bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes
Authors: Carracedo Arkaitz , Gironella Meritxell , Lorente Mar , Garcia Stephane , Guzmán Manuel , Velasco Guillermo , Iovanna Juan L. 
Published: July 2006

Abstract
Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress–related targets activating transcription factor 4 (ATF-4) and TRB3 in Δ9-tetrahydrocannabinol–induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer. (Cancer Res 2006; 66(13): 6748-55)
RUNX3 Is Frequently Inactivated by Dual Mechanisms of Protein Mislocalization and Promoter Hypermethylation in Breast Cancer
Authors: Lau Quek Choon , Raja Erna , Salto-Tellez Manuel , Liu Qiang , Ito Kosei , Inoue Masafumi , Putti Thomas Choudary , Loh Marie , Ko Tun Kiat , Huang Canhua , Bhalla Kapil N. , Zhu Tao , Ito Yoshiaki , Sukumar Saraswati 
Published: July 2006

Abstract
A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-β, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P &lt; 0.0001) and protein (P &lt; 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment. (Cancer Res 2006; 66(13): 6512-20)
Estrogen Receptor-α Methylation Predicts Melanoma Progression
Authors: Mori Takuji , Martinez Steve R. , O'Day Steven J. , Morton Donald L. , Umetani Naoyuki , Kitago Minoru , Tanemura Atsushi , Nguyen Sandy L. , Tran Andy N. , Wang He-Jing , Hoon Dave S.B. 
Published: July 2006

Abstract
The role of estrogen receptor α (ER-α) in melanoma is unknown. ER-α expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-α hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-α methylation status in tumor (n = 107) and sera (n = 109) from American Joint Committee on Cancer (AJCC) stage I to IV melanoma patients was examined by methylation-specific PCR. The clinical significance of serum methylated ER-α was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-α methylation in AJCC stage I, II, and III primary melanomas were 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. Methylated ER-α was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-α was methylated more frequently in metastatic than primary melanomas (P = 0.0003). Of 109 melanoma patients' sera in AJCC stage I, II, III, and IV, methylated ER-α was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-α was detected more frequently in advanced than localized melanomas (P = 0.03) and was the only factor predicting progression-free [risk ratio (RR), 2.64; 95% confidence interval (95% CI), 1.36-5.13; P = 0.004] and overall survival (RR, 2.31; 95% CI, 1.41-5.58; P = 0.003) in biochemotherapy patients. Hypermethylated ER-α is a significant factor in melanoma progression. Serum methylated ER-α is an unfavorable prognostic factor. (Cancer Res 2006; 66(13): 6692-8)
Acidic Extracellular pH Promotes Experimental Metastasis of Human Melanoma Cells in Athymic Nude Mice
Authors: Rofstad Einar K. , Mathiesen Berit , Kindem Kristil , Galappathi Kanthi 
Published: July 2006

Abstract
Extracellular pH (pHe) is lower in many tumors than in the corresponding normal tissue. The significance of acidic pHe in the development of metastatic disease was investigated in the present work. Human melanoma cells (A-07, D-12, and T-22) were cultured in vitro at pHe 6.8 or 7.4 (control) before being inoculated into the tail vein of BALB/c nu/nu mice for formation of experimental pulmonary metastases. Cell invasiveness was studied in vitro by using Matrigel invasion chambers and angiogenesis was studied in vivo by using an intradermal assay. Protein secretion was measured by ELISA and immunocapture assays. Cells cultured at acidic pHe showed increased secretion of proteinases and proangiogenic factors, enhanced invasive and angiogenic potential, and enhanced potential to develop experimental metastases. Acidity-induced metastasis was inhibited by treatment with the general matrix metalloproteinase (MMP) inhibitor GM6001, the general cysteine proteinase inhibitor E-64, or blocking antibody against vascular endothelial growth factor-A (VEGF-A) or interleukin-8 (IL-8). Our study indicates that acidic pHe promotes experimental pulmonary metastasis in A-07, D-12, and T-22 human melanoma cells by a common mechanism involving acidity-induced up-regulation of the proteolytic enzymes MMP-2, MMP-9, cathepsin B, and cathepsin L and acidity-induced up-regulation of the proangiogenic factors VEGF-A and IL-8. One consequence of this observation is that treatment strategies involving deliberate tumor acidification to improve the efficacy of chemotherapy, photodynamic therapy, and hyperthermia should be avoided. Moreover, the possibility that the pHe of the primary tumor may be an important prognostic parameter for melanoma patients merits clinical investigation. (Cancer Res 2006; 66(13): 6699-707)
The Ghostly Prelude to Deutero-Isaiah
Authors: Landy Francis 
Published: July 2006

AbstractThe article is a close reading of Isa. 40:1-11, which focuses on its function as a prologue to Deutero-Isaiah, and hence distinguished by its promise of a new beginning, and on its dependence on, and reversal of, the past, the spectral voices it seeks to repatriate. It is concerned with the secondariness of Deutero-Isaiah, and the consequent ambiguity of its messages. The voice of the poet/prophet is refracted through disembodied voices, which themselves cite other voices, before finally adopting that of the female herald, through whom the advent of God becomes manifest, only to be indefinitely deferred through metaphor and simile. In the background there is the frequently asserted relationship with Isaiah 6 as a metapoetic key to the book. Does its purview extend to Isaiah 40, and is the message of comfort conveyed by Deutero-Isaiah subverted by the incomprehensibility mandated by it? The complexities of the passage, and hence of the book as a whole, require attention to the detail of each its parts, but also to its fragmentariness, as it seeks to reconstruct a fractured reality. This is achieved in part through the emphasis on the materiality of the voice, as flesh (basar) and sonority, and as the matrix (mebasseret) of the future. The analysis proceeds from the voice of maternal comfort in vv. 1-2, to the announcement of the way and the universal theophany in vv. 3-5, to the pathos of transience in vv. 6-8, and finally to the deferred resolution in vv. 9-11. In the conclusion I discuss the relation of the text to the Freudian uncanny, the correspondence and non-correspondence with chapter 6, and the question of the relationship between historical and literary approaches.
The Chaldean Oracles of Zoroaster, Hekate's Couch,and Platonic Orientalism in Psellos and Plethon Die Chaldäischen Orakel des Zoroaster, die Couch der Hekate und platonischer Orientalismus in Psellos und Plēthon
Authors: Burns Dylan 
Published: July 2006

Abstract Die vorliegende Untersuchung geht der Frage nach, auf welche Weise Michael Psellos und Georgios Gemistos Plēthon die Chaldäischen Orakel als eine Quelle uralter orientalischer Weisheit interpretierten. Psellos geht als ein Häresiologe an die Orakel heran, wenn auch mit ambivalenten Aussagen hinsichtlich der Rolle von Magie sowohl in der Lehre der Orakel als in seiner eigenen Philosophie. Der Artikel untersucht, inwieweit in der mittelalterlichen byzantinischen Vorstellung Magie mit Konstruktionen orientalischer “Dekadenz” verbunden war, die ihrerseits Einfluss hatten auf Psellos' eigene Auffassung, bei den Orakeln handele es sich um illegitime östliche Zauberkunst, ungeachtet des Wertes ihrer metaphysischen Lehre. Plēthon hingegen greift die Orakel im Kontext eines Diskurses neopaganer Alterität auf, in welchem er sie mit einer antiken östlichen Weisheit identifiziert, die gegen das orthodoxe Christentum in Stellung gebracht wurde. Obwohl er keinerlei Kenntnisse über persische Religion besaß, schrieb er dem Zoroaster die Autorschaft der Orakel zu, und zwar nicht aus schlichter Naivität, sondern im Zuge eines gängigen Deutungsmusters, das James Walbridge “Platonischen Orientalismus” nennt: die Neigung neoplatonischer Denker, uraltes Wissen nicht nur Platon zuzuschreiben, sondern auch anderen Weisen aus dem Osten. Plēthon, selbsternannter Neuheide in einem christlich orthodoxen Reich, fühlte sich angesprochen von der orientalischen Otherness der Orakel und identifizierte sich mit ihnen. Sein Manuskript der Orakel, welches ursprünglich Psellos gehörte, half ihm bei diesem Unternehmen. Seit Psellos waren wichtige Fragmente, die Askese, Dualismus und pagane Gottheiten betrafen, verloren oder doch unvollständig. Ohne diese fehlenden Fragmente war es ein Leichtes für Plēthon, die Orakel als eine holistische persische Theologie zu lesen, und nicht als eine hellenistische, mittelplatonisch-dualistische. Die Unterschiede zwischen Plēthons Exemplar der Orakel und jenen der frühen Neuplatonisten mögen ein Grund dafür sein, dass Plēthon der erste Platonist war, der Zoraster als den Autor der Orakel identifizierte, eine Zuschreibung, die entscheidend werden sollte für die Rezeption und Interpretation der Orakel in Renaissance und moderner Esoterik.
Clay minerals of the Permian Rotliegend Group in the North Sea and adjacent areas
Authors: Ziegler K. 
Published: July 2006

AbstractThe nature, distribution and origin of clay minerals in the hydrocarbon-bearing Permian Rotliegend sandstones of the North Sea and the adjacent areas of the Netherlands and Germany are reviewed. The clay minerals occur as detrital coatings of smectite and smectite-illite on the surfaces of sandgrains, and as later diagenetic cements of kaolinite, chlorite (two varieties), and illite in the pore spaces of those sandstones. Two diagenetic clay mineral assemblages are predominant in the Rotliegend of the North Sea. The kaolinite-illite assemblage is restricted to the Rotliegend of shelf areas which underwent shallow burial followed by strong Jurassic/Cretaceous (Late Cimmerian) structural inversions, whereas the illite-chlorite assemblage is associated with basinal areas that underwent deep and rapid burial throughout the Mesozoic.The factors controlling mineralogy, crystal chemistry and morphology of those diagenetic clay minerals, as well as their regional distribution and origin, are numerous, complicated, and inter- related. Evidence suggests that the following aspects were important parameters: (1) variations in the original depositional arid desert environment; (2) the chemistry and flow patterns of the porewaters; (3) temperature and timing of clay mineral formation; (4) local burial history; (5) the presence or absence of meteoric water; and (6) the structural setting of the Rotliegend sandstones.Oxygen isotope data indicate that the illite cements formed over a wide range of temperatures (24–140°C) that is consistent with the deep burial conditions prevailing in the palaeo-basins. In contrast, oxygen isotopes indicate that kaolinite cements formed over a more restricted temperature range (40–80°C) and under the influence of meteoric water penetrating the sandstones of the shelf areas as a result of their Late Cimmerian uplift and associated erosion. Hypotheses suggesting that the absence of kaolinite cement from the deeply buried Rotliegend sandstones is caused by its illitization during burial, and that the chlorite cements have formed by the alteration of earlier smectite, smectite-chlorite and corrensite cements, are not supported by evidence.
AMDA: an R package for the automated microarray data analysis
Authors: Pelizzola Mattia , Pavelka Norman , Foti Maria , Ricciardi-Castagnoli Paola 
Published: July 2006

Abstract

Background
Microarrays are routinely used to assess mRNA transcript levels on a genome-wide scale. Large amount of microarray datasets are now available in several databases, and new experiments are constantly being performed. In spite of this fact, few and limited tools exist for quickly and easily analyzing the results. Microarray analysis can be challenging for researchers without the necessary training and it can be time-consuming for service providers with many users.

Results
To address these problems we have developed an automated microarray data analysis (AMDA) software, which provides scientists with an easy and integrated system for the analysis of Affymetrix microarray experiments. AMDA is free and it is available as an R package. It is based on the Bioconductor project that provides a number of powerful bioinformatics and microarray analysis tools. This automated pipeline integrates different functions available in the R and Bioconductor projects with newly developed functions. AMDA covers all of the steps, performing a full data analysis, including image analysis, quality controls, normalization, selection of differentially expressed genes, clustering, correspondence analysis and functional evaluation. Finally a LaTEX document is dynamically generated depending on the performed analysis steps. The generated report contains comments and analysis results as well as the references to several files for a deeper investigation.

Conclusion
AMDA is freely available as an R package under the GPL license. The package as well as an example analysis report can be downloaded in the Services/Bioinformatics section of the Genopolis http://www.genopolis.it/
Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study
Authors: He Jing , Feng Dan , de Vlas Sake J , Wang Hongwei , Fontanet Arnaud , Zhang Panhe , Plancoulaine Sabine , Tang Fang , Zhan Lin , Yang Hong , Wang Tianbao , Richardus Jan H , Habbema J Dik F , Cao Wuchun 
Published: July 2006

AbstractBackgroundHost genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population.MethodsA hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted.ResultsOne polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95%CI) of 0.42 (0.20~0.89) and 0.30 (0.09~0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR= 3.06, 95%CI: 1.25~7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR= 0.38, 95%CI: 0.14~0.98 andOR= 3.22, 95%CI: 1.13~9.18, respectively).ConclusionSNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.
A simple statistical model for prediction of acute coronary syndrome in chest pain patients in the emergency department
Authors: Björk Jonas , Forberg Jakob L , Ohlsson Mattias , Edenbrandt Lars , Öhlin Hans , Ekelund Ulf 
Published: July 2006

Abstract

Background
Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED.

Methods
Multivariable analysis and logistic regression were used on data from 634 ED visits for chest pain. Only data immediately available at patient presentation were used. To make ACS prediction stable and the model useful for personnel inexperienced in electrocardiogram (ECG) reading, simple ECG data suitable for computerized reading were included.

Results
Besides ECG, eight variables were found to be important for ACS prediction, and included in the model: age, chest discomfort at presentation, symptom duration and previous hypertension, angina pectoris, AMI, congestive heart failure or PCI/CABG. At an ACS prevalence of 21% and a set sensitivity of 95%, the negative predictive value of the model was 96%.

Conclusion
The present prediction model, combined with the clinical judgment of ED personnel, could be useful for the early discharge of chest pain patients in populations with a low prevalence of ACS.
FGFR4 Arg388 Allele Is Associated With Resistance to Adjuvant Therapy in Primary Breast Cancer
Authors: Thussbas Christoph , Nahrig Jorg , Streit Sylvia , Bange Johannes , Kriner Monika , Kates Ronald , Ulm Kurt , Kiechle Marion , Hoefler Heinz , Ullrich Axel , Harbeck Nadia 
Published: July 2006

Purpose A recent study presented first evidence that a single nucleotide polymorphism (SNP) at codon 388 of fibroblast growth factor receptor 4 (FGFR4) gene, causing a transmembrane domain missense mutation (Gly388Arg), is associated with disease outcome in node-positive breast cancer. This article addresses the clinical relevance of this SNP, FGFR4 genotype, phenotype, and HER2 regarding patient outcome and influence of adjuvant systemic therapy in a substantial primary breast cancer collective (n = 372; median follow-up, 94.5 months). Methods Polymerase chain reaction restriction fragment length polymorphism analysis of germ-line polymorphism was performed in uninvolved lymph nodes; FGFR4 and HER2 expression were assessed immunohistochemically in tissue microarrays. Results In 51% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between FGFR4 genotype and expression or HER2 status. In node-negative patients, FGFR4 genotype was not correlated with disease outcome. In node-positive patients, however, FGFR4 Arg388 was significantly associated with poor disease-free survival (DFS; P = .02) and overall survival (OS; P = .04). Notably, this association seems to be attributable to relatively poor therapy response in Arg388 carriers, reflected in their significantly shorter DFS (P = .02) and OS (P = .045) among patients receiving adjuvant systemic therapy. It is also seen as a significant interaction term in a multivariate proportional hazards model with Arg388 carriers having only about half as much benefit from adjuvant systemic therapy as wild-type carriers. Conclusion According to this study, FGFR4 Arg388 genotype is a marker for breast cancer progression in patients with adjuvant systemic therapy, particularly chemotherapy, and thus may indicate therapy resistance.