bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5033: The role of the epigenetic regulator SATB2 in colon cancer progression
Authors: Brennan Donal J. , Naicker Kirsha , Das Sudipto , Moran Bruce , Klinger Rut , Ponten Fredrik , Hewitt Stephen , Jirström Karin , Byrne Annette T. , O'Sullivan Jacintha , Gallagher William M. , O'Connor Darran P. 
Published: August 2019

Abstract
SATB2 is a nuclear matrix-associated transcription factor that orchestrates gene expression by regulating higher-order chromatin structure. Using antibody-based screening of 48 normal human tissues and 20 cancer types, we identified SATB2 as a protein almost exclusively expressed in gastrointestinal tissue. We confirmed this observation at the mRNA level in 10,533 human tissue samples. Differential expression of SATB2 was observed in colorectal cancer, with loss of expression occurring along the adenoma-carcinoma sequence. Additionally, SATB2 expression was markedly decreased in metastatic SW620 colon cancer cells and siRNA knockdown of SATB2 expression in parental SW480 cells increased their growth and migratory capacity. Ectopic expression of SATB2 in the metastatic variant reversed the observed phenotype. Using tissue microarray and automated image analysis of SATB2 expression in colorectal cancers (n=309), SATB2 was demonstrated by multivariate Cox regression analysis to be an independent predictor of disease-specific survival (HR=0.52, 95% CI 0.32-0.83, p=0.006). SATB2 mRNA levels were examined in a second cohort (n=290) and again, SATB2 was demonstrated to be an independent predictor of disease-specific survival (HR=0.40, 95% CI 0.18-0.92, p=0.031). Interestingly, in colorectal cancer patients, SATB2 levels significantly correlated with CD3+ T-cell infiltrates in the tumours (p=0.006) and inversely correlated with COX2 expression (p=0.019). In two independent colorectal cancer cohorts (n=467), SATB2-low tumours were found to be significantly enriched in the CMS1 (immune-related) subtype (p&lt;0.001). Gene set enrichment analysis revealed that SATB2 low tumours demonstrated altered immune signalling with significant increases in IFNγ (p=0.001), IL6 (p=0.001), IL8 (p&lt;0.001) TFGβ (p&lt;0.001), which was mirrored by in vitro manipulation of SATB2 expression in colon cancer cells. Furthermore, in a longitudinal cohort of patients with ulcerative colitis, we observed a significant correlation between loss of SATB2 expression and occurrence of future cancers (p=0.013). We therefore postulate that SATB2 acts as a master regulator of the inflammatory response in the gut and loss of expression is significantly associated with the progression of colorectal cancer.
Citation Format: Donal J. Brennan, Kirsha Naicker, Sudipto Das, Bruce Moran, Rut Klinger, Fredrik Ponten, Stephen Hewitt, Karin Jirström, Annette T. Byrne, Jacintha O'Sullivan, William M. Gallagher, Darran P. O'Connor. The role of the epigenetic regulator SATB2 in colon cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5033.
Abstract 5045: Pineal gland volume and risk of prostate cancer
Authors: Bazzi Latifa A. , Sigurdardottir Lara , Sigurdsson Sigurdur , Valdimarsdottir Unnur , Torfadottir Johanna , Aspelund Thor , Launer Lenore , Harris Tamara , Gudnason Vilmundur , Mucci Lorelei , Markt Sarah 
Published: August 2019

Abstract
Background: The parenchyma of the pineal gland, an endocrine gland in the brain, produces the circadian hormone melatonin. Previously, we found low levels of melatonin were associated with an increased risk for advanced prostate cancer. This study used data from men in the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study to evaluate the relationship between pineal volume, melatonin levels, and prostate cancer risk.
Methods: Participants were enrolled in the AGES-Reykjavik Study from 2002 to 2006 and underwent detailed clinical assessments at baseline that included biospecimen collection, MRI of the brain, medical history, and health questionnaires on dietary and lifestyle factors. We included 802 men who had information on pineal size, where parenchyma, calcification, and cyst volume were estimated individually and manually from the MRIs. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals for risk of prostate cancer during follow-up through 2014, comparing parenchyma volume tertiles.
Results: There was a positive association between pineal parenchyma volume and urinary levels of melatonin. During follow-up, 135 men were diagnosed with prostate cancer, 30 of which were advanced prostate cancer. Men with volumes in the upper tertile had no statistically significant increased risk of prostate cancer compared to men with volumes in the lowest tertile (HR: 1.0, 95% CI: 0.7, 1.5), and men with volumes in the middle tertile had only a borderline statistically significant decreased risk of prostate cancer compared to men with volumes in the lowest tertile (HR: 0.7, 95% CI: 0.4, 1.0). Compared to men without pineal cysts, there was a borderline statistically significant association between men with pineal cysts and decreased risk of prostate cancer (HR: 0.7, 95% CI: 0.5, 1.0). Compared to men without pineal calcifications, there was no statistically significant association between men with pineal calcifications and increased risk of prostate cancer (HR: 1.1, 95% CI: 0.7, 1.6).
Conclusions: Pineal parenchyma volume was associated with melatonin levels, but there was no statistically significant association between parenchyma volume alone and prostate cancer risk. Further studies are needed to investigate the relationship between pineal parenchyma volume, presence of calcifications and cysts, melatonin, and prostate cancer.
Citation Format: Latifa A. Bazzi, Lara Sigurdardottir, Sigurdur Sigurdsson, Unnur Valdimarsdottir, Johanna Torfadottir, Thor Aspelund, Lenore Launer, Tamara Harris, Vilmundur Gudnason, Lorelei Mucci, Sarah Markt. Pineal gland volume and risk of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5045.
Abstract 5058: The association between smoking status at diagnosis and breast cancer specific mortality in Ireland: A population based study
Authors: Kiely Maeve , McDevitt Joesph , Sharp Linda 
Published: August 2019

Abstract
Background: Breast cancer is the most commonly diagnosed cancer worldwide and is a leading cause of breast cancer mortality in females. In recent years, 5 year survival rates have greatly improved for breast cancer however a clear disparity exists between survival in countries of high income compared to low and middle income. Disparity in survival also exists within individual countries. The identification of modifiable lifestyle factors can be an impactful and cost effective way to improve breast cancer outcomes worldwide, particularly in low income counties. An association between active smoking at diagnosis and breast cancer specific mortality has been reported by a number of studies to date. However, there is a paucity of studies undertaken in European populations. This large study was conducted to investigate whether smoking status at diagnosis is an independent prognostic factor for breast cancer specific mortality in the Irish female population.
Methods: All data was derived from the National Cancer Registry Ireland database which records all incident cancers in the Republic of Ireland. Completeness of case ascertainment at 5 years after diagnosis is estimated to be at 98%. Multivariable Cox proportional Hazards models were used to compare breast cancer specific mortality in current smokers, ex-smokers and never smokers. Subgroup analyses by breast cancer molecular subtype was also conducted.
Results: Data for women with known smoking status at time of diagnosis included 37,711 invasive breast cancer cases that accrued 263,626 women-years. Current smokers had a significantly increased risk of breast cancer specific mortality compared to never smokers (multi-variable HR, 1.3; 95% CI, 1.19, 1.41). Ex-smokers did not have a significantly different hazard ratio compared to never smokers (HR, 1.02; 95% CI, 0.92, 1.12). In subgroup analyses, risk of dying from breast cancer was increased most for current smokers with HER2+ disease compared to never smokers in the 5 years post diagnosis (HR, 1.53; 95% CI, 1.11, 2.12). This was followed by luminal A disease (HR, 1.39: 95% CI, 1.17, 1.65).
Conclusion. Breast cancer patients who are current smokers at diagnosis have a statistically significant increased risk of breast cancer specific mortality. This risk differs depending on molecular subtype of disease.
Citation Format: Maeve Kiely, Joesph McDevitt, Linda Sharp. The association between smoking status at diagnosis and breast cancer specific mortality in Ireland: A population based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5058.
Abstract 5069: Breast cancer prevention by triterpenoids from allspice
Authors: Gao Jie , Mamouni Kenza , Kallifatidis Georgios , Panda Siva , Thangaraju Muthusamy , Lokeshwar Bal L. 
Published: August 2019

Abstract
Breast cancer ranks second as a lethal cancer in women. Although survival following initial diagnosis is ~ 100% in first five years, cancer progression and mortality is imminent in subsequent years. The slow progression to the lethal form of breast cancer has prompted development of multiple avenues to delay the progression, metastasis and mortality using potent prevention strategies, including the use of nutraceuticals. Oleanolic acid (OA) and ursolic acid (UA) are two triterpenoids found in edible plant parts-fruits and seeds with potent cancer preventive, and selective cytotoxic activities against multiple cancers including breast cancer. We conducted cytotoxic assays of the combination of OA and UA. We found the combination has enhanced efficacy as compared to OA or UA alone. The combination of OA and UA and UA alone caused cell death by increased autophagy but not apoptosis in both MCF7 and MB231 human breast cancer cells. Further analysis revealed increased autopagosomes and autophagic flux, inhibition of either process reduced cytotoxicity, indicating cytotoxic autophagy is the primary mechanism of their action. Therefore, a combination of OA and UA with conventional therapies could enhance their therapeutic efficacy while limiting systemic toxicities of existing therapies.
Citation Format: Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar. Breast cancer prevention by triterpenoids from allspice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5069.
Abstract 509: Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model
Authors: Turbitt William J. , Orlandella Rachael M. , Gibson Justin T. , Norian Lyse A. 
Published: August 2019

Abstract
Finding ways to enhance T cell infiltration into tumors and boost effector function remains a critical knowledge gap that must be addressed to improve responses to immune-stimulatory therapies. Acarbose and metformin are FDA-approved drugs for the treatment of type two diabetes that display potent anti-hyperglycemic activity. A treatment strategy that decreases intra-tumoral glucose could reduce cancer cell viability and render tumors more susceptible to immunotherapy-mediated clearance. The goal of the current study was to determine if acarbose and/or metformin reduce tumor burdens and promote anti-tumor immunity in a preclinical model of breast cancer. Eight-week-old female C57BL/6 mice were orthotopically injected with EO771-Fluc mammary tumor cells then randomized to control (CTRL), CTRL+acarbose (ACA), CTRL+metformin (MET), or acarbose+metformin (ACA+MET) for four weeks. Compared to CTRL, single-agent ACA reduced primary tumor growth (50% decrease; p&lt;0.001) and spontaneous lung metastases (48% decrease; p=0.035) without altering body weight. No effects of single-agent MET or the combination of ACA+MET on EO771 tumor growth or spontaneous lung metastases were observed. nanoString analysis of whole-tumors revealed increased dendritic cell-, T cell-, T helper 1 cell-, CD8+ T cell-, and exhausted CD8+ T cell-based gene signature scores in ACA compared to CTRL-fed mice. Cellular analysis revealed an ACA-induced increase in the percent of tumor-infiltrating PD-1+CD8+ T cells (p=0.042) and a trend toward decreased tumor-infiltrating myeloid-derived suppressor cells, resulting in improved CD8:MDSC ratios. The beneficial effects of ACA on intra-tumoral immunity, specifically promoting T cell immunity within the tumor microenvironment, illustrate the potential for future combined use of ACA with immunotherapies, such as PD-1 or CTLA-4 blockade.
Citation Format: William J. Turbitt, Rachael M. Orlandella, Justin T. Gibson, Lyse A. Norian. Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 509.
Abstract 5100: Optimization of amplicon design for polymerase chain reaction
Authors: He Bolong , Qin Hao , Li Fugen , Yang Hanyan 
Published: August 2019

Abstract
Amplicon design is critical important in DNA sequencing technology. Previously the amplicon designer uses exhaustive trial and error method, relying on the individual experience to compare the cost of different amplicon combinations. However, optimization of amplicon design has remained challenging due to the lack of a systematic method. As the magnitude of target DNA region and amplicon combination increases, the complexity of manual calculation and judgment will grow exponentially. In this study, our aim was to design a mathematical model to minimize the cost of amplicon combination. For given amplicon design problem, a linear integer programming model is constructed according to the optimization target and the restrictions. Let’s denote our target regions by R_1⋯ R_M, and amplicon by A_1,⋯, A_N, and conflict value c_ij for the amplicon pair A_i and A_j. The model’s restriction is to find a set of amplicons that could cover the target regions as much as possible, and for each R_i we have at most two A_j which will cover it simultaneously. The model’s optimization target is to minimize the total conflict value. The model is implemented by Python programming and uses Gurobi optimization software. In a project to design amplicon for DNA sequencing, the target regions consist of about 90,000 bits, and there are about 35,000 amplicon available. The above optimization method running on the personal computer with 8GB and 2.2GHz Intel i5-5200 CPU, take about 24 hours and produce total conflict value of 1374. The best trial and error practice took more than one week and produced total conflict value of 4527. Optimization of amplicon design for polymerase chain reaction proves to be more precise and efficient than the exhaustive trial and error method. Using optimization method will help standardize the product design for DNA sequencing.
Citation Format: Bolong He, Hao Qin, Fugen Li, Hanyan Yang. Optimization of amplicon design for polymerase chain reaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5100.
Abstract 5109: National cyberinfrastructure and bioinformatic analysis support available to the cancer research community
Authors: Papudeshi Bhavya , Ganote Carrie , Sanders Sheri , Doak Thomas G. 
Published: August 2019

Abstract
National Center for Genomic Analysis Support (NCGAS) is an NSF-funded center whose goal is to help biologists optimize their bioinformatic pipelines to best address their research questions. To help reach these goals, NCGAS provides a range of services based on the researchers needs. We currently host gateways, Trinity Galaxy and Genepattern, with built-in workflows to support cancer researchers who have little background in command line work. Both these gateways are projects funded by the Information Technologies in Cancer Research (ITCR) program of NIH, NCI, to aid in the genomic and transcriptomic characterization of cancers. NSF-funded researchers comfortable in command line can gain access to IU cyberinfrastructure (HIPAA compliant), to run or develop bioinformatic workflows. Bioinformatic packages are already installed system wide, with reference databases, and new programs are always added upon user’s request. NCGAS is also an ambassador of Extreme Science and Engineering Discovery Environment (XSEDE) resources, providing access to other HIPAA compliant national cyberinfrastructure (Texas Advanced Computing Center, Pittsburgh Supercomputing Center, etc.), available to the entire research community. XSEDE resources include the Jetstream cloud, based at IU and TACC, allowing researchers to use preconfigured virtual machines (VMs) already setup, create custom VM environments for their own work, and to share with classes and collaborators. Data can be transferred and managed between all of these resources securely with already available Globus endpoints which allows transfer for terabytes of data quickly. Additionally, NCGAS hosts workshops to help researchers get started. These training events can be scheduled online or at your local university upon request. NCGAS currently supports projects working on transcriptome, genome-level assembly, phylogenetics, metagenomics, and meta-transcriptomics analysis through providing a range of compute resources that best serve the research project.
Citation Format: Bhavya Papudeshi, Carrie Ganote, Sheri Sanders, Thomas G. Doak. National cyberinfrastructure and bioinformatic analysis support available to the cancer research community [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5109.
Abstract 5116: Benchmarking the HLA typing performance of three HLA assay and two software
Authors: Meng Rui , Zhu Tao , Gong Yu , Chen Yanan , Dong Hua , Yizhou Ye , Li Fugen , Liu Ping , Yao Minya 
Published: August 2019

Abstract
Background:The adaptive immune response intrinsically depends on hyper variable human leukocyte antigen (HLA) genes. Correct HLA typing is crucial for successful donor-patient matching in organ transplantation and recently is also an emerging biomarker for immune checkpoint inhibitor. With the great progress on next generation sequencing (NGS) technology, sequencing accuracy and throughput have increased while the cost for data have decreased faster than Moore's Law, thus HLA tying by NGS has been widely used from laboratory to clinic. Method:We tested three NGS assay for HLA typing and two recently published HLA typing software from 24 samples. Three assays involve two target capture methods (WES and HLA target sequencing) and one amplification sequencing method. Two software involve Xhla and HLAHD, respectively. First, we compared 3 assay performance based on PE150 read length and xHLA software by both 4 alleles and 8 alleles. Second, we compared the performance of two widespread HLA typing software xHLA and HLA-HD according to different assay type, read depth, read length and speed. Results:First of all, for PE150 datasets on three assay, the accuracy rate of HLAHD is all 100%, while xhla in WES is 99%, amplicom 98.6%, target HLA sequencing 100%. On reads length evaluation, the accuracy of HLAHD decreases gradually from PE150 to PE100 and PE75, and the capture method is more sensitive to reads length than the amplification assay, while Xhla is very robust on read length. On coverage evaluation, when the amplicom sequencing data was down-sampled 500X to 10X, the accuracy of HLAHHD and XHLA is both 100% in 50X and above and decrease gradually when less than 50X. In terms of time, with the increase in sequencing depth, running time for both software increase. HLAHD prediction from fastq file is longer than that from bam file, especially when the panel data is relatively large, the time will increase exponentially. Conclusions:Our benchmarking dataset show that current HLA assay and computational methods for HLA typing generally provide satisfactory results, while different assay type matched with different software, read depth and read length do affect the performance.
Citation Format: Rui Meng, Tao Zhu, Yu Gong, Yanan Chen, Hua Dong, Ye Yizhou, Fugen Li, Ping Liu, Minya Yao. Benchmarking the HLA typing performance of three HLA assay and two software [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5116.
Abstract 512: Adrenergic modulation of inflammatory cytokines in ovarian cancer
Authors: Colon-Echevarria Claudia B. , Ortiz Tatiana , Maldonado-Laboy Lizette , Hidalgo-Vargas Melanie J. , Aquino Alexandra N. , Armaiz-Pena Guillermo N. 
Published: August 2019

Abstract
Work from our group and others suggest that chronic stress accelerates growth of existing tumors by activating the sympathetic nervous system. Specifically, our data suggest that sustained adrenergic signaling can induce tumor growth, secretion of pro-inflammatory cytokines and macrophage infiltration. Moreover, increased macrophage infiltration was associated with decreased survival in ovarian cancer patients. Hence, we investigated role of adrenergic-stimulated macrophages in ovarian cancer biology. To assess the effect of adrenergic stimulation in pro-tumoral functional outputs, we used cytokine arrays and invasion assays. A pre-clinical orthotopic model of ovarian cancer was used to assess the in vivo effect of daily restraint stress on tumor growth and adrenergic-induced macrophages. Cytokine array analyses showed that adrenergic stimulation modulated pro-inflammatory cytokine secretion in a SKOV3ip1 (ovarian cancer cells) /U937 (macrophages) co-culture system. Among these, 23 significantly upregulated cytokines were identified in both, epinephrine and norepinephrine, treated co-culture systems. PDGF-AA, ENA-78, Angiogenin, VEGF, GM-CSF, IL-5, Lipocalin-2, MIF, and TfR were among upregulated cytokines shared between treatment groups. In addition, daily restraint stress resulted in increased ovarian cancer growth and infiltration of CD68+ macrophages in two orthotopic models of ovarian cancer (SKOV3ip1 and HeyA8), while zoledronic acid (a bisphosphonate that has been shown to impair macrophage activity) abrogated this effect. Immunohistochemistry analyses showed restraint stress increased expression of PDGF-AA and ENA-78 inflammatory cytokines. Here, we show that adrenergic regulation of macrophages might play a key role in the progression of ovarian cancer.
Citation Format: Claudia B. Colon-Echevarria, Tatiana Ortiz, Lizette Maldonado-Laboy, Melanie J. Hidalgo-Vargas, Alexandra N. Aquino, Guillermo N. Armaiz-Pena. Adrenergic modulation of inflammatory cytokines in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 512.