bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2684: Pan-cancer neutrophil profiling illuminates anti-tumor antigen-presenting potency
Authors: Wu Ying Cheng , Ma Jiaqiang , Gao Qiang 
Published: March 2024

Abstract
Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life and fragile proliferation, it remains challenging to explore how neutrophils adapt to specific fates in cancer. Here we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples, 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct cell states along differentiation paths including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T-cell responses. Neutrophil delivery or leucine diet fine-tuned the immune balance to boost anti-PD-1 therapy in various murine cancers. In summary, these data not only unravel the neutrophil divergence across cancers, but also offer therapeutic opportunities such as antigen-presenting neutrophil delivery.
Citation Format: Ying Cheng Wu, Jiaqiang Ma, Qiang Gao. Pan-cancer neutrophil profiling illuminates anti-tumor antigen-presenting potency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2684.
Abstract 2765: Novel WNT-RIP1-GDF15 pathway promotes migration and invasion of colorectal cancer cells
Authors: Kang A-Ram , Kim Do Hoon , Park Jong Kuk 
Published: March 2024

Abstract
Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor β (TGF-β) family protein, also known as NSAID-activated gene 1 (NAG-1) or macrophage inhibitory cytokine 1 (MIC-1), and is a major cause of cancer cachexia, cardiovascular disease, and various inflammatory diseases. Roles of GDF15 as major inflammatory response factor also have been demonstrated in animal models, and it has also showed various malignant functions such as regulating metabolism, promoting metastasis by inducing EMT in cancer. Here, we revealed a novel potential role for RIP1 in colorectal cancer (CRC) in enhancing metastasis by controlling WNT-RIP1-GDF15 signaling. We showed that WNT3A treatment increased the expression of GDF15 and GFRAL. Immunohistochemical analysis of human CRC tissue arrays consisting of primary cancer and metastatic cancer also confirmed that the expression of GDF15 and GFRAL was increased in metastatic cancer. Human XL cytokine assay, western blot, and ELISA results confirmed that GDF15 expression was reduced in cell lines in which RIP1 was knocked down. Reduction of GDF15 expression and secretion by RIP1 knockdown showed suppression of EMT induction resulting to decrease of migration and invasion of CRC cells. Taken together, these results suggest a novel EMT-enhancing role for RIP1 in the WNT pathway and suggest a novel WNT-RIP1-GDF15 pathway contributing to CRC malignancy by promoting EMT.
Citation Format: A-Ram Kang, Do Hoon Kim, Jong Kuk Park. Novel WNT-RIP1-GDF15 pathway promotes migration and invasion of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2765.
Abstract 2767: Exploring ADAR1 dependencies in breast cancer brain-metastases
Authors: Sposito Teresa , Klacking Emma E. , Ruiz Antonio W. , Pham Jessica , Jamieson Catriona 
Published: March 2024

Abstract
Background: Adenosine deaminase acting on double-stranded RNA (ADAR1) is a recognized driver of epitranscriptomic (post-transcriptional) remodeling and tumor progression. Changes in amino acid sequence, mRNA splicing, and/or polyadenylation sites are only some of the adenosine-to-inosine (A-to-I) RNA editing effects. Under physiological conditions, ADAR1 activity prevents autoinflammation by inhibiting the accumulation of endogenous immunostimulatory double-stranded RNA and by suppressing the Z-RNA sensor ZBP1. Such mechanisms are exploited by cancer cells to desensitize tumor response to therapies, therefore augmenting aggressiveness. Approximately 10 to 20% of patients diagnosed with breast cancer (BC) will develop metastatic disease, which remains the leading cause of death in individuals with BC. We have hypothesized that ADAR1 and its interferon-inducible p150 isoform, play a pivotal role in promoting BC metastases since high levels of ADAR1 are associated with a worse prognosis in patients with high grade BC, especially in the triple-negative BC subgroup (TNBC), which is the most likely to develop brain metastases.
Methods: We established a humanized mouse model of breast cancer brain metastases (BC-BrM) using neonatal intracerebroventricular inoculation of MDA-MD-231 TNBC cells and primary patient derived metastatic cells in Rag2−/−γc−/− mice. Before implantation, MDA-MD-231 cells were transduced with a nanoluc-GFP reporter for tracing ADAR1 enzymatic activity in the brain metastatic niche. Lentiviral shRNA knockdown vectors targeting ADAR1, combined with over-expression vectors of full-length ADAR1 or the p150 deleted isoform were adopted to detect editing changes in the metastatic model through RNA-sequencing of BC-BrM.
Results: BrM derived from MDA-MD-231 implants display upregulation of ADAR1 p150 and activation of the WNT/β-catenin pathway compared to the non-implanted cell lines. Upon shRNA knockdown of ADAR1, decreased expression of BC stem cell markers was detected via FACS in MDA-MD-231 ADAR1 knocked-down versus control BC-BrM isolated cells. We are now exploring molecular pathways affected by ADAR1 loss/overexpression in establishing BrM.
Future Directions: We have developed a biorepository of primary patient-derived metastatic breast cancer samples and have begun the process of tracking metastatic kinetics and ADAR1 activation with the ADAR1 reporter in an orthotopic mouse model. Overall, this study will provide new insights into the molecular role of ADAR1 deaminase activity in establishing and maintaining metastatic niches.
Citation Format: Teresa Sposito, Emma E. Klacking, Antonio W. Ruiz, Jessica Pham, Catriona Jamieson. Exploring ADAR1 dependencies in breast cancer brain-metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2767.
Abstract 2814: Rectal implantation paves the path to evaluate the metabolic machinery responsible for CRC metastasis
Authors: Afify Said M. , Shen Chen , Merugu Siva B. , Wynn Daniel T. , Nayak Anmada , Lu Wenhui , Calderin Ricardo M. , Pannkuk Evan , Hong Sung H. , Ayad Nagi G. , Robbins David J. 
Published: March 2024

Abstract
Introduction: Colorectal carcinoma patients die most often from distant metastases in liver and lung. It is crucial to develop metastatic models for the CRC in order to better understand the process, which will help in treatment.
Method: Using orthotropic transplantation techniques, we tried to test whether rectal implantation could produce spontaneous metastases in-vivo mimicking colorectal cancer. The rectum was injected orthotopically with 0.2 × 106 HCT116 cells. In order to confirm metastasis, histopathological examinations were performed. Further, we generated cancer organoids to evaluate population susceptibility to CRC metastasis and metabolic mechanisms responsible for metastasis process.
Results: We found that rectal implantation was an effective method for simulating CRC cancer metastasis using H&E staining and immunohistochemistry. In less than four weeks after the implant, HCT116 spontaneously metastasized to the liver, lungs, and D lymph node. When compared with cancer organoids derived from primary tumors, liver and lung metastases organoids proliferated more often, were more aggressive, and displayed distinct characteristics. Using non-targeting metabolomic analysis, it was found that metastases derived organoids and primary tumors derived organoids were distinguished by novel metabolites.
Conclusion: By implantation in the rectal cavity, we can evaluate the metabolic machinery that leads to CRC metastasis. In the future, implantation of patient-derived samples will become increasingly important.
Citation Format: Said M. Afify, Chen Shen, Siva B. Merugu, Daniel T. Wynn, Anmada Nayak, Wenhui Lu, Ricardo M. Calderin, Evan Pannkuk, Sung H. Hong, Nagi G. Ayad, David J. Robbins. Rectal implantation paves the path to evaluate the metabolic machinery responsible for CRC metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2814.
Abstract 2829: Strategies to overcome challenges in randomization and grouping methodologies in in vivo studies using the power of animal study workflow software
Authors: Ramachandra Raghu 
Published: March 2024

Abstract
Preclinical research in Oncology requires using a wide variety of animal models. Robust, clinically relevant distribution methods including randomized and non-random methods appropriate to the model are essential to ensure unbiased group assignments and reliable experimental outcomes. This presentation will explore flaws and inconveniences in prevalent randomization methods and strategies to overcome them using animal study workflow software and demonstrate the power of each with unique examples. Strategies for randomizing individual animals into groups and randomizing mouse cages into groups will be explored. Strategies for exclusion criteria, robust documentation, multi-parameter randomization, re-randomization, and clinical relevance of these strategies will be discussed. Standardization and automation of distribution methods help improve process integrity, research quality, and reproducibility.
Citation Format: Raghu Ramachandra. Strategies to overcome challenges in randomization and grouping methodologies in in vivo studies using the power of animal study workflow software [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2829.
Abstract 2839: The mouse models of human cancer database (MMHCdb)
Authors: Begley Dale A. , Krupke Debra M. , Jocoy Emily , Neuhauser Steven B. , Bult Carol J. 
Published: March 2024

Abstract
The laboratory mouse plays a pivotal role as an experimental system for investigations into the genetic and genomic basis of cancer susceptibility, initiation, and progression and for preclinical research on novel treatment strategies for cancer. Advances in mouse models include humanized mice, transplant compliant mouse strains, and panels of genetically diverse mice (e.g., Diversity Outbred and Collaborative Cross). The distributed and heterogenous nature of information about these model systems presents a significant challenge to finding and aggregating information about mouse models and to identifying the most relevant models for a particular research question. The Mouse Models of Human Cancer database (http://tumor.informatics.jax.org) is an expertly curated FAIR-compliant knowledgebase that applies community annotation standards and nomenclature standards for genes, alleles, and strains to support accurate and comprehensive search results for mouse models of human cancer. The data in MMHCdb are curated from peer-reviewed scientific publications and direct data submissions from individual investigators and large-scale programs. A primary focus of the resource is to reflect the impact that genetic background has on the cancer-related characteristics of mouse models. The database includes information on spontaneous and genetically engineered cancer models as well as Patient Derived Xenografts and diversity panels. The database supports faceted searching for models by multiple criteria including, tumor type, genetic background of the mouse model, somatic mutations, and publication. Model descriptions include summaries of observed frequencies of tumors observed in the model and histopathology images. Information in MMHCdb is linked to cancer model data from other bioinformatics resources including the Patient Derived Cancer Models database (PDCM), PathBase, the Gene Expression Omnibus (GEO), and ArrayExpress.
MMHCdb is supported by NCI R01 CA089713
Citation Format: Dale A. Begley, Debra M. Krupke, Emily Jocoy, Steven B. Neuhauser, Carol J. Bult. The mouse models of human cancer database (MMHCdb) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2839.
Abstract 2872: GLUT3 promotes metabolic plasticity that drives radiation resistance in glioblastoma
Authors: Abdulrahman Lobna , Bailleul Justine , Hoang Hanna , Tang Aaron , Vlashi Erina 
Published: March 2024

Abstract
Glioblastomas (GBM) are the most common and malignant brain tumors in adults. While radiation therapy (RT) offers a significant advantage for GBM patients, improving long-term survival remains elusive largely due to the remarkable resistant nature of these tumors. We have shown that metabolic plasticity, especially rewiring of glucose metabolism, promotes radiation survival in GBM. In this study, we investigate the role of glucose transporter 3 (GLUT3) translocation to the cell surface in radiation resistance of GBM. The effect of radiation on GLUT3 total protein levels was determined in patient-derived gliomaspheres via westerns blots, while cellular localization of GLUT3 was determined via immunofluorescence, flow cytometry and cell fractionation assays. The role of the AMPK and αvβ3 integrin in the radiation-induced GLUT3 translocation to the cell membrane was probed via small molecule inhibitors and activators. To determine the role of GLUT3 in radiation survival, GLUT3 levels were knocked down via siRNA and shRNA, followed by functional in vitro and in vivo assays. We provide evidence that irradiated gliomaspheres translocate GLUT3 to the plasma membrane, in a radiation-induced oxidative stress-dependent manner, effectively increasing their glucose uptake and promoting radiation survival. Our data also suggest that GLUT3 translocation to the cell surface contributes to RT resistance. AMPK and αvβ3 integrin are linked to radiation-induced translocation of GLUT3 to the cell membrane, suggesting that targeting these pathways is a potential approach to sensitize GBM tumors to radiation therapy.
Citation Format: Lobna Abdulrahman, Justine Bailleul, Hanna Hoang, Aaron Tang, Erina Vlashi. GLUT3 promotes metabolic plasticity that drives radiation resistance in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2872.
Abstract 2882: Investigating mechanisms of radioresistance in TYK2 knockout head and neck cancer cells
Authors: Constante Nicole Mayerli , Kelley Vanessa , Contessa Joseph 
Published: March 2024

Abstract
Radiation therapy is the primary form of treatment of head and neck squamous cell carcinoma (HNSCC). However, more than half of patients experience disease progression with standard of care treatment. To investigate novel therapeutic targets, a CRISPR screen was done to identify genes that are associated with radioresistance. The screening results indicated that JAK1 and TYK2 knockout (KO) resulted in radioresistance in HNSCC. Preliminary data suggests that loss of JAK1 causes an enhanced G2/M arrest phenotype and enhanced genome stability that contribute to radioresistance. To investigate whether TYK2 KO caused changes to the cell cycle and genome stability as observed in JAK1 KO, Western blots, cell cycle assays, and micronuclei staining experiments were performed. Cal27, a HNSCC cell line, was used. Cal27 cells were transduced with a non-targeting control (NT2) guide RNA (gRNA) or two different gRNAs targeting TYK2 to generate TYK2 KO cells. Western Blot analysis was performed to determine changes in signaling upon TYK2 KO. Additional conditions included radiation and treatments with Interferon gamma, Interferon alpha and Interleukin-6 to activate the canonical JAK-STAT pathways. Overall, there were minimal changes in downstream signaling between the treatments and the knockouts. Cell cycle analysis via flow cytometry revealed no changes between the NT2 and TYK2 KO cells, potentially corroborating signaling results. Forty percent of TYK2 KO cells were arrested at the G2/M checkpoint at 8 hrs and 24 hrs after radiation treatment, but twenty percent returned to the G1 phase at 24 hrs. This indicates that loss of TYK2 is not responsible for cell cycle arrest. Lastly, micronuclei formation was observed to measure genomic instability. Twenty thousand Cal27 NT2 and TYK2 KO cells were seeded. They were allowed to incubate for 48 hrs before treatment with 4 Gy. Micronuclei staining revealed minimal differences between NT2 and TYK2 KO cell lines, although there were significant differences between the control and the radiation groups. Overall, radioresistance by TYK2 KO is not caused by changes in cell cycle or genomic instability as demonstrated with JAK1 KO. To understand how TYK2 is causing radioresistance in HNSCC, next steps would be to see if there are changes in proliferation. If MTT assays demonstrate significant changes, downstream signaling in growth pathways will be measured. If there is no increased proliferation, we will examine changes in DNA damage repair.
Citation Format: Nicole Mayerli Constante, Vanessa Kelley, Joseph Contessa. Investigating mechanisms of radioresistance in TYK2 knockout head and neck cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2882.
Abstract 289: Temporal and spatial dynamics of glial cells apolipoprotein E expression in astrocytoma microenvironment
Authors: Chien Ting-Yi , Chiang Chi-Shiun 
Published: March 2024

Abstract
Introduction: Brain tumors have proven challenging to treat due to the complex and sensitive architecture of the brain. Previous research has shown that GBM cells depend highly on cholesterol uptake, and apolipoprotein E (APOE) is required to transport cholesterol among tissues or cells. APOE is primarily synthesized by astrocytes and has been extensively studied in neurodegenerative diseases. While extensively studied in neurodegenerative diseases, limited studies are focusing on their roles in brain tumor development. Here, we analyzed the temporal and spatial expression of APOE during brain tumor progression in a murine astrocytoma tumor model.
Material and method: ALTS1C1 astrocytoma cells were intracranially injected into the mouse brain. The animal was sacrificed, and the left hemisphere, right hemisphere, and tumor tissue were collected for flow cytometry analysis. CD45, CD11b, and GFAP were used to recognize macrophages, microglia, and astrocytes. CD68, TMEM119, and GFAP were used for tissue immunostaining to label macrophages, microglia, and astrocytes, respectively.
Results and Discussion: Flow cytometry analysis revealed upregulated APOE in tumor-infiltrating microglia, macrophages, and lymphocytes. GFAPhigh astrocytes displayed lower APOE levels than GFAPlow astrocytes. IHC analysis showed that CD68+ macrophages exhibited higher APOE expression at the tumor edge than normal tissue. On the contrary, GFAP+ astrocytes at the tumor edge displayed a lower APOE signal than the normal tissue. Previous studies have shown the participation of APOE in regulating immune response in various cancers. Further studies to analyze the dynamic change of APOE on the gene expression level with in situ hybridization and the quantification of cholesterol levels in the microenvironment may help uncover their roles in the glioma microenvironment.
Conclusion: This study demonstrated that APOE was temporal and spatial differentially expressed in macrophages and astrocytes in the brain tumor microenvironment. Tumor-infiltrating cells showed an elevated APOE expression, while GFAP+ astrocytes expressed reduced APOE levels. Although the mechanism of these alterations remains unclear, this study provides a basis for future studies about the roles of APOE in the brain tumor microenvironment.
Citation Format: Ting-Yi Chien, Chi-Shiun Chiang. Temporal and spatial dynamics of glial cells apolipoprotein E expression in astrocytoma microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 289.
Abstract 2903: CTHRC1 induces PSCs (pancreatic stellate cells) into myCAFs (myofibroblast-like cancer-associated fibroblasts)
Authors: Lee Jin Gyeong , Kang Min Kyung , Jiang Fen , Ryu Kyoungjin , Kim Juwon , Park Yun-Yong , Koh Sang Seok 
Published: March 2024

Abstract
Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.
Citation Format: Jin Gyeong Lee, Min Kyung Kang, Fen Jiang, Kyoungjin Ryu, Juwon Kim, Yun-Yong Park, Sang Seok Koh. CTHRC1 induces PSCs (pancreatic stellate cells) into myCAFs (myofibroblast-like cancer-associated fibroblasts) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2903.