/proteins.

Conclusion
The Autoimmune Disease Database provides the researcher with a tool to navigate potential gene-disease relationships in Medline abstracts in the context of autoimmune diseases.
Comparative analysis and integrative classification of NCI60 cell lines and primary tumors using gene expression profiling data
Authors: Wang Huixia , Huang Shuguang , Shou Jianyong , Su Eric W , Onyia Jude E , Liao Birong , Li Shuyu 
Published: August 2006

Abstract

Background
NCI60 cell lines are derived from cancers of 9 tissue origins and have been invaluable in vitro models for cancer research and anti-cancer drug screen. Although extensive studies have been carried out to assess the molecular features of NCI60 cell lines related to cancer and their sensitivities to more than 100,000 chemical compounds, it remains unclear if and how well these cell lines represent or model their tumor tissues of origin. Identification and confirmation of correct origins of NCI60 cell lines are critical to their usage as model systems and to translate in vitro studies into clinical potentials. Here we report a direct comparison between NCI60 cell lines and primary tumors by analyzing global gene expression profiles.

Results
Comparative analysis suggested that 51 of 59 cell lines we analyzed represent their presumed tumors of origin. Taking advantage of available clinical information of primary tumor samples used to generate gene expression profiling data, we further classified those cell lines with the correct origins into different subtypes of cancer or different stages in cancer development. For example, 6 of 7 non-small cell lung cancer cell lines were classified as lung adenocarcinomas and all of them were classified into late stages in tumor progression.

Conclusion
Taken together, we developed and applied a novel approach for systematic comparative analysis and integrative classification of NCI60 cell lines and primary tumors. Our results could provide guidance to the selection of appropriate cell lines for cancer research and pharmaceutical compound screenings. Moreover, this gene expression profile based approach can be generally applied to evaluate experimental model systems such as cell lines and animal models for human diseases.
Plasma levels of soluble tumor necrosis factor-α receptors are related to total and LDL-cholesterol in lean, but not in obese subjects
Authors: Straczkowski Marek , Kowalska Irina , Nikolajuk Agnieszka , Adamska Agnieszka , Karolczuk-Zarachowicz Malgorzata , Karczewska-Kupczewska Monika , Kozlowska Agnieszka , Gorska Maria 
Published: August 2006

Abstract

Background
Tumor necrosis factor-α (TNFα) is a mediator of insulin resistance. Plasma levels of soluble TNFα receptors (sTNFR1 and sTNFR2) probably reflect paracrine action of the cytokine. TNFα is also a regulator of lipid metabolism, however, data about impact of obesity on the relationships between TNFα and plasma lipids remain controversial.

Aim
The purpose of the present study was to examine the associations of TNFα system with plasma lipids in lean and obese subjects with normal glucose metabolism.

Methods
We examined 63 subjects, 33 lean (BMI<25 kg × m-2) and 30 with marked overweight or obesity (BMI>27.8 kg × m-2). Anthropometric and biochemical parameters were measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed.

Results
Obese subjects were markedly more insulin resistant and had higher levels of both TNFα receptors. Total (TC) and LDL-cholesterol (LDL-C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in the obese group. In obese subjects, both receptors were significantly related to TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All those correlations disappeared after controlling for insulin sensitivity. In lean subjects, both receptors were related to TC, HDL-C and LDL-C. In that group, sTNFR1 predicted values of all those parameters independently of BMI, plasma glucose and insulin, and insulin sensitivity.

Conclusion
We conclude that TNFα receptors are associated with plasma lipids in different way in lean and in obese subjects. TNFα system is probably important in determining cholesterol levels in lean subjects, while in obese this effect might be masked by other metabolic abnormalities.
A novel system for gene silencing using siRNAs in rice leaf and stem-derived protoplasts
Authors: Bart Rebecca , Chern Mawsheng , Park Chang-Jin , Bartley Laura , Ronald Pamela C 
Published: August 2006

Abstract

Background
Transient assays using protoplasts are ideal for processing large quantities of genetic data coming out of hi-throughput assays. Previously, protoplasts have routinely been prepared from dicot tissue or cell suspension cultures and yet a good system for rice protoplast isolation and manipulation is lacking.

Results
We have established a rice seedling protoplast system designed for the rapid characterization of large numbers of genes. We report optimized methods for protoplast isolation from 7–14 day old etiolated rice seedlings. We show that the reporter genes luciferase GL2 and GUS are maximally expressed approximately 20 h after polyethylene glycol (PEG)-mediated transformation into protoplasts. In addition we found that transformation efficiency varied significantly with plasmid size. Five micrograms of a 4.5 kb plasmid resulted in 60–70% transformation efficiency. In contrast, using 50 μg of a 12 kb plasmid we obtained a maximum of 25–30% efficiency. We also show that short interfering RNAs (siRNAs) can be used to silence exogenous genes quickly and efficiently. An siRNA targeting luciferase resulted in a significant level of silencing after only 3 hours and up to an 83% decrease in expression. We have also isolated protoplasts from cells prepared from fully green tissue. These green tissue-derived protoplasts can be transformed to express high levels of luciferase activity and should be useful for assaying light sensitive cellular processes.

Conclusion
We report a system for isolation, transformation and gene silencing of etiolated rice leaf and stem-derived protoplasts. Additionally, we have extended the technology to protoplasts isolated from fully green tissue. The protoplast system will bridge the gap between hi-throughput assays and functional biology as it can be used to quickly study large number of genes for which the function is unknown.
Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma
Authors: Zhang Mao , Liu Zhi-Hai , Yang Jian-Xin , Gan Jian-Xin , Xu Shao-Wen , You Xiang-Dong , Jiang Guan-Yu 
Published: August 2006

Abstract
Introduction
Early detection of pneumothorax in multiple trauma patients is critically important. It can be argued that the efficacy of ultrasonography (US) for detection of pneumothorax is enhanced if it is performed and interpreted directly by the clinician in charge of the patients. The aim of this study was to assess the ability of emergency department clinicians to perform bedside US to detect and assess the size of the pneumothorax in patients with multiple trauma.

Methods
Over a 14 month period, patients with multiple trauma treated in the emergency department were enrolled in this prospective study. Bedside US was performed by emergency department clinicians in charge of the patients. Portable supine chest radiography (CXR) and computed tomography (CT) were obtained within an interval of three hours. Using CT and chest drain as the gold standard, the diagnostic efficacy of US and CXR for the detection of pneumothorax, defined as rapidity and accuracy (sensitivity, specificity, positive predictive value, negative predictive value), were compared. The size of the pneumothorax (small, medium and large) determined by US was also compared to that determined by CT.

Results
Of 135 patients (injury severity score = 29.1 ± 12.4) included in the study, 83 received mechanical ventilation. The time needed for diagnosis of pneumothorax was significantly shorter with US compared to CXR (2.3 ± 2.9 versus 19.9 ± 10.3 minutes, p < 0.001). CT and chest drain confirmed 29 cases of pneumothorax (21.5%). The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy for US and radiography were 86.2% versus 27.6% (p < 0.001), 97.2% versus 100% (not significant), 89.3% versus 100% (not significant), 96.3% versus 83.5% (p = 0.002), and 94.8% versus 84.4% (p = 0.005), respectively. US was highly consistent with CT in determining the size of pneumothorax (Kappa = 0.669, p < 0.001).

Conclusion
Bedside clinician-performed US provides a reliable tool and has the advantages of being simple and rapid and having higher sensitivity and accuracy compared to chest radiography for the detection of pneumothorax in patients with multiple trauma.