bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel peroxisome proliferator–activated receptor γ ligand, MCC-555, induces apoptosis via posttranscriptional regulation of NAG-1 in colorectal cancer cells
Authors: Yamaguchi Kiyoshi , Lee Seong-Ho , Eling Thomas E. , Baek Seung Joon 
Published: May 2006

Abstract
Apoptosis and/or differentiation induction caused by the peroxisome proliferator–activated receptor γ (PPARγ) ligand is a promising approach to cancer therapy. The thiazolidinedione derivative MCC-555 has an apoptotic activity in human colorectal cancer cells, accompanied by up-regulation of a proapoptotic nonsteroidal anti-inflammatory drug–activated gene (NAG-1) in a PPARγ-independent manner. Treatment with MCC-555 resulted in the induction of NAG-1 expression and apoptosis in HCT-116 cells. Down-regulation of NAG-1 by small interfering RNA suppressed MCC-555-induced apoptosis. MCC-555 was found to affect NAG-1 mRNA stability. To further define the underlying mechanism of RNA stability affected by MCC-555, we cloned the 3′-untranslated region (3′UTR) of human NAG-1 mRNA, which contains four copies of an AU-rich element (ARE), downstream from the luciferase gene. The reporter activity was reduced to ∼70% by inserting the 3′UTR. In addition, deletion of ARE sequences in the 3′UTR or MCC-555 treatment substantially restored activity. This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal–regulated kinase (ERK) pathway inhibitors. Subsequently, rapid phosphorylation of ERK1/2 by MCC-555 treatment was detected. Moreover, ERK small interfering RNA suppressed MCC-555-induced NAG-1 expression. These results suggest that ARE sequences in the 3′UTR of the NAG-1 gene contribute to mRNA degradation and ERK1/2 phosphorylation is responsible for the stabilization of NAG-1 mRNA. These findings may provide a novel explanation for the antitumorigenic and/or proapoptotic action of MCC-555 in human colorectal cancer and the ability of pharmacologic approaches to be used against diseases caused by alterations of RNA stability. [Mol Cancer Ther 2006;5(5):1352–61]
Experimental therapy of malignant gliomas using the inhibitor of histone deacetylase MS-275
Authors: Eyüpoglu Ilker Y. , Hahnen Eric , Tränkle Christian , Savaskan Nicolai E. , Siebzehnrübl Florian A. , Buslei Rolf , Lemke Dieter , Wick Wolfgang , Fahlbusch Rudolf , Blümcke Ingmar 
Published: May 2006

Abstract
Inhibitors of histone deacetylases are promising compounds for the treatment of cancer but have not been systematically explored in malignant brain tumors. Here, we characterize the benzamide MS-275, a class I histone deacetylase inhibitor, as potent drug for experimental therapy of glioblastomas. Treatment of four glioma cell lines (U87MG, C6, F98, and SMA-560) with MS-275 significantly reduced cell growth in a concentration-dependent manner (IC90, 3.75 μmol/L). Its antiproliferative effect was corroborated using a bromodeoxyuridine proliferation assay and was mediated by G0-G1 cell cycle arrest (i.e., up-regulation of p21/WAF) and apoptotic cell death. Implantation of enhanced green fluorescent protein–transfected F98 glioma cells into slice cultures of rat brain confirmed the cytostatic effect of MS-275 without neurotoxic damage to the organotypic neuronal environment in a dose escalation up to 20 μmol/L. A single intratumoral injection of MS-275 7 days after orthotopic implantation of glioma cells in syngeneic rats confirmed the chemotherapeutic efficacy of MS-275 in vivo. Furthermore, its propensity to pass the blood-brain barrier and to increase the protein level of acetylated histone H3 in brain tissue identifies MS-275 as a promising candidate drug in the treatment of malignant gliomas. [Mol Cancer Ther 2006;5(5):1248–55]
Grape seed extract induces anoikis and caspase-mediated apoptosis in human prostate carcinoma LNCaP cells: possible role of ataxia telangiectasia mutated–p53 activation
Authors: Kaur Manjinder , Agarwal Rajesh , Agarwal Chapla 
Published: May 2006

Abstract
Prostate cancer is the second leading cancer diagnosed in elderly males in the Western world. Epidemiologic studies suggest that dietary modifications could be an effective approach in reducing various cancers, including prostate cancer, and accordingly cancer-preventive efficacy of dietary nutrients has gained increased attention in recent years. We have recently shown that grape seed extract (GSE) inhibits growth and induces apoptotic death of advanced human prostate cancer DU145 cells in culture and xenograft. Because prostate cancer is initially an androgen-dependent malignancy, here we used LNCaP human prostate cancer cells as a model to assess GSE efficacy and associated mechanisms. GSE treatment of cells led to their detachment within 12 hours, as occurs in anoikis, and caused a significant decrease in live cells mostly due to their apoptotic death. GSE-induced anoikis and apoptosis were accompanied by a strong decrease in focal adhesion kinase levels, but an increase in caspase-3, caspase-9, and poly(ADP-ribose) polymerase cleavage; however, GSE caused both caspase-dependent and caspase-independent apoptosis as evidenced by cytochrome c and apoptosis-inducing factor release into cytosol. Additional studies revealed that GSE causes DNA damage–induced activation of ataxia telangiectasia mutated kinase and Chk2, as well as p53 Ser15 phosphorylation and its translocation to mitochondria, suggesting this to be an additional mechanism for apoptosis induction. GSE-induced apoptosis, cell growth inhibition, and cell death were attenuated by pretreatment with N-acetylcysteine and involved reactive oxygen species generation. Together, these results show GSE effects in LNCaP cells and suggest additional in vivo efficacy studies in prostate cancer animal models. [Mol Cancer Ther 2006;5(5):1265–74]
Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics
Authors: Gerweck Leo E. , Vijayappa Shashirekha , Kozin Sergey 
Published: May 2006

Abstract
The extracellular pH of tumor tissue is significantly lower than the extracellular pH of normal tissue, whereas the intracellular pH of both tissues is similar. In principle, extracellular acidity may be expected to enhance the intracellular uptake and cytotoxicity of weak acid chemotherapeutics that are membrane permeable in their uncharged state and inhibit the efficacy of weak bases. However, procedures for assessing the role of the gradient as a determinant of drug efficacy in vivo by altering the pH gradient may also alter drug availability and thus mask or exaggerate the effect of the gradient change. In the present study, we have altered the extracellular pH of tumors and compared the effect of the resultant pH gradient change on the efficacy of a weak acid versus a weak base. This experimental design gives rise to a change in the ratio of chlorambucil- to doxorubicin-induced tumor growth delay, independent of possible changes in drug availability. The extracellular pH of the 54A human tumor in NCr/Sed/nu/nu mice was altered by administration of 5 mg/g i.v. glucose. The resultant 0.2 pH unit increase in the tumor cell pH gradient gives rise to a predicted 2.3-fold increase in the ratio of chlorambucil to doxorubicin growth delay. The experimentally measured change in the growth delay ratio was 2.1. The results provide compelling evidence that the pH gradient in a determinant of the efficacy of weak electrolytes in the complex in vivo environment and may be exploited for the treatment of cancer. [Mol Cancer Ther 2006;5(5):1275–9]
Angiogenic Murine Endothelial Progenitor Cells Are Derived From a Myeloid Bone Marrow Fraction and Can Be Identified by Endothelial NO Synthase Expression
Authors: Loomans C.J.M. , Wan H. , de Crom R. , van Haperen R. , de Boer H.C. , Leenen P.J.M. , Drexhage H.A. , Rabelink T.J. , van Zonneveld A.J. , Staal F.J.T. 
Published: May 2006

Objective—Endothelial progenitor cells (EPCs) contribute to postnatal neovascularization and are therefore of great interest for autologous cell therapies to treat ischemic vascular disease. However, the origin and functional properties of these EPCs are still in debate.Methods and Results—Here, ex vivo expanded murine EPCs were characterized in terms of phenotype, lineage potential, differentiation from bone marrow (BM) precursors, and their functional properties using endothelial NO synthase (eNOS)–green fluorescent protein transgenic mice. Despite high phenotypic overlap with macrophages and dendritic cells, EPCs displayed unique eNOS expression, endothelial lineage potential in colony assays, and angiogenic characteristics, but also immunologic properties such as interleukin-12p70 production and low levels of T-cell stimulation. The majority of EPCs developed from an immature, CD31+Ly6C+myeloid progenitor fraction in the BM. Addition of myeloid growth factors such as macrophage–colony-stimulating factor (M-CSF) and granulocyte/macrophage (GM)-CSF stimulated the expansion of spleen-derived EPCs but not BM-derived EPCs.Conclusion—The close relationship between EPCs and other myeloid lineages may add to the complexity of using them in cell therapy. Our mouse model could be a highly useful tool to characterize EPCs functionally and phenotypically, to explore the origin and optimize the isolation of EPC fractions for therapeutic neovascularization.
Refraction of Surface Gravity Waves by Shear Waves
Authors: Henderson Stephen M. , Guza R. T. , Elgar Steve , Herbers T. H. C. 
Published: May 2006

Abstract
Previous field observations indicate that the directional spread of swell-frequency (nominally 0.1 Hz) surface gravity waves increases during shoreward propagation across the surf zone. This directional broadening contrasts with the narrowing observed seaward of the surf zone and predicted by Snell’s law for bathymetric refraction. Field-observed broadening was predicted by a new model for refraction of swell by lower-frequency (nominally 0.01 Hz) current and elevation fluctuations. The observations and the model suggest that refraction by the cross-shore currents of energetic shear waves contributed substantially to the observed broadening.
Impact of Atmospheric Intraseasonal Oscillations on the Indian Ocean Dipole during the 1990s*
Authors: Han Weiqing , Shinoda Toshiaki , Fu Lee-Lueng , McCreary Julian P. 
Published: May 2006

Abstract
Effects of atmospheric intraseasonal oscillations (ISOs) on the Indian Ocean zonal dipole mode (IOZDM) are investigated by analyzing available observations and a suite of solutions to an ocean general circulation model, namely, the Hybrid Coordinate Ocean Model (HYCOM). Data and model solutions for the period 1991–2000 are analyzed, a period that includes two strong IOZDM events, during 1994 and 1997, and a weak one, in 1991. Both the data analysis and model results suggest that atmospheric ISOs play a significant role in causing irregularity of the two strong IOZDM events and the premature termination of the weak one. Of particular interest is a basinwide, wind-driven oceanic resonance with a period near 90 days, involving the propagation of equatorial Kelvin and first-meridional-mode Rossby waves across the basin. Before the onset of the strong 1997 dipole, wind variability had significant power near 90 days, and the resonance was strongly excited. Associated with the resonance was a deepened thermocline in the eastern basin during August and early September, which reduced the upwelling in the eastern antinode region of the IOZDM, thereby delaying the reversal of the equatorial zonal SST gradient—an important indicator of a strong IOZDM—by over a month. A similar deepened thermocline in the eastern basin also contributed to the premature termination of the weak 1991 dipole. During the 1994 IOZDM, the winds had little power near 90 days, and the resonant mode was not prominent. The ISOs influenced the IOZDM through both surface fluxes and thermocline variability. They enhanced warming in the western antinode region during October, the peak phase of the IOZDM, intensifying its strength. During November, strong winds significantly cooled the western and central basin through upwelling and surface fluxes, cooling SST there and contributing to the early and quick termination of the 1994 event.
Bryan Wilson’s Contributions to the Study of Secularization
Authors: Dobbelaere Karel 
Published: May 2006

English For Bryan Wilson, secularization refers to the fact that religion has lost influence at the societal, the institutional and the individual level. For him, individual secularization is about the loss of authority of the Churches to define what people should believe, practise and accept as moral principles guiding their lives. In other words, individual piety may still persist, however, if it develops independently of religious authorities, then it is an indication of individual secularization. Wilson has furthermore stressed the consequences of the process of societalization in modern societies and on this basis he formulated his thesis that secularization is linked to the decline of community and is a concomitant of societalization. It is also typical of Wilson that he uses the Catholic Church as his reference to evaluate institutional secularization. Finally, in Wilson ’s work a moral evaluation is present: since a society, even a modern one, cannot survive on procedural values alone, it needs substantive values as well. Consequently, he asked: which institution will socialize the new generations in such values now that religion has lost its impact and the educational system has taken on the characteristics of modern society itself? French Pour Bryan Wilson, la sécularisation se réfère au fait que la religion a perdu son influence aux niveaux sociétal, institutionnel et individuel. Selon lui, la sécularisation individuelle résulte de la perte d'autorité des Eglises qui ne peuvent plus définir ce que les personnes doivent croire, pratiquer et accepter comme principes moraux pour guider leur vie. En d'autres termes, la piété individuelle peut encore persister. Mais si elle se développe indépendamment des autorités religieuses, il s'agit alors d'un indicateur de la sécularisation individuelle. Par ailleurs, Wilson a insisté sur les conséquences du processus de sociétalisation dans les sociétés modernes et, sur cette base, il a développé la thèse selon laquelle la sécularisation est liée au déclin de la communauté et coïncide avec la sociétalisation. De manière caractéristique, Wilson a pris pour exemple l'Eglise catholique afin d'évaluer la sécularisation institutionnelle. Pour finir, les travaux de Wilson contiennent une évaluation d'ordre moral: une société, même moderne, ne peut survivre uniquement grâce à des valeurs pratiques et bureaucratiques, elle a également besoin de valeurs substantives. En conséquence, quelle institution, se demandait-il, va socialiser les nouvelles générations à ces valeurs, à présent que la religion a perdu son impact et que le système éducatif a lui-même épousé les caractéristiques de la société moderne?
Modernité tardive, religion et mutation du public et du privé (à partir de l ’exemple français)
Authors: Baubérot Jean 
Published: May 2006

English The author examines the privatization of religion in France and emphasizes its relationship with the expansion of the private sphere in general. The use of an approach based on historical sociology reveals three typical periods: the rise of modernity, triumphant modernity and late modernity. The distinguishing characteristics of this last typical period include the shift of responsibility from institutions to individuals and the privatization and individualization of religion. Actors must now construct their identity by themselves. The claims that are made for the recognition of identity are probably associated with these social changes, reflecting the many intrusions of aspects of the public sphere into what used to be considered private. This softening of the notion of the separation between the public and the private is linked to the loss of the utopian ideals associated with the secularization that is entrenched in modern societies. French En prenant pour exemple le cas français, l'auteur analyse le processus de privatisation de la religion, en soulignant son interaction avec l'élargissement de la sphère privée en général. Une démarche de sociologie historique permet de repérer trois périodes typiques: la modernité ascendante, la modernité hégémonique et la modernité tardive. Cette dernière période type est marquée par un déplacement de la responsabilité de l'institution vers l'individu, et par une privatisation et une subjectivisation du religieux. Les acteurs doivent alors eux-mêmes construire leur identité. Les revendications identitaires sont sans doute un miroir grossissant de ces mutations sociales et correspondent aux multiples intrusions d'éléments de la sphère publique dans ce qui était considéré comme privé. L'euphémisation de la représentation sociale d'une séparation du public et du privé se trouve liée à la désutopisation d'une sécularisation devenue établie dans les sociétés modernes.
The Search for Privacy and the Return of a Grand Narrative: Religion in a Post-Communist Society
Authors: Agadjanian Alexander 
Published: May 2006

English The author analyses major trends in the recent religious history of Russia by drawing upon one particular episode-a controversial art exhibit accused in court of being sacrilegious. Religion (most importantly, Russian Orthodoxy) has been increasingly active in the public square in the post-Communist context which was favourable, though often selectively, to religion. A sharp opposition has revived between secular liberal and religious discourses where religion is thematized as a grand narrative representing national values. Yet another trend, which is in line with late modern religious patterns found in Western Europe, consists of the emergence of a highly privatized, individual, diffused religiosity. This mixed picture questions established notions of private and public religion and reveals new modes of interaction between secular and religious forces in the 21st century. French L'auteur analyse les tendances majeures de l'histoire récente religieuse russe à partir d'un cas particulier, une exposition artistique controversée, accusée d'être sacrilège et poursuivie en justice. La religion (l'orthodoxie russe principalement) devient de plus en plus active au sein de la sphère publique dans un contexte post-communiste favorable - bien que souvent de manière sélective - à la religion. A été ranimée une nette opposition entre discours séculiers libéraux et discours religieux, au sein desquels la religion est un thème narratif utilisé pour incarner les valeurs nationales. Par ailleurs, une autre tendance, en affinité avec les modèles religieux modernes que l'on trouve en Europe occidentale, concerne l'émergence d'une religiosité individuelle diffuse, hautement privatisée. Cette image plurielle interroge les notions établies de religion publique et de religion privée, et révèle de nouveaux modes d'interaction entre le séculier et le religieux dans le 21ème siècle.
Peur et religion: de la violence d’Etat à la violence privatisée
Authors: Corten André 
Published: May 2006

English Where violence is monopolized by the state, the social construction of fear often takes the form of the fear of God. Civil society and the fear of God have been subtly interwoven for a long time in Europe and North America. The “democratic transition” has taken the shape in several countries of Latin America of growing civil violence. This violence is no longer openly monitored by the state and seems to arise from unbridled individualism reinforced by neoliberalism. Street gangs and mafia networks are clear signs of this privatized violence. The fear of being killed is also experienced as the danger of falling into a state of indifference towards being a killer oneself; and this gives rise to feelings that verge on a state of “conversion”. These new social constructions of fear help to explain the success of Pentecostalism and, more broadly, of charismatic movements. French Là où la violence est monopolisée par l'Etat, la construction sociale de la peur prend souvent la forme de la crainte de Dieu. En Europe et en Amérique du Nord, de subtiles complémentarités se sont longtemps tissées entre société civile et crainte de Dieu. La 'transition démocratique' en Amérique latine s'est concrétisée dans de nombreux pays par un accroissement de la violence civile. Cette violence n'est plus ouvertement contrôlée par l'Etat et semble relever d'un individualisme débridé, renforcé par le néo-libéralisme. Les gangs de rue et les connexions mafieuses sont une manifestation de cette violence privatisée. La peur d'être tué se vit en même temps comme péril de tomber dans une indifférence à tuer soi-même et mobilise l'émotion vers un état de 'conversion'. Ce nouvel imaginaire social de la peur rend en partie compte du succès du pentecôtisme et plus largement des mouvements charismatiques.
Espace ouvert, identités plurielles: les recompositions contemporaines du croire
Authors: Michel Patrick 
Published: May 2006

English If we consider identity, relations to space and religion as well as the connections between these three things, it is clear that a stable centre serving as a trusted point of reference for everyone has disappeared. This realization is supported by the reiterations of this centre that are brought about precisely by its inability to inspire trust. The problem is no longer to draw maps in space of some lower-level sets organized around a central point of reference, which appears to be absolute, as an arrangement that would be likely to lend substance to their insular character. In these subsets, reference to centrality and construction of homogeneity used to be joined together in order to mark the boundaries where territoriality and identity coincided. Although identity still partially overlaps with territory, it is no longer subsumed by it and is therefore no longer exhausted in the fiction of a coincidence. This is the perspective from which the author explores three hypotheses about religion as space, resource and language. French Lorsque l'on considère l'identité, la relation à l'espace et la religion, ainsi que les liens qu'elles tissent entre elles, le constat de la disparition d'une centralité stable comme référence globalement crédible doit être fait. Ce constat est renforcé par les réitérations de cette centralité suscitées précisément par l'incapacité dans laquelle elle se trouve de faire croire en elle. Le problème n'est plus dès lors de cartographier, dans l'espace, des sous-ensembles organisés autour d'une référence centrale, présentée comme absolue, en un agencement susceptible d'accréditer leur caractère insulaire. Dans ces sous-ensembles, référence à la centralité et construction de l'homogénéité se conjuguaient pour tracer les frontières d'une coïncidence entre territorialité et identité. Or, si cette dernière continue à être liée à un territoire, elle ne se laisse plus récapituler par lui, ne s'épuise donc plus dans la fiction d'une coïncidence. C'est dans cette perspective que sont explorées ici trois hypothèses, oË le religieux intervient comme espace, comme ressource et comme langage.