bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4160: Characterization of cytotoxic resilient T cells in patients with advanced cancers in response to salvage radiation therapy or chemotherapy
Authors: Gicobi Joanina K. , Yan Yiyi , Zeng Hu , Park Sean , Dong Haidong 
Published: April 2023

Abstract
Although cancer burden in patients with advanced diseases results in T cell exhaustion and failed prior therapies, some of them achieved durable clinical responses to salvage therapy (chemotherapy or radiation therapy) implying a presence of tumor-reactive resilient T cells in them. However, the phenotype and functional features of resilient T cells have not been clearly defined. We found that CX3CR1+ CD8+ T cells with low mitochondrial membrane potential demonstrated features of resilient T cells: (a) their cytotoxic T cell function (degranulation/CD107a expression) recovered quickly after tumor burden has been reduced by radiation therapy or chemotherapy; (b) they maintain a low profile of glycolysis but produce optimal levels of ATP; (c) they express lower levels of PD-1 and TOX; (4) they share a feature of stem-like T cells (TCF1+PD-1+) that can be responsive to immunotherapy; (5) they avoid accumulation of a harmful level of cytosolic reactive oxygen species (ROS) that may cause T cell exhaustion; (6) they upregulate malic enzyme 1 (ME1) to balance glycolysis and ROS, and to expand cytotoxic effector T cells. These unique features of resilient T cells may not only be used as T cell biomarker to design rational combination therapy to control advanced cancers but can also be used to convey a resilient functional state to T cells in patients who lack them.
Citation Format: Joanina K. Gicobi, Yiyi Yan, Hu Zeng, Sean Park, Haidong Dong. Characterization of cytotoxic resilient T cells in patients with advanced cancers in response to salvage radiation therapy or chemotherapy. [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 4160.
Abstract 4162: T-cell metabolic profiling with bioluminescent assays
Authors: Bach Maggie , Karassina Natasha , Gilden Julia , Leippe Donna , Valley Mike , Sylvester Kayla , Vidugiriene Jolanta 
Published: April 2023

Abstract
Cellular energy metabolism is crucial for cell survival and the balance of metabolic pathways determines the health of the cell. Determining and understanding metabolic profiles of cells can aid in overall insight of cell health and improvement of cell therapeutics, especially for immune interventions. T-cells actively regulate their metabolic profile from quiescent to a highly metabolically active state after activation. Activation rewires the cell to drive glycolysis and oxidative phosphorylation for production of reducing power and ATP for cell growth and proliferation. A small population of these cells then transition to a more quiescent state and persist as memory cells to aid in secondary responses. Although the trend of T-cell metabolism after activation has been studied, the method of investigation is cumbersome and lacks depth of information of overall cell health. To address this, we developed a bioluminescence NAD(P)H core technology and applied it to build a set of cell-based assays covering diverse metabolic pathways including glucose, glycogen, and amino acid metabolism, and the TCA cycle. Here we utilize those assays to investigate changes in metabolic profiles of naïve, effector, and memory T-cells as they transition from a state of oxidative phosphorylation to increased glycolytic rates, dependence on different fuel consumption and storage, including an increase in fatty acid oxidation and glycogen accumulation. We demonstrate flexibility of the assays for detecting multiple metabolites from the same sample and monitoring metabolite changes over time by assaying multiple samples. We show that the assays are amenable to various volumes (96-,384-well plates) and low cell numbers. For example, activity of dehydrogenases involved in glycolysis, pentose phosphate and TCA cycles can be detected with less than 400 cells/well. In conclusion, understanding the processes governing dynamic metabolic changes of T-cells during their transition from naïve to activated to memory phenotypes is required for next-generation cell therapy development. The developed bioluminescence cell-based assays provide the sensitivity, throughput and robustness required for rapid evaluation of such changes.
Citation Format: Maggie Bach, Natasha Karassina, Julia Gilden, Donna Leippe, Mike Valley, Kayla Sylvester, Jolanta Vidugiriene. T-cell metabolic profiling with bioluminescent assays. [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 4162.
Abstract 4193: N-NOSE technology based on C. elegans olfaction. Multi-cancer early detection with high sensitivity using urine. Pancreatic-cancer-specific early detection with high sensitivity using urine
Authors: Luccio Eric Di , Hirotsu Takaaki 
Published: April 2023

Abstract
N-NOSE (Nematode Nose) is a cancer screening test based on the chemotactic characteristics of the nematode C. elegans. C. elegans shows avoidance of the urine of healthy individuals while displaying a chemotactic attraction toward the urine of patients with 15 types of cancer (stomach, colon-rectum, lung, breast, pancreas, liver, prostate, uterus, esophagus, gallbladder, bile duct, kidney, urinary bladder, ovary, oropharynx) rendering N-NOSE a primary multi-cancer screening test. N-NOSE has a high sensitivity of 87.5% and 90.2% specificity, on average, from early stage 0-I. N-NOSE is non-invasive because it relies on a urine sample and is affordable (JPY 13,800, ~USD 100).N-NOSE by Hirotsu Bio Science has been available in Japan since late 2020 and is a commercial hit with over 250,000 screenings performed, rapidly increasing. In this presentation, we outline the N-NOSE technology and business in Japan. We review N-NOSE clinical research and critical findings compared to competitors that highlight its excellent performance as a non-invasive primary cancer screening for early detection. N-NOSE is a multi-cancer early detection test. Next, we introduce an evolution of N-NOSE for identifying the cancer type. Pancreatic cancer is the 12th most common cancer worldwide but remains one the deadliest cancer with a 5-year relative survival rate at only 11%, all stages combined. An affordable, non-invasive, and highly sensitive early-stage pancreatic cancer screening test is sorely needed. As an evolution of N-NOSE we genetically engineered C. elegans by knocking out in AWC olfactory neurons a specific olfactory receptor (GPCR), triggering a chemotactic response particular to the only pancreatic cancer urine specimen at an early stage. In this study, we outline, for the first time, the critical discovery of cr-4 GPCR in AWC, which is crucial for a specific chemotaxis response to the urine of patients with pancreatic cancer. Next, we briefly conclude by outlining the link between N-NOSE primary cancer screening followed by N-NOSE cancer type identification, effectively completing the whole cancer screening and identification process in a non-invasive way.
Citation Format: Eric Di Luccio, Takaaki Hirotsu. N-NOSE technology based on C. elegans olfaction. Multi-cancer early detection with high sensitivity using urine. Pancreatic-cancer-specific early detection with high sensitivity using urine. [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 4193.
Abstract 42: In vivo subcutaneous and orthotopic cancer xenograft modeling in the SRG immunodeficient rat
Authors: Begemann Diane , Javidan Aida , Dunn Cynthia , Johnston Nicolas , Walton R. Grace , Steffey Valeriya , Corbin Ian , Fulcher Niveen , De Oliveira Cleusa , Xu Hu , Uzelac Mila , Deweyert Andrew , Ronald John A. , Schmid Susanne , Hebb Matthew O. , Noto Fallon K. 
Published: April 2023

Abstract
Human cancer xenografts are a vital tool for understanding tumor biology, growth kinetics, and therapeutic efficacy using animal models. Historically, immunodeficient mice have been the standard rodent species for cancer xenograft modeling. However, an immunodeficient rat that supports a wide variety of human cancer cell types would provide a larger rodent strain for easier surgical manipulation, serial blood sampling, and provide a single model in which efficacy, pharmacokinetics, and toxicology can be performed. We have created a Sprague Dawley Rag2 -/-, Il2rg -/- rat (SRGTM OncoRat®) that provides a highly supportive environment for growing tumors of human origin. The SRG rat lacks B, T, and NK cells and readily supports the growth of multiple human cancer cell lines. The SRG rat is more immunodeficient than the Nude rat, suggesting it may be permissive to a wider variety of human cancer types. Here we demonstrate the utility of the SRG rat for both subcutaneous and orthotopic xenograft modeling. The SRG rat supports the growth of both lung and liver orthotopic cancers. In addition, the SRG rat supports the growth of orthoptic human glioblastoma multiforme in the brain. We use in vivo imaging to visualize tumor establishment and growth in subcutaneous, orthotopic, and metastatic models. Furthermore, our data show the ability of the SRG rat to support the growth of multiple different human cancer cell types subcutaneously in two different matrices, Matrigel® and VitroGel®. These data confirm that the SRG rat is an excellent host for studying human cancer. Our data demonstrate that the SRG rat has a high utility for studies using in vivo imaging, orthotopic tumor implantation, and standard subcutaneous tumor modeling. As the most immunodeficient rat commercially available, the SRG rat supports the growth of multiple human cancer types in a larger rodent strain relative to commercially available mouse models.
Citation Format: Diane Begemann, Aida Javidan, Cynthia Dunn, Nicolas Johnston, R. Grace Walton, Valeriya Steffey, Ian Corbin, Niveen Fulcher, Cleusa De Oliveira, Hu Xu, Mila Uzelac, Andrew Deweyert, John A. Ronald, Susanne Schmid, Matthew O. Hebb, Fallon K. Noto. In vivo subcutaneous and orthotopic cancer xenograft modeling in the SRG immunodeficient rat [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 42.
Abstract 4246: Synergistic inhibition of prostate tumor growth and progression by the combination of curcumin and ursolic acid in HiMyc mice
Authors: Friedman Chelsea A. , Saha Achinto , DiGiovanni John 
Published: April 2023

Abstract
Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. According to the World Health Organization, approximately one-third of all cancer deaths could be prevented through an increased consumption of natural compounds. Through the use of a two-tiered screening method in PCa cells (depletion of cellular ATP level followed by glutamine uptake) of a phytochemical library, curcumin and ursolic acid were selected for further investigation. Twenty-four hour treatment of LNCaP, 22Rv1 and HMVP2 cells with the combination resulted in significant decreases in expression of members of the miR-17-92 and miR-106b-25 clusters, which are upregulated in PCa and have been shown to be involved in tumorigenesis, cell survival, and metastasis. In the HiMyc mouse model, where mice spontaneously develop primary PCa, supplementing diets with the combination of curcumin (1%) and ursolic acid (0.2%) resulted in significant inhibition of tumor growth and progression compared to diets containing either compound alone. There were no differences in body weight or food consumption in any of the diet groups during the tumor experiment. The current data suggests that the combination of curcumin and ursolic acid synergistically inhibits PCa growth and progression in HiMyc mice, which may be in part due to their effects on microRNA expression. Ongoing studies are further examining the role of specific miRNAs as well as oncogenic signaling pathways potentially involved in the mechanism of synergistic chemopreventive action of this combination. The current data suggest that this novel combination could be a valuable therapeutic option for prevention and/or treatment of PCa. Funding: This work was supported by NIH Grant CA228404.
Citation Format: Chelsea A. Friedman, Achinto Saha, John DiGiovanni. Synergistic inhibition of prostate tumor growth and progression by the combination of curcumin and ursolic acid in HiMyc mice. [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 4246.
Abstract 4252: CCNE1 amplification in high-grade serous ovarian cancer: analysis of the GENIE database
Authors: Al-Akhras Ashaar , Tashtoush Shaden , Ghazou Alina 
Published: April 2023

Abstract
Background: High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer as well as the most lethal. A primary oncogenic driver in a subset of HGSOC patients, CCNE1 amplification is associated with poorer outcomes and resistance to standard treatment. This study aims to investigate the copy number gain of CCNE1 and the genetic mutations associated with CCNE1 amplification using a large cohort of clinico-genomic data. Methods: We queried the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange (GENIE) registry database v12.1 for patients with HGSOC. We studied CCNE1 amplification and the clinical, demographic, and genetic mutation associations. Results: A total of 3297 HGSOC samples were extracted from the registry. The mean age of patients at sequencing was 62 ± 10 years. Out of 2416 samples profiled for copy number alterations, CCNE1 amplification was found in 13.6%, being the most commonly amplified gene, followed by AGO2 (11.7%) and MYC (9.7%). Co-amplification between CCNE1 and AKT2 was demonstrated. Between the 397 samples with CCNE1 amplification and 2088 without, the genes that were more frequently mutated in the CCNE1 amplified group were AKT2 (20.4% vs 3.2%, p&lt;0.001), KRAS (11.3% vs 4.3%, p&lt;0.001), BRD4 (8.0% vs 4.4%, p = 0.006), and ERBB2 (7.9% vs 4.0%, p = 0.003). Other genes were less frequently mutated in the CCNE1 amplified cohort such as NF1 (7.6 % vs 12.9%, p = 0.009), BRCA1 (3.7% vs 10.0%, p&lt;0.001), BRCA2 (2.7% vs 7.4%, p = 0.003), RB1 (2.7% vs 6.4%, p = 0.013), and PTEN (1.2% vs 4.0%, p = 0.02). Frequencies of MYC, PIK3CA, KMT2D, CDK12, and TSC2 mutations were similar between the two groups. TP53 was mutated in 100% of samples. There were no significant differences between the two groups in primary race or total mutation count, and mean age at sequencing was similar. Conclusion: Somatic sequencing is warranted to identify patients of this subset of HGSOC, and understanding the co-amplifications and co-mutations is essential so that they are targeted for optimal survival outcomes.
Citation Format: Ashaar Al-Akhras, Shaden Tashtoush, Alina Ghazou. CCNE1 amplification in high-grade serous ovarian cancer: analysis of the GENIE database. [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 4252.
Abstract 4319: The need for new publication standards in cancer genomics, lessons from curating COSMIC database
Authors: Holmes Alexander , Ward Sari A. , Sondka Zbyslaw 
Published: April 2023

Abstract
A consequence of the progress in cancer genomics is the exponential growth in data produced by research and clinical projects. Given the limited capacity within a scientific manuscript to share experimental data, various approaches have been developed: some data are simply excluded from the publication, moved to the supplementary materials, external repositories are used, and big research programmes present their integrated results on dedicated websites. This last approach has been extremely successful in generating comprehensive and unbiased datasets used by legions of scientists to discover new mechanisms driving cancer, biomarkers and drug targets. However, journal publications are still delivering more data globally, especially from rare cancers and underrepresented populations. To bring the full potential of these data and to make all this knowledge fully available, several challenges need to be addressed. COSMIC (Catalogue of Somatic Mutations in Cancer) has an in-house expert curation team that extracts information about genetic variants, their significance, patients and their response to therapy from publications and integrates it into a standardised cross-referenced database available to the scientific community. Although curators are able to extract data presented in non-standard forms (e.g. manuscript figures), interpret and translate between various data formats, they cannot extract data that are not included in the publication. Approximately one third of manuscripts that are curateable are discarded due to the absence of data generated in the research process but not included in the publication. This clearly shows an urgent need for bringing researchers, publishers, and curators together to develop new publication standards that would allow communities to fully exploit the potential of published data and make them re-usable for further discoveries. We would like to propose several suggestions to start this discussion: - Use accepted naming conventions and standards to make your data interoperable, think about your work as part of the world heritage - Include all data you generate; even if not directly relevant to the manuscript topic, they may be invaluable for somebody else’s research - Share full data and use service providers that share all the data with you - When possible, share the data per patient or sample, not per cohort - Publishing a manuscript is not an endpoint, there’s a huge potential in your data to be further utilised to fight cancer
Citation Format: Alexander Holmes, Sari A. Ward, Zbyslaw Sondka. The need for new publication standards in cancer genomics, lessons from curating COSMIC database. [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 4319.
Abstract 4320: A novel digitally directed tissue microdissection platform integrates digital pathology with molecular analysis: Case study in metastatic colorectal cancer
Authors: Butler John H. , Chaudhuri Bidhan , Konigsfeld Katie , Pai Rish 
Published: April 2023

Abstract
Artificial intelligence (AI) based digital pathology has been getting rapid adoption over the last 2 to 3 years
These AI based digital pathology models can analyze samples at high resolution and scale
Retaining that resolution at scale through molecular analysis is key to the discovery of novel biomarkers
We have developed a technology that can integrate AI-supported digital pathology (DP) algorithms to identify informative tissue regions for selective microdissection to improve molecular analysis of FFPE material
The system is capable of extracting DNA, RNA or proteins with cellular (10 micron) resolution from FFPE tissue sections. The samples are ready for use in off-the-shelf molecular analysis workflows (qPCR, Next Gen Sequencing, etc)
The system decreases the tumor cellularity requirements for clinical analysis by extracting only the area enriched for informative biomarkers
To demonstrate the capability of the system we used an AI based digital pathology model that was developed to identify multiple cellular phenotypes from a H&E stained colorectal cancer FFPE tissue sections
We used the digital pathology output to guide the microdissection of RNA from tumor buds, carcinoma, immature stroma and inflammatory stroma in a paired designed RNA seq experiment
The data showed that the system is capable of enriching the tumor-bud tissue content from&lt;1% in the tissue to ~50% purity in the crude lysate
Bioinformatic analysis of the RNAseq signatures showed that the tumor buds had a distinct RNAseq signature relative to the other three cell types and that the gene expression pattern was consistent with EMT pathways. The methodology is scalable, robust, and simpler than current microdissection techniques. This technology can be used to develop novel tests by integrating with AI algorithms, targeting tissue enriched for predictive biomarkers, and enabling low tumor cellularity samples to be analyzed with high precision.
Citation Format: John H. Butler, Bidhan Chaudhuri, Katie Konigsfeld, Rish Pai. A novel digitally directed tissue microdissection platform integrates digital pathology with molecular analysis: Case study in metastatic colorectal cancer. [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 4320.
Abstract 4416: IL-1 blockade prevents cardiac toxicity and improves immunotherapy efficacy
Authors: Talele Nilesh P. 
Published: April 2023

Abstract
Background: Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, but they are often associated with severe immune related adverse events (irAEs). These severe irAEs are more often seen in patients with obesity or concomitantly treated with cytotoxic therapies.
Methods: We aimed to understand the mechanisms of ICB-induced irAEs, in the context of obesity and ICB/chemotherapy combinations. We developed a mouse model of cardiac irAEs, which is the most fatal type of irAE in ICB-treated cancer patients, with clinically relevant features: (i) an ICB-resistant cancer (pancreatic ductal adenocarcinoma or PDAC), (ii) obesity induced with high-fat diets, and (iii) a combination treatment of ICB (α-PD1 + α-CTLA4) and chemotherapy (FOLFIRINOX).
Results: Our FDA and single institution retrospective analyses indicate that patients treated with ICB had greater relative risk of developing myocarditis as compared to other anti-cancer therapies. Mice with orthotopic PDAC and obesity developed irAEs after treatment with ICB and chemotherapy as compared to chow diet. These irAEs recapitulated those observed in patients with cancer and obesity, including cardiac dysfunction consistent with myocarditis, cardiac fibrosis, and increased circulating levels of interleukin-1 beta (IL-1b). IL-1β blockade prevented myocarditis and reduced cardiac fibrosis after immunotherapy. Importantly, IL-1β blockade also enhanced the anti-tumor effects of ICB + FOLFIRINOX combination therapy, and increased mouse survival.
Conclusions: We developed a translationally relevant 'triple hit' mouse model and discovered that IL-1β mediates ICB-induced cardiotoxicity. In addition, we found that IL-1β blockers, which are already used in the clinic for cardiology indications, both reduce adverse events and simultaneously enhance the antitumor effects triggered by immunotherapy.
Citation Format: Nilesh P. Talele. IL-1 blockade prevents cardiac toxicity and improves immunotherapy efficacy. [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 4416.