bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER kinase activation confers resistance to MET tyrosine kinase inhibition in MET oncogene-addicted gastric cancer cells
Authors: Bachleitner-Hofmann Thomas , Sun Mark Y. , Chen Chin-Tung , Tang Laura , Song Lin , Zeng Zhaoshi , Shah Manish , Christensen James G. , Rosen Neal , Solit David B. , Weiser Martin R. 
Published: October 2008

Abstract
Tumor cells with genomic amplification of MET display constitutive activation of the MET tyrosine kinase, which renders them highly sensitive to MET inhibition. Several MET inhibitors have recently entered clinical trials; however, as with other molecularly targeted agents, resistance is likely to develop. Therefore, elucidating possible mechanisms of resistance is of clinical interest. We hypothesized that collateral growth factor receptor pathway activation can overcome the effects of MET inhibition in MET-amplified cancer cells by reactivating key survival pathways. Treatment of MET-amplified GTL-16 and MKN-45 gastric cancer cells with the highly selective MET inhibitor PHA-665752 abrogated MEK/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling, resulting in cyclin D1 loss and G1 arrest. PHA-665752 also inhibited baseline phosphorylation of epidermal growth factor receptor (EGFR) and HER-3, which are transactivated via MET-driven receptor cross-talk in these cells. However, MET-independent HER kinase activation using EGF (which binds to and activates EGFR) or heregulin-β1 (which binds to and activates HER-3) was able to overcome the growth-inhibitory effects of MET inhibition by restimulating MEK/MAPK and/or PI3K/AKT signaling, suggesting a possible escape mechanism. Importantly, dual inhibition of MET and HER kinase signaling using PHA-665752 in combination with the EGFR inhibitor gefitinib or in combination with inhibitors of MEK and AKT prevented the above rescue effects. Our results illustrate that highly targeted MET tyrosine kinase inhibition leaves MET oncogene-“addicted” cancer cells vulnerable to HER kinase-mediated reactivation of the MEK/MAPK and PI3K/AKT pathways, providing a rationale for combined inhibition of MET and HER kinase signaling in MET-amplified tumors that coexpress EGFR and/or HER-3. [Mol Cancer Ther 2008;7(11):3499–508]
A RNA antagonist of hypoxia-inducible factor-1α, EZN-2968, inhibits tumor cell growth
Authors: Greenberger Lee M. , Horak Ivan D. , Filpula David , Sapra Puja , Westergaard Majken , Frydenlund Henrik F. , Albæk Charlotte , Schrøder Henrik , Ørum Henrik 
Published: October 2008

AbstractHypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the α-subunit of HIF-1 (HIF-1α), which occurs in response to hypoxia or activation of growth factor pathways, is associated with poor prognosis in many types of cancer. Therefore, down-regulation of HIF-1α protein by RNA antagonists may control cancer growth. EZN-2968 is a RNA antagonist composed of third-generation oligonucleotide, locked nucleic acid, technology that specifically binds and inhibits the expression of HIF-1α mRNA. In vitro, in human prostate (15PC3, PC3, and DU145) and glioblastoma (U373) cells, EZN-2968 induced a potent, selective, and durable antagonism of HIF-1 mRNA and protein expression (IC50, 1-5 nmol/L) under normoxic and hypoxic conditions associated with inhibition of tumor cell growth. Additionally, down-regulation of HIF-1α protein by EZN-2968 led to reduction of its transcriptional targets and of human umbilical vein endothelial cell tube formation. In vivo, administration of EZN-2968 to normal mice led to specific, dose-dependent, and highly potent down-regulation of endogenous HIF-1α and vascular endothelial growth factor in the liver. The effect can last for days after administration of single dose of EZN-2968 and is associated with long residence time of locked nucleic acid in certain tissues. In efficacy studies, tumor reduction was found in nude mice implanted with DU145 cells treated with EZN-2968. Ongoing phase I studies of EZN-2968 in patients with advanced malignancies will determine optimal dose and schedule for the phase II program. [Mol Cancer Ther 2008;7(11):3598–608]
Carprofen induction of p75NTR-dependent apoptosis via the p38 mitogen-activated protein kinase pathway in prostate cancer cells
Authors: Khwaja Fatima S. , Quann Emily J. , Pattabiraman Nagarajan , Wynne Shehla , Djakiew Daniel 
Published: October 2008

Abstract
The p75 neurotrophin receptor (p75NTR) functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR-mediated decreased survival. Using the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico database of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3 and DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR-associated loss of survival than breast (MCF-7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant-negative form of p75NTR before carprofen treatment partially rescued cell survival, showing a cause-and-effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF-7 and 3T3 cells. Furthermore, small interfering RNA knockdown of the p38 mitogen-activated protein kinase (MAPK) protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 min. Expression of a dominant-negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR-dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. [Mol Cancer Ther 2008;7(11):3539–45]
Introduction
Authors: Rivière Françoise 
Published: October 2008

AbstractThe principle of democracy is one of equal dignity for all cultures. But today the relationship between culture and politics, though close, often appears tense and occasionally contradictory. The introduction to this issue of Diogenes sketches the work done by UNESCO in the frame of the ‘Pathways of Thought' Programme, particularly relating to the way in which a pluralist identity is created in multicultural nations, and to the relationship between non-material heritage, democracy and the quest for new forms of governance.
Trust, Strangeness and Hospitality
Authors: Cornu Laurence 
Published: October 2008

AbstractThis paper presents a way of building social cohesion open to diversity, assuming that democracy is alive only when it is reinvented. It challenges social trust to welcome diversity, thus allowing for a continual reinvention of democratic cohesion. Articulating cultural diversity and trust represents a major challenge for democratic coexistence. Philosophy is called to take into account the existing models of social cohesion and trust, and to reinvent democracy by defining a new paradigm of trust integrating social and cultural diversity.
The Non- and Anti-Democratic in Post-Modernity
Authors: Hamashita Masahiro 
Published: October 2008

AbstractIs, or has, democracy a universal value? This is the main question raised by this paper, which distinguishes between two aspects of democracy: political institution in opposition to despotism, and political belief against any kind of slavery and subordination. The role played by intellectuals in the development of contemporary democracy, and the relation of democracy to mass culture and the influence of mass media on a true democratic attitude, are studied within the frame of an overall ‘mass aesthetization' which characterizes contemporary societies.
International Law and Democracy
Authors: Martin-Chenut Kathia 
Published: October 2008

AbstractThis contribution intends to examine the role of democracy in the evolution of international law, and equally the role of the latter in the advancement of democracy, or, one might say, in its ‘reinvention'. Two aspects of this broad theme are addressed: the influence of processes of democratization at the level of the individual nation on the evolution of international law, and the extent of penetration of democracy and democratic mechanisms within the processes of creation and application of international law. A rich record of examples drawn by international jurisprudence is used to illustrate these complementary processes.
Democracy versus Republic: Inclusion and Desire in Social Struggles
Authors: Ribeiro Renato Janine 
Published: October 2008

AbstractThis paper argues that the idea of inclusion is linked to the democratic tradition rather than to the republican one. By analyzing the origins and meaning of these two concepts, the author holds that democracy is rather linked to desire and republic to will (and to the expression of desire), and concludes that, since North Atlantic political tradition has not given a key role to desire, democracy, in order to overcome the difficulties it has been encountering in all parts of the world, should take more account of desire and of the social struggles it brings to the fore.
Equality and Democracy
Authors: Vermeren Patrice 
Published: October 2008

AbstractThis paper analyzes the relations between public space, language, and democracy. It describes how dissensus, democratic citizenship, domination, and political speech are linked together in contemporary French political philosophy, referring in particular to Jacques Rancière, Miguel Abensour, Alain Badiou and Claude Lefort. Hannah Arendt's political thought represents a theoretical frame or reference for most of these authors, who relate to her work in different, and often discrepant, ways.
Tocqueville Reinvented or ‘Democracy in Brazil’
Authors: Freitag Barbara 
Published: October 2008

AbstractThis paper compares Tocqueville's concept of democracy to the social and political evolution of Brazil. It draws attention to the different points of departure which marked the establishment of American and Brazilian societies, through the works of authors such as Laura de Mello e Souza, Gilberto Freyre, Florestan Fernandes, Celso Furtado, and Sérgio Buarque de Holanda. It notes that, despite conditions being more favourable for the formation of a democratic society in the United States than in Brazil, subsequent to the founding periods a certain coming together occurred in the process of formation of the two societies. The ‘similarity of differences' between American and Brazilian societies becomes clear as soon as one brings together the roles played by the three constituent ethnic groups of these societies, which, by their simple existence, link difference to inequality.
Republic, Nation and Democracy: The Challenge of Diversity
Authors: Villavicencio Susana 
Published: October 2008

AbstractThis paper analyzes how cultural diversity in Argentina is calling into question modern political concepts like republic, nation or democracy. The phenomenon of population movements, the demand for recognition of indigenous people's rights, or the conflicts arising from claims to regions' right to life and identity - as in the case of the town of Gualeguaychú in Argentina - challenge the logic of the nation-state and its sovereignty as well as the republican principles of liberty, equality and fraternity. The author examines how far the representation of the Argentinean republic at the time of its foundation included a standardizing vision of diversity, and how the legacy of this representation brought about an ambivalence between a universalist wish to take part in the progress of humanity and the reality of an exclusive democracy that valued one culture over others. It studies the narrative of national identity and attempts to describe how, proceeding from this narrative, the opposition between civilization and barbarity affects the way Latin Americans see the great challenges presented by the future of democracy, and by the recognition of the plurality of cultural allegiances.
Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications
Authors: Chng Wee J. , Remstein Ellen D. , Fonseca Rafael , Bergsagel P. Leif , Vrana Julie A. , Kurtin Paul J. , Dogan Ahmet 
Published: October 2008

AbstractWe conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma (n = 33) and compared the results to GEP of other B- and T-cell lymphomas and normal lymphocytes to identify novel markers and deregulated pathways. MALT has a prominent T-cell signature and a marginal zone/memory B-cell profile. Four novel transcripts were specifically overexpressed in MALT, and 2 of these, MMP7 and SIGLEC6, were validated at the protein level. GEP also revealed distinct molecular subsets in MALT. One subset, characterized by MALT1 translocations, showed overexpression of nuclear factor-κB (NF-KB) pathway genes but also was enriched for chemokine signaling pathways. Another subset showed increased plasma cells and a prominent plasma cell gene signature. By analyzing several genes with very high (“spiked”) expression in individual cases, we identified clusters with different biologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation having high FKBP11 expression, and samples with high RGS13 expression tending to have trisomy 3 and reactive follicles. In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets.
Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980s to the early 21st century
Authors: Pulte Dianne , Gondos Adam , Brenner Hermann 
Published: October 2008

Abstract
Acute lymphoblastic leukemia (ALL) is an uncommon but highly fatal disease in adults. We used period analysis to data from the Surveillance, Epidemiology, and End Results (SEER) database to disclose changes in outcomes for patients diagnosed with ALL in the United States in the 2 decades between 1980–1984 and 2000–2004. Major improvement in survival was observed for patients less than 60 years of age. Improvement in survival was greater for women than for men, but was significant for both genders. The greatest improvement was seen in patients aged 15 to 19, in whom 5-year relative survival improved from 41.0% to 61.1%, and 10-year survival improved from 33.0% to 60.4%. Lesser but significant improvements were seen for age groups 20–29, 30–44, and 45–59. Survival for patients aged 60 and over remained essentially unchanged at levels around or below 10%, respectively. Survival has improved for patients with ALL over the time period studied, but treatment of older patients remains a difficult issue.
CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation
Authors: Bashey Asad , Medina Bridget , Corringham Sue , Pasek Mildred , Carrier Ewa , Vrooman Linda , Lowy Israel , Solomon Scott R. , Morris Lawrence E. , Holland H. Kent , Mason James R. , Alyea Edwin P. , Soiffer Robert J. , Ball Edward D. 
Published: October 2008

AbstractRelapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at http://clinicaltrials.gov under NCI protocol ID P6082.
Protozoa in respiratory pathology: a review
Authors: Martínez-Girón R. , Esteban J. G. , Ribas A. , Doganci L. 
Published: October 2008

Among the micro-organisms that may affect the respiratory apparatus are the protozoa. The diseases they may give rise to constitute a relatively uncommon group of respiratory ailments with, in the majority of cases, an underlying clinical situation corresponding to states of suppressed immunity (AIDS, transplants, malign haemopathies, corticotherapy,etc.). Other factors, such as visits to endemic areas and immigration, also have to be taken into account.In view of the probable increase in the number of cases and the appearance of new emerging diseases, it is the intention of the present work to review the publications available, in different fields of medicine, that refer to the principal kinds of protozoa (Entamoeba, Acanthamoeba, Balamuthia, Leishmania, Trypanosoma, Trichomonas, Lophomonas, Cryptosporidium, Cyclospora, Toxoplasma, Plasmodium, Babesia, Encephalitozoon, Enterocytozoon and Balantidium) and, at the same time, detail and comment on the latest findings on this subject.
Pathomechanisms of cyst formation in pulmonary light chain deposition disease
Authors: Colombat M. , Caudroy S. , Lagonotte E. , Mal H. , Danel C. , Stern M. , Fournier M. , Birembaut P. 
Published: October 2008

Cystic lung light chain deposition disease (CL-LCDD) is a recently described rare disorder characterised by numerous cysts and diffuse monoclonal nonamyloid light chain deposits surrounded by macrophagic giant cells. The mechanisms responsible for cyst development remain unknown.The objectives of the present study were to analyse the major components of the pulmonary extracellular matrix in CL-LCDD and to determine the influence of metalloproteinases (MMPs) by comparison with other cystic lung disorders.A virtually complete degradation of the elastic network was found in CL-LCDD. To a lesser degree, loss of fibrillar and basement membrane collagens was also observed. Macrophagic giant cells expressed MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 andin situzymography highlighted a strong gelatinolytic activity. As in CL-LCDD, cystic lesions in Langerhans' cell histiocytosis (LCH) and lymphangioleiomyomatosis (LAM) were characterised by the lack of elastic fibres. Similarly, MMP were expressed in CL-LCDD and LCH but the labelled cells were different. In contrast, few MMPs were detected in LAM.In conclusion, elastolysis is common to cystic lung light chain deposition disease and other cystic lung disorders, suggesting its implication in cyst formation. Moreover, in cystic lung light chain deposition disease, a role of metalloproteinases in elastolysis is strongly indicated by the metalloproteinase expression and activity pattern.
Case–control study of suicide in Karachi, Pakistan
Authors: Khan Murad Moosa , Mahmud Sadia , Karim Mehtab S. , Zaman Mohammad , Prince Martin 
Published: October 2008

BackgroundIn recent years suicide has become a major public health problem in Pakistan.AimsTo identify major risk factors associated with suicides in Karachi, Pakistan.MethodA matched case–control psychological autopsy study. Interviews were conducted for 100 consecutive suicides, which were matched for age, gender and area of residence with 100 living controls.ResultsBoth univariate analysis and conditional logistic regression model results indicate that predictors of suicides in Pakistan are psychiatric disorders (especially depression), marital status (being married), unemployment, and negative and stressful life events. Only a few individuals were receiving treatment at the time of suicide. None of the victims had been in contact with a health professional in the month before suicide.ConclusionsSuicide in Pakistan is strongly associated with depression, which is under-recognised and under-treated. The absence of an effective primary healthcare system in which mental health could be integrated poses unique challenges for suicide prevention in Pakistan.
Mood changes after delivery: role of the serotonin transporter gene
Authors: Sanjuan J. , Martin-Santos R. , Garcia-Esteve L. , Carot J. M. , Guillamat R. , Gutierrez-Zotes A. , Gornemann I. , Canellas F. , Baca-Garcia E. , Jover M. , Navines R. , Valles V. , Vilella E. , de Diego Y. , Castro J. A. , Ivorra J. L. , Gelabert E. , Guitart M. , Labad A. , Mayoral F. , Roca M. , Gratacos M. , Costas J. , van Os J. , de Frutos R. 
Published: October 2008

BackgroundPolymorphic variations in the serotonin transporter gene (5-HTT) moderate the depressogenic effects of tryptophan depletion. After childbirth there is a sharp reduction in brain tryptophan availability, thus polymorphic variations in5-HTTmay play a similar role in the post-partum period.AimsTo study the role of5-HTTpolymorphic variations in mood changes after delivery.MethodOne thousand, eight hundred and four depression-free Spanish women were studied post-partum. We evaluated depressive symptoms at 2–3 days, 8 weeks and 32 weeks post-partum. We used diagnostic interview to confirm major depression for all probable cases. Based on two polymorphisms of5-HTT(5-HTTLPR and STin2 VNTR), three genotype combinations were created to reflect different levels of5-HTTexpression.ResultsOne hundred and seventy-three women (12.7%) experienced major depression during the 32-week post-partum period. Depressive symptoms were associated with the high-expression5-HTTgenotypes in a dose–response fashion at 8 weeks post-partum, but not at 32 weeks.ConclusionsHigh-expression5-HTTgenotypes may render women more vulnerable to depressive symptoms after childbirth.