bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 7319: Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis
Authors: Jun So Yon , Cho Sooyoung , Kim Min Jung , Park Ji Won , Jeong Seung Yong , Shin Aesun 
Published: March 2024

Abstract
Background: Clinical diabetic traits have been reported to be associated with increased colorectal cancer risk (CRC) in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients.
Methods: We conducted a two-sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single-nucleotide polymorphisms robustly associated (P&lt;5 × 10−8) with the three glycemic traits were obtained from the Meta-Analyses of Glucose and Insulin-related traits Consortium, Asian Genetic Epidemiology Network, and Korea Biobank Array. Three-year and five-year overall survival (OS) and progression-free survival (PFS) were used as outcomes. Survival analysis was conducted using subgroup analysis by cancer stage and subsite in a multivariate Cox proportional hazards model adjusted for age and sex to examine whether glycemic traits affected survival.
Results: A total of 509 patients were included in our final analysis. MR analysis showed that HbA1c levels were associated with poor three-year OS (β=4.20, P=0.02). Sensitivity analyses did not show evidence of any violations of the MR assumptions. In the cancer subgroup analysis of the Cox proportional hazards model, pooled hazard ratios for FG were significantly associated with poor three-year OS and PFS regardless of cancer stage. FI was not significantly associated with any three-year survival endpoints. Among stage III patients, three glycemic traits were significantly associated with both five-year OS and PFS. Location-specific subgroup analysis showed a significant association between three glycemic traits and five-year PFS in patients with left-sided colon cancer. FG was associated with poor three-year survival for colon cancer but not rectal cancer.
Conclusions: Our results suggest that FG and HbA1c could be used to predict prognosis in CRC patients. Lifestyle and/or pharmacological interventions targeting glycemic traits could help improve survival for CRC patients.
Citation Format: So Yon Jun, Sooyoung Cho, Min Jung Kim, Ji Won Park, Seung Yong Jeong, Aesun Shin. Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis [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 7319.
Abstract 7368: Sentinel omics signatures: Comparative clinical and blood sample analysis from canine mammary tumor patients and their human guardian
Authors: Son Keun Hong , Nam A-Reum , Park Hyoung-Min , Kim HuiSu , Lee Jeong-Woon , Cho Je-Yoel 
Published: March 2024

Abstract
Breast cancer remains a leading cause of morbidity and mortality worldwide, necessitating innovative approaches for early detection and intervention. This study leverages the comparative biology paradigm, exploring the shared oncological pathways between humans and canines through a unique multi-omics approach. We have gathered a diverse cohort comprising healthy dogs, canine mammary tumor patients, and their respective human guardians, collecting comprehensive clinical data alongside blood samples. Employing RNA-seq, MBD-seq, and LCMS, we aim to construct a detailed transcriptomic, methylomic, and proteomic landscape to elucidate potential sentinel biomarkers indicative of an oncogenic environment shared between species. While results are forthcoming, the premise of our research rests on the hypothesis that environmental factors contributing to mammary cancer may manifest systemically, potentially affecting both canines and humans. By delineating these interspecies molecular signatures, we hope to advance the field of precision medicine, offering insights into early detection and the systemic nature of cancer pathobiology. This abstract presents the foundation and direction of our ongoing investigation, with a commitment to providing a comprehensive update, inclusive of significant findings, at the conference.
Citation Format: Keun Hong Son, A-Reum Nam, Hyoung-Min Park, HuiSu Kim, Jeong-Woon Lee, Je-Yoel Cho. Sentinel omics signatures: Comparative clinical and blood sample analysis from canine mammary tumor patients and their human guardian [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 7368.
Abstract 7383: G2PT: Mechanistic genotype-phenotype translation using hierarchical transformers
Authors: Lee Ingoo , Park Sungjoon , Nam Hojung , Ideker Trey 
Published: March 2024

Abstract
Motivation: Many machine learning models have been proposed that use genotypes to predict various phenotypes. Recently, these models have focused not only on an accurate prediction but mechanistic interpretation, in that they attempt to describe the hierarchy of biological systems underlying the predicted phenotype. Such models still face major challenges, however, including how to robustly quantify the importance of systems mediating phenotypic outcomes and how to represent the bidirectional flow of information among genes, systems, phenotypes, and cell environment.
Results: To address these challenges we introduce G2PT, a general Genotype-to-Phenotype Transformer, which we apply here to the classic G2P problem of modeling tumor cell sensitivity to drugs. We show that the framework of hierarchical transformers can represent biological systems spanning a wide range of physical scales and provide a quantitative assessment of the interplay between biological components important for phenotype prediction. When used to analyze a high-throughput cell screen of 436 drugs exposed to 1,097 cell types, we show that the model achieves good performance in predicting cell sensitivity for 83% of drugs (⍴ &gt; 0.5 in cross-validation). G2PT provides a robust and interpretable model with potential application to many challenges in genotype-phenotype translation.
Citation Format: Ingoo Lee, Sungjoon Park, Hojung Nam, Trey Ideker. G2PT: Mechanistic genotype-phenotype translation using hierarchical transformers [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 7383.
Abstract 7384: Regulation of phosphorylated VGLL1 by the positively charged binding pocket on the surface of TEAD4
Authors: Choi Jae Mun , Van Le Huong , Park Young Bin , Yun Yu Kyung , Kim Jun Hong , Wilianto Jonathan , Shadiev Nuzup , Sung Chul , Ku Bonsu , Chang Kwan-Young , Won Misun 
Published: March 2024

Abstract
Vestigial-like 1 (VGLL1) is a transcriptional co-activator that binds to TEA domain-containing transcription factors (TEADs), regulating hippo pathway. High expression of VGLL1 is associated with gastric cancer, breast cancer, and pancreatic cancers. VGLL1 is transcriptionally regulated by PI3K/β-catenin signaling and is phosphorylated by ribosomal S6 kinase 2 (RSK2) in the presence of TGF-β. It is clear that phosphorylation at S84 of the VGLL1 protein is critical for its interaction with TEAD4 to express their target genes involved in the proliferation and metastasis of cancer cells. In the isothermal titration calorimetry study, we observed S84-phosphorylated VGLL1 peptide bound to TEAD4. However, it is difficult to understand structure-based molecular mechanism of the phosphorylated VGLL1 at S84 due to lack of the detailed human VGLL1-TEAD4 complex structure for rational drug design. In this study, we modeled full-length human VGLL1-TEAD4 or YAP1-TEAD4 complexes and performed MMPBSA calculations or Kd/Ki predictions followed by MD simulations using Pharmaco-Net's CNN-based artificial intelligence model. Our study suggests that a positively charged binding pocket on the surface of TEAD4 can regulate interaction between Trp243 from YAP1 and phosphorylated-Ser84 from VGLL1. The newly identified binding pocket is composed of Lys297, Val414, and Tyr429, which can interact with phosphorylated Ser84 residue and maintain Omega loop-like structure shown in YAP1-TEAD4 complex. The computed binding energy for phosphorylated-VGLL1-TEAD was -134.80 +/- 8.20 Kcal/mol which was a similar binding energy to YAP1-TEAD4 complex. In addition, global peptide docking using S84-containing-VGLL1 peptide (SCVP) indicated that SCVP can bind to the same binding pocket with average 1.39 μM. This suggested that there could be a novel therapeutic approach targeting this interaction with SCVP, an agent that seems to mimic phosphor-VGLL1 interaction and thus demonstrates promise as a potential therapeutic intervention. Nevertheless, further experimental verification and clinical investigations are needed to validate these innovative findings.
Citation Format: Jae Mun Choi, Huong Van Le, Young Bin Park, Yu Kyung Yun, Jun Hong Kim, Jonathan Wilianto, Nuzup Shadiev, Chul Sung, Bonsu Ku, Kwan-Young Chang, Misun Won. Regulation of phosphorylated VGLL1 by the positively charged binding pocket on the surface of TEAD4 [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 7384.
Abstract 7435: PATTY: A bias estimation and correction model for bulk and single-cell CUT&Tag data
Authors: Hu Sheng'en Shawn , Chen Qingying , Grieco Megan , Zang Chongzhi 
Published: March 2024

Abstract
The accurate detection of transcription factor (TF) binding sites and histone modifications (HM) on the genome-wide scale is essential for studying functional epigenetics and gene regulation. Cleavage Under Targets & Tagmentation (CUT&Tag) is a low-cost and easy-to-implement epigenomic profiling method that can be performed on a low number of cells and on the single-cell level. CUT&Tag experiments use the hyperactive transposase Tn5 for tagmentation. We find that Tn5 is subject to intrinsic sequence insertion bias (intrinsic bias). Additionally, the preference of Tn5 insertion toward accessible chromatin also affects the distribution of CUT&Tag reads (open chromatin bias). Both types of biases can significantly confound bulk and single-cell CUT&Tag data analysis, which requires careful assessment and new analytical methods. To address this challenge, we present PATTY (Propensity Analyzer for Tn5 Transposase Yielded bias), a computational method for systematic characterization and correction of biases in CUT&Tag data. We demonstrate that histone modification signals (H3K27me3 and H3K27ac) detected from CUT&Tag data after bias correction using PATTY are better associated with orthogonal biological features such as gene expression. PATTY-corrected single-cell CUT&Tag signals for histone modification can better cluster cells into their true cell types. This new computational method can improve both bulk and single-cell CUT&Tag data analysis.
Citation Format: Sheng'en Shawn Hu, Qingying Chen, Megan Grieco, Chongzhi Zang. PATTY: A bias estimation and correction model for bulk and single-cell CUT&Tag data [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 7435.
Abstract 7445: Association between C-reactive protein and cognitive impairment in IDH-mutant gliomas
Authors: Kauss McKenzie C. , Wright Michelle L. , Raval Dhaivat , Hsieh Emory , Slattery Kaitlynn , Armstrong Terri S. , Mendoza Tito R. , Guedes Vivian A. 
Published: March 2024

Abstract
Cognitive impairment is common in primary brain tumor (PBT) patients, as a result of the disease and secondary damage from directed and systemic therapy. Recently, the risk in patients with IDH-mutant gliomas and role of interconnectivity of the tumor with neurons and the tumor microenvironment has heightened interest in exploration of biomarkers of impairment to inform care. Here, we investigate Montreal Cognitive Assessment (MoCA) scores and peripheral blood levels of C-reactive protein (CRP) in a cross-sectional cohort of 47 adult IDH-mutant PBT patients enrolled in a natural history study (NHS, NCT02851706: PI T. Armstrong). MoCA raw scores (range 0-30) were dichotomized (≤ 25 = cognitive dysfunction). Baseline CRP was quantified in banked serum samples in duplicate using (V-Plex/Vascular Injury Panel-2, Meso Scale Discovery [MSD], Rockville, MD) in a QuickPlex SQ 120 instrument (MSD). Lab personnel were blinded to diagnosis and clinical status. To reduce skewness in CRP raw values, we used log transformation. Descriptive statistics, Pearson’s correlation, and logistic regression were conducted using IBM SPSS and SAS Statistics software. The sample was predominately male (62%), white (70%), with high-grade gliomas (III/IV) (68%) and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The mean MoCA score was 25 (SD: 5; median: 26; range: 11-30). Dichotomizing MoCA scores showed that less than half (43%) of participants exhibited moderate-severe (≤ 25) cognitive impairment. MoCA binary group was negatively correlated with levels of CRP (r=-0.42, p&lt;.003). The log mean concentration of CRP was higher in participants with cognitive impairment (7.99, SD=0.47 vs 7.57, SD=0.45, p&lt;.003) than those without impairment. Finally, when controlling for age and sex, CRP remained predictive of cognitive impairment (OR 8.18, 95% CI 1.70,39.23). Higher levels of CRP were associated with lower MoCA scores in a cross-sectional sample of patients with IDH-mutant gliomas, suggesting an association between the severity of inflammation and cognitive impairment in IDH-mutant glioma patients. Further analysis in large, more diverse longitudinal cohorts will be needed to validate these findings in this population and compare to those with IDH-WT tumors and develop predictive models to inform biomarker development.
Citation Format: McKenzie C. Kauss, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, Kaitlynn Slattery, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Association between C-reactive protein and cognitive impairment in IDH-mutant gliomas [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 7445.
Abstract 7461: Obesity promotes breast cancer progression via complement 1q
Authors: Zhang Tao , Liu Shimeng , Brown Myles 
Published: March 2024

Abstract
Obesity markedly impacts the onset and progression of various tumors. Yet, the mechanisms by which obesity-driven remodeling in macrophages modulates tumor progression are not yet fully elucidated. Using single-cell RNA sequencing and in vivo syngeneic murine models, we identified an enriched subset of macrophages expressing high levels of C1q complex genes in the adipose tissue of obese mice. Intriguingly, these C1q-positive macrophages are also prevalent within the tumor microenvironment. Our data suggest that obesity induces cell apoptosis in both adipocytes and tumor cells, and that macrophages engulf these apoptotic cells via a C1q-dependent pathway, thus promoting immunosuppression. Moreover, C1q deficiency in mice impairs tumor growth. Notably, C1q is upregulated in human breast cancer and is associated with poor prognosis. Our results suggest that targeting C1q could be an effective method for breast cancer treatment.
Citation Format: Tao Zhang, Shimeng Liu, Myles Brown. Obesity promotes breast cancer progression via complement 1q [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 7461.
Abstract 7477: Isoxanthohumol inhibits LPS-induced inflammatory responses in macrophages
Authors: Kao Tzu-Han , Li Chia-yang 
Published: March 2024

Abstract
Background: Pathogen infection, such as bacteria, viruses, and fungus, frequently leads to septicemia through a series of inflammatory responses that have very high fatality rates. And, servere inflammation may cause gene mutation which is beginning of cancer. Macrophages are a critical type of antigen-presenting cells that control both innate and adaptive immune responses. During pathogen infection, activated macrophages secret many proinflammatory mediators and cytokines, including nitric oxide (NO), TNF-α and IL-6 against pathogens; however, an overwhelming inflammatory response provokes abundant cells to undergo apoptosis. In the present study, we aimed to examine the anti-inflammatory effect of isoxanthohumol, a prenylflavonoid from hops and beer.
Method: We used lipopolysaccharide (LPS) as a pathogenic stimulus to induce inflammatory responses by J774A.1 macrophages. MTT assay was used to detect cell viability. The secretion of NO was analyzed by Griess reagent assay, while the production of TNF-α, IL-6, IL-1β was measured by enzyme-linked immunosorbent assay (ELISA). The expression of iNOS, COX-2, and MAPKs was examined by Western blotting. The activity of NF-κB was analyzed by promotor reporter assay. The activation of NLRP3 inflammasome was examined by ELISA and immunofluorescence staining. In addition to that, we explored the secretion of cytokines, IL-1β, in THP-1 cell.
Result: We found that isoxanthohumol significantly suppresses the secretion of NO and attenuates the production of TNF-α and IL-6 by LPS-induced macrophages. In addition, isoxanthohumol also inhibits the expression of iNOS and COX-2, suppresses the phosphorylation of JNK, and attenuates the activity of NF-κB by LPS-induced macrophages. Moreover, isoxanthohumol decreases the activation of NLRP3 inflammasome by reducing the production of IL-1β and repressing the ASC speck formation of NLRP3 inflammasome in LPS/ATP-induced macrophages.
Conclusion: Our experimental results demonstrated that isoxanthohumol effectively inhibits LPS-induced inflammatory responses in macrophages, suggesting that isoxanthohumol might have benefits for attenuating inflammation.
Citation Format: Tzu-Han Kao, Chia-yang Li. Isoxanthohumol inhibits LPS-induced inflammatory responses in macrophages [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 7477.
Abstract 7499: Circulating tumor cell enumeration and protein expression by CapioCyte and Allegro Plus imaging
Authors: Lim Ju-heon , Johnson Chassidy , Kaplan Tal , Poellmann Michael J. , Harari Yuval , Kfir Elad , Wang Andrew Z. , Hong Seungpyo 
Published: March 2024

Abstract
Radiation or chemoradiation followed by surgical resection is the current standard of therapy for many diseases. These treatments are increasingly supplemented with monoclonal antibodies, such as epidermal growth factor receptor (EGFR)-targeting and programmed death ligand 1 (PD-L1) checkpoint-blocking antibodies. The use of these therapies is typically dependent on solid tissue biopsy to confirm elevated expression of these markers in the solid tumor, which carries complications and may only be sampled at diagnosis. In contrast, a liquid biopsy may detect these markers with minimal invasiveness and at multiple points throughout treatment and recovery. Here, we describe the development of an automated and integrated workflow for circulating tumor cell (CTC) analysis. We previously demonstrated that the CapioCyte method is a highly sensitive approach for enrichment of CTCs using a combination of biomimetic rolling on recombinant E-selectin and antibody-mediated capture on a nanostructured polymer surface within a flow chamber for capture. Here we report a fully automated CapioCyte instrument for CTC purification and immunofluorescence staining using epithelial, white blood cell and nuclear makers to identify and distinguish CTCs from WBCs while also quantifying EGFR or PD-L1 presence on respective CTCs. The immunostaining conditions were developed and validated for high analytical sensitivity and specificity using cell lines and health donor white blood cells with known biomarker status. The final assay conditions were transferred to the CapioCyte for automated immunostaining. CapioCyte enriched and stained CTC samples are paired with the BioView Allegro Plus platform, an imaging and analysis solution using machine learning and customized algorithms for automated imaging and CTC candidate identification based on high-resolution Z-stack images. The reported comprehensive and automated workflow was used to enumerate CTCs in patients with non-small cell lung carcinoma (NSCLC) in a feasibility cohort. Median CTC counts from NSCLC patients was 7.5 CTC/ml (n=26, mean 51.7, range 0.3 - 406.2). Studies are on-going to expand the cohort including testing blood from head and neck cancer patients and respective EGFR and PD-L1 status. The combined and automated CapioCyte-Allegro Plus workflow shows great potential for routine quantification of CTCs and EGFR and PD-L1 status.
Citation Format: Ju-heon Lim, Chassidy Johnson, Tal Kaplan, Michael J. Poellmann, Yuval Harari, Elad Kfir, Andrew Z. Wang, Seungpyo Hong. Circulating tumor cell enumeration and protein expression by CapioCyte and Allegro Plus imaging [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 7499.