bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5352: Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac proteins in the rat
Authors: Rosen Elliot T. , Kryndushkin Dmitry , Aryal Baikuntha , Gonzalez Yanira , Chehab Leena , Dickey Jennifer , Rao V. Ashutosh 
Published: September 2020

Abstract
Radiation-induced heart disease represents a significant health risk in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the Wistar-Kyoto and spontaneously hypertensive rat models, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body irradiation at two, four, and fifty-two weeks. We examined irreversible oxidative protein carbonylation in the heart immediately following irradiation. Both males and females sustained reduced growth and anemic conditions over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected via elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0Gy treatment revealed inflammation and a decrease in cardiac output in the short term, but significant differences were not observed at the one-year timepoint. Cardiac output was decreased in both males and females after two weeks, and statistically significant in females. Following 10.0 Gy irradiation, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated γ-H2AX. Using proteomic analyses, several novel proteins showed a marked carbonylation profile including those associated with mitochondrial homeostasis and cardiac contractility. Overall, we present findings of acute oxidative protein, DNA damage, and long-term cardiomyopathy in the irradiated animals, along with oxidative proteomic markers of acute damage.
Citation Format: Elliot T. Rosen, Dmitry Kryndushkin, Baikuntha Aryal, Yanira Gonzalez, Leena Chehab, Jennifer Dickey, V. Ashutosh Rao. Acute total body ionizing radiation induces long-term cardiac effects and immediate changes in oxidative carbonylation of cardiac proteins in the rat [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5352.
Abstract 5368: A multiparameter assay for HER2 protein detection on circulating tumor cells in non-small cell lung cancer
Authors: Lo Edward , Campton Daniel , Costandy Lillian , Itamoto Heather , Huston Ryan , Gardner Braden , Reese Steve , Ramirez Arturo , Kaldjian Eric P. , George Tad , Wang I-Ming , Pirie-Shepherd Steven 
Published: September 2020

Abstract
Lung cancer biopsy can be difficult to perform successfully; it has a 30% adverse event risk and often provides insufficient material to test. Therefore, a liquid biopsy method to analyze the tumor is advantageous. Analysis of circulating tumor cells (CTCs) by multiparameter immunofluorescence (IF) microscopy allows non-invasive characterization of cancer cell biomarker expression. HER2 is a well-known therapeutic target in breast cancer and studies have shown that HER2 status on CTCs may provide prognostic information about response to anti-HER2 therapies. Less is understood about its frequency and clinical importance in non-small cell lung cancer (NSCLC). The RareCyte platform is uniquely suited for CTC identification and phenotypic characterization with a sensitive, accurate, simple and repeatable workflow from blood collection to CTC characterization and single-cell isolation. We developed an assay for detecting HER2 expression on lung CTCs using the RareCyte platform and validated the assay on model CTC spike-in samples with high (BT-474), medium (MDA-MB-453), low (H1650 and OVCAR-3) and absent (MDA-MB-468) HER2 protein levels. Blood was processed to slides using the AccuCyte Sample Preparation System and stained with anti-HER2 together with the RarePlex Kit for CTC identification (nuclear dye, anti-CD45 to exclude WBC, and anti-cytokeratin/EpCAM for CTCs). The spike-in samples showed the expected trend in per-cell HER2 mean fluorescence intensity values. The percentage of HER2-positive cells was &gt; 90% for the HER2-high, medium and low cell lines, and &lt; 5% for the HER2-negative cell line. The assay was applied to 10 advanced stage (III or IV) post-treatment NSCLC patient samples. At least 1 CTC was found in 6 samples (range 0-2043) and HER2 expression was confirmed in 5 out of the 6 samples, indicating this assay is useful for characterizing HER2 expression in CTCs in NSCLC.
Citation Format: Edward Lo, Daniel Campton, Lillian Costandy, Heather Itamoto, Ryan Huston, Braden Gardner, Steve Reese, Arturo Ramirez, Eric P. Kaldjian, Tad George, I-Ming Wang, Steven Pirie-Shepherd. A multiparameter assay for HER2 protein detection on circulating tumor cells in non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5368.
Abstract 5400: Pharmacogenomics in the primary and metastatic osteosarcoma: Gene expression profile associated with outcome
Authors: Trujillo-Paolillo Alini , Tesser-Gamba Francine , Petrilli Antonio Sergio , Alves Maria Teresa , Garcia-Filho Reynaldo Jesus , Oliveira Renato , Toledo Silvia Regina 
Published: September 2020

Abstract
Purpose: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Drug resistance and unfavorable outcome are problems that still affect an important percentage of OS patients. Thus, the aim of the present study was to analyze the expression of genes related to pharmacogenomics in OS.
Procedure: The expression of 32 target genes in 80 paired specimens (pre-chemotherapy primary tumors, post-chemotherapy primary tumors and pulmonary metastases), from 33 patients diagnosed with OS, were analyzed by the real-time PCR methodology. Five normal bone specimens were used as calibrators (control). The target genes are related to drug transport, drug detoxification, doxorubicin and folate pathway, DNA repair, cell cycle and apoptosis. Results: The higher ABCC3 gene expression in pre-chemotherapy primary tumors was associated with worse event-free survival (EFS) (p=0.048, HR=3.41). The higher TOP2A gene expression in post-chemotherapy primary tumors was associated with worse overall survival (OAS) and EFS (p=0.015, HR=5,37; p=0.006, HR=6.36; respectively). The lower MTHFR gene expression in pulmonary metastases was associated with worse OAS and EFS (p=0.027, HR=3.27; p=0.024, HR=3.1; respectively), as well as the lower BCL2L1 gene expression (p=0.018, HR=3.53; p=0.019, HR=3.29). Furthermore, lower expression of the RALBP1, ABCC2 and SOD1 genes in the pulmonary metastasis specimens were associated with worse EFS (p=0.022, HR=3.26; p=0.048, HR=3.16; p=0.027, HR=3.14; respectively). Moreover, the pulmonary metastases presented higher expression of the ABCC1 and ABCC4 genes (p=0.049; p =0.039; respectively) and lower expression of the ABCC10, ERCC2, MSH2, SLC22A1, SOD1 and TOP2A genes (p=0.049; p=0.043; p=0.043; p=0.017; p=0.048; p=0.005; respectively) than pre-chemotherapy primary tumors.
Conclusion: Therefore, the pharmacogenomics profile may be useful as prognostic factors as well as therapeutic targets. Thus, our findings may, in the future, contribute to clinical management in the primary and metastatic OS.
Citation Format: Alini Trujillo-Paolillo, Francine Tesser-Gamba, Antonio Sergio Petrilli, Maria Teresa Alves, Reynaldo Jesus Garcia-Filho, Renato Oliveira, Silvia Regina Toledo. Pharmacogenomics in the primary and metastatic osteosarcoma: Gene expression profile associated with outcome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5400.
Abstract 541: CLL-1 specific chimeric antigen receptor T cells (CART) as a novel AML therapy
Authors: Freitas Antonio , Gautron Anne-Sophie , Sugita Mayumi , Goswami Srinjoy , Galetto Roman , Garton Andrew , Smith Julianne , Gouble Agnes , Becker Michael W. , Roboz Gail J. , Guzman Monica L. 
Published: September 2020

Abstract
Acute myeloid leukemia (AML) is a disease with high incidence of relapse that is originated and maintained from leukemia stem cells (LSCs). Hematopoietic stem cells (HSCs) can be distinguished from LSCs by an array of markers including CD123, CLL-1, amongst others. Thus, these are thought to be unique candidates to eliminate LSCs using a variety of targeted approaches, including chimeric antigen receptor (CAR) T cells. Here, we evaluated the potential of CLL-1 as a therapeutic target for LSCs using allogeneic gene-edited CAR T cells (UCARTCLL1). UCARTCLL1 cells are TCRαβneg human T cells derived from healthy donors, and expressing an anti-CLL-1 CAR under the control of the endogenous TRAC promoter. This is achieved following a 2-in-1 TRAC knock-out CAR knock-in strategy using TALEN® gene-editing technology. UCARTCLL1 cells are also knocked-out for the beta 2 microglobulin gene. We first assessed the expression of CLL-1 across samples from 41 AML patients and 4 healthy donors. The AML samples included 32 de novo and 9 relapse samples. Using multi-parameter flow cytometry, we evaluated CLL-1 expression on blasts and phenotypically defined leukemic stem cells (CD34pos CD38neg). We found that the majority of the blasts were positive for CLL-1. Furthermore, we found that 36 out of 41 primary AML samples had phenotypically defined stem cells (CD34pos CD38neg) from which 35 showed more than 0.1% CLL-1pos cells. Previous work has shown that individuals with more than 0.1% putative LSCs will have worse outcomes (Van Renhen et al). Thus, this data suggests that there is a subset of putative CLL-1 positive LSCs that if not eliminated by current therapies could lead to disease relapse. Therefore, we sought to determine the therapeutic potential of UCART cells targeting CLL-1. First, we evaluated cytotoxic efficacy of UCARTCLL1 cells at different effector to target ratios in 7 primary AML samples with different levels of CLL-1 expression. We observed a significant cytotoxic effect specific to the CLL1pos subsets. Notably, CLL-1pos cells in the AML samples treated with 5:1 and 1:1 ratios were completely eliminated. Currently, we are evaluating the in vivo activity of UCARTCLL1 cells in AML-PDX mouse models to determine their efficacy at eliminating AML blasts, progenitors and LSCs.
Citation Format: Antonio Freitas, Anne-Sophie Gautron, Mayumi Sugita, Srinjoy Goswami, Roman Galetto, Andrew Garton, Julianne Smith, Agnes Gouble, Michael W. Becker, Gail J. Roboz, Monica L. Guzman. CLL-1 specific chimeric antigen receptor T cells (CART) as a novel AML therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 541.
Abstract 5436: Purification and mRNA profiling of extracellular vesicles for early detection of hepatocellular carcinoma
Authors: Lee Yi-Te , Sun Na , Zhang Ryan Y. , Kao Rueihung , Chen Pin-Jung , Teng Pai-Chi , Wang Jasmine J. , Yang Yingying , Kim Minhyung , Posadas Edwin M. , You Sungyong , Yang Ju Dong , Agopian Vatche G. , Tseng Hsian-Rong , Zhu Yazhen 
Published: September 2020

Abstract
Hepatocellular carcinoma (HCC) is the 4th most common cause of cancer-related deaths worldwide. The poor prognosis of HCC is due to the fact that diagnosis is often made at an advanced stage in disease development. It is crucial to develop a non-invasive liquid biopsy-based diagnostic solution for early detection of HCC. In this study, we developed a covalent chemistry-based nanostructured silicon substrate (“EV Click Chip”) for the isolation of HCC extracellular vesicles (EVs). The EV Click Chip leverages specific click chemistry reactions and sensitive multi-marker cocktail antibody identification of the HCC EVs. The EV Click Chip also allows for the subsequent release of the captured HCC EVs and is optimal for the downstream molecular analysis. A well-validated 10 liver-specific genes were quantified using reverse transcription droplet digital PCR (RT-ddPCR) in HCC EVs purified by the optimized EV Click Chips for the detection of HCC. Our EV Click Chip-based HCC-EV Assay is able to differentiate HCC from non-HCC controls (chronic liver diseases, healthy donors and other cancers) and outperformed clinical AFP test for distinguishing early-stage HCC from at-risk cirrhotic patients.
Citation Format: Yi-Te Lee, Na Sun, Ryan Y. Zhang, Rueihung Kao, Pin-Jung Chen, Pai-Chi Teng, Jasmine J. Wang, Yingying Yang, Minhyung Kim, Edwin M. Posadas, Sungyong You, Ju Dong Yang, Vatche G. Agopian, Hsian-Rong Tseng, Yazhen Zhu. Purification and mRNA profiling of extracellular vesicles for early detection of hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5436.
Abstract 5442: The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers
Authors: Decatur Christina L. , Durante Michael A. , Correa Zelia M. , Aaberg Thomas M. , Mruthyunjaya Prithvi , Schefler Amy C. , Harbour J. William 
Published: September 2020

Abstract
Introduction: Uveal melanoma (UM) is a highly aggressive eye cancer that leads to metastatic death in up to half of patients. UM has a propensity to undergo early micrometastasis prior to treatment of the primary tumor, with later emergence of overt metastatic disease. UM can be stratified into Class 1 (low metastatic risk) and Class 2 (high metastatic risk) using a prospectively validated 12-gene expression profile (GEP) molecular prognostication classifier. The Collaborative Ocular Oncology Group Study 2 (COOG2) is being conducted to prospectively evaluate new prognostic biomarkers in UM, including expression of PRAME, and prognostic driver mutations in BAP1, SF3B1, and EIF1AX.
Methods: The COOG2 is a 24 center, prospective study of UM patients undergoing prognostic testing using the CLIA-certified DecisionDx-UM test (Castle Biosciences, Inc) between July 2017 and December 2019. Molecular analysis is performed on residual clinical samples. Data collected include clinical annotations, patient outcomes, GEP, PRAME status, and mutations in BAP1, SF3B1, and EIF1AX.
Results: To date, there are 1300 participants enrolled. The baseline characteristics are as follows: 52% male, and 48% female; 87% non-Hispanic, 3% Hispanic, and 10% unknown. GEP classification is 66% class 1 and 34% class 2. PRAME status is 68% PRAME (-) and 32% PRAME (+). Targeted sequencing has been performed on 650 samples and is being analyzed.
Conclusions: The COOG2 will establish a new standard of prognostic testing accuracy from a single fine needle biopsy in UM. The resulting integrated prognostic testing platform will be used as a stratification tool for entry into clinical trials of adjuvant therapy in high-risk patients.
Citation Format: Christina L. Decatur, Michael A. Durante, Zelia M. Correa, Thomas M. Aaberg, Prithvi Mruthyunjaya, Amy C. Schefler, J. William Harbour. The Collaborative Ocular Oncology Group study number 2: A prospective multi-center evaluation of uveal melanoma prognostic biomarkers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5442.
Abstract 5446: Genetic bases of testicular seminoma and non-seminoma tumors
Authors: Martin-Gimeno Paloma , Paumard-Hernandez Beatriz , Calvete Oriol , Benitez Javier 
Published: September 2020

Abstract
Testicular Germ Cell Tumor (TGCT) is the most common cancer type in men between 15-45 years old (1 per 250 men). Around 1-2% of all cases are familial (with at least two affected individuals within the same family), between 3-5% are bilateral (they develop two tumors, one in each testicle), and the rest are sporadic patients. There are two main types of histologies, seminomas and non-seminomas, and there are also tumors that contain both seminoma and non-seminoma cells, and are called mixed tumors. No great genetic differences have been found so far between them.
In order to identify susceptibility genes that could explain these histological differences, we performed Whole Exome Sequencing (WES) in peripheral blood of 61 members from 17 families with at least two affected members with TGCT. Twenty one members had seminoma, seven members had non-seminomas, and nine had mixed tumor. We did not find significant genetic differences between the two histological types at the germline level. Therefore, an evaluation at a somatic level was carried out to determine if the differences between the tumor types are in the tumor.
To this end, WES of blood and tumor tissue was performed in three bilateral cases with different histologies (a seminoma in one testicle and a non-seminoma in the other). The comparison between pairs of tumors from each of the patients showed that they shared in average a 30% of the somatic mutations between both the histologies. Even more, 27 genes were shared among the two tumors in the three patients. We next performed independency tests, comparing the somatic similarities and differences between the two tumors from each patient (intrapatient) and the two histologies (interpatients), which suggest a common genetic background that could predispose to testicular cancer development. We are currently performing gene ontology analysis with the genes that were shared among the pairs of tumors from each patient.
Partially supported by CIBERER and FIS 16/00440
Citation Format: Paloma Martin-Gimeno, Beatriz Paumard-Hernandez, Oriol Calvete, Javier Benitez. Genetic bases of testicular seminoma and non-seminoma tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5446.
Abstract 5448: Integrative analysis of microRNA expression identifies two biologically distinct and clinically relevant subtypes of head and neck squamous cell carcinoma
Authors: Holt Jeremiah R. , Jo Heejoon , Walter Vonn , Zhao Xiaobei , Hayes David Neil , Ko Yoon Ho 
Published: September 2020

Abstract
Purpose: The objective of this study is to investigate the potential role of microRNAs (miRNA) as molecular markers of tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC).
Experimental Design: Here, we analyzed 562 HNSCC samples, 88 from a novel cohort and 474 from The Cancer Genome Atlas (TCGA), using miRNA-microarray and miRNA-seq, respectively. Using an integrative correlations method followed by miRNA expression-based hierarchical clustering, we validated miRNA clusters across cohorts, and evaluation of clusters by logistic regression and gene ontology approaches revealed subtype-based clinical and biological characteristics.
Results: We identified two statistically significant tumor subtypes and named them ‘epithelial' and ‘stromal' based on correlations with functional target gene ontology in relation to differing stages of epithelial cell differentiation. Each subtype demonstrated significant differences in terms of mRNA signature (p &lt; 0.001), primary tumor sites (p &lt; 0.001) and HPV status (p &lt; 0.001), and multivariate analysis associated the stromal subtype with a worse prognosis (HR = 1.5646, p = 0.006). We also observed several dysregulated miRNA families and clusters that function as regulators of subtype-specific gene expression networks in HNSCC.
Conclusion: Our findings suggest miRNAs determine HNSCC subclassifications through coordinating growth and differentiation programs in epithelial cells. These results delineate developmental miRNA signatures characterizing the phenotypic diversity between HNSCC subtypes, providing an expanded framework for the pathogenesis and personalized treatment of HNSCC.
Citation Format: Jeremiah R. Holt, Heejoon Jo, Vonn Walter, Xiaobei Zhao, David Neil Hayes, Yoon Ho Ko. Integrative analysis of microRNA expression identifies two biologically distinct and clinically relevant subtypes of head and neck squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5448.
Abstract 5454: A data driven pipeline to detect somatic mutations in oncology
Authors: Shortt Katherine , Johnson Christopher , Ramesh Archana , Neuwerth Tom , Giauque Chris , Raghunath Sharanya 
Published: September 2020

Abstract
The analysis of Next Generation Sequencing (NGS) data relies on workflows that integrate different bioinformatics tools. Designing workflows that are assay agnostic and have a robust computational framework for result generation in a timely manner is particularly important for clinical applications of NGS. These technologies play an important role in classifying a patient's tumor at a molecular level however, there is still a need to develop workflows that generate consistent mutation profiles for oncology. We developed a bioinformatics tool to analyze DNA and RNA sequencing data in a single pipeline and to specifically detect somatic mutations in oncology clinical workflows. Our automated pipeline report contains extensive quality metrics for each sample and generates a robust mutation annotation and filtration module vital for clinical use. We use data driven filters and algorithms that predict the effectiveness of mutations to filter out mutations of poor quality or mutations without clinical significance. We applied our pipeline to standard cell lines and various cancer FFPE samples acquired from the Intermountain Healthcare Biorepository. Our pipeline successfully processes different mutation classes including Single Nucleotide Variants (SNVs), small (&lt;20 bp) and large (&gt;21 bp) insertions and deletions (InDels), gene fusions, and exon skipping mutations. In addition, we established a reference set that allows us to call Copy Number Variants (CNVs) in a gene panel designed to detect clinically relevant mutations in lung cancers. Comparison of this pipeline to a validated external workflow yield high concordance of clinically significant mutations. We conclude that our pipeline offers a sensitive and specific methodology to analyze DNA and RNA sequencing data to clinically relevant results from low input amplicon-based assays for various solid tumor cancer types.
Citation Format: Katherine Shortt, Christopher Johnson, Archana Ramesh, Tom Neuwerth, Chris Giauque, Sharanya Raghunath. A data driven pipeline to detect somatic mutations in oncology [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5454.