bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-88: Transient exposure to low-dose decitabine and azacytidine reprograms cancer cells to produce a prolonged antitumor response
Authors: Tsai Hsing-Chen , Van Neste Leander , Li Huili , Cai Yi , Robert Carine , Shin James J. , Pappou Emmanouil , Yen Ray-Whay , Minn IL , Ahuja Nita , Brock Malcolm V. , Rassool Feyruz V. , Jang Yoon-Young , Sharkis Saul J. , Matsui William , Zahnow Cynthia A. , Baylin Stephen B. 
Published: February 2011

Abstract
Reversing abnormal promoter DNA hypermethylation to induce expression of abnormally silenced genes is an attractive cancer therapeutic strategy. The DNA methylation inhibitors, decitabine (5-aza-2′-deoxycytidine) and azacytidine (5-azacytidine), have proven clinically effective against hematological neoplasms especially with use of low, minimally toxic, doses. While, experimentally, high doses of these drugs induce DNA damage and cytotoxicity, the prolonged time for patient responses does not suggest acute tumor cell lysis. We now separate, for these drugs, cytotoxic effects at high doses from cellular reprogramming effects at low nanomolar doses. These latter subsequently reduce tumorigenicity of human leukemia and solid tumor cells, and for leukemia cells, blunt long term self-renewal. We correlate these effects with sustained, genome wide, promoter DNA de-methylation and gene re-expression, and an anti-tumor reprogramming of multiple central cancer pathways which regulate cell cycle entry, mitosis, proliferation, apoptosis, and dependence upon anaerobic glycolysis. Thus, decitabine and azacytidine represent drugs that can, at low nanomolar doses, simultaneously reverse major cancer pathways each of which are the focus of intense drug targeting efforts. This suggests these drugs are broadly applicable to cancer management.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-88.
Abstract LB-90: Sox17 antagonizes Wnt/ß-catenin signaling pathway in HCC
Authors: Guo Mingzhou , Jia Yan , Yang Yunsheng 
Published: February 2011

Abstract
Background: SRY-box containing gene 17 (Sox17) is a candidate tumor suppressor gene, which is indispensable for the embryonic development by antagonizing the canonical Wnt/ß-catenin signaling pathway. We investigated the function and epigenetic regulation of Sox17 in human hepatocellular carcinoma (HCC).
Methods: Methylation and expression of Sox17 were analyzed in 62 HCC tissues and HCC cell lines by MSP and RT-PCR. Inhibitory effects of Sox17 in Wnt/ß-catenin pathway was detected by IHC and luciferase reporter assay. Function as tumor suppressor gene was tested via colony formation assay.
Results: Methylation of Sox17 promoter region occurs in 82.26% of HCC tissues and is associated with nucleus location of -catenin. Restoration of Sox17 in HepG2 cells inhibits colony formation and ß-catenin/TCF-dependent transcription with the presence of HMG box.
Conclusions: Sox17 negatively regulates canonical Wnt/ß-catenin signaling pathway, and inhibits human HCC cells growth through epigenetic mechanism.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-90.
The Transcription Factor E74-Like Factor Controls Quiescence of Endothelial Cells and Their Resistance to Myeloablative Treatments in Bone Marrow
Authors: Sivina Mariela , Yamada Takeshi , Park Chun Shik , Puppi Monica , Coskun Suleyman , Hirschi Karen , Lacorazza H. Daniel 
Published: February 2011

Objective—
The regeneration of the hematopoietic system in bone marrow after chemotherapy depends on a balance between the quiescence and proliferation of lineage-specific progenitor cells. Even though the vascular network in bone is damaged by cytoablation, the transcriptional control of quiescence in endothelial cells is not well known. In this study, we investigated the role of the transcription factor E74-like factor (ELF4) in the proliferation of endothelial cells in bone marrow.

Methods and Results—

Loss-of-function models were used to study the role of ELF4 in human and murine endothelial cells. ELF4 promotes cell cycle entry by activating cyclin-dependent kinase-4 in human umbilical vein endothelial cells.
Elf4
-null mice exhibited enhanced recovery of bone marrow CD45
−
CD31
+
endothelial cells and sinusoidal blood vessels following administration of 5-fluorouracil.

Conclusion—
Loss of ELF4 leads to increased quiescence in bone marrow endothelial cells by the deregulation of cyclin-dependent kinase-4 expression and to enhanced regeneration of sinusoidal blood vessels.
Plasma Biomarkers That Reflect Determinants of Matrix Composition Identify the Presence of Left Ventricular Hypertrophy and Diastolic Heart Failure
Authors: Zile Michael R. , DeSantis Stacia M. , Baicu Catalin F. , Stroud Robert E. , Thompson Sheila B. , McClure Catherine D. , Mehurg Shannon M. , Spinale Francis G. 
Published: February 2011

Background—
Chronic pressure overload (such as arterial hypertension) may cause left ventricular (LV) remodeling, alterations in cardiac function, and the development of diastolic heart failure. Changes in the composition of the myocardial extracellular matrix may contribute to the development of pressure-overload–induced LV remodeling. We hypothesized that a specific pattern of plasma biomarker expression that reflected changes in these pathophysiological mechanisms would have diagnostic application to identify (1) patients who have development of LV hypertrophy (LVH) and (2) patients with LVH who have development of diastolic heart failure.

Methods and Results—

Plasma concentration of 17 biomarkers (matrix metalloproteinase [MMP]-1, -2, -3, -7, -8, and -9; tissue inhibitors -1, -2, -3, and -4;
N
-terminal propeptide of brain natriuretic peptide (NT-proBNP); cardiotrophin; osteopontin; soluble receptor for advanced glycation end products; collagen I teleopeptide; collagen I NT-proBNP; and collagen III
N
-terminal propetide [PIIINP]), an echocardiogram, and 6-minute hall walk were performed on 241 referent control subjects, 144 patients with LVH but no evidence of heart failure, and 61 patients with LVH and diastolic heart failure (DHF). A plasma multibiomarker panel consisting of increased MMP-7, MMP-9, TIMP-1, PIIINP, and NT-proBNP predicted the presence of LVH with an area under the curve of 0.80. A plasma multibiomarker panel consisting of increased MMP-2, TIMP-4, PIIINP, and decreased MMP-8 predicted the presence of DHF with an area under the curve of 0.79. These multibiomarker panels performed better than any single biomarker including NT-proBNP and better than using clinical covariates alone (area under the curve, 0.73 for LVH and 0.68 for DHF).

Conclusions—
Plasma biomarkers reflecting changes in extracellular matrix fibrillar collagen homeostasis, combined into a multibiomarker panel, have discriminative value in identifying the presence of structural remodeling (LVH) and clinical disease (DHF).
Cardiac Resynchronization Therapy Reduces the Risk of Cardiac Events in Patients With Diabetes Enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)
Authors: Martin David T. , McNitt Scott , Nesto Richard W. , Rutter Martin K. , Moss Arthur J. 
Published: February 2011

Background—
Data are limited regarding whether the presence of diabetes mellitus (DM) influences the benefit of cardiac resynchronization with defibrillator therapy (CRT-D) in heart failure (HF) patients.

Methods and Results—

The effect of CRT-D was evaluated in 1817 patients who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Patients were minimally symptomatic (New York Heart Association class I or II), with ejection fraction ≤0.30 and QRS ≥130 ms. We used Cox regression to determine hazard ratio (HR) of CRT-D versus implantable cardioverter-defibrillator (ICD) therapy for the risk of HF event or death, whichever came first (MADIT-CRT primary end point), in DM (n=552) and non-DM (n=1265) patients. Compared with the non-DM patients, those with DM had more coronary risk factors. During an average follow-up of 2.4 years, DM patients had significantly more primary end point events than non-DM patients (26.6% versus 18%,
P
<0.001). CRT-D was associated with a significant reduction in risk of primary end point in both DM (HR=0.56,
P
<0.001) and non-DM patients (HR=0.67,
P
=0.003). Compared with non-DM patients, CRT-D:ICD HRs in DM patients were lower in the total population, and in subgroups with ischemic cardiomyopathy (0.63 versus 0.64), nonischemic cardiomyopathy (0.39 versus 0.73), and left bundle-branch block (0.36 versus 0.50). There were no significant differences in ventricular remodeling, arrhythmia events, or device-related complications between DM and non-DM patients.

Conclusions—
Patients with diabetes, left ventricular dysfunction, mildly symptomatic HF, and wide QRS complex derive similar benefit from CRT-D compared with patients without diabetes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00180271.
Distinct Effects of Tissue-Type Plasminogen Activator and SMTP-7 on Cerebrovascular Inflammation Following Thrombolytic Reperfusion
Authors: Miyazaki Takuro , Kimura Yuji , Ohata Hisayuki , Hashimoto Terumasa , Shibata Keita , Hasumi Keiji , Honda Kazuo 
Published: February 2011

Background and Purpose—
Thrombolysis therapy using tissue-type plasminogen activator (t-PA) is occasionally accompanied by harmful outcomes, including intracerebral hemorrhage. We have reported that Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a candidate thrombolytic drug, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice; however, little is known regarding whether this agent influences cerebrovascular inflammation following thrombolytic reperfusion. The current study aimed to compare the effects of recombinant t-PA (rt-PA) and SMTP-7 on cerebrovascular inflammation.

Methods—
The impact of rt-PA- and SMTP-7-induced thrombolytic reperfusion on leukocyte dynamics was investigated in a photochemically induced thrombotic middle cerebral artery occlusion (tMCAo) model in mice.

Results—
Both rt-PA and SMTP-7 administration in tMCAo mice (each 10 mg/kg) resulted in thrombolytic reperfusion. The SMTP-7-administered mice showed relatively mild rolling and attachment of leukocytes to the vascular wall in the middle cerebral vein, with weak peroxynitrite reactions and proinflammatory gene expression (IL-1β, TNF-α, ICAM-1, and VCAM-1); thus, a small infarct volume compared with rt-PA-administered mice. In vitro study suggested that rt-PA at 20 μg/mL, but not SMTP-7 at a similar concentration, promotes cytokine-induced reactive oxygen species generation in cultured endothelial cells; moreover, SMTP-7 suppressed cytokine-induced VCAM-1 induction in the cells and leukocyte/ endothelial cell adhesions.

Conclusions—
Relatively mild cerebrovascular inflammation and cerebral infarction in the SMTP-7 mice, compared with in rt-PA mice, is thought to be caused at least in part by direct antioxidative actions of SMTP-7 in ECs.
Home Time Is Extended in Patients With Ischemic Stroke Who Receive Thrombolytic Therapy
Authors: Mishra Nishant K. , Shuaib Ashfaq , Lyden Patrick , Diener Hans-Christoph , Grotta James , Davis Stephen , Davalos Antoni , Ashwood Tim , Wasiewski Warren , Lees Kennedy R. 
Published: February 2011

Background and Purpose—
“Home time” (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or a relative's home versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data.

Methods—
We estimated HT in the Stroke Acute Ischemic NXY Treatment (SAINT) I neuroprotection trial. We compared outcomes between thrombolyzed (T) and nonthrombolyzed comparators (C) using HT and the modified Rankin Scale. For our primary analysis, we adjusted for baseline covariates that significantly influence HT and in sensitivity analyses considered all variables that differed between groups at baseline. We report ordinal logistic regression and analysis of covariance with 95% CIs. We describe the relationship of HT with baseline National Institutes of Health Stroke Scale and its components and with Day 90 modified Rankin Scale and Barthel Index.

Results—

SAINT I included 1699 patients from 23 countries, of whom 28.7% received alteplase. HT correlated with age, baseline severity, alteplase use, side of ischemic lesion, presence of diabetes, and country of patient enrolment (each
P
<0.05). We found an association between use of alteplase with better adjusted outcomes by either measure (OR for extended HT, 1.36; 95% CI, 1.08 to 1.72;
P
=0.009; analysis of covariance
P
=0.007 with a 5.5-day advantage; OR for more favorable modified Rankin Scale, 1.6; 95% CI, 1.28 to 2.00;
P
<0.0001; Cochran-Mantel-Haenszel
P
=0.046). HT was significantly associated with baseline National Institutes of Health Stroke Scale and each component of the National Institutes of Health Stroke Scale except level of consciousness, dysarthria, and ataxia. HT was significantly associated with Day 90 modified Rankin Scale and Barthel Index.

Conclusions—
HT is a responsive measure for use in multinational acute stroke trials. Its inclusion as a complementary outcome is reasonable. We propose treatment effects are adjusted for age, baseline National Institutes of Health Stroke Scale, side of stroke lesion, country of enrollment, and the presence of diabetes.
Restenosis After Carotid Surgery
Authors: van Lammeren Guus W. , Peeters Wouter , de Vries Jean-Paul P.M. , de Kleijn Dominique P.V. , De Borst Gert-Jan , Pasterkamp Gerard , Moll Frans L. 
Published: February 2011

Background and Purpose—
Carotid endarterectomy (CEA) of stable atherosclerotic plaques is associated with an increased risk for restenosis. Patients with transient ischemic attack and patients with and stroke have relatively unstable atherosclerotic plaques. However, carotid plaques stabilize over time after a cerebrovascular event due to plaque repair after rupture. These findings raised 2 questions: (1) Is preoperative clinical presentation related to restenosis after CEA? (2) Does delayed revascularization result in a higher risk for restenosis compared with CEA in the short term after a cerebrovascular event?

Methods—
Between 2002 and 2009, 1203 patients undergoing CEA were included. The impact of clinical presentation on the occurrence of restenosis 1 year after CEA was investigated and corrected for cardiovascular risk factors, medication use, and type of arteriotomy closure. Patency was assessed with standardized duplex ultrasound imaging at 1 year after CEA. Restenosis was defined as recurrent luminal narrowing ≥50% at the endarterectomy site.

Results—
At 1 year of follow-up, restenosis was observed more frequently in asymptomatic patients than in patients with transient ischemic attack and patients with stroke. The adjusted odds ratio (95% CI) for restenosis was 0.56 (0.35 to 0.89) for patients with transient ischemic attack and 0.49 (0.27 to 0.87) for patients with stroke compared with asymptomatic patients. Subgroup analysis showed an increased risk for restenosis if CEA was performed >30 days after stroke (adjusted OR, 2.23; 1.02 to 5.73).

Conclusions—
Asymptomatic patients have an increased risk for restenosis at 1 year after CEA compared with patients with transient ischemic stroke and patients with stroke. CEA within 30 days after stroke is associated with a decreased risk of restenosis, which supports the current strategy for early surgical intervention after stroke.
Evaluation of Biases in JRA-25/JCDAS Precipitation and Their Impact on the Global Terrestrial Carbon Balance
Authors: Saito Makoto , Ito Akihiko , Maksyutov Shamil 
Published: February 2011

AbstractThis study evaluates a modeled precipitation field and examines how its bias affects the modeling of the regional and global terrestrial carbon cycle. Spatial and temporal variations in precipitation produced by the Japanese 25-yr reanalysis (JRA-25)/Japan Meteorological Agency (JMA) Climate Data Assimilation System (JCDAS) were compared with two large-scale observation datasets. JRA-25/JCDAS captures the major distribution patterns of annual precipitation and the features of the seasonal cycle. Notable problems include over- and undersimulated areas of precipitation amount in South America, Africa, and Southeast Asia in the 30°N–30°S domain and a large discrepancy in the number of rainfall days. The latter problem was corrected by using a stochastic model based on the probability of the occurrence of dry and wet day series; the monthly precipitation amount was then scaled by the comparison data. Overall, the corrected precipitation performed well in reproducing the spatial distribution of and temporal variations in total precipitation. Both the corrected and original precipitation data were used to simulate regional and global terrestrial carbon cycles using the prognostic biosphere model Vegetation Integrative Simulator for Trace Gases (VISIT). Following bias correction, the model results showed differences in zonal mean photosynthesis uptake and respiration release ranging from −2.0 to +3.3 Pg C yr−1, compared with the original data. The difference in the global terrestrial net carbon exchange rate was 0.3 Pg C yr−1, reflecting the compensation of coincident increases or decreases in carbon sequestration and respiration loss. At the regional scale, the ecosystem carbon cycle and canopy structure, including seasonal variations in autotrophic and heterotrophic respiration and total biomass, were strongly influenced by the input precipitation data. The results highlight the need for precise precipitation data when estimating the global terrestrial carbon balance.
Gain Affected by the Interior Shape of the Ear Canal
Authors: Yu Jen‐Fang , Chen Yen‐Sheng , Cheng Wei‐De 
Published: February 2011

ObjectiveThis study investigated the correlation of gain distribution and the interior shape of the human external ear canal.Study DesignCross‐sectional study of gain measurement at the first bend and second bend.SettingChang Gung Memorial Hospital and Chang Gung University.Subjects and MethodsThere were 15 ears in patients aged between 20 and 30 years (8 men/7 women) with normal hearing and middle ears. Stimulus frequencies of 500, 1000, 2000, 3000, and 4000 Hz were based on the standard clinical hearing test. Measurements closer to the tympanic membrane and the positions at the first and second bends were confirmed by using otoscope. Real ear measurement to analyze the canal resonance in human external ears was adopted.ResultsThis study found that gain at stimulus frequencies of 4000 Hz was affected by the interior shape of the ear canal (P <. 005), particularly at the first and second bends, whereas gain was only affected by the length of the ear canal for stimulus frequencies of 2000 Hz (P <. 005).ConclusionThis study found that gain was affected not only by the length of the external auditory canal (EAC) but also by the interior shape of the EAC significantly. The findings of this study may have potential clinical applications in canalplasty and congenital aural atresia surgery and may be used to guide surgeries that attempt to reshape the ear canal to achieve more desirable hearing outcomes.
Massive Facial Trauma following Improvised Explosive Device Blasts in Operation Iraqi Freedom
Authors: Salinas Nathan L. , Brennan Joseph , Gibbons Mark D. 
Published: February 2011

ObjectiveTo investigate the association of massive facial trauma with brain and eye injuries, injury severity scores, and blood transfusion utilization.Study DesignRetrospective study.SettingAir Force Theater Hospital, Balad, Iraq.Subjects and MethodsRetrospective review of US service members injured by improvised explosive devices and treated at the Air Force Theater Hospital in Iraq from October 2004 to September 2007. Massive facial trauma was defined as any injury to the face involving 3 or more facial aesthetic units. The anatomic injury patterns, injury severity scores, and blood transfusion rates of simple and massive facial trauma were compared.ResultsOne hundred four patients who sustained facial trauma from improvised explosive device blasts were reviewed, including 29 patients with massive facial trauma. The average injury severity score was 13.9 in the simple facial trauma group and 21.7 in the massive facial trauma group (P =. 006). Sixteen (55%) of the patients in the massive facial trauma group received transfusions compared with only 21 (28%) in the simple facial trauma group (P =. 009). The rate of associated eye injury was 55% in the massive facial trauma group and 27% in the simple facial trauma group (P =. 006). Brain injuries occurred in 48% of the patients with massive facial trauma and 28% of the patients with simple facial trauma (P =. 05).ConclusionThere is an association between massive facial trauma higher injury severity scores, higher transfusion rates, and an increased risk for eye and brain injuries.
Amplitude and Strength of Muscle Contraction Are Reduced in Experimental Tears of the Rotator Cuff
Authors: Meyer Dominik C. , Gerber Christian , Von Rechenberg Brigitte , Wirth Stephan H. , Farshad Mazda 
Published: February 2011

Background: Chronic tendon tears lead to retraction, fatty infiltration, and atrophy of the respective muscle. These muscle changes are decision-making criteria in rotator cuff tear management. Purpose: To investigate the functional implications of these morphological changes in a sheep rotator cuff tear model. Study Design: Controlled laboratory study. Methods: The authors established chronic retraction of the musculotendinous unit accompanied with fatty infiltration and atrophy of the infraspinatus muscle in 20 sheep. The contractile force and passive tension of the muscle as a function of its length were measured and the active work capacity determined. Results: After tendon release and chronic retraction (by 5.7 ± 0.9 cm), fatty infiltrated and atrophied infraspinatus muscles (with a density of 22.4 ± 10.4 Hounsfield units [HU] and a cross-sectional area of 65% ± 16% of the contralateral control side) had a mean contractile amplitude and strength of 2.7 ± 0.4 cm and 235 ± 71 N compared with the contralateral control shoulder of 4.1 ± 0.7 cm and 485 ± 78 N ( P < .05), respectively. The mean active work of the muscle was 2.8 ± 0.9 N·m for retracted and 8.8 ± 2.4 N·m for control muscles ( P < .05). The correlation of total active work to fatty infiltration ( r = 0.78, P < .001) was significant. Conclusion: Chronic tendon tears are associated not only with retraction, fatty infiltration, and atrophy but also with loss of strength and contractile amplitude. The functional changes can only indirectly and approximately be predicted by computed tomography imaging findings. Clinical Relevance: The current criteria (atrophy, retraction, and fatty infiltration) may help to quantify the structural reparability of a chronically retracted musculotendinous unit after rotator cuff tendon tear but may only approximately predict the remaining function of the muscle.