bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ED06-04: Methodology for benchmarking recruitment of minority and lower SES populations to clinical trials
Authors: Morgenlander Keith H. 
Published: May 2012

Abstract
Background: The National Cancer Institute (NCI) has historically evaluated the participation of underserved minorities within University of Pittsburgh Cancer Institute (UPCI) clinical trials in relation to the African Americans (AA) general population within the UPCI primary service area of Allegheny County (12%). This standard appeared to be unrealistically high, due to a younger age distribution of AAs within the county.
Methods: The proportion of AAs within four separate county populations were compared, using data from 2000–2004: (a) general population, (b) invasive cancer cases (c) invasive cancer cases diagnosed or treated at UPCI-affiliated facilities and (d) patients enrolled on UPCI's clinical therapeutic trials.
Results: The proportion of AAs within the general population was approximately 12%. However, only 9.8% of patients diagnosed with invasive cancers were AA. Approximately 9.5% of all cancer cases diagnosed or treated at UPCI facilities was AA, comparable to the county-wide percent of AA cancer patients. Recruitment of AAs to oncology clinical trials was 7.6%, revealing a significant disparity.
Discussion: The NCI benchmark did not reflect the actual “pool” of potential AA patients. As an alternative, we compared the percentage of AAs contributing to cancer incidence with the percentage AA cancer patients treated at the research-affiliated institutions and with the proportion of AAs enrolled on clinical therapeutic trials.
Conclusions: This methodology was successfully utilized by UPCI and should be useful as a mechanism for benchmarking recruitment of underserved and minority cancer patients at other cancer centers.
Primary Reference: Morgenlander KH, Winters SB, Lin CJ, Robertson LB, Heron DE, Herberman RB. A novel method for benchmarking clinical trial recruitment of African American cancer patients. J Clin Oncol. 2008 Nov 1;26(31):5074–7.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):ED06-04.
Abstract ED07-02: Effects of chronic stress on cancer metastasis
Authors: Sood Anil K. , Lutgendorf Susan K. , Cole Steve W. 
Published: May 2012

Abstract
The notion that psychosocial factors can affect malignant progression has long been suspected. Clinical and epidemiological studies have recognized that specific psychosocial factors, such as stress, chronic depression, and lack of social support are risk factors for more rapid progression of cancer. However, the underlying mechanisms for this association are poorly understood. Cancer metastasis is a sequential and complex process that results in widespread dissemination of cancer cells. We have performed a series of in vitro and in vivo experiments using mechanistic manipulations to identify specific neuroendocrine signaling pathways that mediate direct effects of chronic stress on tumor cell biology. These studies focused on the effects of catecholamine neurotransmitters on angiogenic pathways that support the growth and progression of human ovarian carcinoma as well as other steps in the metastatic cascade. Findings indicate that chronic stress affects multiple steps during metastasis, resulting in greater tumor burden and more invasive growth in orthotopic mouse models. Moreover, catecholamines modulate the expression of genes encoding angiogenic factors (e.g., VEGF) via β-adrenergic receptors expressed on the human tumor cell surface. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the 2-adrenergic receptor. These data implicate β-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis and growth. At a clinical level, circulating levels of angiogenic factors such as VEGF and IL-6 are correlated with greater distress and inversely related to social support. Our recent studies demonstrate that relationships between psychosocial factors and angiogenic factors extend to the tumor microenvironment as well. Dissecting these pathways by which chronic stress provides support for angiogenesis and other steps in metastasis could have therapeutic implications for cancer management.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):ED07-02.
Abstract ED07-04: Identifying environment-gene interactions that link social stress to altered cancer biology
Authors: Conzen Suzanne D. , McClintock Martha K. 
Published: May 2012

Abstract
Identifying the potential mechanisms linking psychosocial factors (e.g. chronic “stress”) to human disease susceptibility has been the subject of intense interest by both social and biological scientists for many years. Together, the endocrine and the autonomic nervous systems modulate an individual's physiological response to social stress; both systems can mediate signaling pathways and gene expression changes at the subcellular level that have the potential to alter tumor biology. However, it is only recently that the detailed molecular components connecting biobehavioral factors and cancer biology have begun to be uncovered. For example, in preclinical models of both breast and ovarian cancer, there is growing evidence linking environmental stressors and ensuing changes in neuroendocrine dynamics to the promotion of tumor growth. These mechanisms include decreasing tumor cell apoptosis and increasing cell proliferation, tumor invasion, and angiogenesis. Assessing the mechanisms of gene by social environment interaction requires an appreciation of the subtleties of measuring the social environment, the individual's behavioral and neuroendocrine response, as well as the tumor and its microenvironment.
While cancer biologists are accustomed to examining the effects of a single physical variable on a well-defined and measurable outcome, examining the physiological outcomes of an adverse social environment on tumor biology requires expanding expertise beyond the usual expertise of a tumor biologist. These studies require developing models that require scientists from diverse backgrounds of expertise to look beyond single agents and to consider the complexity of the individual's interaction with the social environment, and the resultant molecular sequelae as it influences tumor development.
Our laboratories' recent collaborative development of a model of social isolation as it pertains to a transgenic model of human breast cancer (SV40Tag) and a Sprague-Dawley female rat model of spontaneous mammary gland cancer will be presented. In both models, we found that chronic social isolation results in altered exploratory behavior to an open field as well as a heightened corticosterone response to a superimposed acute restraint stressor. In the SV40 Tag model, we were able to examine gene expression differences in the mammary glands of isolated versus grouped female mice prior to invasive tumor development and uncovered a significant increase in the expression of genes encoding lipid synthesis and glycolytic pathway enzymes, suggesting an association of the environment with cancer-associated metabolic changes. The implications and limitations of these two breast cancer models - one transgenic and one spontaneous - will be discussed within the context of understanding mechanisms that confer biological risk in association with an unfavorable social environment.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):ED07-04.
Abstract PL01-03: Epigenetics, aging, and cancer: From DNA methylation to microRNAs
Authors: Esteller Manel 
Published: May 2012

Abstract
An altered pattern of epigenetic modifications is central to many common human diseases, including cancer. Many studies have explored the mosaic patterns of DNA methylation and histone modifications in cancer cells on a gene-by-gene basis, among them the seminal finding of transcriptional silencing of tumor suppressor genes by CpG island promoter hypermethylation. Epigenetic gene inactivation in transformed cells involves many “belts of silencing”. We are in the process of completing the molecular dissection of the entire epigenetic machinery involved in methylation-associated silencing, such as DNA methyltransferases, methyl-CpG binding domain proteins, histone deacetylases, histone methyltransferases, histone demethylases and Polycomb proteins. The first indications are also starting to emerge about how the combination of cellular selection and targeted pathways leads to abnormal DNA methylation. In addition to classical tumorsuppressor and DNA repair genes, epigenetic gene silencing includes genes involved in premature aging and microRNAs with growth inhibitory functions. Recent technological advances are now enabling cancer epigenetics to be studied genome-wide. It is time to “upgrade” cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using genomics approaches to unravel the epigenome.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL01-03.
Abstract PL03-02: Public health genomics: A scientific foundation for using genetic information in cancer prevention
Authors: Khoury Muin J. 
Published: May 2012

Abstract
With the accelerating pace of discoveries of human genetic variation, and molecular, biochemical, and cellular technologies for cancer care and prevention, there is an urgent need to develop population-level research, policy and practice processes to translate basic science discoveries into actions that reduce the population burden of cancer in the United States. The emerging scientific translation needs in the genomics era are substantial. Clinical and population sciences are now urgently needed to assess the distribution of genetic variants and their products biomarkers, and interactions with other genes and environmental factors. New methods are needed to assess the contribution of genes and gene-environment interactions (behavior, nutrition, chemicals, and other exposures) to individual and population risks for various cancers. Behavioral and social sciences are needed to assess how genetic information can be used to effect behavior change to reduce the burden of cancer. As importantly, delivery research on clinical utility, effectiveness, and economics of genomics-based health care applications are needed to assess their added value in cancer care and prevention. Genomics and related fields will also affect surveillance, dissemination and diffusion research as well as evaluation of cancer progression and survivorship. Without the expansion of clinical and population sciences in genomics, the promise of genome research and discoveries may not reach its full potential in the genomics era.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL03-02.
Abstract PL04-03: Folate and cancer: Is timing everything?
Authors: Ulrich Cornelia M. 
Published: May 2012

Abstract
Folate is an essential B vitamin utilized for one-carbon transfer reactions, including those related to the methylation of DNA and nucleotide synthesis. Epidemiologic and experimental studies show that a low-folate status is associated with an increased risk of colorectal neoplasia. However, the actions of folate in cancer prevention appear to be modulated by both genetic susceptibility and timing with respect to carcinogenic progression. Functional polymorphisms in genes encoding several key enzymes in folate metabolism have been linked to cancer risk and exemplify the importance of nutrigenetic interactions in this biologic pathway. Yet, perhaps more importantly, the timing of folate administration during carcinogenesis may also impact the outcome and result in opposing effects: A higher folate status is expected to protect against mutations and, thus, may reduce the progression from normal tissue to pre-malignant lesions; however, a higher folate status may subsequently enhance the growth of pre-malignant lesions or any existing tumors, due to the supporting role of folate in the provision of nucleotides for DNA synthesis. Data from clinical trials suggest potential increases in risk of colorectal polyps and prostate cancer in folic acid intervention arms. Mathematical models from our group suggest that supplementation early in life could be beneficial, but adversely affect cancer rates later in life. These influences appear predominantly driven by effects on thymidylate synthesis. Because at this point available data are incomplete, prior to making recommendations, investigation is needed of the effects of folate supplementation among cancer patients, who are at risk of recurrence, as well as among individuals with cancer precursors.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-03.
Abstract PR-06: Upregulation of microRNA-21 (miR-21) in human bronchial epithelial cells chronically exposed to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus nicotine and modulation of these effects by diindolylmethane
Authors: Kassie Fekadu , Jarcho Michael , Endalew Abaineh 
Published: May 2012

Abstract
MicroRNAs (miRNAs) represent a class of naturally occurring small noncoding RNA molecules that regulate genes by either inducing mRNA degradation or inhibiting translation. The expression of miRNAs is deregulated in several cancers, including lung cancer. However, most studies have been carried out using full-blown cancer tissues and the regulation of miRNAs during early-stage tumorigenesis is unknown. In the present study, we used an in vitro model of lung tumorigenesis to assess the effect of chronic treatment with tobacco compounds on the expression of miR-21, one of the most deregulated miRNAs in lung cancer, in human bronchial epithelial cells (HBEC). Freshly prepared NNK (10 µM) and nicotine (10 µM) were added to the culture media containing NHBC every 3 days for 3 weeks. Beginning the second week of NNK plus nicotine treatment, the dietary chemopreventive agent diindolylmethane (DIM) was added, every 3 days, to the culture media until the termination of the study. Then, the cells were harvested, RNA prepared and the expression level of miR-21 and its target genes PDCD4 and RECK were analyzed by QRT-PCR. Levels of PDCD4 and RECK were also examined by Western immunoblotting. NNK plus nicotine treatment significantly elevated miR-21 levels but markedly decreased expression of PDCD4 and RECK at both gene and protein levels. The effect of the tobacco compounds on miR-21 as well PDCD4 and RECK was reversed by treatment with DIM. This study shows that miR-21 levels are deregulated beginning the early phase of lung tumorigenesis and miR-21 is a valuable target for chemopreventive agents.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-06.
Abstract PR-09: Genetic variations in the sonic hedgehog pathway and clinical outcomes in bladder cancer
Authors: Chen Meng , Kamat Ashish , Hildebrandt Michelle A.T. , Zhang Xiaofan , Grossman H. Barton , Dinney Colin P. , Wu Xifeng 
Published: May 2012

Abstract
The sonic hedgehog (Shh) pathway plays an important role in embryonic development and stem cell maintenance. Abnormal activation of Shh pathway has been implicated in the development of various cancers, and also in the progression to metastatic disease. We hypothesized that genetic variations in the Shh pathway may affect bladder cancer (BC) patients' clinical outcomes. We evaluated the association of 151 SNPs in nine Shh genes in a follow-up study of 738 bladder cancer patients for recurrence and progression risk in superficial BC patients, and survival in muscle-invasive and metastasis (MiM) BC patients. In superficial BC patients, GLI2 variants rs11685068 (HR: 2.12, 95% CI: 1.44–3.12) and rs7605011 (HR:1.94, 95% CI: 1.33–2.85) were significantly associated with higher recurrence risk. Individuals with rs11685068 (median survival time (MST): 7.3 months, Log-Rank P: 0.004) and rs7605011 (MST: 7.6 months, Log-Rank P: 0.002) variant alleles had shorter recurrence-free median survival time compared to patients with wild-type genotypes (MST: 16.7 months). In the subgroup receiving Bacillus Calmette-Guérin treatment, GLI3 variants rs6463089 (HR: 2.30, 95% CI: 1.44–3.66) and rs3801192 (HR: 2.57, 95% CI: 1.48–4.46) were significantly associated with higher recurrence risk and shorter recurrence-free survival durations. We also explored the cumulative effect of multiple SNPs and higher-order gene-gene interactions in modulating the recurrence. No significant associations were observed in the progression and survival analysis after correcting for multiple testing. This is the first study to evaluate the role of germline genetic variations in Shh pathway as predictors of bladder cancer outcomes. These findings warrant further replication in independent populations to identify BC patients at a high risk for a poor outcome and prognosis.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-09.
Abstract PR-10: The association of neighborhood socioeconomic context and mortality in a large national cohort in the United States: The NIHA-ARP Diet and Health Study
Authors: Doubeni Chyke , Laiyemo Adeyinka O. , Lian Min , Park Yikyung , Schootman Mario , Schatzkin Arthur 
Published: May 2012

Abstract
Background: Although several studies have reported that persons from lower socioeconomic groups have poorer health outcomes, few prospective studies have examined whether neighborhood socioeconomic context is associated with mortality. In this study, we prospectively evaluated whether persons residing in socioeconomically deprived neighborhoods have higher mortality risk compared to more resourced neighborhoods among a large geographically dispersed cohort.
Methods: Between 1995 and 1996, the NIH-AARP Diet and Health Study recruited an ethnically diverse prospective cohort of 566,402 persons, 50–71 years of age, from six U.S. states and two metropolitan areas. Detailed data were collected on diet, lifestyle, and medical history through questionnaires. Neighborhood socioeconomic information was obtained through linkage to the 2000 U.S. Census data at the tract level. We excluded 705 subjects with incomplete information for geocoding and computed an empirically derived index of neighborhood socioeconomic deprivation using principal component analyses. Mortality was ascertained through December 31, 2006. Two-level continuous-time survival models were used to derive hazard ratios of time to death from any cause stratified by gender.
Results: Of the 565,697 eligible subjects at baseline, the mean age was 62 years, 60% were male, 91% were non-Hispanic whites, 4% non-Hispanic blacks and 9% reported a history of cancer. A higher percentage of those in the most deprived neighborhoods reported poorer general health, higher average BMI, and lower Mediterranean diet scores. In multilevel Cox models analyses controlling for dietary and lifestyle factors, the risk of death increased with increasing levels of deprivation in the neighborhood of residence. Compared to the least deprived neighborhood, those residing in areas in the highest quintile of deprivation had a higher risk for death (men: hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.18–1.25); women: HR: 1.23, 95% CI: 1.17–1.29).
Conclusion: Our study suggests that living in socioeconomically deprived neighborhoods is associated with a higher risk for death independent of lifestyle and dietary risk factors.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):PR-10.
Hypertension Control Among Patients Followed by Cardiologists
Authors: Navar-Boggan Ann Marie , Boggan Joel C. , Stafford Judith A. , Muhlbaier Lawrence H. , McCarver Catherine , Peterson Eric D. 
Published: May 2012

Background—
Hypertension control is an important and modifiable risk factor for cardiovascular disease. The overall rate of hypertension control among patients followed in cardiology clinics, as well as clinician variability in control rates, is unknown.

Methods and Results—
We conducted a retrospective cohort study of patients with hypertension (n=5979) routinely followed in a cardiology clinic (n=47 physicians). Overall, 30.3% of patients with hypertension had suboptimal control (blood pressure [BP] ≥140/90 mm Hg) at the end of a 13-month follow-up period. Patient-level factors associated with control were younger age, male sex, white ethnicity, having a primary care provider at Duke, private insurance, Medicare/Medicaid, and comorbid diagnoses of heart failure or coronary artery disease. Unadjusted rates of suboptimal BP control among clinicians' clinic patient panels ranged from 16% to 44%. Even after adjusting for patient factors, patients' odds of BP control varied 6-fold, depending on their treating clinician. Using a patient's average BP rather than their most recent BP did not result in significant changes in provider performance. In chart reviews (n=300), clinicians failed to document a plan to address hypertension in 38% of patients with elevated BP in the clinic.

Conclusions—
Up to one-third of patients followed routinely by cardiologists in clinic have suboptimally controlled BP, with wide variability in performance across individual clinicians. This variability, alongside evidence that elevated BP is often not acted on during clinic visits, demonstrates a potential opportunity for quality improvement.
Impact of the Presence and Extent of Incomplete Angiographic Revascularization After Percutaneous Coronary Intervention in Acute Coronary Syndromes
Authors: Rosner Gregg F. , Kirtane Ajay J. , Genereux Philippe , Lansky Alexandra J. , Cristea Ecaterina , Gersh Bernard J. , Weisz Giora , Parise Helen , Fahy Martin , Mehran Roxana , Stone Gregg W. 
Published: May 2012

Background—
The clinical significance of incomplete coronary revascularization (ICR) after percutaneous coronary intervention in patients with acute coronary syndromes is unknown.

Methods and Results—

We performed quantitative angiography of the entire coronary tree in 2954 patients with acute coronary syndromes in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. ICR was variably defined if any lesion with diameter stenosis (DS) cutoffs ranging from ≥30% to ≥70% with reference vessel diameter ≥2.0 mm remained after percutaneous coronary intervention. The primary outcome was 1-year composite rate of major adverse cardiac events (death, myocardial infarction, or ischemia-driven unplanned revascularization). With the use of DS cutoffs ≥30%, ≥40%, ≥50%, ≥60%, and ≥70%, the prevalence of ICR after percutaneous coronary intervention was 75%, 55%, 37%, 25%, and 17%, respectively. The 1-year major adverse cardiac event rate was increased among patients with ICR using all of the DS cutoffs. ICR (≥50% DS) was associated with higher 1-year rates of myocardial infarction (12.0% versus 8.2%; hazard ratio, 1.50; 95% confidence interval, 1.18–1.89;
P
=0.0007) and ischemia-driven unplanned revascularization (15.7% versus 10.2%; hazard ratio, 1.58; 95% confidence interval, 1.28–1.96;
P
<0.0001), with a trend toward increased mortality (3.1% versus 2.2%; hazard ratio, 1.43; 95% confidence interval, 0.90–2.27;
P
=0.13). By multivariable analysis, ICR (≥50% DS) was an independent predictor of 1-year major adverse cardiac events (hazard ratio, 1.36; 95% confidence interval, 1.12–1.64;
P
=0.002). The impact of ICR on major adverse cardiac events was similar regardless of chronic total occlusion presence, but it was more pronounced with a greater number of nonrevascularized lesions.

Conclusions—
Depending on the threshold of percent DS, ICR was present in 17% to 75% of patients with acute coronary syndromes after percutaneous coronary intervention. Regardless of the threshold, ICR was strongly associated with 1-year myocardial infarction, ischemia-driven unplanned revascularization, and major adverse cardiac events.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00093158.