bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4434: Comprehensive bioinformatic analysis of immune composition and genes for survival prediction in sarcoma
Authors: Chen Hongmin 
Published: September 2020

Abstract
Introduction
Sarcomas, a broad family of mesenchymal malignancies, exhibit remarkable histologic diversity. Previous study has reported that the infiltration of immune and stromal cells in tumor microenvironment contribute significantly to prognosis. ESTIMATE, an algorithm to calculate immune and stromal scores, predicts the infiltration of non-cancer components. The Cancer Genome Atlas (TCGA) database is available to grasp potential correlations between gene set prolife and overall survival of malignancies, including sarcomas. To better understand the proportions of immune cells in the tumor microenvironment, We used CIBERSORT deconvolution software and ssGSEA to infer the relative proportions of several distinct leukocyte cell types in the tumors from microarray gene expression data of sarcoma patients. By taking advantage of both TCGA database of sarcomas cohorts and ESTIMATE algorithm, we extracted a list of genes that predict poor outcomes in sarcoma patients. Finally, we validated these genes in an independent sarcoma cohort from the GSE17679. Thus, we obtained a list of tumor microenvironment-related genes that predict poor outcomes in sarcoma patients.
Methods
Gene expression profile and clinical data for sarcoma patients was obtained from the TCGA data portal. Immune scores and stromal scores were calculated by applying the ESTIMATE algorithm to the downloaded database. Batch adjusted data was subsequently analyzed using CIBERSORT to resolve the immune composition. For validation, gene expression profiles for Ewing sarcoma patients were obtained from the Gene Expression Omnibus dataset GSE17679.
Results
The immune and stromal score are associated with prognosis. The type 2 macrophages in sarcoma makes up the largest composition of all immune cells in the tumor microenvironment of sarcoma (except synovial sarcoma), which predicts poor outcomes. From functional enrichment analysis of TCGA database applied by ESTIMATE algorithm-based immune scores, we extracted that NR1H3, VAMP5, GIMAP2, GBP2, HLA-E and CRIP1 are highly expressed in the immune microenvironment, predicting good outcomes in sarcoma patients.
Conclusion
We extracted a list of tumor microenvironment related genes. These genes were validated in an independent sarcoma cohort and that may represent promising novel signatures for the diagnosis and prognosis prediction of sarcoma. The immune composition analysis could be useful for outlining the prognosis.
Citation Format: Hongmin Chen. Comprehensive bioinformatic analysis of immune composition and genes for survival prediction in sarcoma [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 4434.
Abstract 447: Integrated omics modeling of transcriptional regulation in medulloblastoma subtypes
Authors: Chapman Owen S. , Ehrenberger Tobias , Archer Tenley C. , Gold Maxwell P. , Mundt Filip , Adam Miriam , Mah Clarence K. , Krug Karsten , Chandran Sahaana , Dixon Jesse R. , Pomeroy Scot L. , Fraenkel Ernest , Mesirov Jill P. , Chavez Lukas 
Published: September 2020

Abstract
Medulloblastoma (MB) is one of the most common pediatric brain tumors. Current treatment options carry substantial risk for lifelong cognitive and neurological impairment. Consequently, there is a pressing need to elucidate molecular mechanisms with the ultimate goal of developing targeted tumor-specific therapies. In a recent study on proteomes and phospho-proteomes of primary MB tumors, we identified proteomic MB subtypes that were not apparent from transcriptional or methylation data. To identify gene regulatory circuitries that drive these MB subtypes, we have now mapped accessible chromatin and 3D chromosome conformation in 23 and 13 MB tumors from the same cohort, using ATAC-seq and Hi-C respectively. We identify subtype-specific accessible regulatory chromatin regions, including a subset of regions not identifiable by the enhancer mark H3K27ac. We associate regulatory regions to their target gene promoters by correlating transcription with ATAC-seq signal strength, and confirm these relationships using the newly generated Hi-C data. Using an unpublished adaptation of the GSEA algorithm, which we tailored for an enrichment analysis of non-coding regulatory elements instead of genes, we identify transcription factors and master regulators with binding sites specific to an MB subtype. By associating these master regulators with their transcriptional targets, we have derived models of regulatory circuitry in MB which implicate central mechanisms of MB pathogenesis and may inform future therapeutic targeting.
Citation Format: Owen S. Chapman, Tobias Ehrenberger, Tenley C. Archer, Maxwell P. Gold, Filip Mundt, Miriam Adam, Clarence K. Mah, Karsten Krug, Sahaana Chandran, Jesse R. Dixon, Scot L. Pomeroy, Ernest Fraenkel, Jill P. Mesirov, Lukas Chavez. Integrated omics modeling of transcriptional regulation in medulloblastoma subtypes [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 447.
Abstract 4485: Comparison of two commercially available T cell receptor repertoire sequencing assays
Authors: Mason Jennifer , Buchkovich Martin , Sims Jennifer , Hurban Patrick 
Published: September 2020

Abstract
Background: Deep sequencing of the T-cell receptor complementarity-determining regions assists with resolving T-cell diversity, and, in oncology, detects specific clones or changes in clonality associated with anti-tumor responses. However, the extreme diversity of the T-cell repertoire represents a major analytical challenge, while a gold standard method for the repertoire analysis has not yet been identified. Here, we evaluated performance of the Oncomine TCR Beta squencing assay in PBMC and formalin-fixed paraffin-embedded (FFPE) tissues, and compared it to another commercially available TCR sequencing assay.
Method: RNA derived from PBMCs or tumor FFPE tissue were prepared using the Oncomine TCR Beta-SR (short read) and LR (long read) assays, and a comparator assay. Library preparation using the TCR Beta SR and LR assays required cDNA synthesis followed by TCR gene specific amplification, sample barcoding, and sequencing on the Ion Torrent S5. Comparator assay entailed gene specific cDNA synthesis, preparation of sequencing libraries, TCR gene specific amplification, sample barcoding and 2 × 150 bp sequencing on Illumina's NextSeq. Libraries generated from RNA derived from PBMCs and FFPE were sequenced to a depth of 25M and 10M reads, respectively, for the TCR Beta-SR and a comparator assay. All samples prepared with the TCR Beta-LR assay were sequenced to 3M reads. On target reads, reproducibility, sensitivity, and robustness of input were used to measure assay performance.
Results: Higher fractions of on target TCR reads were identified in PBMC and FFPE libraries generated with the TCR Beta-SR and LR assays. The TCR Beta-SR and LR assays had mean pairwise correlations for replicate samples of 0.95 and 0.99, respectively, and 0.86 for a comparator assay. Rare clones at frequencies 10−5 and 10−6 in PBMC samples were detected by the Oncomine TCR Beta-SR and LR assays in samples with an input of 50 - 300 ng, where a comparator assay had inconsistent detection of the rare clones at a frequency of 10−5, independent of input.
Conclusions: Thermo Fisher's Oncomine TCR Beta assay reproducibly amplifies TCR specific sequences with high sensitivity. The assay is suitable for characterization of TCR clones from RNA derived from PBMC and tissue FFPEs.
Citation Format: Jennifer Mason, Martin Buchkovich, Jennifer Sims, Patrick Hurban. Comparison of two commercially available T cell receptor repertoire sequencing assays [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 4485.
Abstract 4555: Selection of CD3 affinity allows generation of T-cell redirecting bispecific antibodies with unique pharmacokinetic and biodistribution properties
Authors: Haber Lauric , Olson Kara , Babb Robert , Kelly Marcus , Crawford Alison , Retter Marc , DiLillo David , Ullman Erica , Finney Jennifer , Canova Lauren , Pawashe Arpita , Chiu Danica , Vazzana Kristin , Ram Priyanka , Mohrs Katja , Dorvilliers Amanda , Xiao Jenny , Makonnen Sosina , Hickey Carlos , Arnold Cody , Giurleo Jason , Patel Supriya , Tavare Richard , Chen Ya Ping , Chen Gang , Olson William , Thurston Gavin , Lin John Chia-Yang , Hermann Aynur , Kirshner Jessica , Smith Eric J. 
Published: September 2020

Abstract
T-cell redirecting bispecific antibodies are an emerging class of therapeutic agents designed to simultaneously bind to T cells (via CD3) and tumor cell specific antigens (TSA), with the goal of inducing T cell-mediated killing of tumor cells. Despite promising pre-clinical and clinical efficacy from TSAxCD3 antibodies, these agents have associated toxicities that remain challenging. Here we present findings from a series of bispecific antibodies that were engineered to have a range of CD3 affinities, but which retained the same binding affinity to the selected tumor antigen. These agents were tested for killing of tumor cells in vitro, and for biodistribution, serum half-life, and anti-tumor activity in vivo. By altering the binding strength for CD3, bispecifics were generated that maintained potent killing of TSA+ cells but displayed differential profiles of cytokine release, pharmacokinetics, and biodistribution. Our results suggest that tuning CD3 affinity is a promising method to improve the therapeutic window of T cell-engaging bispecific antibodies.
Citation Format: Lauric Haber, Kara Olson, Robert Babb, Marcus Kelly, Alison Crawford, Marc Retter, David DiLillo, Erica Ullman, Jennifer Finney, Lauren Canova, Arpita Pawashe, Danica Chiu, Kristin Vazzana, Priyanka Ram, Katja Mohrs, Amanda Dorvilliers, Jenny Xiao, Sosina Makonnen, Carlos Hickey, Cody Arnold, Jason Giurleo, Supriya Patel, Richard Tavare, Ya Ping Chen, Gang Chen, William Olson, Gavin Thurston, John Chia-Yang Lin, Aynur Hermann, Jessica Kirshner, Eric J. Smith. Selection of CD3 affinity allows generation of T-cell redirecting bispecific antibodies with unique pharmacokinetic and biodistribution properties [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 4555.
Abstract 4560: Conditionally active biologics (CAB): A novel class of molecules targeting solid tumors
Authors: Wang Jing , Xing Charles , Liu Haizhen , Cugnetti Ana Paula G. , Wheeler Christina , Lucas Matthew , Frey Gerhard , Chang Cathy , Boyle William J. , Short Jay M. 
Published: September 2020

Abstract
Conditionally Active Biologics (CAB) technology is a proprietary platform that selects antibodies binding to target antigens in the context of diseased tissues, but not normal tissues, taking advantage of the unique conditions in the tumor microenvironment. Using our CAB technology, we have developed CAB ADCs to various well-established tumor associated antigens (TAA), including Nectin-4, Her2 and CD46. Each of these molecules play an important role in cancer biology and are attractive targets for the development of therapeutic antibodies. These targets, however, are expressed on many normal tissues and have been implicated in a wide range of biological processes; therefore, limiting the use of traditional ADCs as cancer therapy. Using CAB technology, we have developed conditionally active ADCs that have no or very little binding to the target antigen in healthy tissue (normal physiological conditions), but have strong binding in the context of diseased tissues (tumor microenvironment) based on the glycolytic tumor metabolism (including Warburg effect). In vitro and in vivo efficacy data demonstrating the abilities of CAB ADCs to induce cytotoxicity of human target-expressing tumor cell lines, and to inhibit tumor growth in human tumor xenograft models will be presented. In conclusion, our data is consistent with our previous work on EpCAM, our clinical stage AXL and ROR2 CAB ADCs, and suggests that conditionally active ADCs generated using the CAB technology will provide a new generation of biologics with increased safety margin and therapeutic index in the clinic.
Citation Format: Jing Wang, Charles Xing, Haizhen Liu, Ana Paula G. Cugnetti, Christina Wheeler, Matthew Lucas, Gerhard Frey, Cathy Chang, William J. Boyle, Jay M. Short. Conditionally active biologics (CAB): A novel class of molecules targeting solid 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 4560.
Abstract 4574: A novel method for inactivating tumor cells for use in a personalized cancer vaccine
Authors: Guth Amanda Michele , Goodrich Raymond , Park Haemin , Gladstone Matthew , Shanley Crystal , Hartson Lindsay , Weston Jon 
Published: September 2020

Abstract
With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumor vaccine trials have not produced convincing results due, in part, to poor patient selection and inactivation methods that are harsh on the cells. Such methods can inadvertently alter protein structure and antigenic profile in ways that make vaccine candidates ineffective in stimulating immune response to autochthonous tumor cells. We decided to investigate a novel method for inactivating tumor cells that uses UVA/UVB light and the benign chemical riboflavin (Riboflavin and UV Light Inactivation, RF+UV). This process is fast and results in complete inactivation of the tumor cells, but preserves tumor cell integrity and antigenicity due to its rapid, yet gentle inactivation process. Our results demonstrate that the inactivation is complete, that proteins are preserved on the surface of the tumor cells, and that the inactivated tumor cells are immunogenic in that they induce dendritic cell maturation, increased IFNγ production, and the generation of tumor cell-specific IgG immune responses. Moreover, when formulated with an adjuvant (“Innocell vaccine”) and tested in two different murine primary tumor models and one metastatic tumor model, the vaccine led to decreased tumor growth, prolonged survival and decreased metastatic disease. In addition, immune cells obtained from tumor tissue following vaccination showed a decrease in exhausted and regulatory cells, suggesting that activation of intratumoral T cells may be playing a role leading to the reduce tumor growth. Lastly, tumor tissue was obtained from 3 client-owned dogs with spontaneous tumors and used to generate an autologous Innocell vaccines. The vaccine was well-tolerated and induced an inflammatory response in 2 of the 3 dogs. This data suggests that the RF+UV process of inactivating tumor cells for use as antigen-presenting agents in cancer vaccine therapy may provide a more rapid, safer and gentler way to generate autologous whole tumor cell vaccines for use in cancer patients.
Citation Format: Amanda Michele Guth, Raymond Goodrich, Haemin Park, Matthew Gladstone, Crystal Shanley, Lindsay Hartson, Jon Weston. A novel method for inactivating tumor cells for use in a personalized cancer vaccine [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 4574.
Abstract 4603: Detection of pancreatic cancer using rapid dielectrophoresis based recovery of tumor derived extra cellular vesicles and exosomes from plasma
Authors: Modestino Augusta , Alvarez Jesus Bueno , Heller Michael , Ibsen Stuart 
Published: September 2020

Abstract
Tumor derived extracellular vesicles, including exosomes, carry cancer related proteins on their outer surfaces making them a valuable source of tumor biomarkers in blood. However, these vesicles are difficult to recover from plasma and this prevents them from being widely used for clinical diagnostic tests. Here we present a technique that uses high conductance dielectrophoresis to rapidly recover these vesicles from plasma allowing for immunofluorescence detection of cancer related biomarkers. We demonstrate this technique can be used to detect biomarkers that successfully distinguish patients with pancreatic cancer from those with benign pancreatic disease, such as pancreatitis, as well as healthy individuals. What makes dielectrophoresis different from other vesicle recovery techniques is that it takes advantage of the large contrast in the dielectric properties between the vesicles and the surrounding plasma. The dielectrophoretic force preferentially draws vesicles to an electrode array at the bottom of a microfluidic chip where they are held in place allowing a fluidic wash to remove the bulk plasma. The vesicles are concentrated at the electrode edge thereby increasing the signal to noise ratio of the fluorescent immunostaining signal and placing the particles in known locations allowing for automated detection and quantification of biomarker levels. This technique takes 30 min to complete, requires 30-50 µl of plasma, and can be highly automated to reduce labor effort making it a promising technology for future translation into the clinical laboratory setting and enabling the use of extracellular vesicles and exosomes for diagnostic applications.
Citation Format: Augusta Modestino, Jesus Bueno Alvarez, Michael Heller, Stuart Ibsen. Detection of pancreatic cancer using rapid dielectrophoresis based recovery of tumor derived extra cellular vesicles and exosomes from plasma [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 4603.
Abstract 4616: Functional genomic analyses of 21q22.3 locus identify potential functional variants and candidate gene YBEY for breast cancer risk
Authors: Shidal Chris , Shu Xiang , Wu Jie , Wang Jifeng , Huang Shuya , Bauer Joshua , Guo Xingyi , Zheng Wei , Shu Xiao-Ou , Cai Qiuyin 
Published: September 2020

Abstract
We have previously identified SNP rs3541811, located in the 21q22.3 locus, to be associated with breast cancer risk in Asians. However, the underlying causal functional variants and gene(s) responsible for this association are unknown. In this study, we performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association. Functional annotation for SNPs highly correlated with rs3541881, using epigenetic data from the Encyclopedia of DNA Elements (ENCODE) and Roadmap projects, showed evidence of promoter and/or enhancer activities of five putative functional SNPs, including rs35418111, rs2078203, rs8134832, rs57385578, and rs8126917. These SNPs were assessed for interactions with nuclear proteins by EMSA assay. Our results showed that compared to the reference allele, alternate allele rs2078203 (A &gt; G) significantly increased DNA-protein interactions, while an opposite trend was observed for rs35418111 (G &gt; A). Cis-expression quantitative loci (eQTL) analysis, using data from the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and the Shanghai Breast Cancer Study, indicated that the risk allele rs35418111 is associated with a decreased expression of the YBEY (C21or57) gene, indicating its putative oncogenic function that may contribute to breast cancer risk. The gene YBEY is a relatively uncharacterized endoribonuclease in humans, which is thought to function in rRNA cleavage and maturation, similar to its bacterial homologues. We further investigated whether YBEY may have any biological effect in human breast cancers by knocking-down YBEY gene expression using siRNA in MCF-7, T47D, and MDA-MB-231 cell lines. Transient knockdown of YBEY gene expression in three breast cancer cell lines consistently affected cell proliferation, colony formation, and migration/invasion, regardless of hormone receptor status. Our study provides support for a significant role for human YBEY gene in breast cancer pathogenesis and the association between the rs35418111/21q22.3 locus and breast cancer risk, which may be mediated through its correlated potential functional SNPs that regulate expression of the YBEY gene.
Citation Format: Chris Shidal, Xiang Shu, Jie Wu, Jifeng Wang, Shuya Huang, Joshua Bauer, Xingyi Guo, Wei Zheng, Xiao-Ou Shu, Qiuyin Cai. Functional genomic analyses of 21q22.3 locus identify potential functional variants and candidate gene YBEY for breast cancer risk [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 4616.
Abstract 4646: Association between dietary vitamin B intake and risk of endometrial cancer in the prospective Singapore Chinese Health Study
Authors: Lei Ming , Adambekov Shalkar , Edwards Robert , Wang Renwei , Yuan Jianmin , Lopa Samia , Linkov Faina 
Published: September 2020

Abstract
Background:
Endometrial cancer (EC) is the 6th most common cancer worldwide. However, only few studies addressed dietary factors influencing EC risk in Asia. We explored the association between dietary risk factors and endometrial cancer in the prospective Singapore Chinese Health Study.
Methods:
A population of 34,028 ethnically Chinese women aged 45-74 residing in Singapore were enrolled in a longitudinal prospective cohort study between 1993 and 1998, and followed up to Dec 31, 2010. Data on baseline demographics, dietary, and reproductive factors were collected via a structured questionnaire. Endometrial cancer cases were identified from the Singapore Cancer Registry. Poisson regression was used to estimate the incidence rate ratio (IRR) on established and dietary risk factors.
Results:
166 EC cases were identified (age 53.6±7.2; BMI 24.1±3.3). Obesity (IRR=1.84, 95%CI 1.06-3.06) and having a higher number of live births (IRR=0.43, 95%CI 0.24-0.79, 5+ vs nulliparous) were associated with EC. Overall, compared with the lowest quartile, elevated risk of EC was observed for the highest quartile of dietary thiamine (IRR 1.74, 95%CI 1.02-2.58), riboflavin (IRR 1.58, 95%CI 1.01-2.53), vitamin B6 (IRR 1.71, 95%CI 1.07-2.80), and folate (IRR1.56, 95%CI 1.00-2.47). The highest quartiles of riboflavin (IRR 1.74, 95%CI 1.00-3.12), vitamin B6 (IRR 1.91, 95%CI 1.04-3.65), and folate (IRR 1.89, 95%CI 1.01-3.64) were associated with elevated EC risk in postmenopausal women, but not among premenopausal women.
Conclusion:
Obesity, parity, and higher intake of dietary vitamin B were associated with elevated EC risk in our analysis. More studies are needed to evaluate the association of supplementary vitamin B complex and EC risk.
Citation Format: Ming Lei, Shalkar Adambekov, Robert Edwards, Renwei Wang, Jianmin Yuan, Samia Lopa, Faina Linkov. Association between dietary vitamin B intake and risk of endometrial cancer in the prospective Singapore Chinese Health Study [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 4646.