bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C66: Insulin-like growth factor binding protein-6 is differentially methylated in African American, African, and Amish HapMap cell lines
Authors: Ford DeJuana , Bennett Briana , Rivera Myrielis , Hire Rupali , Davis Melissa 
Published: May 2015

Abstract
African American women, while having lower lifetime incidence of breast cancer (BrCa) than Caucasian women, have higher BrCa mortality rates, partially due to a higher incidence of the more aggressive, basal-like molecular subtype of BrCa. Correlations of this subtype within African ancestral groups suggest a potential link to African Ancestry and basal-like BrCa. While socioeconomic factors may also play a role in higher mortality rates, there is mounting evidence that the differential epigenetic regulation of cancer genes may also contribute to this disparity. To address this, our lab is investigating the epigenetic regulation of genes in the insulin-like growth factor pathway using qPCR, Immunohistochemistry (IHC) and Bisulfite-DNA Sequencing. This presentation specifically highlights novel data on the expression of insulin-like growth factor binding protein-6 (IGFBP-6), an IGF-II regulator and agent of cell proliferation, which has been shown previously to be epigenetically modified in cancer cells. Our qPCR and IHC data demonstrates higher IGFBP-6 transcription and protein expression in basal-like BrCa cells when compared to normal breast and ER+ BrCa cells. To address potential ancestry-specific expression, we also evaluated IGFBP-6 expression in African and African-American HapMap lymphoblast cell lines compared to CEPH-European (Amish) cell lines. Both qPCR and IHC data indicate higher overall expression of this gene in African lineages. Lastly, we have measured the differential methylation in two regions of the IGFBP-6 CpG island among African, African-American, and Amish cell lines. We show that IGFBP-6 methylation correlates with the expression patterns. Differential methylation could be due to Ancestral-Specific polymorphisms in this region, altering potential methylation sites. We conclude that the distinct levels of IGFBP-6 expression and promoter methylation in African and African-American cell lines may correspond to the increased incidence of basal-like BrCa in these populations, due to prolonged half-life and activity of the IGF-II growth signal. Our future studies include evaluation of whether this epigenetically-mediated up-regulation of IGFBP-6 directly leads to the excessive proliferation of basal-like tumors.
Citation Format: DeJuana Ford, Briana Bennett, Myrielis Rivera, Rupali Hire, Melissa Davis. Insulin-like growth factor binding protein-6 is differentially methylated in African American, African, and Amish HapMap cell lines. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C66. doi:10.1158/1538-7755.DISP13-C66
Abstract C74: Epigenetic changes in postpartum breast cancer amongst Hispanic women
Authors: Munoz-Rodriguez Jose L. , Vrba Lukas , Hu Chengcheng , Thompson-Carino Patricia A. , Martinez Maria Elena , Futscher Bernard W. 
Published: May 2015

Abstract
The risk of breast cancer has been shown to increase immediately following pregnancy. Breast cancers that occur in the post-partum period are more aggressive, more likely to metastasize and are associated with worse patient outcomes. They also tend to affect younger women, and may represent a substantial proportion of early onset breast cancer, a phenomenon that disproportionately affects racial and ethnic minority groups, such as Hispanics. Hispanic women are more likely to have higher parity, are diagnosed with breast cancer at a younger age, and have a worse survival after diagnosis. The goal of this study, therefore, is to compare breast cancers diagnosed in Hispanic women in the high-risk post-partum period with those diagnosed outside of this time period to identify epigenetic features associated with the aggressive post-partum cancer. RNA and DNA were isolated from formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues from a Hispanic population within the Ella Binational Breast Cancer study participants. Using a quantitative real-time reverse transcriptase approach (Exiqon miRCURY LNA™ Universal RT microRNA PCR panels), we were able to test for the expression of 360 human microRNAs (miRNAs) that our laboratory previously identified as miRNAs that are specific for human mammary cells. MiRNAs are short-stranded, non-coding RNAs that are often deregulated in breast cancer. We have identified seven miRNAs that are differentially expressed in breast cancer that occurs in the post-partum period including: hsa-miR-137, hsa-miR-31, hsa-miR-342-3p, hsa-miR-342-5p, hsa-miR-542-5p, hsa-miR-190b, and hsa-miR-103. Previously, our laboratory showed that epigenetic modifications, such as DNA methylation, deregulate miRNA expression in breast cancer. Consequently, we used a Sequenom MassARRAY platform to determine whether these miRNAs are also being epigenetically regulated. We are also investigating the mechanistic role these miRNAs may play in the early onset post-partum breast cancers.
Citation Format: Jose L. Munoz-Rodriguez, Lukas Vrba, Chengcheng Hu, Patricia A. Thompson-Carino, Maria Elena Martinez, Bernard W. Futscher. Epigenetic changes in postpartum breast cancer amongst Hispanic women. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C74. doi:10.1158/1538-7755.DISP13-C74
Abstract PL02-01: Inclusion of African Americans in cancer clinical trials: Potential quality of life, comorbidity, and pharmacogenetic-related barriers
Authors: Goldberg Richard M. 
Published: May 2015

Abstract
Murthy et al showed that 9.2% of patients enrolled on NCI funded clinical trials between 1996 and 2002 were African American (AA) while census estimates suggest that more than 14% of the US population self-identify as AA. Clearly this minority group is underrepresented in NCI sponsored cancer research studies. Much thought has been given to why this disparity exists and how it can be overcome. Patient, physician, and protocol related barriers can inhibit individuals from choosing a cancer clinical trial option. Multiple validated tools exist to assess quality of life (QOL) that range from the simple Uniscale that assesses global QOL along a line with 10 subdivisions to multipage forms with hundreds of individual questions. QOL is frequently assessed at the time of trial entry and at prescribed points during the patient's time on many studies. Baseline assessments can provide insight into disparities among the subpopulations that enter trials. Understanding the QOL issues that handicap or prevent patients from enrolling in studies are incompletely captured by queries that poll only enrolled patients. It is clear that issues such as performance score, social support, economic status, transportation barriers, comorbidities, familial attitudes, baseline QOL and potential toxicities influence whether an individual agrees to be in a clinical trial. Those factors may be distinctly different in their frequencies among AAs versus other populations. Emerging data also suggest the potential for pharmacogenetic variability among populations that influence drug related toxicities and correlate with race. Study designers cognizant of these issues can minimize barriers to accrual and maximize the value of studies for minority as well as majority populations.
Citation Format: Richard M. Goldberg. Inclusion of African Americans in cancer clinical trials: Potential quality of life, comorbidity, and pharmacogenetic-related barriers. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL02-01. doi:10.1158/1538-7755.DISP13-PL02-01
Abstract PL02-02: Lessons learned from the Walking Forward Program in recruiting American Indians on clinical trials
Authors: Petereit Daniel G. , Kanekar Shalini , Guadagnolo Ashleigh , Boylan Amy , Cina Kristin , Burhansstipanov Linda 
Published: May 2015

Abstract
Purpose/Objective(s): American Indians (AIs) present with more advanced stages of cancer and, therefore, suffer from higher cancer mortality rates compared to non-AIs. Under the National Cancer Institute Cancer Disparities Research Partnership Program (CDRP), we have been researching methods of improving cancer treatment and outcomes since 2002, for AIs in Western South Dakota, through the Walking Forward (WF) Program.
Materials/Methods: This program consists of a) a culturally-tailored patient navigation program that facilitated access to innovative clinical trials in conjunction with a comprehensive educational program encouraging screening and early detection, b) surveys to evaluate barriers to access, c) clinical trials focusing on reducing treatment length as AIs live a median of 140 miles from the cancer center, d) a molecular study (ATM - Ataxia telangectasia mutation) to address whether there is a molecular profile that increases toxicity risks, and e) a recently funded project using mHealth (mobile) technology to address the high smoking rates in this population.
Results: To date, over 3,700 AIs have participated in various WF research studies. Critical outcomes include the establishment of trust within tribal communities, identification of barriers to cancer screening, creation of research infrastructure, higher completion rates and patient satisfaction for patients undergoing cancer treatment, enrollment of patients on phase II trials with excellent clinical outcomes, and the establishment of new research partners. Recent analysis suggests that AI cancer patients with screen detectable cancers are now presenting with earlier stages of disease and higher cure rates. Lessons learned will also be presented.
Conclusions: This NCI funded pilot program has achieved some initial measures of success. A research infrastructure has been created in a community setting to address new research questions and interventions. One critical objective of the CDRP program was to create sustainable, community research programs that has been achieved at our site.
Citation Format: Daniel G. Petereit, Shalini Kanekar, Ashleigh Guadagnolo, Amy Boylan, Kristin Cina, Linda Burhansstipanov. Lessons learned from the Walking Forward Program in recruiting American Indians on clinical trials. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL02-02. doi:10.1158/1538-7755.DISP13-PL02-02
Abstract PR11: Exome sequencing identifies germline mutations in African American families with hereditary prostate cancer
Authors: Wang Zemin , Qian Chiping , Eledet Elisa M. , Washington George , Zabaleta Jovanny , Hu Jennifer J. , Mandal Diptasri , Liu Wanguo 
Published: May 2015

Abstract
Prostate cancer (PCa) is the most common malignancy and the second leading cause of cancer death among men in the United States. Although it has been demonstrated that genetics plays a strong role in PCa, the genetic risk factors responsible for PCa remain poorly understood. Family history is a significant risk factor for PCa and African American (AA) men have the highest PCa incidence among ethnic/racial groups. Genetic analysis of AA families with PCa could facilitate the identification of genetic components contributing to PCa susceptibility. However, this area of research has not been sufficiently explored. We performed Exome sequencing on one affected and one unaffected man from one AA hereditary PCa family, which consists of 9 affected and 18 unaffected men in three generations. We identified 226 novel nonsynonymous variants in the affected man. We examined these mutations in remaining family members and narrowed down to 12 novel mutations which cosegregate with the disease in this family. Further analysis of the 12 mutations in affected and unaffected men from an additional 19 AA hereditary PCa families, 95 AA men with sporadic PCa and 95 unaffected AA control subjects identified three candidate gene mutations. One of the mutations was detected in three and the other two in two AA PCa families but they were either absent or were present in a very low frequency in unaffected control subjects. The three candidate mutations are now under further investigation in additional AA PCa families. The detailed bioinformatics analysis and the significance of these mutations in PCa susceptibility will be discussed.
This abstract is also presented as Poster C67.
Citation Format: Zemin Wang, Chiping Qian, Elisa M. Eledet, George Washington, Jovanny Zabaleta, Jennifer J. Hu, Diptasri Mandal, Wanguo Liu. Exome sequencing identifies germline mutations in African American families with hereditary prostate cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR11. doi:10.1158/1538-7755.DISP13-PR11
Abstract SS01-01: The microbiome and colon cancer risk
Authors: O'Keefe Stephen J. 
Published: May 2015

Abstract
Geographical and migration epidemiological studies, backed up by experimental studies, have produced overwhelming evidence that diet drives colon cancer risk, with high intakes of meat and fat increasing risk, and high consumption rates of fiber rich foods, such as grains, fruits and vegetables, reducing risk. To test our hypothesis that cancer risk is determined by the effect the diet has on the composition and function of the microbiota to produce metabolites that either promote mucosal health or are inflammatory and neoplastic, we have conducted studies in populations of high and low risk, namely African Americans who have the highest risk in the USA, and rural Africans, who rarely get the disease, and confirmed that high meat and fat intakes in Americans were associated with increased mucosal proliferation rates – a biomarker of cancer risk, while high fiber African diets were associated with low proliferation rates. We have demonstrated that dietary switch between these two populations produces reciprocal changes in the microbiome, metabolome, and mucosal biomarkers of risk within 2 weeks, leading to the conclusion that modification of the diets of westernized populations to contain high fiber (&gt;45g/d) foods, such as grains and beans, together with lower intakes of animal fats, can be expected to immediately reduce cancer risk in African Americans.
Citation Format: Stephen J. O'Keefe. The microbiome and colon cancer risk. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr SS01-01. doi:10.1158/1538-7755.DISP13-SS01-01
Systems Genetics Analysis of Genome-Wide Association Study Reveals Novel Associations Between Key Biological Processes and Coronary Artery Disease
Authors: Ghosh Sujoy , Vivar Juan , Nelson Christopher P. , Willenborg Christina , Segrè Ayellet V. , Mäkinen Ville-Petteri , Nikpay Majid , Erdmann Jeannette , Blankenberg Stefan , O’Donnell Christopher , März Winfried , Laaksonen Reijo , Stewart Alexandre F.R. , Epstein Stephen E. , Shah Svati H. , Granger Christopher B. , Hazen Stanley L. , Kathiresan Sekar , Reilly Muredach P. , Yang Xia , Quertermous Thomas , Samani Nilesh J. , Schunkert Heribert , Assimes Themistocles L. , McPherson Ruth 
Published: May 2015

Objective—
Genome-wide association studies have identified multiple genetic variants affecting the risk of coronary artery disease (CAD). However, individually these explain only a small fraction of the heritability of CAD and for most, the causal biological mechanisms remain unclear. We sought to obtain further insights into potential causal processes of CAD by integrating large-scale GWA data with expertly curated databases of core human pathways and functional networks.

Approaches and Results—

Using pathways (gene sets) from Reactome, we carried out a 2-stage gene set enrichment analysis strategy. From a meta-analyzed discovery cohort of 7 CAD genome-wide association study data sets (9889 cases/11 089 controls), nominally significant gene sets were tested for replication in a meta-analysis of 9 additional studies (15 502 cases/55 730 controls) from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) Consortium. A total of 32 of 639 Reactome pathways tested showed convincing association with CAD (replication
P
<0.05). These pathways resided in 9 of 21 core biological processes represented in Reactome, and included pathways relevant to extracellular matrix (ECM) integrity, innate immunity, axon guidance, and signaling by PDRF (platelet-derived growth factor), NOTCH, and the transforming growth factor-β/SMAD receptor complex. Many of these pathways had strengths of association comparable to those observed in lipid transport pathways. Network analysis of unique genes within the replicated pathways further revealed several interconnected functional and topologically interacting modules representing novel associations (eg, semaphoring-regulated axonal guidance pathway) besides confirming known processes (lipid metabolism). The connectivity in the observed networks was statistically significant compared with random networks (
P
<0.001). Network centrality analysis (degree and betweenness) further identified genes (eg,
NCAM1
,
FYN
,
FURIN
, etc) likely to play critical roles in the maintenance and functioning of several of the replicated pathways.

Conclusions—
These findings provide novel insights into how genetic variation, interpreted in the context of biological processes and functional interactions among genes, may help define the genetic architecture of CAD.
Resident Endothelial Cells and Endothelial Progenitor Cells Restore Endothelial Barrier Function After Inflammatory Lung Injury
Authors: Mao Sun-Zhong , Ye Xiaobing , Liu Gang , Song Dongmei , Liu Shu Fang 
Published: May 2015

Objective—
Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow–derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury.

Approach and Results—

We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. RECs and BMDEPCs participate in barrier repair. Immunofluorescence staining demonstrated that RECs proliferate in situ on endothelial layer and that BMDEPCs are engrafted into endothelial layer of lung microvessels at the active barrier repair phase. In lungs, 8 weeks after lipopolysaccharide-induced injury, the number of REC-derived ECs (CD45
−
/CD31
+
/BrdU
+
/rtTA
+
) or BMDEPC-derived ECs (CD45
−
/CD31
+
/eNOS
+
/GFP
+
) increased by 22- or 121-fold, respectively. The suppression of REC or BMDEPC proliferation by blocking REC or BMDEPC intrinsic nuclear factor-κB at the barrier repair phase was associated with an augmented endothelial permeability and impeded endothelial barrier recovery. RECs and BMDEPCs contributed differently to endothelial barrier repair. In lungs, 8 weeks after lipopolysaccharide-induced injury, REC-derived ECs constituted 22%, but BMDEPC-derived ECs constituted only 3.7% of the total new ECs.

Conclusions—
REC is a major and BMDEPC is a complementary source of new ECs in endothelial barrier restoration. RECs and BMDEPCs play important roles in endothelial barrier restoration after inflammatory lung injury.
The VASOGRADE
Authors: de Oliveira Manoel Airton Leonardo , Jaja Blessing N. , Germans Menno R. , Yan Han , Qian Winnie , Kouzmina Ekaterina , Marotta Tom R. , Turkel-Parrella David , Schweizer Tom A. , Macdonald R. Loch ,   The SAHIT Collaborators, Etminan Nima , Hanggi Daniel , Hasan David , Johnston S. Claiborne , Le Roux Peter , Mayer Stephan , Molyneux Andrew , Noble Adam , Quinn Audrey , Schenk Thomas , Spears Julian , Todd Michael , Torner James , Tseng Ming , van den Bergh William , Vergouwen Mervyn D.I. , Wong George K.C. , Tseng Ming-Yuan 
Published: May 2015

Background and Purpose—
Patients are classically at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading scale—the VASOGRADE—for prediction of DCI.

Methods—
We used data of 3 phase II randomized clinical trials and a single hospital series to assess the relationship between the VASOGRADE and DCI. The VASOGRADE derived from previously published risk charts and consists of 3 categories: VASOGRADE-Green (modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale [WFNS] 1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1–3); and VASOGRADE-Red (WFNS 4 or 5, irrespective of modified Fisher grade). The relation between the VASOGRADE and DCI was assessed by logistic regression models. The predictive accuracy of the VASOGRADE was assessed by receiver operating characteristics curve and calibration plots.

Results—

In a cohort of 746 patients, the VASOGRADE significantly predicted DCI (
P
<0.001). The VASOGRADE-Yellow had a tendency for increased risk for DCI (odds ratio [OR], 1.31; 95% CI, 0.77–2.23) when compared with VASOGRADE-Green; those with VASOGRADE-Red had a 3-fold higher risk of DCI (OR, 3.19; 95% CI, 2.07–4.50). Studies were not a significant confounding factor between the VASOGRADE and DCI. The VASOGRADE had an adequate discrimination for prediction of DCI (area under the receiver operating characteristics curve=0.63) and good calibration.

Conclusions—
The VASOGRADE results validated previously published risk charts in a large and diverse sample of subarachnoid hemorrhage patients, which allows DCI risk stratification on presentation after subarachnoid hemorrhage. It could help to select patients at high risk of DCI, as well as standardize treatment protocols and research studies.