bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1990: Targeting cancer stem cells is an answer to the curing lung cancer
Authors: Song Keum-Soo , Nimse Satish Balasaheb , Kim Taisun 
Published: April 2023

Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Mainly, non-small cell lung cancer (NSCLC, about 80% of cases) and small cell lung cancer (SCLC, about 20% of cases) are the major types of lung cancer. Adenocarcinoma (30-50%) and squamous cell carcinoma (30%) are the major subtypes of NSCLC. Even though there are considerable advancements in the drugs against lung cancer, the 5-year survival rate is meager. Unfortunately, the drug resistance for currently available anticancer drugs results in a 5-year survival of only 5%. The remarkable lung cancer recurrence despite definitive local and/or systemic therapy indicate that residual cancer stem cells (CSCs) possess tumorigenic potential. Therefore, drugs targeting the CSCs and killing them quickly can cure lung cancer without any relapse and improve the 5-year survival rate. Herein, we present the application of the recently reported ID-Checker technology (Journal of Medicinal Chemistry 2022 65 (19), 12883-12894) for killing lung cancer stem cells (LCSC). The ID-Checker that is decorated with the glucose tag allows highly specific absorption and macroscale delivery of anticancer drugs to the LCSC through the GLUT channels. ID-Checker inhibits the microtubule formation resulting in the cell cycle arrest in the G2/M phase followed by apoptosis. The inhibition of microtubule formation by ID-Checker also leads to the inhibition of GLUT channel deployment in the LCSC. Thus, the glucose-deprived LCSC undergoes apoptosis within 72 hours of ID-Checker treatment. Hence, we believe the ID-Check technology presented here can kill the LCSC and completely cure lung cancer.
Citation Format: Keum-Soo Song, Satish Balasaheb Nimse, Taisun Kim. Targeting cancer stem cells is an answer to the curing lung 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 1990.
Abstract 2038: Epstein-Barr virus shapes the tumor microenvironment in classical Hodgkin lymphoma
Authors: Pourmaleki Maryam , Jones Caitlin J. , Mellinghoff Sabrina D. , Greenstein Brian , Kumar Priyadarshini , Roshal Mikhail , Hollmann Travis J. , Socci Nicholas D. , Dogan Ahmet , Mellinghoff Ingo K. 
Published: April 2023

Abstract
The histopathologic appearance of classical Hodgkin lymphoma (cHL) is characterized by rare multinucleated malignant Hodgkin Reed-Sternberg (HRS) cells within a rich inflammatory tumor microenvironment (TME). A subset of cHL cases are associated with Epstein-Barr virus (EBV) infection, which is considered to play a part in cHL pathogenesis. Since EBV+ and EBV- cHL exhibit differing mechanisms of pathogenesis, we hypothesized that the composition and spatial architecture of the TME in EBV-associated cHL differs from that of EBV- cHL, with implications for stratifying patients for specific treatment regimens based on EBV positivity. Here, we designed a multimodal approach using spatially resolved multiplexed protein profiling, flow cytometry, immunohistochemistry, and transcriptomics to profile EBV positive and EBV negative cHL tumors. We measured over 27 million single cells and 1,000 unique proteomic cell states derived using 29 proteins in addition to the transcriptome in 43 patient tumors. We uncovered significant differences between EBV+ and EBV- cHL in relative abundance of specific immune cell types, immune activation state, and spatial organization of the HRS cell neighborhoods. We present a multidimensional characterization of cHL in relation to EBV with implications for therapeutic stratification of patients with virus-associated cHL.
Citation Format: Maryam Pourmaleki, Caitlin J. Jones, Sabrina D. Mellinghoff, Brian Greenstein, Priyadarshini Kumar, Mikhail Roshal, Travis J. Hollmann, Nicholas D. Socci, Ahmet Dogan, Ingo K. Mellinghoff. Epstein-Barr virus shapes the tumor microenvironment in classical Hodgkin lymphoma [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 2038.
Abstract 2039: Predicting abundance and expression of immune cells in patients’ head & neck tumor microenvironment from blood single-cell transcriptomics
Authors: Cao Yingying , Chang Tiangen , Schischlik Fiorella , Sinha Sanju , Wang Kun , Jiang Peng , Ruppin Eytan 
Published: April 2023

Abstract
The tumor microenvironment (TME) is a key determinant of immunotherapy efficacy, yet, not readily accessible. Here, we ask if the immune cell fractions (ICFs) and gene expression patterns in the TME can be predicted from the blood single-cell RNA sequencing (scRNA-Seq) data. To the best of our knowledge, the immune status of the TME has not been comprehensively evaluated and predicted from the blood previously. Addressing this challenge, we analyzed 26 paired head and neck squamous cell carcinoma (HNSCC) patients matched blood and tumor samples with CD45+ scRNA-Seq data and clinical information. We developed a machine learning predictor of ICFs and gene expression levels of major immune cell types in the TME from the matching blood transcriptomics and pertaining clinical information, termed the Tumor Immune MicroEnvironment Predictor (TIMEP). We find that the ICFs, all 11 major immune cell types in the TME were predictable from the blood. 17-47% genes expressed in different immune cells were predictable from the blood, with the highest coverage in dendritic cells and helper, cytotoxic and regulatory T cells. Furthermore, the ICF ratio (ICFR) signature of (Treg - Bmemory)/(Treg + Bmemory) in the TME, as predicted from the blood, can robustly predict the response to immune checkpoint blockade (AUC &gt; 0.72 on three independent single-cell and bulk expression datasets). These results are the first to demonstrate the feasibility of employing single-cell transcriptomics liquid biopsy to predict the immune status in patients TME in patients, facilitating future personalized cancer precision therapy.
Citation Format: Yingying Cao, Tiangen Chang, Fiorella Schischlik, Sanju Sinha, Kun Wang, Peng Jiang, Eytan Ruppin. Predicting abundance and expression of immune cells in patients’ head & neck tumor microenvironment from blood single-cell transcriptomics [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 2039.
Abstract 2055: Prevalent focal amplification of oncogene in lung adenocarcinomas without canonical driver alterations
Authors: Park Seongyeol , Lim Joonoh , Yi Kijong , Yi Boram , Kim Ryul , Koo Jaemo , Na Kwon Joong , Park Samina , Park In Kyu , Kang Chang Hyun , Lee Jeong Seok , Ju Young Seok , Kim Young Tae 
Published: April 2023

Abstract
Lung adenocarcinoma (LADC) is the most common type of lung cancer and a leading cause of death worldwide. Typical oncogenes that drive LADCs when mutated (referred to as canonical drivers) include EGFR (30-60%), KRAS (10-30%), and fusion oncogenes (~10%) involving ALK, RET, and ROS1. However, approximately 30% of lung adenocarcinomas lack canonical drivers, implying unseen kinds of genomic alterations. Here, we explore alterations beyond the scope of canonical drivers in LADCs (referred to as non-canonical drivers) using large-scale whole-genome sequencing (WGS) of LADCs. We gathered total 183 WGS of LADCs, 138 of which were from our previous study (Lee et al. Cell. 2019) and 45 were newly sequenced from surgically resected LADCs. For raw data processing, we used a standard WGS analysis pipeline from read mapping to variant calling. Variant filtering and downstream analyses were performed using in-house scripts. Genomic variants analyzed in this study include single-base substitution (SBS), indel, structural variation (SV), and copy number variation (CNV). As a result, we found that 53 cases (29%) had no canonical drivers (ND group). Intriguingly, LADCs without canonical drivers had a contrasting genomic landscape compared to LADCs with canonical drivers (CD group). First, the point-mutation burden was ~3-fold higher in the ND group than in the CD group (52,500 vs. 17,900 for SNVs, p&lt;0.001). Mutational signature analysis revealed that these additional mutations are attributable mainly to tobacco smoking (by mutational signature SBS4) and APOBEC-mediated mutagenesis (SBS12 and SBS13) and that they are more enriched in the ND group (4,800 vs 2,600, p=0.03). Second, the ND group harbored more frequent focal amplifications. Recurrently amplified genes include TERT, IL7R, NKX2-1, CCND1, CCND3, CCNE1, and EGFR. The pattern of SVs suggest that the amplifications occurred through the formation of extra-chromosomal DNA involving multiple chromosomes or following chromothripsis. Overall, this study broadens our understanding of non-canonical drivers of LADCs. Similar analyses of thousands of cancers with clinical information of the patient will likely yield the functional impact of these driver mutations and may offer more opportunities for LADC treatment in the future.
Citation Format: Seongyeol Park, Joonoh Lim, Kijong Yi, Boram Yi, Ryul Kim, Jaemo Koo, Kwon Joong Na, Samina Park, In Kyu Park, Chang Hyun Kang, Jeong Seok Lee, Young Seok Ju, Young Tae Kim. Prevalent focal amplification of oncogene in lung adenocarcinomas without canonical driver alterations [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 2055.
Abstract 2060: The exploratory analysis of dysregulated transcription factor FOXC1 in pan-cancer
Authors: Brown Alanna , Wu Zexun , Cao Huan , Falzarano Sara M. , Buxbaum Sarah G. , Rhie Suhn K. 
Published: April 2023

Abstract
FOXC1 is a transcription factor that is reported to play a key role in the development of cancer. For example, we showed that epigenetic dysregulation of FOXC1 is associated with meningioma progression. Moreover, we reported that FOXC1 is overexpressed in drug-resistant bladder cancer cells. To further characterize the molecular mechanisms of FOXC1 in carcinogenesis of different cancer types, we analyzed DNA-seq and RNA-seq datasets of over 30 cancer types generated from The Cancer Genome Atlas (TCGA) and Oncology Research Information Exchange network (ORIEN) consortia, using cBioportal. cBioportal is a tool that is used to visualize and analyze large-scale cancer genomic data. When we analyzed whole exome sequencing and DNA array datasets to search genetic alterations such as mutation, amplification, and deletion events that occur in the FOXC1 gene, we revealed that over 10 cancer types have genetic alterations. By analyzing RNA sequencing datasets through the cBioportal, we found that more than 10 cancer types have overexpression of FOXC1. Unlike TCGA, ORIEN has generated whole exome sequencing and RNA sequencing datasets from cancer patients who are treated. We are currently in the process of analyzing ORIEN data to determine FOXC1 alterations and its association with drug resistance in different cancer types. Moreover, we are evaluating the relationship between FOXC1 dysregulation and cancer patient survival. Overall, this analysis will denote the key role that FOXC1 plays in different cancer types and supply valuable knowledge for drug resistance.
Citation Format: Alanna Brown, Zexun Wu, Huan Cao, Sara M. Falzarano, Sarah G. Buxbaum, Suhn K. Rhie. The exploratory analysis of dysregulated transcription factor FOXC1 in pan-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 2060.
Abstract 2087: Sherlock-Genome: a R shiny app for genomic analysis and visualization
Authors: Klein Alyssa , Landi Maria Teresa , Zhang Tongwu 
Published: April 2023

Abstract
Over the last few decades, next generation sequencing technologies, including whole genome sequencing (WGS), have been increasingly used in cancer genomics studies. However, there is no efficient way to manage, visualize and integratively analyze sample-level WGS results across different bioinformatic pipelines, particularly for non-bioinformaticians. This greatly limits the usability of WGS data for biological discovery. Following the FAIR principles (findability, accessibility, interoperability, and reusability), we developed Sherlock-Genome, a R Shiny app designed for data harmonization, visualization and integrative analyses for WGS-based cancer genomics studies. Specifically, Sherlock-Genome provides pipelines for WGS analyses coupled with detailed guidelines on data preparation. The users can download the pipelines on their local computer, run the analyses and then upload the sample-level results into the Sherlock-Genome for data harmonization and integrative analyses across different genomic features. Sherlock-Genome also implements rigorous WGS-related data QC steps based on NGSpurity, a workflow that estimates the tumor purity, ploidy and clonal architecture by integrating somatic copy number alterations (SCNA), single nucleotide variants (SNV) and cancer cell fraction. Currently, Sherlock-Genome includes a few independent modules that allow users to generate a variety of interactive data inspection and visualization images, and perform many integrative analyses also using clinical and epidemiological data. These modules include study information and sample-level data QC (study overview, manifest information, NGSpurity), summaries of major genomics alterations (mutations, SCNA, structural variants), reports of advanced genomics analyses (mutational signatures, genomic landscape, clonal evolution) and functions related to different types of integrative analyses (survival analysis, integrative analysis). In addition, all plots in the Sherlock-Genome app can be downloaded as publication-ready figures from each module. Sherlock-Genome can be deployed in both local and cloud environments, allowing users to share sample-level analytical results together with the related publications. Sherlock-Genome has the potential to be widely used in cancer genomics allowing sample-level integrative analyses across multiple WGS and additional multi-omics features. A Sherlock-Genome demo with major module functions could be presented to allow users to know about this new interactive user-friendly tool for data analysis and visualization that can greatly advance biological discoveries.
Citation Format: Alyssa Klein, Maria Teresa Landi, Tongwu Zhang. Sherlock-Genome: a R shiny app for genomic analysis and visualization [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 2087.
Abstract 2228: Genome-wide mapping of SMYD3 in HPV-negative head and neck squamous cell carcinoma
Authors: Saeed Abbas , Sevilla Samantha , Saloura Vassiliki 
Published: April 2023

Abstract
HPV-negative head and neck squamous cell carcinoma (HNSCC) carries a particularly poor prognosis and novel therapeutic targets are thus urgently needed. We recently found that SET and MYND domain-containing 3 (SMYD3), a protein methyltransferase which has been reported to regulate global levels of trimethylated H3K4 (H3K4me3), an activating mark, and H4K20 (H4K20me3), a repressive mark, is overexpressed in HPV-negative HNSCC. Furthermore, we found that SMYD3 depletion impaired the colony formation capacity, cell cycling and the proliferation of HPV-negative HNSCC cell lines. Additionally, SMYD3 KO cell lines demonstrated decreased migratory potential. Accordingly, NSG xenograft mouse models of SMYD3 KO cell lines exhibited significantly decreased tumor growth compared to a parental HPV-negative HNSCC cell line. Based on the above preliminary results, this study aims to elucidate the specific mechanism(s) through which SMYD3 regulates the proliferative and migratory capacity of HPV-negative HNSCC cells. Nuclear/cytoplasmic fractionation of a panel of HPV-negative HNSCC cell lines showed that SMYD3 is expressed both in the nuclear as well as the cytoplasmic compartments. siRNA-mediated knockdown of SMYD3 for 6 days induced A 40% decrease in global H3K4me3 and more than 80% decrease in global H4K20me3 levels. Genome-wide mapping of SMYD3, H3K4me3 and H4K20me3 was pursued using CUT&RUN assays in parental and SMYD3 KO cell lines. The GoPeaks software was utilized to call significant peaks affected by 30% (p.adj&lt;0.05). 515 genes were annotated to H3K4me3 peaks and were found to have significantly decreased H3K4me3 peaks with concordant mRNA downregulation by more than 30%. 185 genes were annotated to H4K20me3 peaks and were found to have significantly decreased H4K20me3 peaks with concordant mRNA upregulation by more than 30%. Amongst these genes, cell cycle regulators and EMT genes were identified. SMYD3 peaks were called successfully and analysis of its genome-wide mapping is ongoing, with particular focus on cell cycle and EMT genes. To assess whether SMYD3 regulates the global H3K4me3 and H4K20me3, mass spectrometry analysis in SMYD3 KO cells has been conducted and analysis is ongoing. Validation of candidate genes directly regulated by SMYD3, H3K4me3 and H4K20me3 is planned by qPCR and Western blotting. This study is the first to report genome-wide mapping results of human SMYD3, and provides mechanistic insights into the oncogenic function of SMYD3 in HPV-negative HNSCC.
Citation Format: Abbas Saeed, Samantha Sevilla, Vassiliki Saloura. Genome-wide mapping of SMYD3 in HPV-negative head and neck squamous cell carcinoma [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 2228.
Abstract 2384: Quantitative phase imaging provides new insights into diverse morphologies in cell lines and their behavior in response to alternative cancer treatments
Authors: Khan Rida , McDonald Meaghan , Mikhaylova Albina , Rehman Fatima K. 
Published: April 2023

Abstract
Quantitative phase imaging (QPI) through holographic time-lapse microscopy allows for non-invasive measurements of cell dry mass and the ability to track cells for long periods of time with minimal damage, making it most beneficial for research on cancer treatment. Research with this enhanced method of observation can help decipher various morphologies present in specific cell lines and show how each cell can respond differently to provided signals. In this assay, we studied N2a murine neuroblast differentiation in response to Retinoic acid, as well as the anticancerous activity of Saffron and UV in MDA-MB-468 breast carcinoma and HCT116 colon carcinoma cell lines. Cells were observed using Telight’s Q-Phase, a multimodal microscope that utilizes QPI holographic time-lapse technology with label-free monitoring. The cells were able to survive in optimum conditions for up to 96 hours without any appreciative loss of viability.  With the emergence of phytochemicals being used as alternative cancer treatments, specific pigments in saffron have shown therapeutic effects against cancer tissues such as apoptosis and decreased carcinogen presence. A microanalysis of the effects of saffron on reducing the invasion potential, viability, and tumorigenicity of breast cancer cell lines was performed. QPI microscopy was performed on MDA-MB-468 human breast adenocarcinoma and HCT116 colon carcinoma cell lines treated with varying doses of saffron and ultraviolet radiation. Cell lines were observed under the microscope for 58-hour periods for changes in mass, movement, and replication. The quantitative data showed a reduction of projections from saffron treatment but did not show any significant reduction in cell movement over the 58-hours. These results were later confirmed through scratch wound and Boyden chamber assays. Similarly, when examining the process of N2a neuroblast differentiation, it was observed that cells do not move towards differentiation in a linear manner, but rather changed their direction and path several times before committing to their final phenotype. These types of observations are critical in understanding the biological processes behind differentiation and drug response and could not have been done without using the various quantitative and analysis tools provided by the QPI technology.
Citation Format: Rida Khan, Meaghan McDonald, Albina Mikhaylova, Fatima K. Rehman. Quantitative phase imaging provides new insights into diverse morphologies in cell lines and their behavior in response to alternative cancer treatments [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 2384.
Abstract 2507: Chronic stress promotes tumor progression and metastasis through the tumor microenvironment in triple-negative breast cancer
Authors: Zhang Chao , Wang Lizhong , Liu Runhua 
Published: April 2023

Abstract
Background: Breast cancer is the most common cancer diagnosed in American women. Triple-negative breast cancer (TNBC) is three times more likely to end in death than other breast cancer subtypes and disproportionately affects young African American women. Chronic stress as a risk factor promotes tumor progression, but its role in TNBC progression and metastasis remains elusive.
Methods: In this study, mice were implanted with 4T1-luciferase cells in the tibia or the fourth mammary pad of BALB/c mice and NSG mice. After four weeks of restraining inducing chronic stress and (or) β-adrenergic receptor inhibitor treatment, the impact of chronic stress on the progression and metastasis of tumor, tumor microenvironment was assessed.
Results: Our results showed that chronic stress facilitated tumor progression and metastasis in both BALB/c mice and NSG TNBC mice models. In contrast, chronic stress reduced the number and function of tumor-infiltrating TCD8+ cells but increased the expression of the β2-adrenergic receptor of TCD8+ cells in the TNBC tumor microenvironment (TME) of BALB/c mice. Interestingly, chronic stress increased the density of neuron fiber in the TME of both BALB/c and NSG TNBC mice. Notably, the treatment of Propranolol (Prop, a β1- and β2-adrenergic receptor inhibitor) significantly decreased the tumor burden and metastasis of both BALB/c mice and NSG TNBC mice model. Accompany by recovering the function and number of TCD8+ cells in the TME of BALB/c mice.
Conclusion: Our study indicates that chronic stress promotes TNBC progression and metastasis by regulating the tumor-immune network in the TME.
Citation Format: Chao Zhang, Lizhong Wang, Runhua Liu. Chronic stress promotes tumor progression and metastasis through the tumor microenvironment in triple-negative breast 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 2507.