bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic Activation of the Human Pygopus2 Promoter by E74-Like Factor-1
Authors: Andrews Phillip G.P. , Kennedy Mark W. , Popadiuk Cathy M. , Kao Kenneth R. 
Published: February 2008

Abstract
Pygopus is a component of the T-cell factor/β-catenin transcriptional complex essential for activation of Wnt target genes and is also required for cell regulation in the absence of Wnt signaling. Human Pygopus2 (hPygo2) is overexpressed in a high proportion of breast and epithelial ovarian malignant tumors and is required for the growth of several cell lines derived from these carcinomas. The mechanisms regulating hPygo2 gene activation, however, are unknown. Here, we have determined cis- and trans-interacting factors responsible for hPygo2 expression in cancer. The minimal region required for a maximal 109-fold activation of the hPygo2 promoter in MCF-7 breast cancer cells is 48 bp upstream of the start of transcription. Within 25 bp of the transcriptional start, there are two overlapping tandem Ets transcription factor–binding sites, which are critical for hPygo2 promoter activity. In vitro DNA pull-down assays and proteomic analyses identified the Ets family members Elk-1 and E74-like factor-1 (Elf-1) as potential hPygo2 promoter binding factors, whereas in vivo chromatin immunoprecipitation assays verified that only Elf-1 specifically bound to the hPygo2 promoter in MCF-7 cells. Modulation of elf-1 in MCF-7 cells by silencing via RNA interference or overexpression caused a corresponding decrease or increase, respectively, in hPygo2 promoter activity. Overexpression of Elf-1 in HeLa cells, in which Elf-1 is expressed at a lower level than in MCF-7 cells, caused a 4-fold increase in endogenous hPygo2 mRNA levels. These results provide new evidence that Elf-1 is involved in transcriptional activation of hPygo2. Like hPygo2, previous studies implicated Elf-1 in breast and ovarian cancer and our present findings suggest that the oncogenic requirement of hPygo2 is fulfilled, in part, by Elf-1. (Mol Cancer Res 2008;6(2):259–66)
c-Myc Inhibits Ras-Mediated Differentiation of Pheochromocytoma Cells by Blocking c-Jun Up-Regulation
Authors: Vaqué José P. , Fernández-García Belén , García-Sanz Pablo , Ferrandiz Nuria , Bretones Gabriel , Calvo Fernando , Crespo Piero , Marín María C. , León Javier 
Published: February 2008

Abstract
Although mutant Ras proteins were originally described as transforming oncoproteins, they induce growth arrest, senescence, and/or differentiation in many cell types. c-Myc is an oncogenic transcription factor that cooperates with Ras in cellular transformation and oncogenesis. However, the Myc-Ras relationship in cellular differentiation is largely unknown. Here, we have analyzed the effects of c-Myc on PC12-derived cells (UR61 cell line), harboring an inducible N-Ras oncogene. In these cells, Ras activation induces neuronal-like differentiation by a process involving c-Jun activation. We found that c-Myc inhibited Ras-mediated differentiation by a mechanism that involves the blockade of c-Jun induction in response to Ras signal. Accordingly, ectopically expressed c-Jun could bypass c-Myc impediment of Ras-induced differentiation and activator protein 1 activation. Interestingly, it did not rescue the proliferative arrest elicited by Ras and did not enhance the differentiation-associated apoptosis. The blockade of Ras-mediated induction of c-Jun takes place at the level of c-Jun proximal promoter. Mutational analysis revealed that c-Myc regions involved in DNA binding and transactivation are required to block differentiation and c-Jun induction. c-Myc does not seem to require Miz-1 to inhibit differentiation and block c-Jun induction. Furthermore, Max is not required for c-Myc activity, as UR61 cells lack a functional Max gene. c-Myc–inhibitory effect on the Ras/c-Jun connection is not restricted to UR61 cells as it can occur in other cell types as K562 or HEK293. In conclusion, we describe a novel interplay between c-Myc and c-Jun that controls the ability of Ras to trigger the differentiation program of pheochromocytoma cells. (Mol Cancer Res 2008;6(2):325–39)
Salvicine Inactivates β1 Integrin and Inhibits Adhesion of MDA-MB-435 Cells to Fibronectin via Reactive Oxygen Species Signaling
Authors: Zhou Jin , Chen Yi , Lang Jing-Yu , Lu Jin-Jian , Ding Jian 
Published: February 2008

Abstract
Integrin-mediated adhesion to the extracellular matrix plays a fundamental role in tumor metastasis. Salvicine, a novel diterpenoid quinone compound identified as a nonintercalative topoisomerase II poison, possesses a broad range of antitumor and antimetastatic activity. Here, the mechanism underlying the antimetastatic capacity of salvicine was investigated by exploring the effect of salvicine on integrin-mediated cell adhesion. Salvicine inhibited the adhesion of human breast cancer MDA-MB-435 cells to fibronectin and collagen without affecting nonspecific adhesion to poly-l-lysine. The fibronectin-dependent formation of focal adhesions and actin stress fibers was also inhibited by salvicine, leading to a rounded cell morphology. Furthermore, salvicine down-regulated β1 integrin ligand affinity, clustering and signaling via dephosphorylation of focal adhesion kinase and paxillin. Conversely, salvicine induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. The effect of salvicine on β1 integrin function and cell adhesion was reversed by U0126 and SB203580, inhibitors of MAPK/ERK kinase 1/2 and p38 MAPK, respectively. Salvicine also induced the production of reactive oxygen species (ROS) that was reversed by ROS scavenger N-acetyl-l-cysteine. N-acetyl-l-cysteine additionally reversed the salvicine-induced activation of ERK and p38 MAPK, thereby maintaining functional β1 integrin activity and restoring cell adhesion and spreading. Together, this study reveals that salvicine activates ERK and p38 MAPK by triggering the generation of ROS, which in turn inhibits β1 integrin ligand affinity. These findings contribute to a better understanding of the antimetastatic activity of salvicine and shed new light on the complex roles of ROS and downstream signaling molecules, particularly p38 MAPK, in the regulation of integrin function and cell adhesion. (Mol Cancer Res 2008;6(2):194–204)
MDM2 Gene Amplification Is Correlated to Tumor Progression but not to the Presence of SNP309 or TP53 Mutational Status in Primary Colorectal Cancers
Authors: Forslund Ann , Zeng Zhaoshi , Qin Li-Xuan , Rosenberg Shoshana , Ndubuisi MacKevin , Pincas Hanna , Gerald William , Notterman Daniel A. , Barany Francis , Paty Philip B. 
Published: February 2008

Abstract
Mdm2 is the main regulator of p53 and is amplified in ∼7% of all human cancers. MDM2 gene amplification as well as expression has been correlated to an increased tumorigenic potential. We have analyzed the prevalence of MDM2 gene amplifications and SNP309 in 284 colorectal tumors using a relatively new highly sensitive PCR/ligase detection reaction method in relation to TP53 mutational status and genomic instability. We found MDM2 to be amplified in 9% of the 284 colorectal cancers analyzed and a significantly higher proportion of tumors with high MDM2 gene amplification retained a wild-type p53 gene (P = 0.058). MDM2 gene amplification was significantly correlated to advanced tumor stage. Several small-molecule MDM2 antagonists have already been identified that either physically inhibit the p53-MDM2 binding or the E3 ligase function of MDM2. Our results suggest that MDM2 is a promising target for this type of cancer therapy in a substantial subgroup of colorectal cancers. (Mol Cancer Res 2008;6(2):205–11)
DNMT1 as a Molecular Target in a Multimodality-Resistant Phenotype in Tumor Cells
Authors: Mishra Mark V. , Bisht Kheem S. , Sun Lunching , Muldoon-Jacobs Kristi , Awwad Rania , Kaushal Aradhana , Nguyen Phuongmai , Huang Lei , Pennington J. Daniel , Markovina Stephanie , Bradbury C. Matthew , Gius David 
Published: February 2008

AbstractWe have previously shown that hydrogen peroxide–resistant permanent (OC-14) cells are resistant to the cytotoxicity of several exogenous oxidative and anticancer agents including H2O2, etoposide, and cisplatin; and we refer to this process as an oxidative multimodality-resistant phenotype (MMRP). Furthermore, OC-14 cells contain increased activator protein 1 activity, and inhibition of activator protein 1 reversed the MMRP. In this study, we show that permanent Rat-1 cell lines genetically altered to overexpress c-Fos also displayed a similar MMRP to H2O2, etoposide, and cisplatin as OC-14 cells. Gene expression analysis of the OC-14 cells and c-Fos–overexpressing cells showed increased DNMT1 expression. Where OC-14 and c-Fos–overexpressing cells were exposed to 5-aza-2′-deoxycytidine, which inhibits DNMT activity, a significant but incomplete reversal of the MMRP was observed. Thus, it seems logical to suggest that DNMT1 might be at least one target in the MMRP. Rat-1 cells genetically altered to overexpress DNMT1 were also shown to be resistant to the cytotoxicity of H2O2, etoposide, and cisplatin. Finally, somatic HCT116 knockout cells that do not express either DNMT1 (DNMT1−/−) or DNMT3B (DNMT3B−/−) were shown to be more sensitive to the cytotoxicity of H2O2, etoposide, and cisplatin compared with control HCT116 cells. This work is the first example of a role for the epigenome in tumor cell resistance to the cytotoxicity of exogenous oxidative (H2O2) or systemic (etoposide and cisplatin) agents and highlights a potential role for DNMT1 as a potential molecular target in cancer therapy. (Mol Cancer Res 2008;6(2):243–9)
Sulh and the 18th Century Ottoman Courts of Üsküdar and Adana
Authors: Tamdoğan Işık 
Published: February 2008

AbstractThis article explores and compares cases of sulh (amicable agreement) that are documented in the records of two Ottoman courts—one in Üsküdar, the other in Adana—in the second half of the 18th century. As a dispute resolution practice, sulh draws on three normative systems: shari'a, kanun and 'örf. An abundance of references to sulh agreements in court records testifies not only to the importance of this social practice, but also to complex interrelations between the three normative systems. Sulh documents provide evidence of the interrelation between the shari'a court and other legal arenas. The judges in both Üsküdar and Adana viewed sulh agreements—even those concluded privately and outside of court—as valid and binding. There were, however, significant differences between the two courts regarding the sulh cases; these differences highlight the connection between the location of the court and its specific legal culture.
Notes on the Anomaly of the Shari'a Field in Israel
Authors: Ramadan Moussa Abou 
Published: February 2008

AbstractA close scrutiny of the Islamic religious field in Israel reveals that those responsible for the application of shari'a rules (i.e. judges presiding in shari'a courts), do not possess the "symbolic capital" that is required in order to distinguish them from laymen. Since shari'a judges in Israel enjoy unprecedented centrality within the Islamic religious field, the field itself is not well-distinguished from the secular legal field. This situation results not only from the fact that persons without proper shari'a training have been appointed to the office of shari'a judge (qadi), but also from the fact that the qadis are appointed by a non-Muslim authority and that the shari'a courts are subordinated to Israeli legislation. I argue that the Islamic religious field in Israel is an anomaly, characterized by lack of autonomy, ambiguous boundaries and lack of competition between actors (due to the monopolization of power by qadis).
Reduction of hemodilution in small adults undergoing open heart surgery: a prospective, randomized trial
Authors: Pappalardo F. , Corno C. , Franco A. , Giardina G. , Scandroglio A.M. , Landoni G. , Crescenzi G. , Zangrillo A. 
Published: February 2008

Background. Given that there is an association between the degree of hemodilution during cardiopulmonary bypass (CPB) and postoperative complications, patients-outcome might be improved if the nadir hematocrit concentration is kept within an optimal range. Smaller patients are more likely to have a low hematocrit during CPB: this phenomenon may be related, at least partially, to the extreme hemodilution induced by a large fixed CPB priming volume. Methods. Forty patients with a body surface area (BSA) < 1.7 m2 undergoing open heart operations were randomized to either standard CPB with full prime volume (control group) or reduced prime extracorporeal circuit and vacuum-assisted venous drainage (VAVD) (study group). Results. There were no significant differences between the groups with respect to baseline characteristics, body surface area, hematologic profile and operative data. Clinical outcomes were similar. Nadir hematocrit and hemoglobin on bypass were significantly lower in the control group (22 ± 2.3 vs 24 ± 2.5%, p < 0.02 and 7.4 ± 0.7 vs 8 ± 0.9g/dl, p < 0.04, respectively). Postoperative chest tube drainage was significantly higher in the control group (272 ± 253vs 139 ± 84ml, p < 0.04). There was no difference in blood transfusion in the two groups (0.5 ± 1.14 v 1.0 ± 1.77 units of packed red blood cells (PRBC), p = 0.29). Conclusions. Lowering CPB priming volume by means of using a small oxygenator and vacuum-assisted venous drainage (VAVD) resulted in a significant decrease of intraoperative hemodilution. This technique should be strongly considered for patients with a small BSA (<1.7 m2) undergoing open heart surgery. Perfusion (2007) 22, 317—322.
Influence of early re-infusion of autologous shed mediastinal blood on clinical outcome after cardiac surgery
Authors: Sirvinskas Edmundas , Veikutiene Audrone , Benetis Rimantas , Grybauskas Pranas , Andrejaitiene Judita , Veikutis Vincentas , Surkus Jonas 
Published: February 2008

Various strategies have been proposed to decrease allogeneic blood transfusion requirements after cardiac surgery. The aim of the study was to evaluate the efficacy of collected and re-infused autologous shed mediastinal blood on a patient's postoperative course. Ninety patients who underwent heart surgery with cardiopulmonary bypass (CPB) were studied. The patients were divided into two groups: Group 1 ( n = 41) received the centrifuged autologous shed mediastinal blood collected from the cardiotomy reservoir 4 hours after surgery; in Group 2 ( n = 49) all shed mediastinal blood was discarded (control group). Haemoglobin (Hb), haematocrit (Hct), C-reactive protein values, and leucocyte count were compared before surgery, at 4 h and 20 h after surgery, and on the fifth postoperative day. We have measured serum procalcitonin (PCT) concentration at 4 h and 20 h after CPB. We assessed drained blood loss within 20 postoperative hours. Leucocyte count, Hb, Hct values, C-reactive protein, and procalcitonin concentration did not differ between the groups before and at 4 h after surgery. Hb, Hct level, and leucocyte count were similar at 20 hours and on the fifth day after surgery. At 20 hours after surgery, an increase of serum PCT concentration (>0.5—2 ng/mL) was more frequent in Group 2 (58.3% vs. 33.3%; p = 0.03). On the fifth postoperative day, C-reactive protein concentration was lower in Group 1 (71.74 ± 15.23; p < 0.01) compared to Group 2 (93.53 ± 20.3). Postoperative blood loss did not differ between the groups. Requirement for allogeneic blood transfusion was significantly lower in Group 1 (14.6% vs. 38.8%; p < 0.02). Patients in Group 1 developed less infective complications compared with Group 2 (2.4% and 16.3%, respectively; p < 0.05). The length of postoperative in-hospital stay was shorter in Group 1 compared with Group 2 (9.32 ± 2.55 and 16.45 ± 6.5, respectively; p < 0.05). We conclude that postoperative re-infusion of autologous red blood cells processed from shed mediastinal blood did not increase bleeding tendency and systemic inflammatory response and was effective in reducing the requirement for allogeneic transfusion, the rate of infective complications and the length of postoperative in-hospital stay. Perfusion (2007) 22, 345—352.
The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia
Authors: Van Vlierberghe Pieter , van Grotel Martine , Tchinda Joëlle , Lee Charles , Beverloo H. Berna , van der Spek Peter J. , Stubbs Andrew , Cools Jan , Nagata Kyosuke , Fornerod Maarten , Buijs-Gladdines Jessica , Horstmann Martin , van Wering Elisabeth R. , Soulier Jean , Pieters Rob , Meijerink Jules P. P. 
Published: February 2008

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner that possibly delineate specific T-ALL subgroups. One subgroup, including MLL-rearranged, CALM-AF10 or inv (7)(p15q34) patients, is characterized by elevated expression of HOXA genes. Using a gene expression–based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new patients with elevated HOXA levels. Using microarray-based comparative genomic hybridization (array-CGH), a cryptic and recurrent deletion, del (9)(q34.11q34.13), was exclusively identified in 3 of these 5 patients. This deletion results in a conserved SET-NUP214 fusion product, which was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it interacts with CRM1 and DOT1L, which may transcriptionally activate specific members of the HOXA cluster. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation, and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SET-NUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest.
Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias
Authors: Kim Woo Jae , Okimoto Ross A. , Purton Louise E. , Goodwin Meagan , Haserlat Sara M. , Dayyani Farshid , Sweetser David A. , McClatchey Andrea I. , Bernard Olivier A. , Look A. Thomas , Bell Daphne W. , Scadden David T. , Haber Daniel A. 
Published: February 2008

AbstractCeramide is a lipid second messenger derived from the hydrolysis of sphingomyelin by sphingomyelinases (SMases) and implicated in diverse cellular responses, including growth arrest, differentiation, and apoptosis. Defects in the neutral SMase (nSMase) gene Smpd3, the primary regulator of ceramide biosynthesis, are responsible for developmental defects of bone; regulation of ceramide levels have been implicated in macrophage differentiation, but this pathway has not been directly implicated in human cancer. In a genomic screen for gene copy losses contributing to tumorigenesis in a mouse osteosarcoma model, we identified a somatic homozygous deletion specifically targeting Smpd3. Reconstitution of SMPD3 expression in mouse tumor cells lacking the endogenous gene enhanced tumor necrosis factor (TNF)–induced reduction of cell viability. Nucleotide sequencing of the highly conserved SMPD3 gene in a large panel of human cancers revealed mutations in 5 (5%) of 92 acute myeloid leukemias (AMLs) and 8 (6%) of 131 acute lymphoid leukemias (ALLs), but not in other tumor types. In a subset of these mutations, functional analysis indicated defects in protein stability and localization. Taken together, these observations suggest that disruption of the ceramide pathway may contribute to a subset of human leukemias.
Human Pol II promoter recognition based on primary sequences and free energy of dinucleotides
Authors: Yang Jian-Yi , Zhou Yu , Yu Zu-Guo , Anh Vo , Zhou Li-Qian 
Published: February 2008

Abstract

Background
Promoter region plays an important role in determining where the transcription of a particular gene should be initiated. Computational prediction of eukaryotic Pol II promoter sequences is one of the most significant problems in sequence analysis. Existing promoter prediction methods are still far from being satisfactory.

Results
We attempt to recognize the human Pol II promoter sequences from the non-promoter sequences which are made up of exon and intron sequences. Four methods are used: two kinds of multifractal analysis performed on the numeric sequences obtained from the dinucleotide free energy, Z curve analysis and global descriptor of the promoter/non-promoter primary sequences. A total of 141 parameters are extracted from these methods and categorized into seven groups (methods). They are used to generate certain spaces and then each promoter/non-promoter sequence is represented by a point in the corresponding space. All the 120 possible combinations of the seven methods are tested. Based on Fisher's linear discriminant algorithm, with a relatively smaller number of parameters (96 and 117), we get satisfactory discriminant accuracies. Particularly, in the case of 117 parameters, the accuracies for the training and test sets reach 90.43% and 89.79%, respectively. A comparison with five other existing methods indicates that our methods have a better performance. Using the global descriptor method (36 parameters), 17 of the 18 experimentally verified promoter sequences of human chromosome 22 are correctly identified.

Conclusion
The high accuracies achieved suggest that the methods of this paper are useful for understanding the difficult problem of promoter prediction.
A mixture model approach to sample size estimation in two-sample comparative microarray experiments
Authors: Jørstad Tommy S , Midelfart Herman , Bones Atle M 
Published: February 2008

AbstractBackgroundChoosing the appropriate sample size is an important step in the design of a microarray experiment, and recently methods have been proposed that estimate sample sizes for control of the False Discovery Rate (FDR). Many of these methods require knowledge of the distribution of effect sizes among the differentially expressed genes. If this distribution can be determined then accurate sample size requirements can be calculated.ResultsWe present a mixture model approach to estimating the distribution of effect sizes in data from two-sample comparative studies. Specifically, we present a novel, closed form, algorithm for estimating the noncentrality parameters in the test statistic distributions of differentially expressed genes. We then show how our model can be used to estimate sample sizes that control the FDR together with other statistical measures like average power or the false nondiscovery rate. Method performance is evaluated through a comparison with existing methods for sample size estimation, and is found to be very good.ConclusionA novel method for estimating the appropriate sample size for a two-sample comparative microarray study is presented. The method is shown to perform very well when compared to existing methods.