bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect ofN-acetylcysteine on the antitumor activity of ifosfamide
Authors: Chen Nancy , Hanly Lauren , Rieder Michael , Yeger Herman , Koren Gideon 
Published: June 2011

Ifosfamide-induced nephrotoxicity is a serious adverse effect in children undergoing chemotherapy. Our previous cell and rodent models have shown that the antioxidant N-acetylcysteine (NAC), used extensively as an antidote for acetaminophen poisoning, protects renal tubular cells from ifosfamide-induced nephrotoxicity at a clinically relevant concentration. For the use of NAC to be clinically relevant in preventing ifosfamide nephrotoxicity, we must ensure there is no effect of NAC on the antitumor activity of ifosfamide. Common pediatric tumors that are sensitive to ifosfamide, human neuroblastoma SK-N-BE(2) and rhabdomyosarcoma RD114-B cells, received either no pretreatment or pretreatment with 400 µmol/L of NAC, followed by concurrent treatment with NAC and either ifosfamide or the active agent ifosfamide mustard. Ifosfamide mustard significantly decreased the growth of both cancer cell lines in a dose-dependent manner (p < 0.001). The different combined treatments of NAC alone, sodium 2-mercaptoethanesulfonate alone, or NAC plus sodium 2-mercaptoethanesulfonate did not significantly interfere with the tumor cytotoxic effect of ifosfamide mustard. These observations suggest that NAC may improve the risk/benefit ratio of ifosfamide by decreasing ifosfamide-induced nephrotoxicity without interfering with its antitumor effect in cancer cells clinically treated with ifosfamide.
Response of Bicknell’s Thrush (Catharus bicknelli) to boreal silviculture and forest stand edges: a radio-tracking study
Authors: Aubry Yves , Desrochers André , Seutin Gilles 
Published: June 2011

Society and regulatory regimes require that biodiversity conservation, and especially the protection of threatened species, be integrated into land-use planning and management. Bicknell’s Thrush ( Catharus bicknelli (Ridgway, 1882)) is an at-risk species breeding in montane balsam fir ( Abies balsamea (L.) P. Mill.) dominated areas of northeastern North America. We monitored 34 individual Bicknell’s Thrushes by radio telemetry in southern Quebec to examine the size, location, and habitat composition of their home ranges in areas where clear-cutting and precommercial thinning occurred. Home ranges of Bicknell’s Thrush comprised more dense balsam fir stands and fewer thinned stands than available. Within home ranges, thrushes were found more frequently in unthinned balsam fir stands than in thinned stands, and they did not avoid edges. In fact, they were found disproportionately near edges of recently thinned stands. We conclude that Bicknell’s Thrushes may coexist with forest management practices that maintain a landscape mosaic dominated by dense balsam fir patches interspersed with thinned stands.
Phylogenetic history of mustelid fauna in Taiwan inferred from mitochondrial genetic loci
Authors: Hosoda T. , Sato J.J. , Lin L.-K. , Chen Y.-J. , Harada M. , Suzuki H. 
Published: June 2011

Phylogenetic relationships among species of the family Mustelidae were examined using the combined nucleotide sequences of the three mitochondrial genetic loci (cytochrome b (MT-CYB; 1140 bp), NADH dehydrogenase subunit 2 (MT-ND2; 1044 bp), and displacement loop (MT-DLOOP; 540 bp)), with special emphasis on the phylogenetic history of four Taiwanese mustelid species: Martes flavigula (Boddaert, 1785), Melogale moschata (Gray, 1831), Mustela nivalis L., 1766, and Mustela sibirica Pallas, 1773. Maximum likelihood phylogenetic analysis of the combined sequences of the mitochondrial genetic loci produced a topology largely congruent with that of previous studies at the species level. Analyses of intraspecific genetic variations revealed two Melogale moschata individuals from Taiwan and Vietnam that showed genetic distances comparable with interspecific variations within the mustelid lineages. Furthermore, Mustela nivalis, recently discovered in Taiwan, was not as genetically differentiated from other continental conspecific individuals as a previous morphological survey suggested. Divergence time estimations for the mustelid lineages of Taiwan and the Eurasian continent by the Bayesian relaxed molecular clock approach suggested multiple colonization of Taiwan by mustelids from the continent during the Pleistocene, creating a hierarchical pattern of endemism based on the differential isolation history of the mustelid species in Taiwan.
High ALK Receptor Tyrosine Kinase Expression Supersedes ALK Mutation as a Determining Factor of an Unfavorable Phenotype in Primary Neuroblastoma
Authors: Schulte Johannes H. , Bachmann Hagen S. , Brockmeyer Bent , DePreter Katleen , Oberthür André , Ackermann Sandra , Kahlert Yvonne , Pajtler Kristian , Theissen Jessica , Westermann Frank , Vandesompele Jo , Speleman Frank , Berthold Frank , Eggert Angelika , Brors Benedikt , Hero Barbara , Schramm Alexander , Fischer Matthias 
Published: June 2011

Abstract
Purpose: Genomic alterations of the anaplastic lymphoma kinase (ALK) gene have been postulated to contribute to neuroblastoma pathogenesis. This study aimed to determine the interrelation of ALK mutations, ALK expression levels, and clinical phenotype in primary neuroblastoma.
Experimental Design: The genomic ALK status and global gene expression patterns were examined in 263 primary neuroblastomas. Allele-specific ALK expression was determined by cDNA cloning and sequencing. Associations of genomic ALK alterations and ALK expression levels with clinical phenotypes and transcriptomic profiles were compared.
Results: Nonsynonymous point mutations of ALK were detected in 21 of 263 neuroblastomas (8%). Tumors with ALK mutations exhibited about 2-fold elevated median ALK mRNA levels in comparison with tumors with wild-type (WT) ALK. Unexpectedly, the WT allele was preferentially expressed in 12 of 21 mutated tumors. Whereas survival of patients with ALK mutated tumors was significantly worse as compared with the entire cohort of WT ALK patients, it was similarly poor in patients with WT ALK tumors in which ALK expression was as high as in ALK mutated neuroblastomas. Global gene expression patterns of tumors with ALK mutations or with high-level WT ALK expression were highly similar, and suggested that ALK may be involved in cellular proliferation in primary neuroblastoma.
Conclusions: Primary neuroblastomas with mutated ALK exhibit high ALK expression levels and strongly resemble neuroblastomas with elevated WT ALK expression levels in both their clinical and molecular phenotypes. These data suggest that high levels of mutated and WT ALK mediate similar molecular functions that may contribute to a malignant phenotype in primary neuroblastoma. Clin Cancer Res; 17(15); 5082–92. ©2011 AACR.
Molecular Target Characterization and Antimyeloma Activity of the Novel, Insulin-like Growth Factor 1 Receptor Inhibitor, GTx-134
Authors: Liang Sheng-Ben , Yang Xiu-Zhi , Trieu Young , Li Zhihua , Zive Jessica , Leung-Hagesteijn Chungyee , Wei Ellen , Zozulya Sergey , Coss Christopher C. , Dalton James T. , Fantus Ivan George , Trudel Suzanne 
Published: June 2011

Abstract
Purpose: Therapeutic strategies that target insulin-like growth factor 1 receptor (IGF-1R) hold promise in a wide variety of cancers including multiple myeloma (MM). In this study, we describe GTx-134, a novel small-molecule inhibitor of IGF-1R and insulin receptor (IR) and characterized its antitumor activity in preclinical models of MM.
Experimental Design: The activity of GTx-134 as a single agent and in combination was tested in MM cell lines and primary patient samples. Downstream effector proteins and correlation with apoptosis was evaluated. Cytotoxcity in bone marrow stroma coculture experiments was assessed. Finally, the in vivo efficacy was evaluated in a human myeloma xenograft model.
Results: GTx-134 inhibited the growth of 10 of 14 myeloma cell lines (&lt;5 μmol/L) and induced apoptosis. Sensitivity to GTx-134 correlated with IGF-1R signal inhibition. Expression of MDR-1 and CD45 were associated with resistance to GTx-134. Coculture with insulin-growth factor-1 (IGF-1) or adherence to bone marrow stroma conferred modest resistance, but did not overcome GTx-134–induced cytotoxicity. GTx-134 showed in vitro synergies when combined with dexamethasone or lenalidomide. Further, GTx-134 enhanced the activity of PD173074, a fibroblast growth factor receptor 3 (FGFR3) inhibitor, against t(4;14) myeloma cells. Therapeutic efficacy of GTx-134 was shown against primary cells and xenograft tumors. Although dysregulation of glucose homeostasis was observed in GTx-134–treated mice, impairment of glucose tolerance was modest.
Conclusions: These studies support the potential therapeutic efficacy of GTx-134 in MM. Further, they provide a rationale for clinical application in combination with established antimyeloma treatments and novel targeted therapies. Clin Cancer Res; 17(14); 4693–704. ©2011 AACR.
Is Cytomegalovirus a Therapeutic Target in Glioblastoma?
Authors: Sampson John H. , Mitchell Duane A. 
Published: June 2011

Abstract
Several investigators have now demonstrated the expression of genes unique to cytomegalovirus (CMV) in malignant gliomas. Many of these genes promote oncogenesis, alter tumor microenvironment, and serve as immunologic targets. Is the level of CMV infection within tumor cells sufficient to drive important oncogenic or immunosuppressive processes? Can CMV serve as a target for therapeutic intervention? Clin Cancer Res; 17(14); 4619–21. ©2011 AACR.
HSP70 Inhibition by the Small-Molecule 2-Phenylethynesulfonamide Impairs Protein Clearance Pathways in Tumor Cells
Authors: Leu J. I-Ju , Pimkina Julia , Pandey Pooja , Murphy Maureen E. , George Donna L. 
Published: June 2011

AbstractThe evolutionarily conserved stress-inducible HSP70 molecular chaperone plays a central role in maintaining protein quality control in response to various forms of stress. Constitutively elevated HSP70 expression is a characteristic of many tumor cells and contributes to their survival. We recently identified the small-molecule 2-phenylethyenesulfonamide (PES) as a novel HSP70 inhibitor. Here, we present evidence that PES-mediated inhibition of HSP70 family proteins in tumor cells results in an impairment of the two major protein degradation systems, namely, the autophagy-lysosome system and the proteasome pathway. HSP70 family proteins work closely with the HSP90 molecular chaperone to maintain the stability and activities of their many client proteins, and PES causes a disruption in the HSP70/HSP90 chaperone system. As a consequence, many cellular proteins, including known HSP70/HSP90 substrates, accumulate in detergent-insoluble cell fractions, indicative of aggregation and functional inactivation. Overall, PES simultaneously disrupts several cancer critical survival pathways, supporting the idea of targeting HSP70 as a potential approach for cancer therapeutics. Mol Cancer Res; 9(7); 936–47. ©2011 AACR.
Nuclear Morphometry Identifies a Distinct Aggressive Cellular Phenotype in Cutaneous Squamous Cell Carcinoma
Authors: Glazer Evan S. , Bartels Peter H. , Prasad Anil R. , Yozwiak Michael L. , Bartels Hubert G. , Einspahr Janine G. , Alberts David S. , Krouse Robert S. 
Published: June 2011

Abstract
By identifying aggressive cutaneous squamous cell carcinoma (cSCC) in patients who are at high risk for recurrences or second primaries after resection, intensive surveillance and therapy may decrease morbidity and mortality. We investigated the role of nuclear morphometry (karyometry) in differentiating between aggressive and nonaggressive cSCC. We retrospectively analyzed cSCC lesions from 40 male patients. Twenty-two patients had evidence of aggressive cSCC (local/regional recurrence or a second primary cSCC), and 18 patients were identified with similar ages and sites of disease as control patients with nonaggressive cSCC (no evidence of recurrence, metastasis, or second primary). We carried out karyometric analysis to identify nuclear features that discriminate between aggressive and nonaggressive cSCC nuclei. We used statistically significant differences (Kruskal–Wallis test, P &lt; 0.0001) to compose a quantitative aggressive classification score (proportion of aggressive nuclei from 0% to 100%). For comparisons, we used Fisher's exact test or Student's t test. The mean age was 79 ± 7 years for aggressive cSCC and 80 ± 9 years for nonaggressive cSCC (P = 0.66). We analyzed a mean of 96 nuclei in each group. The mean classification score for aggressive cSCC was significantly higher (69% ± 6%) than for nonaggressive cSCC (28% ± 5%, P = 0.00002). Overall, the classification score accurately categorized 80% of our patients (P = 0.0004). In most patients, karyometry differentiated between aggressive and nonaggressive cSCC. We found that classification scores, which provide information on individual lesions, could be used for risk stratification. Cancer Prev Res; 4(11); 1770–7. ©2011 AACR.
Outcome of Patients With ≥70% Symptomatic Intracranial Stenosis After Wingspan Stenting
Authors: Jiang Wei-Jian , Yu Wengui , Du Bin , Gao Feng , Cui Li-Ying 
Published: June 2011

Background and Purpose—
There were limited data on the long-term outcome of patients with symptomatic intracranial atherosclerotic stenosis ≥70% after Wingspan stenting. Using our Wingspan cohort data and the data from the Warfarin and Aspirin for Symptomatic Intracranial Atherosclerotic Disease (WASID) as a historical control, we tested the hypothesis that stenting provided no benefit over antithrombotic therapy alone for these high-risk patients.

Methods—
Between January 2007 and February 2009, 100 consecutive patients with intracranial atherosclerotic stenosis ≥70% and symptoms within 90 days were enrolled into this prospective single-center Wingspan cohort study and followed up until the end of February 2010. Stenosis was measured per the WASID criteria. One-year risk of primary end point (any stroke or death within 30 days and ipsilateral ischemic stroke afterward) was compared with that of ipsilateral ischemic stroke in the WASID patients with ≥70% stenosis.

Results—

The stent placement success rate was 99%. All patients but 1 had clinical follow-up of ≥12 months. During a mean follow-up of 1.8 years, 9 patients developed primary end point events (5 within 30 days and 4 afterward). The 1-year risk of the outcome events was lower than that in similar WASID patients: 7.3% (95% CI, 2.0% to 12.5%) versus 18% (95% CI, 13% to 24%;
P
<0.05).

Conclusions—
The clinical outcome of Wingspan stenting for high-risk intracranial atherosclerotic stenosis patients in this high-volume center study compares favorably with that of antithrombotic therapy alone. A randomized trial comparing medical therapy alone with medical therapy plus Wingspan stenting, conducted at high-volume centers, is needed to confirm the stenting benefit.
Improved Cerebral Vasomotor Reactivity After Exercise Training in Hemiparetic Stroke Survivors
Authors: Ivey Frederick M. , Ryan Alice S. , Hafer-Macko Charlene E. , Macko Richard F. 
Published: June 2011

Background and Purpose—
Animal studies provide strong evidence that aerobic exercise training positively influences cerebral blood flow, but no human studies support the use of exercise for improving cerebral hemodynamics. This randomized study in stroke survivors assessed the effects of treadmill aerobic exercise training (TM) on cerebral blood flow parameters compared to a control intervention of nonaerobic stretching.

Methods—

Thirty-eight participants (19 in TM group and 19 in control group) with remote stroke (>6 months) and mild to moderate gait deficits completed middle cerebral artery blood flow velocity measurements by transcranial Doppler ultrasonography before and after a 6-month intervention period. Middle cerebral artery blood flow velocity was assessed bilaterally during normocapnia and hypercapnia (6% CO
2
). Cerebral vasomotor reactivity (cVMR) was calculated as percent change in middle cerebral artery blood flow velocity from normocapnia to hypercapnia (cVMR percent) and as an index correcting percent change for absolute increase in end tidal CO
2
(cVMR index).

Results—

The TM group had significantly larger improvements than did controls for both ipsilesional and contralesional cVMR index (
P
≤0.05) and contralesional cVMR percent (
P
≤0.01). Statin users in the TM group (n=10) had higher baseline cVMR and lower training-induced cVMR change, indicating that cVMR change among those not using statins (n=9) primarily accounted for the between-group effects. There was a 19% increase in V
o
2
peak for the TM group compared to a 4% decrease in the control group (
P
<0.01), and peak fitness change correlated with cVMR change (
r
=0.55;
P
<0.05).

Conclusions—
Our data provide the first evidence to our knowledge of exercise-induced cVMR improvements in stroke survivors, implying a protective mechanism against recurrent stroke and other brain-related disorders. Statin use appears to regulate cVMR and the cVMR training response.
Short-Term Anomia Training and Electrical Brain Stimulation
Authors: Flöel Agnes , Meinzer Marcus , Kirstein Robert , Nijhof Sarah , Deppe Michael , Knecht Stefan , Breitenstein Caterina 
Published: June 2011

Background and Purpose—
Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy.

Methods—
In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulation over the right temporo-parietal cortex would improve the success of short-term high-frequency anomia training. Twelve chronic poststroke aphasia patients were studied. Naming outcome was assessed after training and 2 weeks later.

Results—
All training conditions led to a significant increase in naming ability, which was retained for at least 2 weeks after the end of the training. Application of anodal transcranial direct current stimulation significantly enhanced the overall training effect compared to sham stimulation. Baseline naming ability significantly predicted anodal transcranial direct current stimulation effects.

Conclusions—
Anodal transcranial direct current stimulation applied over the nonlanguage dominant hemisphere can enhance language training outcome in chronic aphasia.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov/
. Unique identifier: NCT00822068.
US Wingspan Registry
Authors: Fiorella David J. , Turk Aquilla S. , Levy Elad I. , Pride G. Lee , Woo Henry H. , Albuquerque Felipe C. , Welch Babu G. , Niemann David B. , Aagaard-Kienitz Beverly , Rasmussen Peter A. , Hopkins L. Nelson , Masaryk Thomas J. , McDougall Cameron G. 
Published: June 2011

Background and Purpose—
The purpose of this study is to present 12-month follow-up results for a series of patients undergoing percutaneous transluminal angioplasty and stenting with the Gateway-Wingspan stenting system (Boston Scientific) for the treatment of symptomatic intracranial atherostenosis.

Methods—
Clinical and angiographic follow-up results were recorded for patients from 5 participating institutions. Primary end points were stroke or death within 30 days of the stenting procedure or ipsilateral stroke after 30 days.

Results—
During a 21-month study period, 158 patients with 168 intracranial atherostenotic lesions (50% to 99%) were treated with the Gateway-Wingspan system. The average follow-up duration was 14.2 months with 143 patients having at least 3 months of clinical follow-up and 110 having at least 12 months. The cumulative rate of the primary end point was 15.7% for all patients and 13.9% for patients with high-grade (70% to 99%) stenosis. Of 13 ipsilateral strokes occurring after 30 days, 3 resulted in death. Of these strokes, 76.9% (10 of 13) occurred within the first 6 months of the stenting procedure and no events were recorded after 12 months. An additional 9 patients experienced ipsilateral transient ischemic attack after 30 days. Most postprocedural events (86%) could be attributed to interruption of antiplatelet medications (n=6), in-stent restenosis (n=12), or both (n=1). In 3 patients, the events were of uncertain etiology.

Conclusions—
After successful Wingspan percutaneous transluminal angioplasty and stenting, some patients continued to experience ipsilateral ischemic events. Most of these ischemic events occurred within 6 months of the procedure and were associated with the interruption of antiplatelet therapy or in-stent restenosis.
Predictions of 2010’s Tropical Cyclones Using the GFS and Ensemble-Based Data Assimilation Methods
Authors: Hamill Thomas M. , Whitaker Jeffrey S. , Kleist Daryl T. , Fiorino Michael , Benjamin Stanley G. 
Published: June 2011

Abstract
Experimental ensemble predictions of tropical cyclone (TC) tracks from the ensemble Kalman filter (EnKF) using the Global Forecast System (GFS) model were recently validated for the 2009 Northern Hemisphere hurricane season by Hamill et al. A similar suite of tests is described here for the 2010 season. Two major changes were made this season: 1) a reduction in the resolution of the GFS model, from 2009’s T384L64 (~31 km at 25°N) to 2010’s T254L64 (~47 km at 25°N), and some changes in model physics; and 2) the addition of a limited test of deterministic forecasts initialized from a hybrid three-dimensional variational data assimilation (3D-Var)/EnKF method.
The GFS/EnKF ensembles continued to produce reduced track errors relative to operational ensemble forecasts created by the National Centers for Environmental Prediction (NCEP), the Met Office (UKMO), and the Canadian Meteorological Centre (CMC). The GFS/EnKF was not uniformly as skillful as the European Centre for Medium-Range Weather Forecasts (ECMWF) ensemble prediction system. GFS/EnKF track forecasts had slightly higher error than ECMWF at longer leads, especially in the western North Pacific, and exhibited poorer calibration between spread and error than in 2009, perhaps in part because of lower model resolution. Deterministic forecasts from the hybrid were competitive with deterministic EnKF ensemble-mean forecasts and superior in track error to those initialized from the operational variational algorithm, the Gridpoint Statistical Interpolation (GSI). Pending further successful testing, the National Oceanic and Atmospheric Administration (NOAA) intends to implement the global hybrid system operationally for data assimilation.