bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roscovitine, a selective CDK inhibitor, reduces the basal and estrogen‐induced phosphorylation of ER‐α in human ER‐positive breast cancer cells
Authors: Węsierska‐Gądek Józefa , Gritsch David , Zulehner Nora , Komina Oxana , Maurer Margarita 
Published: December 2010

AbstractRoscovitine (ROSC), a selective cyclin‐dependent kinase (CDK) inhibitor, arrests human estrogen receptor‐α (ER‐α) positive MCF‐7 breast cancer cells in the G2 phase of the cell cycle and concomitantly induces apoptosis via a p53‐dependent pathway. The effect of ROSC is markedly diminished in MCF‐7 cells maintained in the presence of estrogen‐mimicking compounds. Therefore, we decided to examine whether ROSC has any effect on the functional status of the ER‐α transcription factor. Exposure of MCF‐7 cells to ROSC abolished the activating phosphorylation of CDK2 and CDK7 in a concentration and time‐dependent manner. This inhibition of site‐specific modification of CDK7 at Ser164/170 prevented phosphorylation of RNA polymerase II and reduced basal phosphorylation of ER‐α at Ser118 in non‐stimulated MCF‐7 cells (resulting in its down‐regulation). In MCF‐7 cells, estrogen induced strong phosphorylation of ER‐α at Ser118 but not at Ser104/Ser106. ROSC prevented this estrogen‐promoted activating modification of ER‐α. Furthermore, we sought to determine whether the activity of ROSC could be enhanced by combining it with an anti‐estrogen. Tamoxifen (TAM), a selective estrogen receptor modulator (SERM), affected breast cancer cell lines irrespective of their ER status. In combination with ROSC, however, it had a different impact, enhancing G1 or G2 arrest. Our results indicate that ROSC prevents the activating phosphorylation of ER‐α and that its mode of action is strongly dependent on the cellular context. Furthermore, our data show that ROSC can be combined with anti‐estrogen therapy. The inhibitory effect of TAM on ER‐negative cancer cells indicates that SERMs crosstalk with other steroid hormone receptors. J. Cell. Biochem. 112: 761–772, 2011. © 2010 Wiley‐Liss, Inc.
Delayed production of arachidonic acid contributes to the delay of proteinase‐activated receptor‐1 (PAR1)‐triggered prostaglandin E2 release in rat gastric epithelial RGM1 cells
Authors: Sekiguchi Fumiko , Ohi Ai , Maeda Yuma , Takaoka Kaori , Sekimoto Teruki , Nishikawa Hiroyuki , Kawabata Atsufumi 
Published: December 2010

AbstractProteinase‐activated receptor‐1 (PAR1), upon activation, exerts prostanoid‐dependent gastroprotection, and increases prostaglandin E2 (PGE2) release through cyclooxygenase‐2 (COX‐2) upregulation in rat gastric mucosal epithelial RGM1 cells. However, there is a big time lag between the PAR1‐triggered PGE2 release and COX‐2 upregulation in RGM1 cells; that is, the former event takes 18 h to occur, while the latter rapidly develops and reaches a plateau in 6 h. The present study thus aimed at clarifying mechanisms for the delay of PGE2 release after PAR1 activation in RGM1 cells. Although a PAR1‐activating peptide, TFLLR‐NH2, alone caused PGE2 release at 18 h, but not 6 h, TFLLR‐NH2 in combination with arachidonic acid dramatically enhanced PGE2 release even for 1–6 h. TFLLR‐NH2 plus linoleic acid caused a similar rapid response. CP‐24879, a Δ5/Δ6‐desaturase inhibitor, abolished the PGE2 release induced by TFLLR‐NH2 plus linoleic acid, but not by TFLLR‐NH2 alone. The TFLLR‐NH2‐induced PGE2 release was not affected by inhibitors of cytosolic phospholipase A2 (cPLA2), Ca2+‐independent PLA2 (cPLA2) or secretory PLA2 (sPLA2), but was abolished by their mixture or a pan‐PLA2 inhibitor. Among PLA2 isozymes, mRNA of group IIA sPLA2 (sPLA2‐IIA) was upregulated following PAR1 stimulation for 6–18 h, whereas protein levels of PGE synthases were unchanged. These data suggest that the delay of PGE2 release after COX‐2 upregulation triggered by PAR1 is due to the poor supply of free arachidonic acid at the early stage in RGM1 cells, and that plural isozymes of PLA2 including sPLA2‐IIA may complementarily contribute to the liberation of free arachidonic acid. J. Cell. Biochem. 112: 909–915, 2011. © 2010 Wiley‐Liss, Inc.
RANKL increases migration of human lung cancer cells through intercellular adhesion molecule‐1 up‐regulation
Authors: Chen Li‐Mien , Kuo Chia‐Hua , Lai Tung‐Yuan , Lin Yueh‐Min , Su Cheng‐Chuan , Hsu His‐Hsien , Tsai Fuu‐Jen , Tsai Chang‐Hai , Huang Chih‐Yang , Tang Chih‐Hsin 
Published: December 2010

AbstractInvasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor‐κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule‐1 (ICAM‐1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion‐dependent cell‐to‐cell interactions. The effects of RANKL on cell migration and ICAM‐1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM‐1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL‐mediated migration and ICAM‐1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal‐regulating kinase (ERK). In addition, an NF‐κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL‐mediated cell migration and ICAM‐1 up‐regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF‐κB, resulting in the activation of ICAM‐1 and contributing to the migration of human lung cancer cells. J. Cell. Biochem. 112: 933–941, 2011. © 2010 Wiley‐Liss, Inc.
Down‐regulation of cyclin E1 expression by microrna‐195 accounts for interferon‐β‐induced inhibition of hepatic stellate cell proliferation
Authors: Sekiya Yumiko , Ogawa Tomohiro , Iizuka Masashi , Yoshizato Katsutoshi , Ikeda Kazuo , Kawada Norifumi 
Published: December 2010

AbstractRecent studies have suggested that interferons (IFNs) have an antifibrotic effect in the liver independent of their antiviral effect although its detailed mechanism remains largely unknown. Some microRNAs have been reported to regulate pathophysiological activities of hepatic stellate cells (HSCs). We performed analyses of the antiproliferative effects of IFNs in HSCs with special regard to microRNA‐195 (miR‐195). We found that miR‐195 was prominently down‐regulated in the proliferative phase of primary‐cultured mouse HSCs. Supporting this fact, IFN‐β induced miR‐195 expression and inhibited the cell proliferation by delaying their G1 to S phase cell cycle progression in human HSC line LX‐2. IFN‐β down‐regulated cyclin E1 and up‐regulated p21 mRNA levels in LX‐2 cells. Luciferase reporter assay revealed the direct interaction of miR‐195 with the cyclin E1 3′UTR. Overexpression of miR‐195 lowered cyclin E1 mRNA and protein expression levels, increased p21 mRNA and protein expression levels, and inhibited cell proliferation in LX‐2 cells. Moreover miR‐195 inhibition restored cyclin E1 levels that were down‐regulated by IFN‐β. In conclusion, IFN‐β inhibited the proliferation of LX‐2 cells by delaying cell cycle progression in G1 to S phase, partially through the down‐regulation of cyclin E1 and up‐regulation of p21. IFN‐induced miR‐195 was involved in these processes. These observations reveal a new mechanistic aspect of the antifibrotic effect of IFNs in the liver. J. Cell. Physiol. 226: 2535–2542, 2011. © 2010 Wiley‐Liss, Inc.
Towards gene therapy for deafness
Authors: Di Domenico Marina , Ricciardi Carmela , Martone Tiziana , Mazzarella Nicoletta , Cassandro Claudia , Chiarella Giuseppe , D'Angelo Luigi , Cassandro Ettore 
Published: December 2010

AbstractMany hearing disorders are associated with the damage or loss of sensory hair cells (HC) which can produce a profound and irreversible deafness. Apoptosis pathway is reported to play an important role leading to rapid expansion of the HC lesion after exposure to intense noise. Furthermore, progress made over the last year in understanding molecular mechanisms involved in the proliferative and regenerative capacity of sensory cells in the mammalian inner ear has raised the possibility that targeted therapies might prevent the loss of these cells and preserve the patient's hearing. A first step towards the successful therapeutic exploitation is a better understanding of the different pathways that control survival and proliferation of sensory cells. In this review, we provide an overview of recent findings concerning the possibility to prevent apoptosis in auditory cells. We also show the current knowledge on the molecular mechanisms involved in the potential regenerative behavior of these cells and the progress of gene therapy to prevent deafness noise‐induced. J. Cell. Physiol. 226: 2494–2499, 2011. © 2010 Wiley‐Liss, Inc.
TGFβ receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release
Authors: Heger Jacqueline , Warga Björn , Meyering Bettina , Abdallah Yaser , Schlüter Klaus‐Dieter , Piper Hans Michael , Euler Gerhild 
Published: December 2010

AbstractTransforming growth factor β (TGFβ) expression is induced in the myocardium during transition from compensated hypertrophy to heart failure. In cardiomyocytes, stimulation with TGFβ results in restricted contractile function and enhanced apoptosis. Nitric oxide (NO) also induces apoptosis and influences cardiac function. Therefore, we wanted to know whether NO is causally involved in TGFβ‐induced apoptosis. In isolated ventricular cardiomyocytes of adult rat incubation with TGFβ1 increased NO release which was inhibited by NOS inhibitor ETU but not with iNOS inhibitor (1400 W) or nNOS inhibitor (TFA). In addition, TGFβ‐induced apoptosis was blocked with ETU and ODQ, but not with 1400 W or TFA. The consequent assumption that endothelial NOS is involved in TGFβ‐induced NO formation and apoptosis was supported by increased phosphorylation of eNOS at serine 1177 and by the fact that TGFβ did not increase NO release in eNOS KO mice. Furthermore, TGFβ‐induced apoptosis, NO formation, SMAD binding activity and SMAD2 phosphorylation were blocked by a TGFβ receptor antagonist, but only apoptosis and NO formation could be blocked with ETU. Expression of SMAD7 was increased after TGFβ stimulation and blocked with TGFβ receptor antagonist but not after blocking NO synthase with ETU. Conclusion: In cardiomyocytes TGFβ‐induced apoptosis is mediated via TGFβ receptor activation that concomitantly activates SMAD transcription factors and the eNOS/NO/sGC pathway. Both of these pathways are needed for apoptosis induction by TGFβ. This reveals a new pathway of cardiac NO release and identifies NO as a possible contributor to heart failure progression mediated by TGFβ. J. Cell. Physiol. 226: 2683–2690, 2011. © 2010 Wiley‐Liss, Inc.
The synthesis and use of [14C]carbon monoxide in Pd‐catalyzed carbonylation reactions
Authors: Elmore Charles S. 
Published: December 2010

AbstractThe [14C]carbonylation reaction is a very powerful method of incorporating C‐14 into a drug molecule late in a radiochemical synthesis. The first and perhaps most critical step in [14C]carbonylation reactions is the generation of 14CO and its subsequent delivery to the reaction flask. There are three published methods for generating 14CO: conversion of 14CO2 with Zn at 400°C, pyrolysis of Ca14CO3, and dehydration of NaOCH. Additionally, a newly published method for the in situ carbonylation of aryl and vinyl halides to give acids has been investigated using NaOCH as the labeled precursor. Finally, the application of 14CO in Pd‐catalyzed [14C]carbonylation reactions will be discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Synthesis of a labeled inhibitor of HIV‐1 attachment: 1‐(4‐benzoylpiperazin‐1‐yl)‐2‐(4,7‐dimethoxy‐1H‐pyrrolo[2,3‐c]pyridinyl‐3‐yl‐[U‐14C]ethane‐1,2‐dione, BMS‐488043‐14C
Authors: Ekhato I. Victor , Rinehart J. Kent 
Published: December 2010

AbstractBMS‐488043 is a potent inhibitor of the interaction between HIV‐1 gp120 and the host cell receptor CD4. We prepared the carbon‐14‐labeled version to support preclinical studies of the compound. It was prepared from ethyl [U‐14C]oxalyl chloride by a sequence using Friedel–Crafts acylation reaction. The overall radiochemical yield was 82% with a purity of >99.9%. Copyright © 2010 John Wiley & Sons, Ltd.
Hip transposition as a limb salvage procedure following the resection of periacetabular tumors
Authors: Gebert Carsten , Wessling Martin , Hoffmann Christiane , Roedl Robert , Winkelmann Winfried , Gosheger Georg , Hardes Jendrik 
Published: December 2010

AbstractBackground and ObjectivesOne of the most difficult problems in tumor surgery is the treatment of pelvic tumors, particularly those in the periacetabular region. This retrospective study serves to analyze clinical and functional outcome of the new surgical technique of hip transposition.Patients and MethodsSixty‐two patients were analyzed (chondrosarcoma 15, Ewing's sarcoma or PNET 26, osteosarcoma 14, synovial cell sarcoma 2, others 5) and clinical, oncological, and functional outcome were evaluated.ResultsThe surgical procedure focused on hip transpositions Type I (n = 9), Type IIa using the MUTARS® attachment tube (n = 36), and Type IIb using the MUTARS® attachment tube with a proximal femur endoprosthesis and bipolar cup (n = 17). In 53 patients (85.5%), wide margins were achieved.The 1‐ and 5‐year overall survival rates were 96.4% and 80.5%, respectively. The 5‐year (10 years) overall survival was 82.1% (82.1%) for Ewing's sarcoma, 60.1% (40.6%) for osteosarcoma, and 92.3% (46.2%) for chondrosarcoma. Wound healing problems were observed in 14 cases, deep infection in 20 cases. The mean Musculoskeletal Tumor Society (MSTS) score was 62% (18.6 Pts ± 3.73).ConclusionHip transposition can be considered as an easy and safe surgical procedure to employ in order to achieve good functional outcome in periacetabular tumors. J. Surg. Oncol. 2011; 103:269–275. © 2010 Wiley‐Liss, Inc.
Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after early failure of adjuvant systemic chemotherapy
Authors: Klaver Yvonne L.B. , de Hingh Ignace H.J.T. , Boot Henk , Verwaal Victor J. 
Published: December 2010

AbstractBackground and ObjectivesFailure to respond to systemic chemotherapy is considered an exclusion criterion by some institutions for treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). However, it is unknown if these patients benefit from HIPEC treatment. This study aimed to report on outcomes of HIPEC in patients who failed to respond to adjuvant systemic chemotherapy.MethodsPatients were selected from a prospective database containing data on all patients who underwent HIPEC, using the following criteria: (1) Metachronous peritoneal carcinomatosis (PC) from colorectal origin, (2) adjuvant chemotherapy after primary tumor resection, (3) development of PC or local recurrence within 18 months after start of chemotherapy. Treatment and survival data were retrospectively collected.ResultsTwenty‐one patients (29% male, mean age 57 years) were included. Median time to recurrence of disease was 9 months (range 2–15) after first chemotherapy administration. Median survival was 28 months (range 3–100). One‐ and 2‐year survival were 71% and 43%, respectively.ConclusionsPatients who initially failed to respond to systemic adjuvant treatment showed a survival after HIPEC similar to results reported in literature in patients with unknown responsiveness. Failure to respond to previous adjuvant systemic treatment should therefore not be considered an exclusion criterion for HIPEC treatment. J. Surg. Oncol. 2011; 103:431–434. © 2010 Wiley‐Liss, Inc.
Prognostic implications of miR‐16 expression levels in resected non‐small‐cell lung cancer
Authors: Navarro Alfons , Diaz Tania , Gallardo Elena , Viñolas Nuria , Marrades Ramon M. , Gel Bernat , Campayo Marc , Quera Angels , Bandres Eva , Garcia‐Foncillas Jesus , Ramirez Jose , Monzo Mariano 
Published: December 2010

AbstractBackgroundMicroRNAs are novel regulators of gene expression that are linked to the main oncogene networks, including the p53 pathway. p53 regulates the maturation process of miR‐16 and miR‐143. We analyzed the role as prognostic markers of miR‐16 and miR‐143 in 70 non‐small‐cell lung cancer (NSCLC) patients.MethodsMicroRNAs were analyzed by TaqMan MicroRNA assays. Disease‐free survival (DFS) and overall survival (OS) were examined using Kaplan–Meier curves with log‐rank tests and the Cox proportional hazard model.ResultsWhen patients were classified in three groups according to their miR‐16 expression levels, those with normal levels had the best outcome while those with high levels had the worst. DFS was 22.4 months for patients with high levels, 71.8 months for those with normal levels, and 55.8 months for those with low levels (P = 0.05). OS was 23.9 months for patients with high levels, 97.6 months for those with normal levels, and 63.5 months for those with low levels (P < 0.001). In the multivariate analyses, high miR‐16 levels emerged as an independent prognostic factor for poor DFS (P = 0.001) and OS (<0.001).ConclusionsOur results provide the first hints that miR‐16 levels in tumor samples may be a prognostic marker in NSCLC. J. Surg. Oncol. 2011; 103:411–415. © 2010 Wiley‐Liss, Inc.
Measurement of creatine kinase reaction rate in human brain using magnetization transfer image‐selected in vivo spectroscopy (MT‐ISIS) and a volume 31P/1H radiofrequency coil in a clinical 3‐T MRI system
Authors: Jeong Eun‐Kee , Sung Young‐Hoon , Kim Seong‐Eun , Zuo Chun , Shi Xianfeng , Mellon Eric A. , Renshaw Perry F. 
Published: December 2010

AbstractHigh‐energy phosphate metabolism, which allows the synthesis and regeneration of adenosine triphosphate (ATP), is a vital process for neuronal survival and activity. In particular, creatine kinase (CK) serves as an energy reservoir for the rapid buffering of ATP levels. Altered CK enzyme activity, reflecting compromised high‐energy phosphate metabolism or mitochondrial dysfunction in the brain, can be assessed using magnetization transfer (MT) MRS. MT 31P MRS has been used to measure the forward CK reaction rate in animal and human brain, employing a surface radiofrequency coil. However, long acquisition times and excessive radiofrequency irradiation prevent these methods from being used routinely for clinical evaluations. In this article, a new MT 31P MRS method is presented, which can be practically used to measure the CK forward reaction rate constant in a clinical MRI system employing a volume head 31P coil for spatial localization, without contamination from the scalp muscle, and an acquisition time of 30 min. Other advantages associated with the method include radiofrequency homogeneity within the regions of interest of the brain using a volume coil with image‐selected in vivo spectroscopy localization, and reduction of the specific absorption rate using nonadiabatic radiofrequency pulses for MT saturation. The mean value of kf was measured as 0.320 ± 0.075 s−1 from 10 healthy volunteers with an age range of 18–40 years. These values are consistent with those obtained using earlier methods, and the technique may be used routinely to evaluate energetic processes in the brain on a clinical MRI system. Copyright © 2010 John Wiley & Sons, Ltd.
A higher‐order extended finite element method for dislocation energetics in strained layers and epitaxial islands
Authors: Oswald Jay , Wintersberger Eugen , Bauer Günther , Belytschko Ted 
Published: December 2010

AbstractThis paper presents a higher‐order method for modeling dislocations with the extended finite element method (XFEM). This method is applicable to complex geometries, interfaces with lattice mismatch strains, and both anisotropic and spatially non‐uniform material properties. A numerical procedure for computing the J‐integral around a dislocation core to determine the energy release rate for a virtual advance of the dislocation line is described. Several examples in three dimensions illustrate the applicability of this method to material interfaces and semiconductor heterostructures, specifically the computation of the energetics of systems of dislocations in SiGe islands deposited on pure Si substrates. Copyright © 2010 John Wiley & Sons, Ltd.
Stable element‐free Galerkin solution procedures for the coupled soil–pore fluid problem
Authors: Hua Leina 
Published: December 2010

AbstractIt is always difficult to solve the coupled soil–pore fluid problem when the soil is saturated and impermeable, because this situation often results in intensive oscillations of the solutions. This topic has been discussed widely in the field of the finite element method but rarely by meshless methods. The Element‐Free Galerkin (EFG) method has outstanding advantages of solving this problem, based on the fact that its interpolation function can be constructed flexibly by the nodes in the compact domain. In this study, an EFG numerical model together with a stabilization technique is proposed to obtain stable solutions, especially for the saturated and impermeable soil. Close agreement between computational results and analytical solutions for one‐and two‐dimensional examples shows that the proposed numerical model not only provides highly accurate solutions for the saturated soil with relatively high permeability, but also eliminates the oscillations of the solutions very effectively for the saturated and impermeable soil. Furthermore, the influences of the hydraulic anisotropy, a typical property of two‐dimensional problems, on the proposed stabilization technique are discussed. It is suggested that the optimal distribution of the nodes of essential variables can be designed, according to the relative importance of the permeability in different directions. Copyright © 2010 John Wiley & Sons, Ltd.
A hierarchical NXFEM for fictitious domain simulations
Authors: Becker Roland , Burman Erik , Hansbo Peter 
Published: December 2010

AbstractWe suggest a fictitious domain method, based on the Nitsche XFEM method of (Comput. Meth. Appl. Mech. Engrg 2002; 191:5537–5552), that employs a band of elements adjacent to the boundary. In contrast, the classical fictitious domain method uses Lagrange multipliers on a line (surface) where the boundary condition is to be enforced. The idea can be seen as an extension of the Chimera method of (ESAIM: Math. Model Numer. Anal. 2003; 37:495–514), but with a hierarchical representation of the discontinuous solution field. The hierarchical formulation is better suited for moving fictitious boundaries since the stiffness matrix of the underlying structured mesh can be retained during the computations.Our technique allows for optimal convergence properties irrespective of the order of the underlying finite element method. Copyright © 2010 John Wiley & Sons, Ltd.