bluuebunny/crossref_metadata_2025_split huggingface dataset:
Luminescence and decay properties of the 1D2 level of Pr3+-doped YPO4
Authors: Collins J. , Bettinelli M. , Di Bartolo B. 
Published: March 2011

This investigation reports on the spectroscopic properties of trivalent Pr in YPO4. In particular, we show how the luminescence from the 1D2 level depends on the polarization of the emission and on the temperature of the sample. We also report on the decay kinetics of the 1D2 level, which show the lifetime decreasing as temperature is increased. Our observed lifetime of 440 µs is at low temperature and is significantly longer than that reported by other workers. We explain the temperature dependence of the 1D2 emission by considering the population redistribution in the 1D2 level, without invoking the existence of multiphonon relaxation. Finally, we estimate the radiative decay rates of individual crystal field levels within the 1D2 manifold.
Effects of different dietary omega-6/3 polyunsaturated fatty acids ratios on infarct size and the limbic system after myocardial infarction
Authors: Rondeau I. , Picard S. , Bah T. M. , Roy L. , Godbout R. , Rousseau G. 
Published: March 2011

Changes in dietary omega-6/3 polyunsaturated fatty acids (PUFA) ratios affect anti- and proinflammatory equilibrium. As reperfused myocardial infarction (MI) is an inflammatory pathology that alters the cell integrity of the myocardium but also of other tissues, such as the hippocampus and amygdala, attenuation of the inflammation could be helpful in maintaining cell integrity after MI. Therefore, we hypothesized that a decrease in the dietary omega-6/3 PUFA ratio, without altering the diet content in total fat, proteins, or carbohydrates, will result in a reduction of infarct size and a diminution of postreperfusion apoptosis observed in the amygdala and hippocampus. Male Sprague–Dawley rats were fed 1 of 3 diets containing different omega-6/3 PUFA ratios for 2 weeks (5:1; 1:1; 1:5). Then, myocardial ischemia was induced by left anterior descending coronary artery occlusion for 40 min, followed by reperfusion. Cardioprotective mechanisms were studied in the myocardium at 15 min of reperfusion, along with myocardial infarct size after 24 h of reperfusion. Apoptosis was evaluated in the hippocampus and the amygdala. We found that infarct size was significantly reduced by 32% in groups 1:5 and 1:1 vs. group 5:1. Akt activity was higher in groups 1:5 and 1:1 compared with group 5:1. Caspase-3 enzymatic activity doubled in area CA1 and the dentate gyrus (DG) in group 5:1 compared with groups 1:1 and 1:5. In addition, caspase-8 enzymatic activity was increased in the DG at 24 h, and caspase-9 was enhanced in CA1 at 24 h in group 5:1 vs. groups 1:1 and 1:5. These results demonstrate that the increase in the dietary omega-3 PUFA, at the expense of omega-6 PUFA, reduces infarct size and helps to inhibit apoptosis in the limbic system after MI.
Adenosine A2 receptors are involved in the activation of ATP-sensitive K+ currents during metabolic inhibition in guinea pig ventricular myocytes
Authors: Pan Sheng-Jun , Li Li-Rong 
Published: March 2011

It has been hypothesized that an interaction among adenosine A1 receptors, protein kinase C (PKC) activation, and ATP-sensitive potassium channels (KATP) mediates ischemic preconditioning in experiments on different animal species. The purpose of this study was to determine if activation of KATP is functionally coupled to A1 receptors and (or) PKC activation during metabolic inhibition (MI) in guinea pig ventricular myocytes. Perforated-patch using nystatin and conventional whole-cell recording methods were used to observe the effects of adenosine and adenosine-receptor antagonists on the activation of KATP currents during MI induced by application of 2,4-dinitrophenol (DNP) and 2-deoxyglucose (2DG) without glucose, in the presence or absence of a PKC activator, phorbol 12-myristate 13-acetate (PMA). Adenosine accelerated the time course activation of KATP currents during MI under the intact intracellular condition or dialyzed condition with l mmol/L ATP in the pipette solution. The accelerated effect of adenosine activation of KATP under MI was not reversed by a nonselective Al adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (SPT), or a specific Al adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). However, the adenosine A2 receptor antagonist alloxazine reversed the time course activation of the KATP current under MI. An adenylate cyclase activator, forskolin, did not further abbreviate the time course activation of KATP with or without adenosine. Application of a PKC blocker, chelerythrine, reversed the time course activation of KATP by adenosine under MI. In addition, pretreatment with a PKC activator, PMA, had similar effects to adenosine, while adenosine did not further shorten the time required for activation of KATP currents during MI with PMA pretreatment. There is no direct evidence of activation of KATP currents by adenosine A1 receptor during metabolic inhibition under our experimental condition. However, adenosine A2 receptor activation is involved in the KATP channel activation in the guinea pig ventricular myocytes, of which effect is not mediated through the increase in intracellular cAMP. Adenosine seems to interact with PKC activation to open KATP during MI, but a possible link between the adenosine A2 receptor and PKC activation in this process needs further elucidation.
Metformin Decreases the Dose of Chemotherapy for Prolonging Tumor Remission in Mouse Xenografts Involving Multiple Cancer Cell Types
Authors: Iliopoulos Dimitrios , Hirsch Heather A. , Struhl Kevin 
Published: March 2011

Abstract
Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients. Cancer Res; 71(9); 3196–201. ©2011 AACR.
Novel Theranostic Opportunities Offered by Characterization of Altered Membrane Lipid Metabolism in Breast Cancer Progression
Authors: Hilvo Mika , Denkert Carsten , Lehtinen Laura , Müller Berit , Brockmöller Scarlet , Seppänen-Laakso Tuulikki , Budczies Jan , Bucher Elmar , Yetukuri Laxman , Castillo Sandra , Berg Emilia , Nygren Heli , Sysi-Aho Marko , Griffin Julian L. , Fiehn Oliver , Loibl Sibylle , Richter-Ehrenstein Christiane , Radke Cornelia , Hyötyläinen Tuulia , Kallioniemi Olli , Iljin Kristiina , Orešič Matej 
Published: March 2011

Abstract
Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor–negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid–like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element–binding protein cleavage–activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone–responsive protein)] indicated that silencing of multiple lipid metabolism–regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment. Cancer Res; 71(9); 3236–45. ©2011 AACR.
Genz-644282, a Novel Non-Camptothecin Topoisomerase I Inhibitor for Cancer Treatment
Authors: Kurtzberg Leslie S. , Roth Stephanie , Krumbholz Roy , Crawford Jennifer , Bormann Christy , Dunham Sarah , Yao Min , Rouleau Cecile , Bagley Rebecca G. , Yu Xian-Jie , Wang Fei , Schmid Steven M. , LaVoie Edmond J. , Teicher Beverly A. 
Published: March 2011

Abstract
Purpose: Genz-644282 [8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one] has emerged as a promising candidate for antitumor agents. This report describes the bone marrow colony-forming unit, granulocyte macrophage (CFU-GM) and tumor cell CFU activity of topoisomerase I (Top1) inhibitors, such as Genz-644282, topotecan, irinotecan/SN-38, and ARC-111, and examines their activity in several human tumor xenograft models.
Experimental Design: Colony-forming assays were conducted with mouse and human bone marrow and eight human tumor cell lines. In addition, 29 human tumor cell lines representing a range of histology and potential resistance mechanisms were assayed for sensitivity to Genz-644282 in a 72-hour exposure assay. The efficacy of Genz-644282 was compared with standard anticancer drugs (i.e., irinotecan, docetaxel, and dacarbazine) in human tumor xenografts of colon cancer, renal cell carcinoma, non–small cell lung cancer, and melanoma.
Results: Human bone marrow CFU-GM was more sensitive to the Top1 inhibitors than was mouse bone marrow CFU-GM. The ratio of mouse to human IC90 values was more than 10 for the camptothecins and less than 10 for Genz-644282, which had more potency as a cytotoxic agent toward human tumor cells in culture than the camptothecins in the colony-forming and 72-hour proliferation assays. Genz-644282 has superior or equal antitumor activity in the human tumor xenografts than the standard drug comparators.
Conclusions: On the basis of preclinical activity and safety, Genz-644282 was selected for development and is currently undergoing phase 1 clinical trial. Clin Cancer Res; 17(9); 2777–87. ©2011 AACR.
Ribavirin Treatment Effects on Breast Cancers Overexpressing eIF4E, a Biomarker with Prognostic Specificity for Luminal B-Type Breast Cancer
Authors: Pettersson Filippa , Yau Christina , Dobocan Monica C. , Culjkovic-Kraljacic Biljana , Retrouvay Hélène , Puckett Rachel , Flores Ludmila M. , Krop Ian E. , Rousseau Caroline , Cocolakis Eftihia , Borden Katherine L. B. , Benz Christopher C. , Miller Wilson H. 
Published: March 2011

Abstract
Purpose: We have evaluated the eukaryotic translation initiation factor 4E (eIF4E) as a potential biomarker and therapeutic target in breast cancer. eIF4E facilitates nuclear export and translation of specific, growth-stimulatory mRNAs and is frequently overexpressed in cancer.
Experimental Design: Breast cancer cells were treated with ribavirin, an inhibitor of eIF4E, and effects on cell proliferation and on known mRNA targets of eIF4E were determined. eIF4E expression was assessed, at the mRNA and protein level, in breast cancer cell lines and in skin biopsies from patients with metastatic disease. Additionally, pooled microarray data from 621 adjuvant untreated, node-negative breast cancers were analyzed for eIF4E expression levels and correlation with distant metastasis–free survival (DMFS), overall and within each intrinsic breast cancer subtype.
Results: At clinically relevant concentrations, ribavirin reduced cell proliferation and suppressed clonogenic potential, correlating with reduced mRNA export and protein expression of important eIF4E targets. This effect was suppressed by knockdown of eIF4E. Although eIF4E expression is elevated in all breast cancer cell lines, variability in ribavirin responsiveness was observed, indicating that other factors contribute to an eIF4E-dependent phenotype. Assessment of the prognostic value of high eIF4E mRNA in patient tumors found that significant discrimination between good and poor outcome groups was observed only in luminal B cases, suggesting that a specific molecular profile may predict response to eIF4E-targeted therapy.
Conclusions: Inhibition of eIF4E is a potential breast cancer therapeutic strategy that may be especially promising against specific molecular subtypes and in metastatic as well as primary tumors. Clin Cancer Res; 17(9); 2874–84. ©2011 AACR.
mTOR Complex 2 Activation by Reconstituted High-Density Lipoprotein Prevents Senescence in Circulating Angiogenic Cells
Authors: Guo Xianrong , Yu Miao , Kang Xiaomin , Yin Hongchao 
Published: March 2011

Objective—
Circulating angiogenic cells (CACs) participate in neovascularization and arterial repair. Although high-density lipoprotein (HDL) is known to enhance the functional activity of CACs, the mechanisms underlying this regulation are poorly understood. Here, we examined the mechanism(s) by which reconstituted HDL (rHDL) affects CAC senescence.

Methods and Results—
CACs isolated from human peripheral blood and treated with rHDL displayed reduced senescence, as measured by acidic β-galactosidase staining. This protective effect was blocked by the mammalian target of rapamycin (mTOR) inhibitor (rapamycin). According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor–dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity. Suppression of rictor gene expression with a small interfering RNA blocked mTOR-rictor complex formation and Akt activation. The suppression also abolished the rHDL-induced inhibition of CAC senescence and promotion of nuclear telomerase activity. Treatment of aged mice with rHDL attenuated spleen-derived CAC senescence. In CACs isolated from rHDL-treated aged mice, the phosphorylated mTOR and Akt levels were significantly enhanced.

Conclusion—
rHDL stimulates sustained mTOR phosphorylation and mTOR-rictor complex formation and inhibits senescence onset in CACs through mTOR complex 2 pathway activation.
Botulinum Toxin for the Upper Limb After Stroke (BoTULS) Trial
Authors: Shaw Lisa C. , Price Christopher I.M. , van Wijck Frederike M.J. , Shackley Phil , Steen Nick , Barnes Michael P. , Ford Gary A. , Graham Laura A. , Rodgers Helen 
Published: March 2011

Background and Purpose—
Botulinum toxin is increasingly used to treat upper limb spasticity due to stroke, but its impact on arm function is unclear. We evaluated botulinum toxin for upper limb spasticity and function poststroke.

Methods—
Three hundred thirty-three patients with stroke with upper limb spasticity and reduced arm function participated in a multicenter randomized controlled trial. The intervention group received botulinum toxin type A injection(s) plus a 4-week therapy program. The control group received the therapy program alone. Repeat injection(s) and therapy were available at 3, 6, and 9 months. The primary outcome was upper limb function at 1 month (Action Research Arm Test). Secondary outcomes included measures of impairment, activity limitation, and pain at 1, 3, and 12 months. Outcome assessments were blinded and analysis was by intention to treat.

Results—

There was no significant difference in achievement of improved arm function (Action Research Arm Test) at 1 month (intervention group: 42 of 167 [25.1%], control group 30 of 154 [19.5%];
P
=0.232). Significant differences in favor of the intervention group were seen in muscle tone at 1 month; upper limb strength at 3 months; basic arm functional tasks (hand hygiene, facilitation of dressing) at 1, 3, and 12 months; and pain at 12 months.

Conclusions—
Botulinum toxin type A is unlikely to be useful for improving active upper limb function (eg, reaching and grasping) in the majority of patients with spasticity after stroke, but it may improve basic upper limb tasks (hand hygiene, facilitation of dressing) and pain.
Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage
Authors: Fujiwara Norio , Mandeville Emiri T. , Geng Xiaokun , Luo Yumin , Arai Ken , Wang Xiaoying , Ji Xunming , Singhal Aneesh B. , Lo Eng H. 
Published: March 2011

Background and Purpose—
Normobaric oxygen (NBO) therapy may be neuroprotective in acute ischemic stroke. However, how NBO may affect intracerebral hemorrhage is unclear. We tested NBO in a rat model of striatal intracerebral hemorrhage.

Methods—
Intracerebral hemorrhage was induced by stereotactic injection of collagenase Type VII (0.5 U) into the right striatum of male Sprague-Dawley rats. One hour later, rats were randomized into controls (n=13) versus NBO treatment (n=13). NBO was applied for 2 hours. Hemorrhagic blood volume, brain water content, and neurological outcomes (forelimb placement test, forelimb asymmetry, neuroscore) were quantified at 72 hours. Experiments were repeated in a second independent laboratory to assess reproducibility in neurological outcomes (n=10 per group).

Results—

NBO did not worsen hemorrhage severity or brain edema. There were no significant differences in hemorrhagic blood volumes (control, 6.4±0.9 μL versus NBO, 7.0±2.1 μL;
P
=0.18) or brain water content (control, 81.9%±1.1% versus NBO, 81.6%±0.5%;
P
=0.58). NBO did not affect any of the neurological outcome tests in the primary or secondary studies.

Conclusions—
NBO therapy may not worsen outcomes in intracerebral hemorrhage.
Pretreatment Diffusion-Weighted Imaging Lesion Volume Predicts Favorable Outcome After Intravenous Thrombolysis With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke
Authors: Kruetzelmann Anna , Köhrmann Martin , Sobesky Jan , Cheng Bastian , Rosenkranz Michael , Röther Joachim , Schellinger Peter D. , Ringleb Peter , Gerloff Christian , Fiehler Jens , Thomalla Götz 
Published: March 2011

Background and Purpose—
Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging–selected, acute stroke patients treated with IV-tPA.

Methods—
We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging–based IV-tPA treatment initiated ≤6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome.

Results—

Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years;
P
=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15;
P
<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL;
P
=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (
P
=0.017), National Institutes of Health Stroke Scale score on admission (
P
<0.001), and diffusion-weighted imaging lesion volume (
P
=0.047) were identified as independent predictors of favorable outcome.

Conclusions—
A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.
Statin Treatment and Functional Outcome After Ischemic Stroke
Authors: Biffi Alessandro , Devan William J. , Anderson Christopher D. , Cortellini Lynelle , Furie Karen L. , Rosand Jonathan , Rost Natalia S. 
Published: March 2011

Background and Purpose—
Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data.

Methods—
We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow-Day test.

Results—

Meta-analysis of all available data identified an association between prestroke statin use and improved functional outcome (OR, 1.62; 95% CI, 1.39 to 1.88), but we uncovered evidence of publication bias. The effect of statin use on functional outcome was found to be larger for small vessel strokes compared with other subtypes (Breslow-Day
P
=0.008).

Conclusions—
Antecedent use of statins is associated with improved outcome in patients with acute ischemic stroke. This association appears to be stronger in patients with small vessel stroke subtype. However, evidence of publication bias in the existing literature suggests these findings should be interpreted with caution.