bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4131: Overcoming aryl hydrocarbon receptor mediated tumor immunosuppression
Authors: Tchaicha Jeremy , Coma Silvia , Walsh Meghan , Cavanaugh Jill , Sanchez-Martin Marta , Zhang X. Michelle , Castro Alfredo , Ecsedy Jeff , Manfredi Mark , McGovern Karen 
Published: August 2019

Abstract
Checkpoint inhibitors (CPIs) have become the cornerstone of immune-based oncology therapy; still many cancer patients do not benefit from these agents. Resistance to checkpoint inhibitors is due in part to the presence of immunosuppressive molecules which prevent immune activation despite T cell checkpoint inhibition. Aryl Hydrocarbon Receptor (AHR) is a transcription factor that mediates the immune response in multiple innate and adaptive immune cells subsequent to binding of a diverse set of endogenous and exogenous ligands. One such AHR agonist is kynurenine. Kynurenine, metabolized from tryptophan by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2), binds to AHR and leads to a net immunosuppressive tumor microenvironment.
Given that kynurenine can be synthesized by both IDO1 and TDO2 and that AHR is activated by endogenous ligands other than kynurenine, AHR inhibition provides a novel approach to reverse immunosuppression in a broad range of tumor types. We demonstrated that AHR antagonism affects multiple immune cell types and can lead to pro-inflammatory phenotypes in human T cells and myeloid cells in vitro and in murine tumor models. AHR antagonism inhibits growth in the B16-IDO, CT26 and MC38 models and reverses the immunosuppressive microenvironment as indicated by changes in T cell and myeloid cell populations. Immune signature changes characterized via Nanostring in multiple tumor models treated with AHR antagonists were also assessed.
Oral dosing of AHR antagonists led to tumor growth inhibition as a single agent and increased anti-tumor activity when combined with checkpoint inhibitors. In addition, beneficial anti-tumor activity occurred with AHR antagonists combined with chemotherapy or with radiation therapy in syngeneic mouse tumor models. Our data indicate that reversing AHR-mediated immune suppression in the tumor microenvironment drives anti-tumor activity alone and in combination with other therapeutic modalities.
Overall, our data demonstrates that AHR is an attractive target for reversing immune suppression in tumors. Therefore, we are developing AHR antagonists and translational insights to treat patients most likely to benefit from this approach.
Citation Format: Jeremy Tchaicha, Silvia Coma, Meghan Walsh, Jill Cavanaugh, Marta Sanchez-Martin, X. Michelle Zhang, Alfredo Castro, Jeff Ecsedy, Mark Manfredi, Karen McGovern. Overcoming aryl hydrocarbon receptor mediated tumor immunosuppression [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 4131.
Abstract 4135: Novel dual A2A A2B adenosine receptor antagonists for cancer immunotherapy: in vitro and in vivo characterization
Authors: Galezowski Michal , Węgrzyn Paulina , Bobowska Aneta , Dziedzic Katarzyna , Szeremeta-Spisak Joanna , Nowogrodzki Marcin , Satala Grzegorz , Obara Alicja , Lozinska-Raj Iwona , Dudek Marcelina , Janiga Anita , Reus Jacek , Wronowski Marek , Zastawna Magdalena , Statkiewicz Grzegorz , Rogacki Maciej , Ziembik Magdalena , Grycuk Karolina , Soukou Foteini , Michalik Kinga , Adamus Agnieszka , Wiatrowska Karolina , Lewandowska Natalia , Golas Aniela , Haberkiewicz Olga , Porter Rod , Brzozka Krzysztof , Nowak Mateusz 
Published: August 2019

Abstract
Adenosine is important messenger molecule that is involved in signal transmission in central nervous, cardiovascular and immunological systems. The immunosuppressive role of adenosine attract attention of many researchers recently and reversal of that effect is addressed by several different approaches i.e.: inhibition of enzymes that are producing the adenosine in tumor microenvironment like CD39 and CD73 but also the antagonization of adenosine receptors mainly A2A and A2B subtypes. Here we present a novel series of unsurmountable, dual A2A/A2B antagonists that retain its nanomolar potency in tumor-like adenosine-rich environment. This advantageous profile comes mainly from long residence time in adenosine receptors which transfers into high receptor occupancy even after full clearance of the compound from plasma. We are demonstrating how our inhibitors restore adenosine depleted immune functionality in the series of functional in vitro assays in primary cells. This includes the cytokine release by activated CD4+ and CD8+ human T-lymphocytes (driven by A2A) and dendritic cells (driven by A2B). Most importantly presented compounds show improved in vivo pharmacological profile in comparison to adenosine inhibitors currently tested in clinical trials manifested by high inhibition of CREB phosphorylation in mouse model.
Citation Format: Michal Galezowski, Paulina Węgrzyn, Aneta Bobowska, Katarzyna Dziedzic, Joanna Szeremeta-Spisak, Marcin Nowogrodzki, Grzegorz Satala, Alicja Obara, Iwona Lozinska-Raj, Marcelina Dudek, Anita Janiga, Jacek Reus, Marek Wronowski, Magdalena Zastawna, Grzegorz Statkiewicz, Maciej Rogacki, Magdalena Ziembik, Karolina Grycuk, Foteini Soukou, Kinga Michalik, Agnieszka Adamus, Karolina Wiatrowska, Natalia Lewandowska, Aniela Golas, Olga Haberkiewicz, Rod Porter, Krzysztof Brzozka, Mateusz Nowak. Novel dual A2A A2B adenosine receptor antagonists for cancer immunotherapy: in vitro and in vivo characterization [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 4135.
Abstract 4166: Hereditary cancer syndromes in Guatemalan population
Authors: Carranza Claudia L. , Guerra Mariela , Osorio Claudia , Zamora Vanessa , Herrera Vivian , Gil Jose , Alvarez Luis 
Published: August 2019

Abstract
BACKGROUND The majority of cancer are sporadic, only around 5 % are considered hereditary. Although it is a low percentage, the study of these cancers are of vital importance, since they require a special clinical monitoring and management. These kind of cancers are caused by the presence of an inherited gene mutation, which increase the risk of developing a tumor. The mutations associated with these tumors are germline mutations, this means that are present in all the patient's cells, including the egg cell an sperm; this is the reason why this type of cancer can transmit to the future generations. There are many syndromes that increase the risk of hereditary cancer development, the most frequent syndromes are: Familial Breast and Ovarian cancer (BRCA1 and BRCA2 gene mutations), Lynch syndrome (MSH2, MLH1, MSH6 and PMS2 mutations), Li-Fraumeni syndrome (TP53 gene mutations) and Familial adenomatous polyposis (APC gene mutations). The aim of this study is to screen the most common hereditary cancer syndromes in Guatemalan population.
METHODS We analyzed 199 blood samples of patients with different types of tumors. We extracted DNA from the samples and then analyzed the gene mutations by next generation sequencing.
RESULTS AND DISCUSSION We have included in the present study, 93 cases with Familial Breast cancer and 106 with another type of tumors. Of all cases, we have found 17 cases with hereditary cancer syndromes (8%). The most frequent is the Breast and Ovarian hereditary syndrome caused by BRCA1 and BRCA2 (12 patients). The other hereditary cancer syndromes are shown in Table 1. The detection of this germline mutations, have a large impact in the familial cases, because these patients and their families could be monitored and evaluated more frequently. This is the first report of these syndromes in our population.
CONCLUSION We reported 6 different syndromes and 17 cases, related to hereditary cancer risk and predisposition in Guatemalan population.
Frequency of hereditary cancer syndromesSYNDROMENUMBER OF PATIENTSCANCER TYPEAGESEXGENE MUTATIONBreast and ovarian hereditary syndrome7Breast cancer29-48FBRCA1Breast and ovarian hereditary syndrome5Breast cancer29-71FBRCA2Lynch syndrome1Breast cancer80FMSH6Li-Fraumeni syndrome1Breast cancer58FTP53Breast hereditary cancer1Breast cancer57FCDH1Peutz-Jeghers syndrome1Pancreatic cancer15FSTK11Familial adenomatous polyposis1Colorectal cancer13MAPC
Citation Format: Claudia L. Carranza, Mariela Guerra, Claudia Osorio, Vanessa Zamora, Vivian Herrera, Jose Gil, Luis Alvarez. Hereditary cancer syndromes in Guatemalan population [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 4166.
Abstract 4174: Familiality of ovarian cancer histotypes in the Utah Population Database
Authors: Barnard Mollie E. , Camp Nicola J. , Doherty Jennifer A. 
Published: August 2019

Abstract
Introduction: Ovarian cancer is a heterogeneous disease; each histotype has distinct molecular origins, risk factors and outcomes. While it is well established that ovarian cancer has a familial risk component, the familiality of ovarian cancer histotypes has not been well described. The Utah Population Database (UPDB) captures over 10 million individuals, including more than 5 million with a minimum of three generations of genealogy data. By linking records from the UPDB to the Utah Cancer Registry (UCR) and other statewide data sources, we sought to describe the familiality of ovarian cancer histotypes.
Methods: Our study includes all ovarian cancer cases in the UPDB and leverages clinical data reported to UCR for the case histotypes. Cases were matched to controls on age, birth cohort and at least three generations of UPDB data versus not. We quantified familiality by comparing the odds of ovarian cancer occurrence among family members of cases to the odds of ovarian cancer among family members of matched controls. We calculated odds ratios for first-degree relatives, second-degree relatives, and first cousins.
Results: As of September 2018, the UPDB included 3,989 ovarian cancer cases. We observed an increased risk of epithelial ovarian cancer among first-degree relatives (OR=1.62, 95%CI=1.36-1.93), second-degree relatives (OR=1.53, 95%CI=1.34-1.74), and first cousins (OR=1.38, 95%CI=1.26-1.53) of ovarian cancer cases. When we analyzed epithelial ovarian cancers by histotype, familiality was most evident for high-grade serous, mucinous, and unclassified cancers. For example, we observed a 1.62-fold increased odds (95%CI=1.14-2.29) of high-grade serous ovarian cancer among the first-degree relatives of high-grade serous cases, and a 5.59-fold increased odds (95%CI=2.09-14.92) of mucinous ovarian cancer among first-degree relatives of mucinous ovarian cancer cases. Familiality patterns were less clear among endometrioid and clear cell cases.
Conclusions: The UPDB has the potential to contribute greatly to family-based studies of the genetics of ovarian cancer histotypes. Despite the possible variations in quality of histotype data across generations, preliminary results suggest some histotypes may be particularly familial and good candidates for gene mapping studies. Work is ongoing to refine the histotype assignments for cases by performing pathology review using the 2014 World Health Organization guidelines. Analyses are also in progress to stratify analyses by BRCA mutation status, and to consider the potential for shared familiality across ovarian cancer histotypes and with cancers at other sites.
Citation Format: Mollie E. Barnard, Nicola J. Camp, Jennifer A. Doherty. Familiality of ovarian cancer histotypes in the Utah Population Database [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 4174.
Abstract 418: Ex vivoisolation and culture of circulating tumor cells using microfluidics chip
Authors: Zhang Huirong , Zhao Pan , Wu Han , Zou Chang 
Published: August 2019

Abstract
Background: Circulating tumor cells (CTCs) are the tumor cells shed from primary tumor, which enter the bloodstream and travel to distant anatomic sites to form metastasis. CTCs have been identified as blood-based biomarkers to guide cancer diagnosis and prognosis in many reports. The huge challenge which limits the clinical utility of CTCs, especially in early stage cancer patients, is the rarity. Specifically, there are only 1-10 CTCs in one milliliter of whole blood.
Methods: A microfluidic CTC capture device was used for capture and analysis of CTCs from gastric cancer patients. The patients’ samples were referred to the regulation of ethnic commission of Shenzhen People’s Hospital and informed parental consent for the study. CTCs were collected by cells adherent culture using the CCC medium. Immunofluorescence, karyotyping and mude mouse tumorigenesis were used to verify the CTCs.
Results: A epithelial phenotype cell cluster which named S-CTC came out in the 24-well plate after 8 days. S-CTC cells can steadily formed clones and showed stem-cell like properties. Positive rate of CD133 were reached to 4.7% which demonstrated by flow cytometry. Immunofluorescence identification of S-CTC were DAPI-positive, Cytokeratin-positive, and CD45-negative. The karyotyping results indicated that the chromosomes were aneuploidthe, the chromosome number of S-CTC varied from 55 to 63. Also S-CTC presented a larger nuclear/cytoplasmic ratio and limitless replicative potential. Furthermore, the S-CTC had huge sphere formation ability, the tumorigenesis of S-CTC cells can be happened by xenografting in immunodeficient mice.
Conclusion: A cell S-CTC were successfully isolated and cultured by the technology microfluidic chip. S-CTC was identified using a series of analysis and can be confirmed to be the tumor cell, which would be provide more drug sensitivity information of the patient and open up novel avenues towards the understanding of gastric cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Huirong Zhang, Pan Zhao, Han Wu, Chang Zou. Ex vivoisolation and culture of circulating tumor cells using microfluidics chip [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 418.
Abstract 4192: Increasing incidence of EBV-related nasopharyngeal carcinoma in the United States
Authors: Argirion Ilona , Zarins Katie R. , Ruterbusch Julie J. , Vatanasapt Patravoot , Sriplung Hutcha , Seymour Erlene K. , Rozek Laura S. 
Published: August 2019

Abstract
Purpose: Incidence of nasopharyngeal carcinoma (NPC) is highly geographically variable and historically rare in the US. While etiological factors differ by histological subtype, Epstein-Barr virus (EBV) is generally accepted as the primary risk factor for non-keratinizing NPC. In light of the changing epidemiology of HPV-associated oropharyngeal cancer, it is important to evaluate temporal incidence of NPC in the US.
Methods: Incidence and survival data from 1973-2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) Program. Stratified analyses were conducted to assess temporal trends in NPC by histological subtype, sex and race. The data were analyzed using SAS 9.4 and Joinpoint Regression Software to determine age-adjusted incidence rates, trends in annual percent change (APC) as well as calculate 5-year relative survival estimates and Kaplan-Meier curves.
Results: Although overall NPC incidence is decreasing in the US, the non-keratinizing differentiated subtype appears to be starkly increasing with an APC of approximately 4% among white males (95%CI: 2.5, 5.2), white females (95%CI: 1.9, 6.2), and black males (95%CI: 2.0, 5.7), 2.7% among black females (95%CI: 0.8, 4.6) and 1.8% among women of other race (95%CI: 0.4, 3.3). When compared to other histological subtypes, patients with keratinizing squamous cell carcinoma had the worst survival (log rank p&lt;0.001). Additional survival disparities were noted, with black males having consistently poorer survival across all histological subtypes, and those individuals in the “other” race category, particularly females, experiencing the highest 5-year relative survival estimates.
Conclusions: Although NPC remains relatively rare in the overall US population, there is evidence to suggest that the EBV-related differentiated subtype is increasing across all genders and races.
Citation Format: Ilona Argirion, Katie R. Zarins, Julie J. Ruterbusch, Patravoot Vatanasapt, Hutcha Sriplung, Erlene K. Seymour, Laura S. Rozek. Increasing incidence of EBV-related nasopharyngeal carcinoma in the United States [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 4192.
Abstract 4201: Patient-level predictors and hysterectomies among women with autoimmune diseases
Authors: Bahrani-Mostafavi Zahra , Huber Larissa R. 
Published: August 2019

Abstract
Introduction: Hysterectomy is the second most common surgical procedure performed among reproductive aged women. The primary reason for hysterectomy among women 35-54 years is uterine fibroids and for older women is uterine prolapse or gynecologic (GYN) cancer. According to the National Center for Health Statistics, an estimated 600,000 hysterectomies are performed annually in the U.S. with an annual cost of $5 billion, which makes hysterectomy a major public health concern. Autoimmune diseases (AD) are among the top ten leading causes of death among U.S. women age 65 and under. This high mortality rate among women with AD has been linked to cancer and other causes. Considering hysterectomy procedures as are invasive and costly procedures, a comprehensive study to investigate the association between patient-level predictors and hysterectomy procedures among AD patients in the U.S. is imperative.
Methods: 2007-2013 data from Florida State Inpatient samples of the Healthcare Cost and Utilization Project were used. The study population (n=699,280) was restricted to women who had any AD. The outcome variable was performance of hysterectomy, identified by CPT codes. Patient-level factors including race/ethnicity, age, insurance type, income level, and other comorbidities were analyzed as explanatory variables. Logistic regression analyses were used to identify independent predictors of hysterectomy procedures.
Results: Among AD subjects, the highest rate of hysterectomy was in Caucasian women (64.64%) and the lowest rate was in minorities other than Black and Hispanic women (3.0%). The odds of hysterectomies are were increased in older women who were older (0.74, 0.70-0.78), women, black (1.45, 1.36-1.54) women, have had private insurance (2.30, 2.14-2.45), and are fromhad lower income levels (1.10, 1.02-1.19), and had with more comorbid conditions, specifically GYN cancer.
Discussion: GYN complications may lead to hysterectomy, and ADs are major diseases among women. Because of the high prevalence of AD among women, more elucidation on the association between hysterectomy procedures and AD is essential for GYN complications management. Any unique combinations of characteristics that describe patients at risk for hysterectomy among AD patients could be used as a potential risk assessment for better management of GYN complications, and in particular GYN cancer.
Citation Format: Zahra Bahrani-Mostafavi, Larissa R. Huber. Patient-level predictors and hysterectomies among women with autoimmune diseases [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 4201.
Abstract 4205: Pan-cancer molecular study of disparities among African Americans
Authors: Lara Olivia D. , Wang Ying , Hu Wei , Zhang Lin , Rauh-Hain Alejandro , Sood Anil 
Published: August 2019

Abstract
Objective: Several factors have been proposed to contribute to racial disparities in gynecologic cancers, however there are no comprehensive studies that have investigated inherent molecular features that may be racially unique. Our objective was to perform a pan-cancer clinical and molecular analysis of African-Americans (AA) and European American (EA) patients.
Methods: We performed cross-platform analyses utilizing cancer registry and molecular databases [Surveillance, Epidemiology and End Results (SEER) and The Cancer Genome Atlas (TCGA)] to evaluate differences in AA vs EA patients. To characterize genetic ancestry we utilized the recently established The Cancer Genetic Ancestry Atlas (TCGAA). We further evaluated epigenetic modifications through non-coding RNA expression in these tumors.
Results: A total of 2,045,500 patients (87.5% EA, 12.5% AA) with 64 primary tumor types were evaluated using SEER to evaluate clinical outcome differences. Compared to white race, AA race had higher rate of death in 45 cancer types (HR&gt;1.0, CI 1.00-5.23). 19 cancer types were then identified to have the largest differences in overall survival (HR&gt;1.2). Utilizing TCGA, we analyzed molecular data of 7028 tumors (88.9% EA, 10.9% AA) having miRSeq data and genetic ancestry data. We identified differentially expressed miRNA’s in five cancer types: breast invasive (300 miRs, p&lt;0.068, FDR&lt;0.1), renal cell (408 miRs, p&lt;0.205, FDR&lt;0.1), prostate (102 miRs, p&lt;2.68e-01, FDR&lt;0.1), thyroid (63 miRs, p&lt;1.28e-.02, FDR&lt;0.1), and uterine corpus endometrial (177 miRs, p&lt;8.18e-02, FDR&lt;0.1) carcinomas. Differentially expressed miRs among all cancer types were associated with canonical pathways of cancer drug resistance by drug efflux, altered T- cell function, and regulation of epithelial-mesenchymal transition using Ingenuity Pathway Analysis (IPA) software. We identified miR-130, miR-180, miR-146, and miR-8 as commonly dysregulated miRs in these cancer types which may represent a molecular signature unique to African Americans.
Conclusions: Our results identify molecular and genetic features unique to African Americans that may contribute to worse survival outcomes. While the cause of cancer disparities is multifactorial, a focus on molecular signatures unique to AA may identify actionable molecular abnormalities.
Note: This abstract was not presented at the meeting.
Citation Format: Olivia D. Lara, Ying Wang, Wei Hu, Lin Zhang, Alejandro Rauh-Hain, Anil Sood. Pan-cancer molecular study of disparities among African Americans [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 4205.