bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4140: Discovery and characterization of novel highly potent A2A adenosine receptor antagonists for cancerimmunotherapy
Authors: Lee Kyungik , Jun Seungah , Byun EunYoung , Lee Hosun , Lee Yongtaek , Moon MiJin , Kim Yu-Yon , Kang Hyun Jeong , Ahn YoungGil , Kim YoungHoon , Suh Kwee Hyun 
Published: August 2019

Abstract
Introduction: Extracellular adenosine produced at high concentrations within the tumor micro-environment (TME) and suppresses immune function via inhibition of immune cell activation. Targeting adenosine receptors has emerged as a novel method to activate anti-tumor immunity. In particular, A2A adenosine receptor (A2AR), one of the G-protein-coupled-receptors, exhibits immunosuppressive functions. Herein, we suggest novel A2AR antagonist lead compounds as a highly potent antagonist of A2AR for immunotherapy.
Materials and Methods: Novel A2AR antagonist lead compounds were designed using CADD and synthesized as the active biologic inhibitory compound. The protein preparation and molecular docking were performed using Glide (Schrödinger). A radioligand binding assay was performed to evaluate the affinities of A2AR Antagonists for the human adenosine A2AR. The potencie of A2AR antagonists were determined by cAMP assay in HEK293-hA2AR cells and cAMP-mediated pCREB assay in human CD8+ T cells from whole blood. In vivo CT26 and MC38 syngeneic tumor models were used to assess the therapeutic effect of A2AR antagonists.
Results: A2AR antagonist lead compounds showed strong binding affinities toward human A2AR. They also potently inhibited the NECA-mediated production of intracellular cAMP in HEK293 cells expressing human A2AR. Elevated intracellular cAMP following A2AR activation results in the phosphorylation of CREB (cAMP response element-binding protein). A2AR antagonist lead compounds treatment inhibited pCREB in NECA-stimulated HEK293-hA2AR and human CD8+ T cells. A2AR antagonist lead compounds inhibited tumor growth of mouse syngeneic tumor models as a single agent and combination with anti-PD-L1. In combination with anti-PD-L1, A2AR antagonist lead compounds had remarkable antitumor activities in multiple mouse tumor models, including restoration of immune responses in models that incompletely responded to anti-PD-L1 monotherapy.
Conclusion: These results showed the potencies of A2AR antagonist lead compounds with high capability of A2AR inhibition. Blockade of the adenosine signaling pathway may be vital for enhancing anti-tumor responses in solid tumors that show an incomplete response to anti-PD-L1 therapy. A2AR antagonist lead compounds demonstrate a novel approach to anti-cancer immunotherapy.
Citation Format: Kyungik Lee, Seungah Jun, EunYoung Byun, Hosun Lee, Yongtaek Lee, MiJin Moon, Yu-Yon Kim, Hyun Jeong Kang, YoungGil Ahn, YoungHoon Kim, Kwee Hyun Suh. Discovery and characterization of novel highly potent A2A adenosine receptor antagonists for cancerimmunotherapy [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 4140.
Abstract 4181: Awareness of human papillomavirus (HPV) infection among men and women with oral cancer
Authors: Miller Assia , Rollins Latrice , Banerjee Ananya 
Published: August 2019

Abstract
Background There is a high level of public awareness of association human papillomavirus (HPV) infection and genital cancer. Though recent research showed that 26 million Americans have oral HPV infection, the information on awareness of association HPV infection with oral cancer among men and women is limited.
Methods The objective of our study was to assess population awareness of and knowledge about the association between HPV and oral cancer among men and women. We obtained cross-sectional data from the National Cancer Institute's Health Information National Trends Surveys (HINTS 2007-2015, N=25,410). We applied a Wald chi-square test to examine the association of HPV awareness in participants with oral cancer compared to participants with other forms of cancer stratified by gender.
Results: Among men with oral cancer (N=10) 16 % were aware of HPV while among men with other forms of cancer (N=3557) 44% were aware of HPV (p=0.0924). Among women with oral cancer (N=5) 56 % were aware of HPV while among women with other forms of cancer (N=5631) 64% were aware of HPV (p=7971).
Conclusion: There is decreased awareness and knowledge of HPV in men with oral cancer promoting opportunities to target communication about a vaccine.
Citation Format: Assia Miller, Latrice Rollins, Ananya Banerjee. Awareness of human papillomavirus (HPV) infection among men and women with oral 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 4181.
Abstract 4187: Racial disparities in kidney cancer incidence across South Texas, Texas, and United States using TCR, SEER and NPCR registries (2004-2014)
Authors: Perez Casey , Shah Pankil K. , Mathews Aaron , Munoz Edgar , Bokov Alex , Kaushik Dharam , Michalek Joel , Ramirez Amelie , Rodriguez Ronald , Shah Dimpy P. 
Published: August 2019

Abstract
Introduction: Despite overall decrease in incidence of cancers in U.S., kidney cancer is one out of the only seven cancers with increasing incidence. Limited research has been conducted using national, state-wide, and regional data, especially comparing racial and ethnic disparities in incidence and outcomes for kidney cancer.
Methods: Kidney cancer incidence and outcomes from 2004 to 2014 were compared using Texas Cancer Registry, National Program for Cancer Registries, and Surveillance, Epidemiology and End Results. Age-adjusted incidence rates (per 100,000 population) and temporal trends, reporting sources, diagnosis, patient and tumor characteristics between Hispanics and Non-Hispanic Whites (NHWs) were compared for each state. The Kaplan-Meier method was used for relative survival analyses, which were limited to Texas due to data availability.
Results: A total of 566,716 patients were identified. The temporal trend shows a sustained increase in kidney cancers in U.S. and a consistently higher incidence in TX and South Texas (STX) over the past decade, with Hispanics in particular having the highest annual percent change (APC) among the 20-29 year old age group (5.3 in U.S. and 7.7 in TX, respectively). Age-adjusted kidney cancer incidence was 26.2 in STX, 24.5 in TX and 21.8 in U.S. Both males and females had a higher incidence in STX and TX compared to U.S. (35.1, 32.5 vs. 29.6 for males and 18.8, 17.9 vs.15.2 for females). Overall, Hispanic males in STX had the highest kidney cancer incidence (37.7) throughout U.S. The difference in incidence rate in Hispanics compared to NHWs was significant in STX (4.9) and TX (3.4), compared to U.S. (-0.9). Tumor grade was only available in 60% of cancers in TCR compared to 70% in U.S. Despite localized tumor stage being the most common presentation for all regions, the 5-year survival was lower in Hispanics compared to NHWs in STX (68% vs. 73%) and TX (69% vs. 71%).
Conclusions: Kidney cancer rates were higher in STX and TX when compared to U.S., especially among Hispanic males. Relative 5-year survival between Hispanics and NHWs were similar in TX and STX. Improvement in cancer reporting and detailed studies examining causes for racial/ethnic disparities in incidence in the top 15 states with highest disparities, especially TX, are needed.
Citation Format: Casey Perez, Pankil K. Shah, Aaron Mathews, Edgar Munoz, Alex Bokov, Dharam Kaushik, Joel Michalek, Amelie Ramirez, Ronald Rodriguez, Dimpy P. Shah. Racial disparities in kidney cancer incidence across South Texas, Texas, and United States using TCR, SEER and NPCR registries (2004-2014) [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 4187.
Abstract 419: Single cell-driven secreted proteins as a surrogate biomarker for Cetuximab therapy in colorectal cancer
Authors: Park Ye-Lim , Kim Hwang-Phill , Kang Jun Kyu , Lim Yoo Joo , Song Sang-Hyun , Han Sae-Won , Kim Tae-You 
Published: August 2019

Abstract
Epidermal growth factor receptor (EGFR) blockade is efficacious in KRAS wild-type of colorectal cancer, but acquired resistance is inevitably generated. Here, we established the 5 acquired resistant single cell models (CR cell lines) to cetuximab and investigated the mechanism of acquired resistance using single cell-based whole-exome sequencing and transcriptional profiling. Of these, 4 cell lines have KRAS Q61L mutation and the other has BRAF V600E mutation. From gene enrichment analysis (GSEA), we found that epithelial to mesenchymal transition (EMT) occurs and CXCL chemokine family, which are known as secreted proteins, are overexpressed in the CR cell lines compared with parental cells. Interestingly, we found that CXCL chemokines were strongly secreted/expressed in KRAS/BRAF mutant cell lines and plasma/serum samples from colorectal cancer patients who acquired KRAS/BRAF mutation during cetuximab therapy. CXCL chemokines are regulated coordinately by Slug and NF-B transcription factors and trans-activate EGFR through CXCR2/MMP1/sHB-EGF axis. This process activates MAPK pathway via autocrine. To overcome the resistance to cetuximab, combination treatment of cetuximab and MEK/BRAF inhibitor had a larger antitumor effect compared to the single agents, decreasing the expression of MAPK pathway and secretion of CXCL chemokines. This finding highlights that CXCL chemokines, as a secreted proteins circulating in the bloodstream, show correlation with KRAS/BRAF mutation and could be clinical biomarkers for predicting resistance to anti-EGFR therapy in CRC.
Citation Format: Ye-Lim Park, Hwang-Phill Kim, Jun Kyu Kang, Yoo Joo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim. Single cell-driven secreted proteins as a surrogate biomarker for Cetuximab therapy in colorectal 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 419.
Abstract 4197: Long-term follow-up of a racially and ethnically diverse population of patients with localized prostate cancer who did not undergo initial active treatment
Authors: Slezak Jeff , Eeden Stephen Van Den , Cannavale Kimberly L. , Chein Gary W. , Chao Chun R. 
Published: August 2019

Abstract
Background: Long-term studies of men who were not initially treated for prostate cancer have been limited, especially among ethnic minorities. We sought to provide detailed long-term outcomes of a large, diverse cohort of men diagnosed with prostate cancer between 1997 and 2007 in a large managed care organization.
Methods: Incident prostate cancer cases diagnosed at localized stage were identified using a SEER cancer registry. Treatments were identified by the cancer registry and patients’ medical records. Men were excluded if an initial course of treatment was started within 6 months of diagnosis. All patients were followed to identify later initiation of treatment, suspected prostate cancer metastasis or death. Suspected metastases were manually reviewed and confirmed. Death due to prostate cancer (PCD) was identified using the underlying cause of death on the death certificate. Competing risks methods were used to estimate the cumulative incidence of treatment initiation or metastasis (naive of treatment), and the incidence of death due to prostate cancer or other causes.
Results: A total of 6207 men were included: 60.4% white, 18.9% Black, 15.2% Hispanic and 5.5% Asian or Pacific Islander (API). At 19 years after diagnosis, the estimated incidence of treatment initiation, metastasis, PCD, and death due to other causes was 39.1%, 13.4%, 12.0% and 52.9%, respectively. Rates of treatment initiation at 19 years were highest in Hispanic (44.5%) and Black (44.7%) men, compared to 35.4% in white and 38.6% in API men. Rates of treatment-naïve metastasis as well as PCD were highest in Blacks (19.3% and 14.1%, respectively) and lowest among Hispanics (7.7% and 9.9%, respectively). API men had low rates of PCD through the first 10 years after diagnosis (2.4% compared to 5.6-6.9% for other groups), after which rates increased and at 19 years their estimated rates of PCD (12.0%) approximated those of whites (11.7%).
Conclusions: Significant risks of metastasis and prostate cancer death remains even 15 years after diagnosis among men who were initially untreated. Notably, there is an apparent increasing risk of PCD in API more than 10 years after diagnosis.
Citation Format: Jeff Slezak, Stephen Van Den Eeden, Kimberly L. Cannavale, Gary W. Chein, Chun R. Chao. Long-term follow-up of a racially and ethnically diverse population of patients with localized prostate cancer who did not undergo initial active treatment [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 4197.
Abstract 4211: Breast cancer risk factors by mode of detection among screened women in the Cancer Prevention Study-II
Authors: Gaudet Mia M. , Deubler Emily , Diver W. Ryan , Puvanesarajah Samantha , Patel Alpa V. , Gansler Ted , Flanders Dana , Sherman Mark , Gapstur Susan 
Published: August 2019

Abstract
Identifying risk factors for women at high risk of symptom-detected breast cancers that were missed by screening would enable targeting of alternative prevention strategies. To identify breast cancer risk factors by mode of detection, we examined these associations in heavily-screened women from the Cancer Prevention Study (CPS)-II Nutrition Cohort. Among 76,406 women followed for a median of 13.8 years, 2,469 screen-detected and 1,189 symptom-detected breast cancer cases were diagnosed. Multivariable-adjusted associations were estimated using joint Cox proportional hazards regression models with person-time calculated contingent on screening. The mean (standard deviation) age at baseline was 62.0 (6.6) years for non-cases, 61.6 (6.1) for screen-detected cases, and 61.5 (6.2) for symptom-detected cases. Women with symptom-detected tumors were diagnosed at a slightly younger age (mean=69.4) and less likely to be diagnosed with a localized tumor (65.3%), than women with a screen-detected tumor (mean age at diagnosis=70.4 and localized tumors=83.3%). Factors associated with higher risks of symptom detected vs. screen detected breast cancer, included: current combined menopausal hormone use (HR=2.04, 95% CI 1.70 - 2.46 vs. HR=1.43, 95% CI 1.25 - 1.63), current estrogen only menopausal hormone use (HR=1.41, 95% CI 1.15 - 1.72 vs. HR=0.94, 95% CI 0.82 - 1.09), and history of benign breast disease (HR=1.89, 95% CI 1.67 - 2.13 vs. HR=1.49, 95% CI 1.36 - 1.62). The opposite pattern of higher risk of screen detected vs. symptom detected breast cancer was observed for greater adult weight gain (HR=2.32, 95% CI 1.91 - 2.82 vs. HR=1.42, 95% CI 1.10 - 1.84) and alcohol intake (HR=1.39, 95% CI 1.24 - 1.64 vs. HR=1.20, 95% CI 0.92 - 1.58). Our results suggest that understanding risk factors for symptom-detected cancers may help identify women who would benefit from more intensive screening to facilitate early detection.
Citation Format: Mia M. Gaudet, Emily Deubler, W. Ryan Diver, Samantha Puvanesarajah, Alpa V. Patel, Ted Gansler, Dana Flanders, Mark Sherman, Susan Gapstur. Breast cancer risk factors by mode of detection among screened women in the Cancer Prevention Study-II [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 4211.
Abstract 4215: Patient and screening characteristics associated with positive lung cancer screening examinations
Authors: Henderson Louise M. , Sites Samantha , Tailor Tina , Bearden Sara C. , Huamani Roger , Throneburg Allison , Nagle Max , Rivera M Patricia 
Published: August 2019

Abstract
Introduction. The likelihood of having a positive low dose computed tomography (LDCT) lung cancer screening (LCS) examination that requires workup may vary according to patients’ characteristics and risk factors. The purpose of this study is to evaluate patient characteristics associated with positive LCS exams.
Methods. We utilized data from 1684 LDCT exams conducted for LCS at five academic and community sites from 2015-2018. During the screening visit, patients were asked to complete a comprehensive questionnaire including socio-demographics, smoking history, occupational and environmental exposures, family history of lung cancer, and comorbid conditions. Information on the LCS examination, including the radiologists’ Lung Reporting and Data System (Lung-RADS) assessment, was obtained from the radiologist report. We dichotomized Lung-RADS into negative (Lung-RADS 1 (negative) or 2 (benign appearance or behavior)) and positive (Lung-RADS 3 (probably benign), 4A (suspicious), or 4B (suspicious)) based on the management recommendation of continuing with annual screening in 12 months or requiring follow-up before 12 months. We compared Lung-RADS results (positive versus negative) by patient characteristics using chi-square tests and examined predictors of positive LCS exams using multivariate logistic regression, reporting adjusted odds ratios (aORs) and 95% confidence intervals (95%CI).
Results. Screened patients ranged in age from 50-78 years, with 46.7% less than 65 years and 53.3% ages 65 or older. Approximately 53.3% were male and 46.7% were female; 84.5% were White, 11.8% were African American, and 3.7% were other races. The majority (76.5%) of screened patients were overweight or obese. Two-thirds (68.5%) of patients had more than one LCS exam. Most (85.0%) LCS exams were negative while 15.0% were positive. There were no significant differences in Lung-RADS assessment by race, gender, education, or body mass index. Lung-RADS were significantly more likely to be positive in those ages 65 and older versus those ages less than 65 (aOR=1.47, 95%CI: 1.03-2.10) and in baseline versus subsequent screening exams (aOR=0.43, 95%CI: 0.30-0.62).
Conclusion. Predictors of having a positive LCS exam requiring work-up before the next recommended annual screening test include being aged 65 and older and having a baseline LCS examination.
Citation Format: Louise M. Henderson, Samantha Sites, Tina Tailor, Sara C. Bearden, Roger Huamani, Allison Throneburg, Max Nagle, M Patricia Rivera. Patient and screening characteristics associated with positive lung cancer screening examinations [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 4215.
Abstract 4236: Evaluating alterations in mRNA biogenesis with TCGA breast cancer sequencing data
Authors: Yan Thomas J. , Burow Matthew E. , Martin Elizabeth C. 
Published: August 2019

Abstract
Alternative splicing leads to the production of multiple mRNA isoforms of a gene transcript with distinct functional characteristics. These events are frequently observed in rapidly dividing cancer cells and are broadly recognized as important signatures for oncogenesis pathways and treatment options. In this study, we utilized data from The Cancer Genome Atlas (TCGA) to identify differences in isoform expression between estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines. RNA sequencing analysis combined with clinical annotation data revealed alterations in isoform expression that were associated with patient survival. These global changes in isoform expression occurred independently of total gene expression in both estrogen receptor-positive and -negative breast cancer. Furthermore, we identified multiple underrepresented isoforms including CDKAL1 and CSTF3 that were associated with favorable prognostic outcomes despite a lack of association observed with their traditional transcripts. These data suggest an underlying role mediated by alternative spliced isoforms in driving clinical outcome in breast cancer, warranting further investigation in delineating isoform expression profiles in previously established cancer pathways.
Citation Format: Thomas J. Yan, Matthew E. Burow, Elizabeth C. Martin. Evaluating alterations in mRNA biogenesis with TCGA breast cancer sequencing data [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 4236.
Abstract 4241: Molecular profile of tumor-associated adipose in obese women with breast cancer
Authors: Infante Niel , Coad James , Primerano Donald , Denvir James , Vona-Davis Linda 
Published: August 2019

Abstract
Breast tumors have a direct physical and vascular interface with white adipose tissue, making them ideal model systems to study the adipose-tumor microenvironment, especially within the context of obesity. As a first initiative to understanding how adipose tissue contributes to breast tumor etiology, we explored cancer-associated adipose tissue in patients with invasive breast cancer. We hypothesized that obesity leads to greater alterations in cancer-associated adipose tissue by expressing genes involved in cellular growth, angiogenesis, and invasion, thus providing support for breast cancer progression. We also proposed that adipocytes adjacent to tumors express a genotype unique to obese breast cancers. Adipose tissue samples (n=10) were obtained from obese and lean women with breast cancer. Within individuals, tissue was sampled proximal and distal (2 cm) to the tumor. Using next-generation whole transcriptome sequencing, we examined genes from cancer-associated adipose tissue in both groups. A heat map of normalized expression values was generated with unsupervised clustering and the fifty most informative genes. Samples from obese individuals with breast cancer tended to cluster together. There were significant gene differences between adipose collected proximal versus distal from the tumor in obese but not in lean women, such as genes associated with myosin heavy chains MYH1, 4, 8, and 11 (adj. p &lt; 0.05). In examining obese women, there were 16 Hallmark pathways that were statistically significant (adj. p &lt; 0.10); whereas a subset of these (11 pathways) were significant in lean women. Of interest, pathways that were significant in both were pathways that regulate EMT, adipogenesis and TGF beta signaling. The molecular signature of cancer-associated adipocytes is different between lean and obese patients. (Supported by NIH P20GM103434 and NIGMS U54GM104942)
Citation Format: Niel Infante, James Coad, Donald Primerano, James Denvir, Linda Vona-Davis. Molecular profile of tumor-associated adipose in obese women with breast 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 4241.