bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B47: External Qi of Yan Xin Qigong induces cell cycle arrest and apoptosis in colon cancer cells through regulation of multiple signaling pathways
Authors: Yan Xin , Shen Hua , Jiang Hongjian , Hu Dan , Zhang Chengsheng , Wang Jun , Wu Xinqi 
Published: May 2012

Abstract
The concept external Qi of Qigong refers to the technology and ability of “Qi deployment” therapy and health preservation of traditional Chinese medicine (TCM). External Qi therapy of TCM has long been one of the medical practices in China. Long-term clinical observations and ongoing studies have shown positive effects of external Qi of Yan Xin Qigong (YXQ-EQ) on patients of various types of cancer. The molecular and cellular mechanisms underlying YXQ-EQ's antitumor effects have recently begun to be addressed. In the present study we investigated YXQ-EQ's effects on the growth and apoptosis of human colon carcinoma HT-29 cells. We show that YXQ-EQ treatment reduced the viability and inhibited clonogenic growth of HT-29 cells. In agreement, YXQ-EQ induced cell cycle G1 arrest and apoptosis in HT-29 cells. YXQ-EQ induced apoptosis is accompanied by DNA fragmentation and cleavage of procaspase-3 and -9 and poly(ribose-ADP) polymerase. YXQ-EQ inhibited phosphorylation of Akt and GSK3β, decreased the levels of cyclin D1 and hyper-phosphorylated Rb, and repressed the expression of antiapoptic proteins Bcl-XL, XIAP, and survivin. Concomitantly, YXQ-EQ increased the expression of cyclin-dependent kinase inhibitor p21CIP1/WAF1. These findings suggest that YXQ-EQ may induce cell cycle arrest and apoptosis in colon cancer cells through regulation of multiple signaling pathways that play important roles in cell proliferation, survival and apoptosis.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B47.
Abstract B51: Discovery of novel genomic targets in the NRF2-mediated antioxidant response pathway by ChIP-on-chip and ChIP-seq
Authors: Campbell Michelle R. , Chorley Brian N. , Wang Xuting , Cho Hye-Youn , Kleeberger Steve R. , Bell Douglas A. 
Published: May 2012

Abstract
Sulforaphane is a dietary isothiocyanate that has been shown to have anticancer, antidiabetic and antimicrobial properties. Found in cruciferous vegetables, sulforaphane acts primarily as a phase II enzyme inducer through the pathway mediated by nuclear factor (erythroid-derived 2)-like 2 (NRF2). NRF2 is the key transcriptional activator in this pathway, binding as a heterodimer with small Maf proteins to cis-acting antioxidant response elements (AREs) found in the promoter regions of downstream oxidative response genes. In Nrf2 knockout mice, oxidative stress exposure causes increased damage to lung, liver and neurological tissue compared to wild type mice. Conversely, an aggressive cancer phenotype has been linked to permanently activated NRF2; indicating NRF2 may directly regulate other pathways unrelated to oxidant defense. In order to investigate NRF2 binding and gene regulation on a genome wide scale, we analyzed chromatin immunoprecipitated (ChIP) NRF2-bound DNA using ChIP-on-chip and ChIP-Seq technologies. Specifically, a human lymphoblastoid cell line (HapMap GM11994) was exposed in triplicate to 10uM sulforaphane, crosslinked, sonicated and immunoprecipitated with NRF2 antibody. NRF2-bound DNA was amplified and hybridized to the Agilent Human Promoter chip, which provides −5.5 to +2.5 kilobase coverage around the majority of gene transcriptional start sites (ChIP-on-chip). Additionally, ChIP NRF2-bound DNA was sequenced using the Solexa GAII second-generation sequencing platform (ChIP-seq). ChIP-on-chip intensity data was input to Agilent's DNA analytics software and 1056 probes in promoter regions of 277 genes displayed sulforaphane - induced NRF2 binding, 20 of which had been previously identified as NRF2-regulated genes. Ingenuity pathway analysis found these 277 genes were involved in oxidative stress, cellular growth and proliferation, cellular development, small molecule biochemistry and other signaling pathways. We cross referenced the ChIP-on-chip data with results from gene expression (induction&gt;1.2-fold/suppression &lt;0.8-fold compared to control, p&lt;2.5X10−6) in 60 sulforaphane-exposed HapMap lymphoblastoid cells lines as determined by Illumina microarray. We identified 32 differentially expressed genes with NRF2 binding, 17 that had not previously been described as regulated by NRF2. Preliminary analysis of the ChIP-seq data has mapped 2.1 million uniquely aligned sequencing reads resulting in 945 bound regions (high quality peaks). Of these, 5% are located near known NRF2-binding regions, and approximately 20% of the regions overlap with the ChIP-on-chip platform. Using both the ChIP-on-chip and ChIP-seq platform in this study has allowed us to investigate NRF2 on a genome-wide scale and identify novel sulforaphane-activated NRF2 gene targets.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B51.
Abstract B87: In vitro DNA binding studies of S- and R-enantiomers of organotin complexes: Antitumor activity of S-enantiomer against human tumor cell lines
Authors: Farukh Arjmand 
Published: May 2012

Abstract
New organotin modulated antitumor drug candidates 1 and 2 derived from R- and S- enantiomer of [4-hydroxy-1-phenylethylimino)pent-2-ol] and 2-amino-2-phenylethanol, respectively were synthesized by de novo synthetic strategy and thoroughly characterized by analytical and various spectroscopic methods. The complexes (S) / (R)−1 and 2 display trigonal bipyramidal and tetrahedral environment, respectively around the tin center. Preliminary complex-DNA interaction studies employing UV-Visible, fluorescence, and viscosity revealed that S-enantiomer displayed more propensities towards the ultimate drug target double helix DNA. This was quantified by Kb and Ksv values of (S)- and (R)-1 and 2, their ligands L and L′ which demonstrated multifold increase in case of S- enantiomer in comparison to their R- enantiomeric form. Nevertheless, both isomers displayed higher Kb values than that of cisplatin. This clearly demonstrates the chiral preference of S- enatiomer over R- enantiomer. Therefore, the in vitro antitumor activity of S-enantiomer of 1 and 2 was evaluated by the Sulforhodamine-B (SRB) assays to assess cellular proliferation against five human cell lines viz, Hop62 (human lung), DWD (human oral), K562 (human leukemia), DU145 (human prostrate) and MCF-7 (human breast). The complex (S)-1 displayed remarkably pronounced and specific activity for K562 (human leukemia) while complex (S)-2 exhibited significant activity towards Hop62 (human lung), DWD(Human oral), DU145 (human prostrate) and MCF-7 (human breast).
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B87.
Abstract CN12-02: Towards the control of melanoma
Authors: Whiteman David C. 
Published: May 2012

Abstract
The incidence of melanoma continues to rise in most fair-skinned populations around the world. This year, 68,720 Americans will be diagnosed with melanoma and more than 8,500 will die from the disease, an enormous toll for a largely preventable cancer. Strategies to control the burden of melanoma include primary prevention, early detection of treatable lesions, and novel therapies for established disease.
Primary prevention requires understanding of the modifiable causal factors, and then developing programs to intervene at the population level to reduce the incidence of new cases. To date, the only modifiable factor yet identified is solar ultraviolet radiation (UVR). Somewhat unusually in cancer research, the most compelling human data for a causal association between sunlight and melanoma come from ecological studies comparing the incidence of melanoma across populations, over time, and following migration. Animal models are limited in number, but mostly confirm that exposure to UVR, particularly early in life, causes melanoma. Data regarding the role of solar UVR from observational epidemiological studies is abundant but inconsistent, and data from intervention trials is almost non-existent. Thus the evidence-base with which to enact primary prevention policies for melanoma is limited. Moreover, recent epidemiologic and molecular findings indicating that melanomas arise through multiple causal pathways pose interesting new challenges for designing primary prevention interventions. Early detection is another approach to reducing the melanoma burden. The strategy to identify and remove threatening melanocytic lesions before harm ensues is widely practiced, although nowhere is this done systematically across entire populations. Several considerations have precluded the formal introduction of melanoma screening programs, particularly the low predictive value of current screening methods and the consequent costs of overdiagnosis of pigmented lesions. Research to improve screening performance, including the identification of high-risk populations using phenotypic and genotypic markers, is currently underway and may lead to new approaches.
The final pillar of melanoma control lies in finding better treatments, especially for disseminated melanoma which has proven to be largely resistant to ‘traditional’ cancer therapies. Research into the mutations occurring within melanoma tumors is anticipated to identify novel targets for treatments, as well as lead to better understanding of the causes of melanoma. Limited success has been made with c-Kit; it is hoped that other targets will follow from molecular characterization of these tumors.
This presentation will introduce these concepts, aspects of which will be addressed in more detail by the panel speakers with respect to both melanoma and keratinocyte cancers.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN12-02.
Abstract PR-04: Blood lipid and lipoprotein levels and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
Authors: van Duijnhoven Fränzel J. , Calligaro Miriam , Jenab Mazda , Pischon Tobias , Jansen Eugène H. , Frohlich Jiri , Ayyobi Amir , Bueno-de-Mesquita H. Bas ,   for the EPIC study group
Published: May 2012

Abstract
Background: Blood lipids and lipoproteins may affect colorectal cancer (CRC) risk, but results are inconsistent. We examined the relation between serum levels of total cholesterol, high density lipoprotein (HDL), low density lipoprotein, triglycerides, apo lipoprotein A–I (apoA), apo lipoprotein B and the incidence of CRC.
Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 1238 first primary incident colorectal cancer cases were matched to 1238 controls by age, gender, center, time of blood collection and fasting status. Serum levels were quantitatively determined by a colorimetric method. Conditional logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (95% CI).
Results: After adjustments, levels of HDL and apoA were inversely associated with colon cancer risk (RR for one standard deviation increase of 0.43 mmol/L in HDL and 0.32 g/L in apoA (95% CI) = 0.78 (0.68–0.89); p&lt;0.01 and 0.82 (0.72–0.94); p&lt;0.01, respectively) and with distal cancer risk (0.79 (0.65–0.96); p=0.02 and 0.83 (0.69–1.01); p=0.07, respectively). Although only slightly weaker, associations with proximal colon cancer risk were not statistically significant (0.82 (0.65–1.03); p=0.09 and 0.86 (0.68–1.07); p=0.18, respectively). Inclusion of other biomarkers or exclusion of the first 2 years of follow-up did not influence the association between HDL and colon cancer risk. No association was observed for rectal cancer risk.
Conclusion: These findings suggest that high HDL levels may decrease colon cancer risk. The mechanism behind this association should be further investigated.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-04.
Abstract PR-07: Skin cancer concerns and genetic risk information seeking in primary care
Authors: Hay Jennifer , Kaphingst Kimberly , Li Yuelin , Baser Raymond , Alford Sharon Hensley , McBride Colleen 
Published: May 2012

Abstract
Skin cancers are among the most rapidly increasing cancers in the United States. The most serious form, melanoma, is relatively common in younger adults and has a high mortality rate if it becomes metastatic. Growing evidence from genome-wide association studies is identifying genetic variants associated with skin cancer risk. Accordingly, it is being suggested that genomic testing for these variants could enable personalized feedback of susceptibility to skin cancer as an innovative approach to motivate adoption of preventive behaviors. Little is known about the receptivity of healthy adults to genetic risk information for common diseases such as cancer. We investigated whether cognitive factors (worry and perceived skin cancer risk), family factors (family health history awareness, family or personal cancer history, family constellation and social influences on health), behavioral factors (sunburn and sunscreen use history), and level of general health information-seeking relate to perceived importance of learning about how genes affect personal health risks. These research questions were examined using baseline assessment data from the Multiplex Initiative, a primary-care based study examining interest and uptake of genetic susceptibility testing for eight common diseases in a large Midwestern health maintenance organization. The sample included 1959 members, ages 25–40, who had not been diagnosed with any of the eight conditions on the genetic test. About 53% of participants were female; 37% were white and 53% black. Most (75%) had at least some college education. Average level of perceived importance of learning about genes was high (X=5.55; 1–7 scale). To highlight interactions between covariates, we used recursive partitioning classification and regression trees (RPART) to identify predictors of perceived importance of learning about genes among white and black respondents. In whites, the tree correctly classified 79% of the participants, such that those participants who perceived that others close to them wanted them to learn more about keeping healthy, were highly worried about skin cancer, and reported lower perceived skin cancer risk were most likely to endorse high levels of perceived importance of learning about genes; other variables did not substantially improve model accuracy. Findings were similar for blacks. This study indicates that the perceived investment of family and friends regarding health-focused information seeking may be a primary motivator for learning about how genes affect health, and that investigation of actual and perceived social support and social influences may improve our understanding of how cognitive and information seeking processes relate to interest and uptake of genetic information in primary care settings.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-07.
The mouse dorsal skinfold chamber as a model for the study of thrombolysis by intravital microscopy
Authors: Rouzaud Marie-Catherine , Loyau Stéphane , Jandrot-Perrus Martine , Bouton Marie-Christine , Boulaftali Yacine , Lamrani Lamia , Ho-Tin-Noé Benoît 
Published: May 2012

SummaryAlthough intravital microscopy models of thrombosis in mice have contributed to dissect the mechanisms of thrombus formation and stability, they have not been well adapted to study long-term evolution of occlusive thrombi. Here, we assessed the suitability of the dorsal skinfold chamber (DSC) for the study of thrombolysis and testing of thrombolytic agents by intravital microscopy. We show that induction of FeCl3-induced occlusive thrombosis is achievable in microvessels of DSCs, and that thrombi formed in DSCs can be visualised by intravital microscopy using brightfield transmitted light, or fluorescent staining of thrombus components such as fibrinogen, platelets, leukocytes, and von Willebrand factor. Direct application of control saline or recombinant tissue-plasminogen activator (rtPA) to FeCl3-produced thrombi in DSCs did not affect thrombus size or induce recanalisation. However, in the presence of hirudin, rtPA treatment caused a rapid dose-dependent lysis of occlusive thrombi, resulting in recanalisation within 1 hour after treatment. Skin haemorrhage originating from vessels located inside and outside the FeCl3-injured area was also observed in DSCs of rtPA-treated mice. We further show that rtPA-induced thrombolysis was enhanced in plasminogen activator inhibitor-1-deficient (PAI-1−/−) mice, and dropped considerably as the time between occlusion and treatment application increased. Together, our results show that by allowing visualization and measurement of thrombus lysis and potential bleeding complications of thrombolytic treatments, the DSC provides a model for studying endogenous fibrinolysis and for first-line screening of thrombolytic agents. Furthermore, using this system, we found that thrombin and clot aging impair the thrombolytic action of rtPA towards FeCl3-produced thrombi.
Clinical Outcome of Catheter Ablation in Patients With Nonparoxysmal Atrial Fibrillation
Authors: Chao Tze-Fan , Tsao Hsuan-Ming , Lin Yenn-Jiang , Tsai Chin-Feng , Lin Wei-Shiang , Chang Shih-Lin , Lo Li-Wei , Hu Yu-Feng , Tuan Ta-Chuan , Suenari Kazuyoshi , Li Cheng-Hung , Hartono Beny , Chang Hung-Yu , Ambrose Kibos , Wu Tsu-Juey , Chen Shih-Ann 
Published: May 2012

Background—
Catheter ablation of atrial fibrillation (AF) became an effective therapy for patients with drug-refractory AF, and the indications have broadened to include nonparoxysmal AF patients. However, data about the long-term effectiveness of ablation in patients with nonparoxysmal AF are lacking. The aim of the present study was to investigate the long-term outcomes of catheter ablation in patients with nonparoxysmal AF.

Methods and Results—

A total of 88 nonparoxysmal AF patients who received a stepwise catheter ablation (isolation of the pulmonary veins plus substrate modification) from 2006 to 2008 were enrolled. Freedom of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after the catheter ablation. There were 63 patients (71.6%) with recurrences (47 patients with AF and 16 patients with atrial flutter/atrial tachycardia) after the initial procedure during a median follow-up period of 36.8 months. A CHADS
2
score of ≥3 and the left atrial (LA) diameter were significant predictors of recurrences in the multivariable analysis. Of the patients with CHADS
2
scores of ≥3 and an LA dimension ≥44 mm, all had recurrences within 1 year after the initial procedure. The overall recurrence-free rate could increase to 47.7% after the second procedure and 51.1% after the third procedure.

Conclusions—

The long-term recurrence-free rate of ablation in nonparoxysmal AF was only 28.4% after a single procedure, and multiple procedures were necessary to raise the recurrence-free rate. The CHADS
2
score and LA dimension may help us to identify patients who will have recurrences after catheter ablations of nonparoxysmal AF.
National Surveillance Definitions for Hypertension Prevalence and Control Among Adults
Authors: Crim Matthew T. , Yoon Sung Sug (Sarah) , Ortiz Eduardo , Wall Hilary K. , Schober Susan , Gillespie Cathleen , Sorlie Paul , Keenan Nora , Labarthe Darwin , Hong Yuling 
Published: May 2012

Background—
Clear and consistent definitions of hypertension and hypertension control are crucial to guide diagnosis, treatment, and surveillance. A variety of surveillance definitions are in frequent use, resulting in variation of reported hypertension prevalence and control, even when based on the same data set.

Methods and Results—
To assess the variety of published surveillance definitions and rates, we performed a literature search for studies and reports that used National Health and Nutrition Examination Surveys (NHANES) data from at least as recent as the 2003 to 2004 survey cycle. We identified 19 studies that used various criteria for defining hypertension and hypertension control, as well as different parameters for age adjustment and inclusion of subpopulations. This resulted in variation of reported age-standardized hypertension prevalence from 28.9% to 32.1% and hypertension control from 35.1% to 64%. We then assessed the effects of varying the definitions of hypertension and hypertension control, parameters for age adjustment, and inclusion of subpopulations on NHANES data from both 2007 to 2008 (n=5645) and 2005 to 2008 (n=10 365). We propose standard surveillance definitions and age-adjustment parameters for hypertension and hypertension control. By using our recommended approach with NHANES 2007 to 2008 data, the age-standardized prevalence of hypertension in the United States was 29.8% (SE, 0.62%) and the rate of hypertension control was 45.8% (SE, 4.03%).

Conclusions—
Surveillance definitions of hypertension and hypertension control vary in the literature. We present standard definitions of hypertension prevalence and control among adults and standard parameters for age-adjustment and population composition that will enable meaningful population comparisons and monitoring of trends.
Use of Tissue-Type Plasminogen Activator Before and After Publication of the European Cooperative Acute Stroke Study III in Get With The Guidelines-Stroke
Authors: Messé Steven R. , Fonarow Gregg C. , Smith Eric E. , Kaltenbach Lisa , Olson DaiWai M. , Kasner Scott E. , Schwamm Lee H. 
Published: May 2012

Background—
The European Cooperative Acute Stroke Study (ECASS) III demonstrated benefit to expanding the intravenous tissue-type plasminogen activator (tPA) window from 3 to 4.5 hours for patients with acute ischemic stroke (AIS). We investigated how this trial influenced use of tPA in clinical practice.

Methods and Results—

Using the Get With The Guidelines-Stroke data set, we identified 217 692 patients who presented to the hospital within 4.5 hours of AIS from April 2003 to March 2011, 106 113 before and 111 579 after the publication of ECASS III in September 2008. The proportion of patients with AIS who presented within 4.5 hours and were treated with tPA in the 3- to 4.5-hour window increased from 1.2% before ECASS III to 3.5% after (
P
<0.0001). The proportion of eligible patients with AIS presenting within 3.5 hours and treated within 4.5 hours increased from 19% (18 484/96 208) to 35% (26 888/77 309) (
P
<0.0001). ECASS III appeared to have no adverse affect on the treatment of patients who presented early because the proportion of eligible patients with AIS presenting within 2 hours and treated within 3 hours increased after ECASS III from 57% to 75% (
P
<0.0001), whereas median door-to-needle times in patients treated within 3 hours decreased from 79 to 74 minutes (
P
<0.0001).

Conclusions—
Following publication of ECASS III, there has been a significant increase in the use of tPA between 3 and 4.5 hours without adversely affecting treatment of patients in the <3-hour window. However, there remains substantial opportunity to further improve treatment rates in the later time window.