bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1840: Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression
Authors: Tejero Joanne D. , Drapela Stanislav , Fernandez-Garcia Juan , Fendt Sarah-Maria , Ilter Didem , Gomes Ana P. 
Published: June 2023

Abstract
Deregulation of cytotoxic CD8+ T cells is a feature of the aging process with important consequences for anti-tumor immunity and consequently affects tumor initiation, progression, and response to immunotherapies. However, our understanding of how the aging process affects CD8+ T cells remains incomplete. Vitamin B12 deficiency is also a feature of old age caused by a well-recognized decrease in vitamin absorption. Interestingly, clinical studies have reported a significant decline in CD8+ T cells in individuals with vitamin B12 deficiency, suggesting that vitamin B12 levels might be a mechanistic link between aging and deregulation of CD8+ T cells. An important and often overlooked consequence of vitamin B12 deficiency is an elevation of methylmalonic acid (MMA) in circulation. Our laboratory has previously established a critical role for age-induced MMA in promoting progression into metastatic disease of breast and lung cancers, which coincided with a robust immunosuppressive signature. Here, we demonstrate that exposure of CD8+ T cells to MMA or culture of CD8+ T cells in the absence of vitamin B12 reduces T cell activation, thereby decreasing T cell numbers and effector function. Conversely, supplementation of vitamin B12 on CD8+ T cells isolated from old mice enhances their ability to activate and increases T cell numbers. Evaluation of the effects of MMA on the CD8+ T cells metabolome revealed a decrease in antioxidant levels, including a pronounced reduction in vitamin C and reduced glutathione, which were accompanied by an increase in both superoxide and hydrogen peroxide, suggesting that an increase in reactive oxygen species might be the link between MMA and CD8+ T cell dysfunction. Together, these results put forward the idea that MMA is an important regulator of immune cell function and that supplementation of vitamin B12 in older people and individuals diagnosed with vitamin B12 deficiency may function as an important strategy to improve immune cytotoxic responses and thereby increase anti-cancer immunosurveillance and the effectiveness of certain immunotherapies.
Citation Format: Joanne D. Tejero, Stanislav Drapela, Juan Fernandez-Garcia, Sarah-Maria Fendt, Didem Ilter, Ana P. Gomes. Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1840.
Abstract 1853: Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma
Authors: Romano Gabriele , Paradiso Francesca , Li Peng , Shukla3 Pooja , Barger Lindsay , Naggar Olivia El , Miller John P. , Liang Roger J. , Helms Timothy L. , Wargo Jennifer A. , Taraballi Francesca , Costello James C. , Kwong Lawrence N. 
Published: June 2023

Abstract
Patients with BRAF-mutant melanoma show significant responses to combined BRAF and MEK inhibition, but most patients relapse within 2 years. A major reservoir for such drug resistance is minimal residual disease (MRD), which is comprised of drug-tolerant tumor cells laying in a dormant state. Towards exploiting potential therapeutic vulnerabilities of MRD, we established a genetically engineered mouse model of BrafV600E-driven melanoma MRD wherein genetic BrafV600E extinction leads to strong but incomplete tumor regression. Transcriptional time-course analysis of tumors after BrafV600E extinction revealed that after an initial surge of immune activation, tumors later became immunologically "cold" after MRD establishment. Computational analysis identified candidate T-cell recruiting chemokines that may be central players in the process, being strongly upregulated initially and then steeply decreasing as the immune response faded. As a result, we hypothesized that sustaining the chemokine signaling could impair MRD maintenance through increased recruitment of effector T-cells. We show that intratumoral administration of recombinant Cxcl9, either naked or loaded in microparticles, significantly impaired the relapse of MRD in BRAF-inhibited tumors, including several complete pathological responses after the triple combination of microparticle-delivered rCxcl9 with BRAF and MEK-inhibition. Our experiments constitute a proof of concept that chemokine-based microparticle delivery systems are a potential strategy to forestall tumor relapse and thus improve the clinical success of frontline treatment methods.
Citation Format: Gabriele Romano, Francesca Paradiso, Peng Li, Pooja Shukla3, Lindsay Barger, Olivia El Naggar, John P. Miller, Roger J. Liang, Timothy L. Helms, Jennifer A. Wargo, Francesca Taraballi, James C. Costello, Lawrence N. Kwong. Microparticle-delivered Cxcl9 prolongs Braf inhibitor efficacy in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1853.
Abstract 2017: A liquid biopsy approach to gastric cancer reveals a signature reflective of epithelial to mesenchymal transition
Authors: Sater Ali H. Abdel , Chen Yihui , Fahrmann Johannes F. , Irajizad Ehsan , Cai Yining , Hsiao Fuchung , Vykoukal Jody V. , Katayama Hiroyuki , Léon-Letelier Ricardo A. , Dou Rongzhang , Ostrin Edwin J. , Pizzi Melissa , Yamashita Kohei , Da Silva Matheus Sewastjanow , Song Shumei , Ajani Jaffer , Hanash Samir 
Published: June 2023

Abstract
Comprehensive proteomic profiling of plasmas collected before and after neo-adjuvant treatment for gastric cancer (GC) yielded 522 proteins exhibiting higher pre-treatment levels compared to healthy controls and among them, 345 proteins decreased after the treatment. Increased levels of cytoskeleton-related proteins were manifest in the plasmas of GC patients. Cytoskeletal proteins are known to play integral roles in modulating epithelial plasticity by altering mechanical strength and structural design that is critical for cancer cell motility, epithelial to mesenchymal transition (EMT), metastasis, and invasion. Ingenuity Pathway Analysis of highly expressed circulating proteins identified key oncogenic upstream transcriptional regulators and proteins that promote EMT, including KRAS, MYC and TGFB. Additionally, pathways involved in remodeling of epithelial adherens junctions, actin cytoskeleton signaling and VEGF signaling that also play a key role in EMT were upregulated. Additional datasets from proteomic profiling of multiple (N=6) GC cell lines were intersected with GC patient plasma profiles provided supporting evidence of a cancer cell origin of circulating cytoskeletal features. ACTC1, ACTN1, ACTR3, MYH9, TUBA1A, TUBA4A and TLN1 were highly expressed in both conditioned media released from GC cell lines and plasma samples of GC patients. Our findings are indicative of a blood-based signature of cytoskeletal proteins that is reflective of EMT in the context of gastric cancer.
Citation Format: Ali H. Abdel Sater, Yihui Chen, Johannes F. Fahrmann, Ehsan Irajizad, Yining Cai, Fuchung Hsiao, Jody V. Vykoukal, Hiroyuki Katayama, Ricardo A. Léon-Letelier, Rongzhang Dou, Edwin J. Ostrin, Melissa Pizzi, Kohei Yamashita, Matheus Sewastjanow Da Silva, Shumei Song, Jaffer Ajani, Samir Hanash. A liquid biopsy approach to gastric cancer reveals a signature reflective of epithelial to mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2017.
Abstract 2022: What can we learn from phosphoproteomics compared to transcriptomics in DNA damage and other processes
Authors: Arad Gali , Pevzner Kirill , Seger Eran , Geiger Tamar 
Published: June 2023

Abstract
The advancement of sequencing technologies made unbiased whole genome and transcriptome studies ubiquitous in the cancer research field. However, these omics analysis methods do not describe post-transcriptional and post-translational levels. With the recent availability of large scale multi-omics datasets, we set out to study the correlation between phosphorylations, protein expression and gene expression. The goal of this analysis is to highlight the cases in which systematic characterization of the whole proteome and phosphoproteome can uncover insights that are undetected with RNA sequencing.
The analysis described below applies RNA-protein-phosphorylation comparisons based on clinical cancer datasets. We make use of the large amount of data generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), which generates unique phosphorylations, protein and mRNA expression data from the exact same samples.
Correlation analysis between the phosphorylation-protein-RNA profiles highlights multiple differences among cancer types and functional pathways. We specifically focus on the various DNA damage response pathways which are mediated by kinase activity, and as expected, show modest mRNA-protein correlations. The protein-RNA discordance is further demonstrated when using an unsupervised clustering of the data based on protein or RNA. This analysis showed substantial differences in tumor classification and the cellular processes that differentiate between clusters.
Altogether, this study demonstrates the opportunity presented by applying proteomics and phosphoproteomics techniques to study multiple systems that are at play in cancer biology, highlighting DNA damage response as a striking example.
Citation Format: Gali Arad, Kirill Pevzner, Eran Seger, Tamar Geiger. What can we learn from phosphoproteomics compared to transcriptomics in DNA damage and other processes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2022.
Abstract 2090: Comprehensive interrogation of gene lists from genome-scale cancer screens with oncoEnrichR
Authors: Nakken Sigve , Gundersen Sveinung , Bernal Fabian L. , Polychronopoulos Dimitris , Hovig Eivind , Wesche Jørgen 
Published: June 2023

Abstract
Genome-scale screening experiments in cancer produce long lists of candidate genes that require extensive interpretation for biological insight and prioritization for follow-up studies. Interrogation of gene lists frequently represents a significant and time-consuming undertaking, in which experimental biologists typically combine results from a variety of bioinformatics resources in an attempt to portray and understand cancer relevance. As a means to simplify and strengthen the support for this endeavor, we have developed oncoEnrichR, a flexible bioinformatics tool that allows cancer researchers to comprehensively interrogate a given gene list along multiple facets of cancer relevance. oncoEnrichR differs from general gene set analysis frameworks through the integration of an extensive set of prior knowledge specifically relevant for cancer, including ranked gene-tumor type associations, literature-supported proto-oncogene and tumor suppressor gene annotations, target druggability data, regulatory interactions, synthetic lethality predictions, as well as prognostic associations, gene aberrations, and co-expression patterns across tumor types. The software produces a structured and user-friendly analysis report as its main output, where versions of all underlying data resources are explicitly logged, the latter being a critical component for reproducible science. We demonstrate the usefulness of oncoEnrichR through interrogation of two candidate lists from proteomic and CRISPR screens. oncoEnrichR is freely available as a web-based workflow hosted by the Galaxy platform (https://oncotools.elixir.no), and can also be accessed as a stand-alone R package (https://github.com/sigven/oncoEnrichR).
Citation Format: Sigve Nakken, Sveinung Gundersen, Fabian L. Bernal, Dimitris Polychronopoulos, Eivind Hovig, Jørgen Wesche. Comprehensive interrogation of gene lists from genome-scale cancer screens with oncoEnrichR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2090.
Abstract 2110: Reprogramming of DNA methylation in NAFLD progression
Authors: Go Hanyong , Kim Seon-Kyu , Kim Mirang 
Published: June 2023

Abstract
NAFLD has several stages in its progression that can lead to non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma (HCC). Whereas NAFL is a simple steatosis, NASH is characterized by cell injury, inflammation, and hepatocyte ballooning that may further progress to fibrosis, cirrhosis, and HCC. DNA methylation is a relatively stable epigenetic mechanism that can regulate gene expression patterns to establish cell identity. Here we investigated liver DNA methylation in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. NAFLD is associated with abnormal DNA methylation, Advanced NAFLD is associated with hypomethylation of genes involved in TNF receptor signaling and apoptosis, and hypermethylation of genes associated with lipid metabolism, digestion and transport. We suggest that reprogramming of DNA methylation contributes to NAFLD progression and aberrant DNA methylation could be a predictive biomarker of NASH associated HCC.
Citation Format: Hanyong Go, Seon-Kyu Kim, Mirang Kim. Reprogramming of DNA methylation in NAFLD progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2110.
Abstract 221: Development of a rapid, highly sensitive cell-free RNA NGS assay for the detection of gene fusion and splicing variants in cancers
Authors: liu fang , sun xiangying , dong jianrong , zhou kemin , huang yong , jia shidong , du pan , xiang Binggang , luo shujun 
Published: June 2023

Abstract
Background: Utility of cell-free nucleic acids (cf-NAs) for early detection and surveillance of tumor represents a new path in personalized medicine. Gene fusions, which usually arise from chromosomal rearrangement, play pivotal roles in numerous human malignancies and have been exploited for disease diagnosis and therapeutics. RNA sequencing, which is not influenced by the complication of introns, is considered superior to DNA sequencing for the identification of fusion genes and splicing variants, and has emerged as a critical tool in cancer liquid biopsy.
Methods: We developed a novel approach of preparing strand-specific RNA-Seq libraries. The cDNA produced from the cell-free RNA (cfRNA) samples were labelled with unique molecular identifiers (UMI) during library construction. The libraries were enriched using hybrid capture and the sequencing data were analyzed using Predicine in-house analysis pipeline. To assess the performance of the newly developed cfRNA assay, we compared it with a variety of commercial RNA library kits.
Results: The new RNA library construction workflow was streamlined, and it reduces the library preparation time from 2 days to 6 hours with less than 1 h of hands-on time. The yield of the library prepared by the new method was higher than those of the commonly used commercial kits on the market. Sequencing analysis and Droplet Digital PCR (ddPCR) measurement both revealed that our assay was more sensitive in detecting gene fusions and splicing variants in cfRNA than other commercial kits. The assay can reliably detect fusion/splicing variants down to the level of &lt;10 copies of input cfRNA with high specificity.
Conclusions: We developed a new RNA library preparation method that produced strand-specific libraries from low input quantities of cfRNA in a fast, simple, and robust manner. This RNA-Seq assay has demonstrated superior performance in known fusion detection and novel fusion discovery in cfRNA.
Citation Format: fang liu, xiangying sun, jianrong dong, kemin zhou, yong huang, shidong jia, pan du, Binggang xiang, shujun luo. Development of a rapid, highly sensitive cell-free RNA NGS assay for the detection of gene fusion and splicing variants in cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 221.
Abstract 2213: Longitudinal tracking of circulating rare events in the liquid biopsy of stage III-IV NSCLC patients during treatment
Authors: Bai Lily , Courcoubetis George , Nieva Jorge , Mason Jeremy , Kuhn Peter , Shishido Stephanie 
Published: June 2023

Abstract
Lung cancer is the most common cause of cancer-related death in the United States. Non Small Cell Lung Cancer (NSCLC) is the most prevalent subtype of lung cancer diagnoses, with significantly worse survival rates as clinical staging progresses. The purpose of this study was to determine the prognostic utility of longitudinal peripheral liquid biopsy as a treatment monitoring tool in stage III-IV NSCLC patients throughout treatment. Liquid biopsy represents a way for physicians to non-invasively continuously monitor and understand tumor progression through analyzing serial patient blood samples. This allows for real-time, in depth analysis of patient status throughout the treatment process. This study used the third generation, enrichment-free High-Definition Single Cell Assay (HDSCA3.0) workflow to detect and characterize rare events in the 48 peripheral blood samples collected from a cohort of 10 stage III-IV NSCLC patients undergoing various treatments. This workflow uses 4 fluorescent channels corresponding to 5 biomarkers. While circulating tumor cells (CTCs) have been shown to be effective as a prognostic tool for measuring treatment efficacy and patient response to treatment, we have additionally identified 6 additional rare cell phenotypes with variable cytokeratin expression, and 3 types of oncosomes. We have established a liquid biopsy profile that is unique to NSCLC as compared to 50 normal donors. Within this cohort, we found significantly higher amounts of rare cells and oncosomes in patient cohorts as compared to normal donors, highlighting the potential utility of both cellular and oncosome subtypes in disease monitoring. In addition, these rare events differ drastically in morphological parameters and channel expression, and also display temporal heterogeneity. Through the analysis of peripheral blood samples across time and treatment methodologies, we observed significant association between liquid biopsy analytes and progression-free and overall survival, supporting the utility of liquid biopsy as a clinical tool. Understanding the dynamics behind these rare groups throughout the courses of treatment may help improve prognostic utility of liquid biopsy.
Citation Format: Lily Bai, George Courcoubetis, Jorge Nieva, Jeremy Mason, Peter Kuhn, Stephanie Shishido. Longitudinal tracking of circulating rare events in the liquid biopsy of stage III-IV NSCLC patients during treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2213.
Abstract 2217: Novel risk stratification utilizing NanoString for HPV+ head and neck cancer patients
Authors: Kim Sulgi , Schrank Travis , Kothari Aditi , Rehmani Hina , Tasoulas Jason , Li Xue , Yarbrough Wendell , Isaeva Natalia 
Published: June 2023

Abstract
Incidence of human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has dramatically increased in the U.S. surpassing cervical cancer since 2012. Among HNSCC, HPV+ HNSCC patients have a favorable prognosis; however, approximately 20-30% suffer recurrence. Given the morbidity of current therapy, therapeutic de-escalation for HPV+ HNSCC is being explored in many clinical trials but is hampered by absence of accurate molecular classifiers to identify tumors at high and low risk of recurrence. Being able to risk stratify patients can help with therapeutic decisions, maintain high cure rates and decrease treatment associated complications. We assemble a NanoString panel to capture our recently developed NF-κB RNA signature that can distinguish patients requiring aggressive therapy from patients who are appropriate for reduced intensity treatment. Our custom gene set can select HPV+ head and neck cancer patients that may benefit from therapy de-escalation. Several advantages of using a NanoString technology, including smaller amounts of patient samples and less processing time that allow real-time patient-specific results. This makes our Nanostring panel suitable to be used in clinic to identify HPV+ head and neck cancer patients for therapeutic de-escalation without compromising their survival.
Citation Format: Sulgi Kim, Travis Schrank, Aditi Kothari, Hina Rehmani, Jason Tasoulas, Xue Li, Wendell Yarbrough, Natalia Isaeva. Novel risk stratification utilizing NanoString for HPV+ head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2217.