bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C32: Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings
Authors: Fairley Temeika L. , Buchanan Natasha , Johnson-Turbes Ashani , Schover Leslie R. , Moore Angela R. , Yancy Brandie , Schleuter Dara , Hall Mary-Ann K. , Hodges Kelly P. , Shoretz Rochelle
Published: May 2015

Introduction/Objectives: Research demonstrates that after a breast cancer diagnosis, young women, especially those of racial and ethnic groups, may experience a more negative impact on their quality of life, emotional functioning, and reproductive health than older women. For women under the age of 45, African American women have the highest breast cancer incidence of any racial/ethnic group, and there is an increased risk of hereditary breast cancer among Jews who carry BRCA mutations. In conjunction with Sisters Network Inc. and Sharsheret, The Centers for Disease Control and Prevention launched a formative evaluation to understand African American and Jewish young breast cancer survivors' (YBCS) psychosocial and reproductive health needs and preferred communication channels to obtain needed health information.

Methods: Sisters Network Inc. conducted four focus groups with African American YBCS. Sharsheret conducted four groups with Jewish YBCS. Thematic analysis identified major themes/patterns within and across the focus groups.

Results: Fertility and sexual health were major YBCS concerns. Participants reported barriers to obtaining psychosocial and reproductive health information, including sexual taboos and lack of provider sensitivity to address these needs. Participants said that breast cancer resources are not tailored to YBCS. Participants preferred to receive breast cancer information via multiple channels, including written materials, the Internet, telephone and smartphone applications.

Discussion/Implications: African American and Jewish women encounter similar barriers to obtaining psychosocial and reproductive health information. Both groups report difficulty in obtaining relevant health information and advice from their medical providers. Study findings may be used for developing of culturally-appropriate communication and interventions for YBCS that would help eliminate breast cancer health disparities in YBCS.

Citation Format: Temeika L. Fairley, Natasha Buchanan, Ashani Johnson-Turbes, Leslie R. Schover, Angela R. Moore, Brandie Yancy, Dara Schleuter, Mary-Ann K. Hall, Kelly P. Hodges, Rochelle Shoretz. Developing culturally appropriate interventions providing psychosocial and reproductive health support to young breast cancer survivors: Evaluation findings. [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 C32. doi:10.1158/1538-7755.DISP13-C32
Abstract C38: The decrease of the survivin protein expression induces chromosomal missegregation in colon cancer patients lymphocytes treated with oxaliplatin and vinflunine
Authors: Alotaibi Amal A.
Published: May 2015

Survivin is a novel member of the IAP family of proteins with a potential dual role in apoptosis inhibition and regulation of mitosis. In addition, survivin is implicated in the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis, and chemoresistance. Survivin is up-regulated in almost all cancers, including colon cancer, but has low or no expression in most normal, differentiated adult tissues. Expression of survivin in cancer cells has been shown to promote tumorigenesis. Besides, the expression levels of survivin strongly correlate with the proliferative activity of the tumours indicating a possible role in cell cycle regulation and cancer progression.

However, the effect of a novel chemotherapy such as oxaliplatin and vinflunine on survivin expression has been not well characterized yet. Therefore, the effects of oxaliplatin and vinflunine treatment on survivin protein expression in lymphocytes from colon cancer patients against healthy volunteers were investigated. Treatment with either oxaliplatin or vinflunine significantly increased the formation of micronuclei with p < 0.01 in dose-dependent manner by using a cytokinesis-block micronucleus (CBMN) assay. In addition, treatment with both compounds increased chromosomal missegregation (p<0.01) as investigated by a combination of the CBMN assay with fluorescence in situ hybridisation (MN-FISH). Survivin protein expression in lymphocytes from colon cancer patients treated with oxaliplatin and vinflunine were evaluated by Western blot assay. The expression of survivin was significantly reduced up to 3-fold and 6-fold in survivin expression in all the concentrations of oxaliplatin and vinflunine tested respectively (p < 0.001).

In conclusion, significant reduction in survivin protein expression was observed in lymphocytes from colon cancer patients exposed to oxaliplatin or vinflunine. Also evidence for mitotic catastrophe has been found for the first time as one plausible mechanism of oxaliplatin and vinflunine induced lymphocyte death. Oxaliplatin and vinflunine effectively induce DNA damage in vitro leading to aneuploidy in human lymphocytes observed in chromosome missegregation during M-phase. Future work will examine the actual impact of DNA damage to improve chemotherapy treatment or open a new approach in cancer therapy.

Citation Format: Amal A. Alotaibi. The decrease of the survivin protein expression induces chromosomal missegregation in colon cancer patients lymphocytes treated with oxaliplatin and vinflunine. [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 C38. doi:10.1158/1538-7755.DISP13-C38
Abstract C41: Palliative care consults in terminal cancer patients dying in a safety-net hospital: Are they underutilized?
Authors: Wiatrek Rebecca L. , Alawadi Zeinab I. , Lew Debbie F. , Zuo Melanie E. , Ferrer Jeanette G. , Ko Tien C. , Kao Lillian S. , Wray Curtis J.
Published: May 2015

Introduction: Terminal patients with limited resources are more likely to die in the hospital which may be due in part to lack of access to palliative care. We hypothesized that the majority of terminal cancer patients who were treated and who died in a safety-net hospital did not receive a palliative care consult.

Methods: A retrospective review of terminal cancer patients who were admitted and died at Lyndon Baines Johnson General Hospital, a safety-net hospital, from January through December 2012 was completed. Terminal cancer was defined as Stage IV or recurrent cancer with only palliative treatment options. Data was gathered on age, race/ethnicity, sex, length of stay (LOS) of final admission, underlying terminal cancer, insurance status, and receipt of a palliative consult. Univariate analysis was performed using chi-square and Kruskal-Wallis test.

Results: Seventy-four patients with terminal cancer died in the hospital. The majority of patients were minorities: African Americans (n=28, 38%), Hispanics (n=27, 36%), Caucasians (n=14, 19%), and Asian/other ethnicities (n=5, 7%). Two-thirds of patients (n=49, 66%) received palliative consults. There was no difference in race/ethnicity, gender, or age between patients who did and did not receive palliative consults. Patients who received a palliative consult were more likely to be uninsured (90% vs. 56%, p=0.003). There was no difference in median LOS (interquartile range, days) of the final admission between patients who did and did not receive a palliative consult (7, 3-16 versus 6, 2-15 days; p=0.47).

Conclusions: In a safety-net hospital, in-hospital deaths still occur among terminal cancer patients even when palliative care consults are received. Further studies are necessary to determine how palliative care can best address the needs of vulnerable patients in order to reduce in-hospital deaths and improve patient-centered outcomes.

Citation Format: Rebecca L. Wiatrek, Zeinab I. Alawadi, Debbie F. Lew, Melanie E. Zuo, Jeanette G. Ferrer, Tien C. Ko, Lillian S. Kao, Curtis J. Wray. Palliative care consults in terminal cancer patients dying in a safety-net hospital: Are they underutilized?. [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 C41. doi:10.1158/1538-7755.DISP13-C41
Abstract C64: Iroquois homeobox gene 3 is temporally regulated in response to vascular endothelial growth factor and modulates endothelial cell migration
Authors: Scarlett Kisha , Vaishnavi Pattabiraman , Anderson Leonard
Published: May 2015

Purpose: Differences in tumor-induced angiogenesis contributes to cancer-related health disparities. Understanding the transcriptional regulation of angiogenesis within endothelial cells (ECs) is essential to the development of anti-angiogenic therapies, and decreasing the health disparity gap in terms of cancer treatment. Here we report that the homeobox gene, irx3 is expressed in human microvascular endothelial cells (HMECs) and modulates their migration and ability to form networks during angiogenesis.

Methods: To test the effects of vascular endothelial growth factor (VEGF) on irx3 expression, HMECs were treated with VEGF for 0 to 48 hours followed by extraction of total RNA and protein. irx3 mRNA and protein expression were determined using qRT-PCR and western immunoblot respectively. Wound-healing and transwell migration assays were performed to investigate the role of irx3 on EC migration in response to VEGF. For migration experiments, HMECs were transduced with adenoviral vectors resulting in the loss-of (Ad.mirIrx3-GFP) or gain-of (Ad.Irx3-V5) irx3 function. We conducted a 672 transcription factor (TF) siRNA screen to identify transcriptional regulators of irx3 expression in response to VEGF. HMECs were reverse-transfected with siRNAs and treated with VEGF for 12 hours. Total RNA was extracted for RT-PCR to determine irx3 expression. Finally, we performed in vitro endothelial cell tubulogenesis assays using HMECs transduced with Ad.Irx3-V5, Ad.mirIrx3-GFP and their respective controls to study changes in endothelial tube formation as a result of differential irx3 expression.

Results: VEGF treatment increases irx3 expression at the mRNA and protein levels, with peak expression at 12 hours. HMECs transduced with Ad.mirIrx3-GFP exhibited decreased migration at 12 hours compared to HMECs transduced with Ad.Irx3-V5. Furthermore, when HMECs are transduced with Ad.Irx3-V5, they exhibit increased migration and invasiveness in transwell migration assays and form more complex networks during tube formation. The siRNA screen suggests that irx3 is regulated by HEY1, a known transcriptional regulator of angiogenesis.

Conclusion: Our results provide compelling evidence that the homeobox gene irx3 regulates EC migration, and is directly regulated by TFs known to govern transcriptional signaling during angiogenesis.

Citation Format: Kisha Scarlett, Pattabiraman Vaishnavi, Leonard Anderson. Iroquois homeobox gene 3 is temporally regulated in response to vascular endothelial growth factor and modulates endothelial cell migration. [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 C64. doi:10.1158/1538-7755.DISP13-C64
Abstract C65: Loss of imprinting of KCNK9 in African American women with triple-negative breast cancer
Authors: Desai Shraddha , Skaar David , Dietze Eric , Ambrose Adrian , Jirtle Randy , Seewaldt Victoria
Published: May 2015

Background: It has been long suspected that prenatal nutrition and environmental toxins play a role in promoting breast cancer. Genomic imprinting is an inherited form of parent-of-origin-specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. Recent studies show that exposure to the environmental plastic bis-phenol A and vitamin D deficiencies promote loss of normal imprinting. African American (AA) women are known to have vitamin D deficiency at a significantly higher frequency than women of Northern European descent. Here we investigated a mechanism that may explain the higher rate of aggressive triple-negative breast cancers (TNBC) in AA women.

Methods and Results: KCNK9 encodes TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. Our studies have identified a differentially methylated region (DMR) for KCNK9 and shown monoallelic expression of KCNK9 in breast tissue. Using patient samples, we show loss of imprinted expression in tumor cells, loss of KCNK9 regulatory methylation in 75% of TNBC samples, and loss of methylation in non-cancerous tissue from high-risk AA women. In live TNBC cells and non-cancerous mammary epithelial cells from high-risk women, loss of KCNK9 DMR methylation correlates with increased mitochondrial membrane potential.

Significance: This is the first identification of the KCNK9 DMR and demonstration that loss of methylation and overexpression of TASK3 increases mitochondrial membrane potential and promotes apoptosis resistance. These novel findings regarding KCNK9 loss of methylation and its disruption in a subset of tumors may lead to new approaches in diagnosis and targeted therapy of breast cancer.

Citation Format: Shraddha Desai, David Skaar, Eric Dietze, Adrian Ambrose, Randy Jirtle, Victoria Seewaldt. Loss of imprinting of KCNK9 in African American women with triple-negative breast 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 C65. doi:10.1158/1538-7755.DISP13-C65
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

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

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

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

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

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

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 (>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.
Hydrogen Sulfide Levels and Nuclear Factor‐Erythroid 2‐Related Factor 2 (NRF2) Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)
Authors: Islam Kazi N. , Polhemus David J. , Donnarumma Erminia , Brewster Luke P. , Lefer David J.
Published: May 2015

Background

Cystathionine γ‐lyase, cystathionine β‐synthase, and 3‐mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen sulfide (H
2
S). Functions of H
2
S are mediated by several targets including ion channels and signaling proteins. Nuclear factor‐erythroid 2‐related factor 2 is responsible for the expression of antioxidant response element–regulated genes and is known to be upregulated by H
2
S. We examined the levels of H
2
S, H
2
S‐producing enzymes, and nuclear factor‐erythroid 2‐related factor 2 activation status in skeletal muscle obtained from critical limb ischemia (
CLI
) patients.

Methods and Results

Gastrocnemius tissues were attained postamputation from human
CLI
and healthy control patients. We found
mRNA
and protein levels of cystathionine γ‐lyase, cystathionine β‐synthase, and 3‐mercaptopyruvate sulfurtransferase were significantly decreased in skeletal muscle of
CLI
patients as compared to control. H
2
S and sulfane sulfur levels were significantly decreased in skeletal muscle of
CLI
patients. We also observed significant reductions in nuclear factor‐erythroid 2‐related factor 2 activation as well as antioxidant proteins, such as Cu, Zn‐superoxide dismutase, catalase, and glutathione peroxidase in skeletal muscle of
CLI
patients. Biomarkers of oxidative stress, such as malondialdehyde and protein carbonyl formation, were significantly increased in skeletal muscle of
CLI
patients as compared to healthy controls.

Conclusions

The data demonstrate that H
2
S bioavailability and nuclear factor‐erythroid 2‐related factor 2 activation are both attenuated in
CLI
tissues concomitant with significantly increased oxidative stress. Reductions in the activity of H
2
S‐producing enzymes may contribute to the pathogenesis of
CLI
.
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.
The genus Elaphopsocus Roesler (Psocodea: `Psocoptera´: Psocidae) with six new species from Brazil and Colombia
Authors: ROMÁN-P. CRISTIAN , OBANDO RANULFO GONZÁLEZ , ALDRETE ALFONSO N. GARCÍA
Published: May 2015

Six new species of Elaphopsocus Roesler from Brazil and Colombia are described and illustrated. Revised generic diagnoses are provided for Elaphopsocoides and Elaphopsocus; based on the structure of the male hypandrium and phallosome three species groups are recognized in Elaphopsocus.
A new Atractides Koch (Acari: Hydrachnidia, Hygrobatidae) species from southwestern Turkey
Authors: GÜLLE PINAR , GÜLLE İSKENDER , BOYACI YUNUS ÖMER
Published: May 2015

Description of a new Atractides species, Atractides reinhardi n. sp., from Burdur Province of Turkey is given.
Rectification of the type locality of Ischnocnema paranaensis (Anura: Brachycephalidae), a missing species of the Atlantic Forest of Brazil
Authors: BORNSCHEIN MARCOS R. , MAURÍCIO GIOVANNI NACHTIGALL , PIE MARCIO R.
Published: May 2015

Ischnocnema paranaensis (Langone & Segalla, 1996) was described on the basis of a specimen collected in 1988 in a high-altitude site in the Atlantic Forest of the state of Paraná, southern Brazil (Langone & Segalla 1996). Since then, no additional records of the species have been obtained, despite being searched for multiple times shortly after its description (Eterovick et al. 2005). Several surveys at high altitudes in Paraná (e.g. Alves et al. 2006, Langone et al. 2008), some of which in the same region where the type was collected (Ribeiro et al. 2005, Fontoura et al. 2011), also failed to find this species. The species was therefore considered endangered in the state of Paraná (Segalla & Langone 2004), and the possibility that it had disappeared from the highlands was also considered (Eterovick et al. 2005). A species without any records for nearly 30 years should be sought mainly at its type locality, yet, the location of the type locality was incorrectly reported in the original description. Therefore, we here rectify the type locality of I. paranaensis.
The male imago of Paramaka incognita Domínguez, Grillet, Nieto, Molineri and Guerrero, 2014 (Ephemeroptera: Leptophlebiidae)
Authors: BOLDRINI R. , BARROSO P. C. S.
Published: May 2015

The genus Paramaka Savage & Domínguez, 1992 (Ephemeroptera: Leptophlebiidae) is restricted to South America, and it is comprised of four species. The male imago of P. incognita is described for the first time based on material from the state of Roraima in northern Brazil. The male adult differs from other described species of the genus by having the following combination of characteristics: Forewing with costal and subcostal areas basally washed with light yellowish brown; hind wing with base of wing washed with yellowish brown; abdominal terga II–V and VI–IX with lateral margins washed with reddish brown; abdominal sterna VI–VIII with lateral blackish stripes; styliger plate median portion with a pointed, posterior projection that is oriented in a posterior direction; and penes with ventral spines length subequal to length of penes, located on the distal third of the penes.
First record of cassava mealybug, Phenacoccus manihoti (Hemiptera: Pseudococcidae), in Malaysia
Authors: SARTIAMI DEWI , WATSON GILLIAN W. , M.N. MOHAMAD ROFF , HANIFAH Y MOHD , A.B IDRIS.
Published: May 2015

Cassava (Manihot esculenta Crantz, Euphorbiaceae) is an important staple food crop in tropical countries. The leaves and tubers are used for human consumption and livestock feed. The tubers are processed into starch (Winotai et al. 2010) and biofuel (Howeler 2007). In Africa, cassava is a particularly important crop because the tubers can be stored to provide staple food during severe droughts (Calatayud & Le Rü 2006).
Description of three new troglobiontic species of Cybaeodes (Araneae, Liocranidae) endemic to the Iberian Peninsula
Authors: RIBERA CARLES , MAS EVA DE
Published: May 2015

Three new troglobiontic species of the spider genus Cybaeodes Simon endemic to caves in the southeastern Iberian Peninsula are described and illustrated: Cybaeodes indalo sp. n. from Almería, C. dosaguas sp. n. from València and C. magnus sp. n. from Alacant. The new species confirm the presence of Cybaeodes on the Iberian Peninsula and its wide distribution throughout the Western Mediterranean including Algeria, Tunisia, Italy, France, Spain and the islands of Sardinia, Sicily and Mallorca. A record of C. liocraninus (Simon), from an Iberian cave was probably based on misidentified specimens of C. magnus sp. n. C. liocraninus is known only from Algeria and should be removed from lists of the Iberian fauna. In addition, the three new species are clear candidates for protection: they have highly restricted ranges and show a high degree of adaptation to the subterranean environment.
First record of the orchid bee genus Eufriesea Cockerell (Hymenoptera: Apidae: Euglossini) in the United States
Authors: GRISWOLD TERRY , HERNDON JAMES D. , GONZALEZ VICTOR H.
Published: May 2015

The orchid bee genus Eufriesea Cockerell is documented for the first time from the southwestern United States, extending its apparent range north well beyond its previous tropical/subtropical boundaries. Eufriesea coerulescens (Lepeletier de Saint Fargeau 1841) is recorded from the Guadalupe Mountains of western Texas and southeastern New Mexico, USA. Whether E. coerulescens is resident in the USA, or merely a vagrant from Mexico, remains unclear. Distinctive morphological traits shared with the holotype are enumerated and illustrated. In addition, observations that question the current species concept and distribution of E. coerulescens are provided.
Using Citizen Science Reports to Evaluate Estimates of Surface Precipitation Type
Authors: Chen Sheng , Gourley Jonathan J. , Hong Yang , Cao Qing , Carr Nicholas , Kirstetter Pierre-Emmanuel , Zhang Jian , Flamig Zac
Published: May 2015

In meteorological investigations, the reference variable or “ground truth” typically comes from an instrument. This study uses human observations of surface precipitation types to evaluate the same variables that are estimated from an automated algorithm. The NOAA/National Severe Storms Laboratory’s Multi-Radar Multi-Sensor (MRMS) system relies primarily on observations from the Next Generation Radar (NEXRAD) network and model analyses from the Earth System Research Laboratory’s Rapid Refresh (RAP) system. Each hour, MRMS yields quantitative precipitation estimates and surface precipitation types as rain or snow. To date, the surface precipitation type product has received little attention beyond case studies. This study uses precipitation type reports collected by citizen scientists who have contributed observations to the meteorological Phenomena Identification Near the Ground (mPING) project. Citizen scientist reports of rain and snow during the winter season from 19 December 2012 to 30 April 2013 across the United States are compared to the MRMS precipitation type products. Results show that while the mPING reports have a limited spatial distribution (they are concentrated in urban areas), they yield similar critical success indexes of MRMS precipitation types in different cities. The remaining disagreement is attributed to an MRMS algorithmic deficiency of yielding too much rain, as opposed to biases in the mPING reports. The study also shows reduced detectability of snow compared to rain, which is attributed to lack of sensitivity at S band and the shallow nature of winter storms. Some suggestions are provided for improving the MRMS precipitation type algorithm based on these findings.
Improving Climate Change Detection through Optimal Seasonal Averaging: The Case of the North Atlantic Jet and European Precipitation
Authors: Zappa Giuseppe , Hoskins Brian J. , Shepherd Theodore G.
Published: May 2015

The detection of anthropogenic climate change can be improved by recognizing the seasonality in the climate change response. This is demonstrated for the North Atlantic jet [zonal wind at 850 hPa (U850)] and European precipitation responses projected by the climate models from phase 5 of CMIP (CMIP5). The U850 future response is characterized by a marked seasonality: an eastward extension of the North Atlantic jet into Europe in November–April and a poleward shift in May–October. Under the RCP8.5 scenario, the multimodel mean response in U850 in these two extended seasonal means emerges by 2035–40 for the lower-latitude features and by 2050–70 for the higher-latitude features, relative to the 1960–90 climate. This is 5–15 years earlier than when evaluated in the traditional meteorological seasons (December–February and June–August), and it results from an increase in the signal-to-noise ratio associated with the spatial coherence of the response within the extended seasons. The annual mean response lacks important information on the seasonality of the response without improving the signal-to-noise ratio. The same two extended seasons are demonstrated to capture the seasonality of the European precipitation response to climate change and to anticipate its emergence by 10–20 years. Furthermore, some of the regional responses (such as the Mediterranean precipitation decline and the U850 response in North Africa in the extended winter) are projected to emerge by 2020–25, according to the models with a strong response. Therefore, observations might soon be useful to test aspects of the atmospheric circulation response predicted by some of the CMIP5 models.