bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251
Authors: Zhou Youxin , Su Zuopeng , Huang Yulun , Sun Ting , Chen Sansong , Wu Tingfeng , Chen Guilin , Xie Xueshun , Li Bin , Du Ziwei 
Published: December 2011

Abstract

Background
Zfx is a zinc finger protein of the Zfy family, whose members are highly conserved in vertebrates. Zfx is a shared transcriptional regulator of both embryonic stem cells (ESC) and hematopoietic stem cells (HSC), which suggests a common genetic basis of self-renewal in embryonic and adult stem cells. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, and leukemia. However, the importance of Zfx in human glioma is largely unknown. In the present study, we examined the role of Zfx in human glioma.

Methods
We detected expression levels of Zfx mRNA in U251 cells, U87 cells, U373 cells, and A172 cells by semi-quantitative RT-PCR. To analyze the expression of Zfx mRNA in glioma tissues, we performed real-time quantitative PCR on 35 pathologically confirmed glioma samples (Grade I-4cases, Grade II-13cases, Grade III-11cases, and Grade IV-7cases) and on 5 noncancerous brain tissue samples. We used lentivirus-mediated small interfering RNAs (siRNAs) to knock down Zfx expression in the human malignant glioma cell line U251. Changes in Zfx target gene expression were determined by real-time RT-PCR. Cell proliferation was examined by a High Content Screening assay. DNA synthesis in proliferating cells was determined by BrdU incorporation. Cell cycle distribution and apoptosis were detected by flowcytometric analysis.

Results
We discovered that Zfx mRNA was expressed in U251 cells, U87 cells, U373 cells, and A172 cells. The expression level of Zfx is significantly higher in gliomas compared to noncancerous brain tissue. Using a lentivirus-based RNAi approach, Zfx expression was significantly inhibited in human glioblastoma U251 cells. The effects of Zfx knockdown on cell proliferation, cell cycle distribution, and apoptosis were assessed. Inhibition of Zfx expression in U251 cells by RNAi significantly impaired cell proliferation, increased apoptosis, and arrested cells in S phase.

Conclusions
The results of our study demonstrate that the Zfx gene is highly expressed in glioma tissue and in glioma cell lines. Furthermore, Zfx may play a critical role in cell proliferation, cell cycle distribution, and apoptosis of human malignant glioma cells.
The synthetic Tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis
Authors: Kümpers Philipp , Gueler Faikah , David Sascha , Van Slyke Paul , Dumont Daniel J , Park Joon-Keun , Bockmeyer Clemens L , Parikh Samir M , Pavenstädt Hermann , Haller Hermann , Shushakova Nelli 
Published: December 2011

Abstract
Introduction
Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis.

Methods
Polymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP). Mice were treated with different dosages of VT or equal volume of phosphate-buffered saline (PBS). Sham-operated animals served as time-matched controls.

Results
Systemic administration of VT induced long-lasting Tie2 activation in vivo. VT protected against sepsis-induced endothelial barrier dysfunction, as evidenced by attenuation of vascular leakage and leukocyte transmigration into the peritoneal cavity. Histological analysis revealed that VT treatment ameliorated leukocyte infiltration in kidneys of septic mice, probably due to reduced endothelial adhesion molecule expression. VT-driven effects were associated with significantly improved organ function and reduced circulating cytokine levels. The endothelial-specific action of VT was supported by additional in vitro studies showing no effect of VT on either cytokine release from isolated peritoneal macrophages, or migratory capacity of isolated neutrophils. Finally, administration of VT pre-CLP (hazard ratio 0.39 [95% confidence interval 0.19-0.81] P < 0.001) and post-CLP reduced mortality in septic mice (HR 0.22 [95% CI 0.06-0.83] P < 0.05).

Conclusions
We provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept.
The relationship between proteome size, structural disorder and organism complexity
Authors: Schad Eva , Tompa Peter , Hegyi Hedi 
Published: December 2011

Abstract
Background
Sequencing the genomes of the first few eukaryotes created the impression that gene number shows no correlation with organism complexity, often referred to as the G-value paradox. Several attempts have previously been made to resolve this paradox, citing multifunctionality of proteins, alternative splicing, microRNAs or non-coding DNA. As intrinsic protein disorder has been linked with complex responses to environmental stimuli and communication between cells, an additional possibility is that structural disorder may effectively increase the complexity of species.

Results
We revisited the G-value paradox by analyzing many new proteomes whose complexity measured with their number of distinct cell types is known. We found that complexity and proteome size measured by the total number of amino acids correlate significantly and have a power function relationship. We systematically analyzed numerous other features in relation to complexity in several organisms and tissues and found: the fraction of protein structural disorder increases significantly between prokaryotes and eukaryotes but does not further increase over the course of evolution; the number of predicted binding sites in disordered regions in a proteome increases with complexity; the fraction of protein disorder, predicted binding sites, alternative splicing and protein-protein interactions all increase with the complexity of human tissues.

Conclusions
We conclude that complexity is a multi-parametric trait, determined by interaction potential, alternative splicing capacity, tissue-specific protein disorder and, above all, proteome size. The G-value paradox is only apparent when plants are grouped with metazoans, as they have a different relationship between complexity and proteome size.
Accurate proteome-wide protein quantification from high-resolution 15N mass spectra
Authors: Khan Zia , Amini Sasan , Bloom Joshua S , Ruse Cristian , Caudy Amy A , Kruglyak Leonid , Singh Mona , Perlman David H , Tavazoie Saeed 
Published: December 2011

AbstractIn quantitative mass spectrometry-based proteomics, the metabolic incorporation of a single source of 15N-labeled nitrogen has many advantages over using stable isotope-labeled amino acids. However, the lack of a robust computational framework for analyzing the resulting spectra has impeded wide use of this approach. We have addressed this challenge by introducing a new computational methodology for analyzing 15N spectra in which quantification is integrated with identification. Application of this method to an Escherichia coli growth transition reveals significant improvement in quantification accuracy over previous methods.
K12/SECTM1, an interferon-γ regulated molecule, synergizes with CD28 to costimulate human T cell proliferation
Authors: Wang Tao , Huang Catherine , Lopez-Coral Alfonso , Slentz-Kesler Kimberly A , Xiao Min , Wherry E John , Kaufman Russel E 
Published: December 2011

ABSTRACT
CD7 is a cell-surface molecule, expressed on T lymphocytes and NK cells, which functions as a costimulatory receptor for T cell proliferation. SECTM1 has been proposed as a ligand for CD7. However, the expression pattern of this molecule in human immune cells and role in human T cell function remain unclear. In the present study, using human rSECTM1, we demonstrate that SECTM1 strongly costimulates CD4 and CD8 T cell proliferation and induces IFN-γ production, likely via a CD7-dependent mechanism. In addition, SECTM1 synergizes with suboptimal anti-CD28 to strongly augment T cell functions. We found a robust induction of IL-2 production when SECTM1 and anti-CD28 signals were present with TCR ligation. Furthermore, addition of SECTM1 into a MLR significantly enhanced proliferation of alloantigen-activated T cells, whereas blockade of SECTM1 inhibited T cell proliferation in a two-way MLR assay. Simultaneously blocking the effect of SECTM1, along with CTLA-4/Fc, diminishes two-way MLR. Finally, we demonstrated that expression of SECTM1 is not detected in monocytes and imMoDCs at the protein level. However, it is strongly induced by IFN-γ in monocytes and imMoDCs, and this induction is STAT1-dependent. These results indicate that SECTM1 is a broadly expressed, IFN-γ-inducible molecule, which functions as a potent costimulatory ligand for T cell activation and is synergistic with anti-CD28.
Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning
Authors: Deprez Sabine , Amant Frederic , Smeets Ann , Peeters Ronald , Leemans Alexander , Van Hecke Wim , Verhoeven Judith S. , Christiaens Marie-Rose , Vandenberghe Joris , Vandenbulcke Mathieu , Sunaert Stefan 
Published: December 2011

PurposeTo uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy by using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment.Patients and MethodsThirty-four young premenopausal women with early-stage breast cancer who were exposed to chemotherapy underwent neuropsychologic testing and DTI before the start of chemotherapy (t1) and 3 to 4 months after treatment (t2). Sixteen patients not exposed to chemotherapy and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all groups, we used paired t tests to study changes in neuropsychologic test scores and whole-brain voxel-based paired t tests to study changes in WM fractional anisotropy (FA; a DTI measure that reflects WM tissue organization), with depression scores and intelligence quotient as included covariates. We correlated changes of neuropsychologic test scores with the mean change of FA for regions that survived the paired t tests in patients treated with chemotherapy.ResultsIn contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory at t2 compared with t1 (P < .05). In the chemotherapy-treated group, we found significant decreases of FA in frontal, parietal, and occipital WM tracts after treatment (familywise error P < .05), whereas for both control groups, FA values were the same between t1 and t2. Furthermore, performance changes in attention and verbal memory correlated with mean regional FA changes in chemotherapy-treated patients (P < .05).ConclusionWe report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.
Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group
Authors: Malempati Suman , Weigel Brenda , Ingle Ashish M. , Ahern Charlotte H. , Carroll Julie M. , Roberts Charles T. , Reid Joel M. , Schmechel Stephen , Voss Stephan D. , Cho Steven Y. , Chen Helen X. , Krailo Mark D. , Adamson Peter C. , Blaney Susan M. 
Published: December 2011

Purpose A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES). Patients and Methods Pediatric patients with relapsed or refractory solid tumors were treated with cixutumumab as a 1-hour intravenous infusion once per week. Two dose levels—6 and 9 mg/kg—were evaluated using a standard three-plus-three cohort design. Patients with refractory ES were treated in an expanded phase II cohort at each dose level. Results Forty-seven eligible patients with a median age of 15 years (range, 4 to 28 years) were enrolled. Twelve patients were treated in the dose-finding phase. Hematologic and nonhematologic toxicities were generally mild and infrequent. Dose-limiting toxicities included grade 4 thrombocytopenia at 6 mg/kg and grade 3 dehydration at 9 mg/kg. Mean trough concentration (± standard deviation) at 9 mg/kg was 106 ± 57 μg/mL, which exceeded the effective trough concentration of 60 μg/mL observed in xenograft models. Three patients with ES had confirmed partial responses: one of 10 at 6 mg/kg and two of 20 at 9 mg/kg. Serum insulin-like growth factor I (IGF-I) levels consistently increased after one dose of cixutumumab. Tumor IGF-I receptor expression by immunohistochemistry did not correlate with response in patients with ES. Conclusion Cixutumumab is well tolerated in children with refractory solid tumors. The recommended phase II dose is 9 mg/kg. Limited single-agent activity of cixutumumab was seen in ES.
Racial Disparities in Stage-Specific Colorectal Cancer Mortality Rates From 1985 to 2008
Authors: Robbins Anthony S. , Siegel Rebecca L. , Jemal Ahmedin 
Published: December 2011

Purpose Since the early 1980s, colorectal cancer (CRC) mortality rates for whites and blacks in the United States have been diverging as a result of earlier and larger reductions in death rates for whites. We examined whether this mortality pattern varies by stage at diagnosis. Methods The Incidence-Based Mortality database of the Surveillance, Epidemiology, and End Results (SEER) Program was used to examine data from the nine original SEER regions. Our main outcome measures were changes in stage-specific mortality rates by race. Results From 1985 to 1987 to 2006 to 2008, CRC mortality rates decreased for each stage in both blacks and whites, but for every stage, the decreases were smaller for blacks, particularly for distant-stage disease. For localized stage, mortality rates decreased 30.3% in whites compared with 13.2% in blacks; for regional stage, declines were 48.5% in whites compared with 34.0% in blacks; and for distant stage, declines were 32.6% in whites compared with 4.6% in blacks. As a result, the black-white rate ratios increased from 1.17 (95% CI, 0.98 to 1.39) to 1.41 (95% CI, 1.21 to 1.63) for localized disease, from 1.03 (95% CI, 0.93 to 1.14) to 1.30 (95% CI, 1.17 to 1.44) for regional disease, and from 1.21 (95% CI, 1.10 to 1.34) to 1.72 (95% CI, 1.58 to 1.86) for distant-stage disease. In absolute terms, the disparity in distant-stage mortality rates accounted for approximately 60% of the overall black-white mortality disparity. Conclusion The black-white disparities in CRC mortality increased for each stage of the disease, but the overall disparity in overall mortality was largely driven by trends for late-stage disease. Concerted efforts to prevent or detect CRC at earlier stages in blacks could improve the worsening black- white disparities.
Anaplastic Lymphoma Kinase Aberrations in Rhabdomyosarcoma: Clinical and Prognostic Implications
Authors: van Gaal J. Carlijn , Flucke Uta E. , Roeffen Melissa H.S. , de Bont Eveline S.J.M. , Sleijfer Stefan , Mavinkurve-Groothuis Annelies M.C. , Suurmeijer Albert J.H. , van der Graaf Winette T.A. , Versleijen-Jonkers Yvonne M.H. 
Published: December 2011

Purpose The aim of this study is to investigate anaplastic lymphoma kinase (ALK) protein expression and underlying genetic aberrations in rhabdomyosarcoma (RMS), with special attention to clinical and prognostic implications. Patients and Methods A total of 189 paraffin-embedded RMS tumor specimens from 145 patients were collected on tissue microarray. ALK protein expression was evaluated by immunohistochemistry. ALK gene (2p23) copy number and translocations were determined by in situ hybridization. cDNA sequencing of the receptor tyrosine kinase domain of the ALK gene was assessed in 43 samples. Results Strong cytoplasmic ALK protein expression was more frequently observed in alveolar RMS (ARMS) than in embryonal RMS (ERMS) (81% v 32%, respectively; P < .001). ALK gene copy number gain was detected in the vast majority of ARMS (88%), compared with 52% of ERMS (P < .001). ALK copy number correlated with protein expression in primary tumors (n = 107). We identified one point mutation (2%) and seven tumors harboring whole exon deletions (16%). In ERMS, specific ALK gain in the primary tumor correlated with metastatic disease (100% in metastatic disease v 29% in nonmetastatic disease; P = .004) and poor disease-specific survival (5-year disease-specific survival: 62% v 82% for nonspecific or no gain; P = .046). Conclusion Because ALK aberrations on genomic and protein levels are frequently found in RMSs, in particular ARMS, and are associated with disease progression and outcome in ERMS, ALK may play a role in tumor biology and may provide a potential therapeutic target for these tumors. Future research should aim at the oncogenic role of ALK and the potential effect of ALK inhibitors in RMS.
A rodent model of rapid-onset diabetes (ROD) induced by glucocorticoids and high-fat feeding
Authors: Shpilberg Yaniv , Beaudry Jacqueline L. , D'Souza Anna , Campbell Jonathan E. , Peckett Ashley , Riddell Michael C. 
Published: December 2011

Summary
Glucocorticoids (GC) are potent pharmacological agents used to treat a number of immune conditions. GCs are also naturally occurring steroid hormones (e.g. cortisol, corticosterone) produced in response to stressful conditions that are thought to increase the preference for calorie dense “comfort” foods. If chronically elevated, GCs may contribute to the development of type 2 diabetes mellitus (T2DM), although mechanisms are not entirely clear. The present study proposes a new rodent model to investigate the combined metabolic effects of elevated GCs and high-fat feeding on ectopic fat deposition and various indexes of insulin resistance that induces rapid-onset diabetes (ROD). Male Sprague-Dawley rats (aged 4 weeks) received exogenous corticosterone or wax (placebo) (4 x 100 mg each) pellets, implanted subcutaneously, and fed either a standard chow diet (SD) or a 60% high-fat diet (HFD) for 16 days (n= 8-10). Animals given corticosterone and a HFD (cort-HFD) had lower body weight (226.1±9.05 versus 358.9±5.57 g, mean ± SEM, p&lt;0.05) and smaller relative glycolytic muscle mass (0.14±0.01 versus 0.09±0.02 g/kg body mass for the epitroclearis muscle, p&lt;0.05), but increased relative epididymal mass (9.81±1.65 versus 4.56±0.54 g/kg, p&lt;0.05), compared to controls (placebo-SD). Cort-HFD rats exhibited severe hepatic steatosis and increased muscle lipid deposition compared to placebo-SD animals. Moreover, cort-HFD animals were found to exhibit severe fasting hyperglycemia (60% increase), hyperinsulinemia (80% increase), insulin resistance (60% increase) and impaired beta cell response (20% decrease) to oral glucose load compared to placebo-SD animals. Thus, a metabolic syndrome/T2DM phenotype can be rapidly induced in young Sprague-Dawley rats by using exogenous GCs if a HFD is consumed. This finding may be valuable in examining the physiological and molecular mechanisms of GC-induced metabolic disease.
Radiological catheter placement for transcatheter arterial steroid injection therapy to treat severe acute hepatic failure: technical feasibility and efficacy
Authors: Ushijima Yasuhiro , Tajima Tsuyoshi , Yoshimitsu Kengo , Irie Hiroyuki , Nishie Akihiro , Hirakawa Masakazu , Ishigami Kousei , Okamoto Daisuke , Kotoh Kazuhiro , Honda Hiroshi 
Published: December 2011

Background Severe acute hepatic failure (SAHF), which progresses to fulminant form in some cases, is a life-threatening disease. Purpose To assess the technical feasibility and the efficacy of transcatheter arterial steroid injection therapy (TASIT) for SAHF. Material and Methods Twenty-seven patients with SAHF, 10 of whom had variant anatomy of the hepatic artery, underwent radiologic placement of an indwelling catheter in the hepatic artery, and TASIT was subsequently performed for three days. The tips of the catheters were inserted as follows: common hepatic artery ( n = 18), proper hepatic artery ( n = 4), and replaced right hepatic artery ( n = 5). The clinical success rate of TASIT and the prognosis after TASIT were evaluated. Results In one patient, intimal injury of the left hepatic artery was encountered; however, TASIT could be resumed and completed via intrahepatic arterial collaterals. In two patients, the catheter tip placement was corrected on the following day because of dislocation. Finally, TASIT could be carried out in all patients. Twenty-two patients (81.5%) responded to TASIT but five patients (18.5%) did not. Among the five non-responders, two patients were transferred to liver transplantation and survived, and three patients died. There was no significant difference in the response rates to TASIT among locations of catheter tip ( P > 0.05) and extent of drug distribution in the liver ( P > 0.05). Conclusion TASIT is a feasible and efficient treatment option for SAHF regardless of the anatomic variation of the hepatic artery. Careful manipulation during the procedure to prevent injury of the hepatic artery may be the most essential factor not only for successful TASIT but also for liver transplantation, which may be performed on TASIT non-responders.
Diffusion-weighted imaging in the diagnosis of enterovirus 71 encephalitis
Authors: Lian Zhou-yang , Huang Biao , He Shao-ru , Liang Chang-hong , Guo Yu-xiong 
Published: December 2011

Background In the early phase of viral encephalitis, conventional MRI may appear normal. Diffusion-weighted imaging (DWI) is a sensitive tool for detecting early changes in cellular function in the central nervous system. Purpose To investigate the usefulness of DWI in the diagnosis of enterovirus 71 (EV71) encephalitis, and to determine whether DWI is superior to conventional MR sequences. Material and Methods MRI scans in 26 patients were retrospectively evaluated for distribution of lesions on T1-weighted images (T1WI), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), and DWI. Contrast-to-noise ratios (CNRs) were calculated for all regions on each sequence and differences in the four MRI sequences were assessed using CNRs. Apparent diffusion coefficient (ADC) values were measured for all regions to look for true restriction of diffusion. Results Fifteen out of 26 cases showed positive findings on MR imaging. The brain stem was involved in 11 patients, cortex and subcortical white matter in four patients. DWI was more sensitive in detecting the abnormalities (89.7%) compared to T2WI (48.7%), FLAIR (41.0%), and T1WI (35.9%), and the positive ratio of DWI was significantly higher compared to other sequences. Furthermore, no significant difference was found between T2WI and FLAIR ( P = 0.649). The corresponding mean CNRs were 8.73 ± 2.57, 83.59 ± 29.28, 24.22 ± 6.22, and 132.27 ± 78.32 on T1WI, T2WI, FLAIR, and DWI, respectively. The absolute values of CNRs of lesions on DWI were significantly greater than those on other sequences. Conclusion DWI appears to be more sensitive in detecting EV71 encephalitis than conventional MRI sequences. This capability may improve the accuracy in diagnosing EV71 encephalitis, especially at the early stage.