bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors
Authors: Jin Zhe , Cheng Yulan , Olaru Alexandru , Kan Takatsugu , Yang Jian , Paun Bogdan , Ito Tetsuo , Hamilton James P. , David Stefan , Agarwal Rachana , Selaru Florin M. , Sato Fumiaki , Abraham John M. , Beer David G. , Mori Yuriko , Shimada Yutaka , Meltzer Stephen J. 
Published: August 2008

AbstractAlthough the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's‐associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty‐nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real‐time methylation‐specific PCR. CDH13 hypermethylation showed discriminative receiver‐operator characteristic curve profiles, sharply demarcating esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma (ESCC) and normal esophagus (NE) (p < 0.0001). CDH13 normalized methylation values (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE (D) and EAC than in NE (p < 0.0000001). CDH13 hypermethylation frequency was 0% in NE but increased early during neoplastic progression, rising to 70% in BE, 77.5% in D and 76.1% in EAC. Both CDH13 hypermethylation frequency and its mean NMV were significantly higher in BE with than without accompanying EAC. In contrast, only 5 (19.2%) of 26 ESCCs exhibited CDH13 hypermethylation. Furthermore, both CDH13 hypermethylation frequency and its mean NMV were significantly higher in EAC than in ESCC, as well as in BE or D vs. ESCC. Interestingly, mean CDH13 NMV was significantly lower in short‐segment than in long‐segment BE, a known clinical risk factor for neoplastic progression. Similarly, BE segment length was significantly lower in specimens with unmethylated than with methylated CDH13 promoters. 5‐aza‐2′‐deoxycytidine treatment of OE33 EAC and KYSE220 ESCC cells reduced CDH13 methylation and increased CDH13 mRNA expression. These findings suggest that hypermethylation of CDH13 is a common, tissue‐specific event in human EAC, occurs early during BE‐associated neoplastic progression, and correlates with known clinical neoplastic progression risk factors. © 2008 Wiley‐Liss, Inc.
PX‐478, an inhibitor of hypoxia‐inducible factor‐1α, enhances radiosensitivity of prostate carcinoma cells
Authors: Palayoor Sanjeewani T. , Mitchell James B. , Cerna David , DeGraff William , John‐Aryankalayil Molykutty , Coleman C. Norman 
Published: August 2008

AbstractOverexpression of hypoxia‐inducible factor‐1α (HIF‐1α) in human tumors is associated with poor prognosis and poor outcome to radiation therapy. Inhibition of HIF‐1α is considered as a promising approach in cancer therapy. The purpose of this study was to test the efficacy of a novel HIF‐1α inhibitor PX‐478 as a radiosensitizer under normoxic and hypoxic conditions in vitro. PC3 and DU 145 prostate carcinoma cells were treated with PX‐478 for 20 hr, and HIF‐1α protein level and clonogenic cell survival were determined under normoxia and hypoxia. Effects of PX‐478 on cell cycle distribution and phosphorylation of H2AX histone were evaluated. PX‐478 decreased HIF‐1α protein in PC3 and DU 145 cells. PX‐478 produced cytotoxicity in both cell lines with enhanced toxicity under hypoxia for DU‐145. PX‐478 (20 μmol/L) enhanced the radiosensitivity of PC3 cells irradiated under normoxic and hypoxic condition with enhancement factor (EF) 1.4 and 1.56, respectively. The drug was less effective in inhibiting HIF‐1α and enhancing radiosensitivity of DU 145 cells compared to PC3 cells with EF 1.13 (normoxia) and 1.25 (hypoxia) at 50 μmol/L concentration. PX‐478 induced S/G2M arrest in PC3 but not in DU 145 cells. Treatment of PC3 and DU 145 cells with the drug resulted in phosphorylation of H2AX histone and prolongation of γH2AX expression in the irradiated cells. PX‐478 is now undergoing Phase I clinical trials as an oral agent. Although the precise mechanism of enhancement of radiosensitivity remains to be identified, this study suggests a potential role for PX‐478 as a clinical radiation enhancer. Published 2008 Wiley‐Liss, Inc.
Prognostic evaluation of epidermal fatty acid‐binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approach
Authors: Li Zhengyu , Huang Canhua , Bai Shujun , Pan Xiaoling , Zhou Rong , Wei Yuquan , Zhao Xia 
Published: August 2008

AbstractWith the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid‐binding protein (E‐FABP) and calcyphosine (CAPS) by MALDI‐Q‐TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E‐FABP and CAPS were increased 2.64‐ and 2.18‐fold in EC by immunoblotting. Immunoreactivity of both E‐FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E‐FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E‐FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E‐FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications. © 2008 Wiley‐Liss, Inc.
Analysis of peripheral and local anti‐tumor immune response in esophageal cancer patients after NY‐ESO‐1 protein vaccination
Authors: Wada Hisashi , Sato Eiichi , Uenaka Akiko , Isobe Midori , Kawabata Ryohei , Nakamura Yurika , Iwae Shigemichi , Yonezawa Kouichiro , Yamasaki Makoto , Miyata Hiroshi , Doki Yuichiro , Shiku Hiroshi , Jungbluth Achim A. , Ritter Gerd , Murphy Roger , Hoffman Eric W. , Old Lloyd J. , Monden Morito , Nakayama Eiichi 
Published: August 2008

AbstractNY‐ESO‐1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY‐ESO‐1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY‐ESO‐1 recombinant protein formulated with cholesterol‐bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T‐cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY‐ESO‐1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T‐cell infiltration, 1 patient with increase in the number of CD68+ macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY‐ESO‐1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY‐ESO‐1. However, the tumors grew eventually by various mechanisms after vaccination. © 2008 Wiley‐Liss, Inc.
Identification of novel Smad2 and Smad3 associated proteins in response to TGF‐β1
Authors: Brown Kimberly A. , Ham Amy‐Joan L. , Clark Cara N. , Meller Nahum , Law Brian K. , Chytil Anna , Cheng Nikki , Pietenpol Jennifer A. , Moses Harold L. 
Published: August 2008

AbstractTransforming growth factor‐beta 1 (TGF‐β1) is an important growth inhibitor of epithelial cells and insensitivity to this cytokine results in uncontrolled cell proliferation and can contribute to tumorigenesis. TGF‐β1 signals through the TGF‐β type I and type II receptors, and activates the Smad pathway via phosphorylation of Smad2 and Smad3. Since little is known about the selective activation of Smad2 versus Smad3, we set out to identify novel Smad2 and Smad3 interacting proteins in epithelial cells. A non‐transformed human cell line was transduced with Myc‐His6‐Smad2 or Myc‐His6‐Smad3‐expressing retrovirus and was treated with TGF‐β1. Myc‐His6‐Smad2 or Myc‐His6‐Smad3 was purified by tandem affinity purification, eluates were subject to SDS–PAGE and Colloidal Blue staining, and select protein bands were digested with trypsin. The resulting tryptic peptides were analyzed by liquid chromatography (LC) and tandem mass spectrometry (MS/MS) and the SEQUEST algorithm was employed to identify proteins in the bands. A number of proteins that are known to interact with Smad2 or Smad3 were detected in the eluates. In addition, a number of putative novel Smad2 and Smad3 associated proteins were identified that have functions in cell proliferation, apoptosis, actin cytoskeleton regulation, cell motility, transcription, and Ras or insulin signaling. Specifically, the interaction between Smad2/3 and the Cdc42 guanine nucleotide exchange factor, Zizimin1, was validated by co‐immunoprecipitation. The discovery of these novel Smad2 and/or Smad3 associated proteins may reveal how Smad2 and Smad3 are regulated and/or uncover new functions of Smad2 and Smad3 in TGF‐β1 signaling. J. Cell. Biochem. 105: 596–611, 2008. © 2008 Wiley‐Liss, Inc.
Regulatory expression of Brachyury and Goosecoid in P19 embryonal carcinoma cells
Authors: Nakaya Kohei , Murakami Masaru , Funaba Masayuki 
Published: August 2008

AbstractMouse P19 embryonal carcinoma cells can differentiate into various cell types depending on culture conditions. Here we show that the expression of the mesodermal genes Brachyury (Bra) and Goosecoid (Gsc) are under regulatory control in P19 cells. When P19 cells were cultured in a tissue culture dish in the presence of serum, Bra and Gsc were unexpectedly expressed. Expression of Bra and Gsc was greatly reduced with culture time, and expression levels at 144 h of culture were below 25% those at 48 h of culture. Members of the Tgf‐β family such as Activin and Nodal have been known to up‐regulate expression of mesodermal genes. Treatment with SB431542, an Alk4/5/7 inhibitor, decreased Bra and Gsc in a dose‐dependent manner, whereas it induced the expression of the neuroectodermal genes Mash‐1 and Pax‐6. Quantitative RT‐PCR and dsRNAi transfection indicated Nodal as a possible ligand responsible for the regulation of Bra and Gsc. In addition, exogenous Nodal increased expression of Bra and Gsc in a dose‐dependent manner. Serum concentration in culture medium positively related to expression of Nodal, Bra, Gsc, and Cripto, which encodes a membrane‐tethered protein required for Nodal signaling. Addition of the culture supernatant of P19 cells at 144 h of culture to medium decreased expression of these genes. The present study reveals that stimulation and inhibition of the Nodal pathway increases mesodermal genes and neuroectodermal genes, respectively, indicating the importance of control of Nodal and Cripto expression for mesodermal formation and neurogenesis. J. Cell. Biochem. 105: 801–813, 2008. © 2008 Wiley‐Liss, Inc.
Lipopolysaccharide suppresses RANK gene expression in macrophages by down‐regulating PU.1 and MITF
Authors: Ishii Junko , Kitazawa Riko , Mori Kiyoshi , McHugh Kevin P. , Morii Eiichi , Kondo Takeshi , Kitazawa Sohei 
Published: August 2008

AbstractReceptor activator of NF‐κB (RANK) is a receptor for RANK ligand (RANKL), and signals transduced by RANK–RANKL interaction are prerequisite for the differentiation and activation of osteoclasts. We cloned and characterized a 6‐kb fragment containing the 5′‐flanking region of the mouse RANK gene. A fragment of 1‐kb from the transcription start sites containing four Sp‐1 sites and putative binding sites for MITF, CRE/AP‐1, and PU.1 was ligated to the pGL3‐basic vector, and the promoter activity was confirmed by transfection studies. By electrophoretic gel motility shift assay, both PU.1 and proximal MITF binding site showed specific DNA‐protein binding. Co‐transfection studies with MITF‐ and PU.1‐expression vectors revealed that MITF and PU.1 increased RANK promoter activity three‐ and twofold, respectively, and sixfold synergistically. Taken together, these results show that RANK transcription is positively regulated by both PU.1 and MITF. The effect of lipopolysaccharide (LPS) on RANK gene expression, analyzed by in situ hybridization using mouse bone tissue, showed that LPS decreased RANK transcripts of both precursor and mature osteoclasts. Furthermore, LPS treatment of RAW.264.7 cells decreased their RANK mRNA expression by 70%, mirroring the decrease of PU.1 and MITF mRNA. Short‐term treatment with LPS decreased the promoter activity of pGL3‐WT by 70%. Although LPS has been reported to promote osteoclastogenesis in chronic and local pyogenic inflammation, we speculate that LPS per se may directly suppress RANK expression in the osteoclastic cell lineage by down‐regulating the expression of PU.1 and MITF genes in acute and systemic severe endotoxemia, such as in septic shock. J. Cell. Biochem. 105: 896–904, 2008. © 2008 Wiley‐Liss, Inc.
Helenalin‐mediated post‐transcriptional regulation of p21(Cip1) inhibits 3T3‐L1 preadipocyte proliferation
Authors: Fernandes Karishma M. , Auld Corinth A. , Hopkins Robin G. , Morrison Ron F. 
Published: August 2008

AbstractWe have previously shown that post‐transcriptional mechanisms involving the 26S proteasome regulate the cyclin‐dependent kinase inhibitors (CKIs), p21(Cip1) and p27(Kip1) during preadipocyte proliferation. Earlier studies further demonstrated that the anti‐inflammatory, anti‐carcinogenic phytochemical, helenalin is a potent inhibitor of periodic Skp2 accumulation, an F‐box protein mediating SCF E3 ligase ubiquitylation and degradation of both CKIs during S phase progression. Data presented here demonstrate that helenalin dose‐dependently induced G1 arrest of synchronously replicating 3T3‐L1 preadipocytes. This effect occurred in the absence of discernable indices of cell toxicity or apoptosis under the conditions used in this study. Our results demonstrate that helenalin markedly increased p21 protein accumulation in both density‐arrested and proliferating preadipocytes in a dose‐dependent manner. This increase in p21 protein abundance occurred without change in mRNA transcript demonstrating that post‐transcriptional mechanisms were involved. This notion was further supported by the modest accumulation of polyubiquitylated p21 following treatment with helenalin suggesting that suppression of targeted p21 proteolysis by the 26S proteasome contributed to helenalin‐mediated p21 accumulation. The increase in p21 protein was compartmentalized to the nucleus where p21 is known to inhibit cell cycle progression. Finally, helenalin increased protein–protein interactions between p21 and cyclin‐dependent kinase 2 (Cdk2) which may account in part for the anti‐proliferative effect in 3T3‐L1 preadipocytes. J. Cell. Biochem. 105: 913–921, 2008. © 2008 Wiley‐Liss, Inc.
PhAST: Pharmacophore alignment search tool
Authors: Hähnke Volker , Hofmann Bettina , Grgat Tomislav , Proschak Ewgenij , Steinhilber Dieter , Schneider Gisbert 
Published: August 2008

AbstractWe present a ligand‐based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text‐based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand‐based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5‐lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence‐based compound screening with substantial scaffold hopping potential. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Application of error‐ranked singular value decomposition for the determination of potential‐derived atomic‐centered point charges
Authors: Tan Jeffrey S. , Boerrigter Stephan X. M. , Scaringe Raymond P. , Morris Kenneth R. 
Published: August 2008

AbstractThe present work provides a detailed investigation on the use of singular value decomposition (SVD) to solve the linear least‐squares problem (LLS) for the purposes of obtaining potential‐derived atom‐centered point charges (PD charges) from the ab initio molecular electrostatic potential (VQM). Given the SVD of any PD charge calculation LLS problem, it was concluded that (1) all singular vectors are not necessary to obtain the optimal set of PD charges and (2) the most effective set of singular vectors do not necessarily correspond to those with the largest singular values. It is shown that the efficient use of singular vectors can provide statistically well‐defined PD charges when compared with conventional PD charge calculation methods without sacrificing the agreement with VQM. As can be expected, the methodology outlined here is independent of the algorithm for sampling VQM as well as the basis set used to calculate VQM. An algorithm is provided to select the best set of singular vectors used for optimal PD charge calculations. To minimize the subjective comparisons of different PD charge sets, we also provide an objective criterion for determining if two sets of PD charges are significantly different from one another. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Application of the dressed time‐dependent density functional theory for the excited states of linear polyenes
Authors: Mazur Grzegorz , Włodarczyk Radosław 
Published: August 2008

AbstractDressed Time‐Dependent Density Functional Theory (Maitra et al., J Chem Phys 2004, 120, 5932) is applied to selected linear polyenes. Limits of validity of the approximation are briefly discussed. The implementation strategy is described. Results for the 21Bu and 21Ag states of selected linear polyenes are presented and compared with accessible experimental and theoretical results. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Prediction of acidity in acetonitrile solution with COSMO‐RS
Authors: Eckert Frank , Leito Ivo , Kaljurand Ivari , Kütt Agnes , Klamt Andreas , Diedenhofen Michael 
Published: August 2008

AbstractThe COSMO‐RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of pKa values in acetonitrile. For a variety of 93 organic acids, the directly calculated values of the free energies of dissociation in acetonitrile showed a very good correlation with the pKa values (r2 = 0.97) in acetonitrile, corresponding to a standard deviation of 1.38 pKa units. Thus, we have a prediction method for acetonitrile pKa with the intercept and the slope as the only adjusted parameters. Furthermore, the pKa values of CH acids yielding large anions with delocalized charge can be predicted with a rmse of 1.12 pKa units using the theoretical values of slope and intercept resulting in truly ab initio pKa prediction. In contrast to our previous findings on aqueous acidity predictions the slope of the experimental pKa versus theoretical ΔGdiss was found to match the theoretical value 1/RT ln (10) very well. The predictivity of the presented method is general and is not restricted to certain compound classes. However, a systematic correction of −7.5 kcal mol−1 is required for compounds that do not allow electron‐delocalization in the dissociated anion. The prediction model was tested on a diverse test set of 129 complex multifunctional compounds from various sources, reaching a root mean square deviation of 2.10 pKa units. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Implementation and use of a direct, partially integral‐driven non‐Dyson propagator method for molecular ionization
Authors: Storchi Loriano , Vitillaro Giuseppe , Tarantelli Francesco 
Published: August 2008

AbstractThe Green's function ADC(3) scheme has been for many years a successful method to predict theoretically the ionization (and electron affinity) spectrum of molecules. However, a dramatic enhancement of the method's power has come only recently, with the development of an approximation method to the one‐particle Green's function which does not make direct use of the Dyson equation. In the present work, we present an efficient computer implementation of this novel approach, with first comparative tests demonstrating its enormous computational advantage over the conventional approach. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009
Who copes well? Obesity‐related coping and its associations with shame, guilt, and weight loss
Authors: Conradt Matthias , Dierk Jan‐Michael , Schlumberger Pia , Rauh Elisabeth , Hebebrand Johannes , Rief Winfried 
Published: August 2008

AbstractThe relationship among weight‐related coping, guilt, and shame was investigated in a sample of 98 obese German individuals over a 6‐month period. In terms of the objectives, the study explored the kind and frequency of typical coping situations in which obese individuals become aware of being obese. Furthermore, the study sought to determine the predictive utility of weight‐related shame and guilt concerning coping responses, and to establish whether there is an association between coping responses and weight change. A longitudinal examination over a 6‐month period was chosen with two measurement points. As typical distressing coping situations, individuals reported mostly negative evaluations through others/self, physical exercise situations, or environmental hazards (mainly shopping for clothes). Weight‐related shame at baseline was a significant negative predictor for problem‐focused engagement coping, whereas weight‐related guilt was a significant positive predictor for problem‐focused engagement strategies and dietary restraint at follow‐up. Although Body Mass Index showed no substantial association with the coping measures, weight loss was accompanied by a substantial drop in problem‐focused disengagement coping (wishful thinking, problem avoidance). Discussion of these findings focuses on the issue of possible effects of weight‐related feelings of guilt and shame on coping behavior, the link between weight loss and disengaging coping strategies, and the possible use of the findings for cognitive–behavioral therapy for obesity. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1–16, 2008.