bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 7489: Peripheral blood liquid biopsy for the screening of lung cancer
Authors: Seo Jiyoun , Shishido Stephanie N. , Mason Jeremy , Velasco Carmen Ruiz , Chen Andrew , Rothwell Dominic , Crosbie Phil , Hicks James , Dive Caroline , Kuhn Peter 
Published: March 2024

Abstract
Lung cancer is the second most common type of cancer in both men and women and the leading cause of cancer-related mortality. Unfortunately, most patients have advanced stages (stage III or IV) at the time of diagnosis and the only U.S. Preventive Services Task Force-recommended screening test, Low Dose CT scan (LDCT), has a high false-positive rate. Therefore, there is an urgent need for the early detection of lung cancer with better discrimination between individuals with lung cancer and those without. In this study, we demonstrate the capability of a non-enrichment-based liquid biopsy workflow, the High Definition Single Cell Assay (HDSCA) to be used as a complementary tool to the current screening methodology. The HDSCA workflow can detect circulating cells of epithelial, mesenchymal, endothelial, and hematological origin, as well as acellular events such as oncosomes. This allows the investigation of the broad spectrum of circulating rare events for the potential identification of biomarkers associated with lung cancer. We investigated 52 peripheral blood samples collected from the second annual screening round of Manchester’s 'Lung Health Check' pilot of a community-based lung cancer screening cohort. Of these, 7 were subsequently diagnosed with non-small cell lung cancer, 2 with small cell lung cancer, and 43 were deemed at high risk of developing lung cancer. We additionally investigated 60 peripheral blood samples from individuals with no known pathology to use as controls. Within the screening cohort, a number of single rare analytes were found to have statistically significant differences between the lung cancer, high-risk cohort, and normal blood donor samples, which can potentially be biomarkers used to differentiate the cohorts. We also built a multi-analyte patient-level classification model utilizing the rare cellular and acellular events that stratified lung cancer patients from the normal donor individuals and high-risk cohort with high accuracy. Our results demonstrate the potential of liquid biopsy as a complementary screening approach for lung cancer.
Citation Format: Jiyoun Seo, Stephanie N. Shishido, Jeremy Mason, Carmen Ruiz Velasco, Andrew Chen, Dominic Rothwell, Phil Crosbie, James Hicks, Caroline Dive, Peter Kuhn. Peripheral blood liquid biopsy for the screening of lung cancer [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 7489.
Abstract 7545: Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation
Authors: Xi Sichuan , Wu Xinwei , Straughan David M , Payabyab Eden C , Wang Haitao , Wang Ruihong , Zhang Mary , Carr Shamus R. , Hoang Chuong D. , Schrump David S. 
Published: March 2024

Abstract
The exact mechanisms underlying the causal relationship between asbestos exposure and malignant mesothelioma (MM) have yet to be elucidated. Widespread genomic and epigenomic alterations are being implicated in rewiring of oncogenic signaling networks which may contribute to initiation and progression of MM. In the present study, we examined the molecular profiles of mesothelial cells exposed to asbestos in-vitro and found that asbestos-induced activation of DNMT1/UHRF1 mediated epigenetic repression of RB1 in normal mesothelial cells as well as mesothelioma cells via promoter-specific methylation mechanisms. RB1, as a noncanonical transcription factor, was capable of also negatively modulating the transcriptional activities of DNMT1/UHRF1 mesothelium and mesothelioma. Functioning as one of the downstream effectors of RB1, NFkB was also involved in the transcriptional regulation of DNMT1/UHRF1 directly in a promoter-selective manner and played a pivotal role in the acute as well as chronic functional and phenotypic changes of mesothelial cells following asbestos exposure. Pharmacological interference of the dysregulated RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit constitutively arrested the invasive growth of MPM cells. In-vivo studies using FVB genetic background wild-type and Bap1+/- mice further revealed involvement of epigenetically dysregulation of the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during asbestos-induced malignant transformation of mesothelial cells. Taken together, our data are the first to describe that asbestos epigenetically rewires the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during mesothelioma development and suggest potential novel strategies to reverse these epigenetic perturbations for MPM treatment in the clinic.
Citation Format: Sichuan Xi, Xinwei Wu, David M Straughan, Eden C Payabyab, Haitao Wang, Ruihong Wang, Mary Zhang, Shamus R. Carr, Chuong D. Hoang, David S. Schrump. Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation [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 7545.
Abstract 7559: Multi-state gene cluster switches determining the adaptive mitochondrial and metabolic landscape of breast cancer
Authors: Menegollo Michela , Bentham Robert , Patani Neill , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy 
Published: March 2024

Abstract
Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution, where they represent important therapeutic targets. However, the full spectrum, characteristics and regulation of existing metabolic switches are unknown. We propose that metabolic switches can be recognised by locating large alternating gene expression patterns and associate them with specific metabolic states. We developed a method to identify interspersed genesets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on major breast cancer transcriptome datasets we discovered a series of gene sets with switch-like behaviour, predicting mitochondrial content, activity and central carbon fluxes in tumours associated with different switch positions. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates and were ultimately extended by geneset analysis to link metabolic alterations to cellular states, thus predicting tumour pathology, prognosis and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.
Citation Format: Michela Menegollo, Robert Bentham, Neill Patani, Robert C. Stein, Mariia Yuneva, Gyorgy Szabadkai. Multi-state gene cluster switches determining the adaptive mitochondrial and metabolic landscape of breast cancer [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 7559.
Abstract 7583: Discovery of a potent small molecule MALT1 protease inhibitor for the treatment of cancer
Authors: Zhou Yuzhen , Fu Bang , Chen Jie , Cai Weidong , Sun Xiao , Li Yinlong , Ren Wei , Shen Qichao , Du Guolong , Zhou Xiaojun , Zou Zhengyao , Chen Haibo , Liu Xiaoyun , Yang Cheng , Liu Xiangyong , Guo Jing , Wu Hao , Ding Lieming , Wang Jiabing , Lan Hong 
Published: March 2024

Abstract
The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), as the core component of CBM complex (CARD9/10/11/14-BCL10-MALT1), plays an essential role in activating the NF-κB pathway and regulating the cell proliferation, differentiation and immunity. Inhibiting of MALT1 is considered a promising therapeutic approach for the treatment of several non-Hodgkin B-cell lymphomas, chronic lymphocytic leukemia (CLL), solid tumors and autoimmune diseases. Herein, we report the discovery of a novel potent MALT1 allosteric inhibitor, BPI-530616, which strongly inhibited MALT1 protease activity with subnanomolar IC50, and low off-target activity on other proteases. BPI-530616 can inhibit the proliferation of B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell line, OCI-ly3, bearing CD79b and CARD11 mutations. The cell line is intrinsically resistant to covalent and non-covalent Bruton's Tyrosine Kinase (BTK) inhibitors. Meanwhile, BPI-530616 suppressed the cellular cytokine secretion (e.g.IL-10, IL-2) or MALT1 direct substrate cleavage (e.g. CYLD). In vivo, BPI-530616 dose-dependently suppressed tumor growth and inhibited the cleavage of CYLD in OCI-ly3 xenograft mouse model. To address the role of MALT1 inhibitor in the contest of immune-oncology, a CT26 syngeneic mouse model was set up. Oral administration of BPI-530616 exhibited a good antitumor effect comparable to that of the anti-PD1 antibody, with no observable adverse effects. Additionally, BPI-530616 displayed desirable drug-like properties, including low clearance and good oral bioavailability across multiple pre-clinical species. Taken together, our research has led to the discovery of a novel, potent, selective, and orally bioavailable small molecule MALT1 inhibitor, BPI-530616. It demonstrated anti-tumor efficacy in the DLBCL animal model and showed promising effects in an immune-oncology animal model.
Citation Format: Yuzhen Zhou, Bang Fu, Jie Chen, Weidong Cai, Xiao Sun, Yinlong Li, Wei Ren, Qichao Shen, Guolong Du, Xiaojun Zhou, Zhengyao Zou, Haibo Chen, Xiaoyun Liu, Cheng Yang, Xiangyong Liu, Jing Guo, Hao Wu, Lieming Ding, Jiabing Wang, Hong Lan. Discovery of a potent small molecule MALT1 protease inhibitor for the treatment of cancer [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 7583.
Abstract 759: Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats
Authors: Hakkak Reza , Melnyk Stepan 
Published: March 2024

Abstract
Obesity is associated with the risk of certain types of cancers development including breast cancer. Previously, we reported that obesity increased mammary tumor development using obese Zucker rat model. Several studies have shown the health benefit of soy protein consumption. However, the effects of soy protein diet on liver of mammary tumor for oxidative stress and DNA reaction is less known. We used DMBA induced-mammary tumor model to investigate the effects of soy protein diet on pro-oxidative environment and oxidative DNA modification in liver of obese DMBA mammary tumors rats. Female obese zucker rats (n=45) were either fed casein as control (OC; n=20) or soy protein isolate (OS; n=25), received DMBA (65mg/kg BW) at the age 50 days and sacrificed 20 weeks later. We used HPLC-ECD, HPLC-UV and LC-MS techniques for liver metabolic analysis. Comparing liver of OS vs. OC, soy protein 1) decreased the level of Methionine (P&lt;0.02), increased 2) free reduced Homocysteine (P&lt;0.02), 3) S-Adenosylmethionine (SAM, P&lt;0.03), 4) S-Adenosyhomocysteine (SAH, P&lt;0.001) and 5) 5methyl-Cytosine (5mC, P&lt;0.03). Also, soy protein decreased (P&lt;0.003) level of free oxidized Glutathione (GSSG), increased (P&lt;0.02) GSH/GSSG oxidative stress ratio, without any changes a level of free reduced Glutathione (GSH), followed decrease (P&lt;0.04) in liver DNA level of 8-OH-Guanosine (8-OH-G) and level (P&lt;0.02) of 5hmethyl-Cytosine (5hmC). Our results shows soy protein diet capable change liver metabolism: a. Modify a methylation status by increasing levels of SAM (universal methyl group donor) following global liver DNA hypermethylation (5mC), and SAH (methylases inhibitor); b. Alleviate level of oxidative stress in liver by decreasing level of GSSG (not active glutathione), increasing GSH/GSSG ratio (antioxidative capacities), following lower ROS liver DNA damages by decrease levels of 8-OH-G and 5hmC. In conclusion, using obese DMBA-induced mammary tumor Zucker rat model, soy diet making a complex and significantly modification of metabolic conditions in liver affecting both methionine cycle and transsulfuration metabolic pathways.
Citation Format: Reza Hakkak, Stepan Melnyk. Soy protein diet changes metabolic profile in liver of 7,12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumors in obese zucker rats [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 759.
Abstract 7593: Photodynamic therapy improves therapeutic management of glioblastoma
Authors: Vasyliv Nazar , Williams Karin 
Published: March 2024

Abstract
Glioblastoma (GBM) remains a formidable challenge in the realm of oncology, primarily due to the limitations of the standard of care therapies. Photodynamic therapy (PDT), which exploits the light-activated potential of 5-aminolevulinic acid (5-ALA), emerges as a promising avenue to combat GBM. In this study, primary patient-derived cell lines, Ox5 core, and G7, served as critical subjects, exposed to light excitation at wavelengths of 410 nm, 528 nm, and 810 nm, both with and without 5-ALA (protoporphyrin IX). The central objective was to rigorously assess the efficacy of PDT, either with or without 5-ALA, in reducing cell viability and curtailing clonogenic expansion. This evaluation was performed within the context of the existing standard of care for GBM, encompassing Temozolomide (TMZ) and Radiotherapy. Our results unveiled striking insights into the potential of PDT as an innovative therapeutic strategy. Notably, Ox5 cells exhibited a remarkable reduction in viability, exceeding 70%, following exposure to PDT with 410 nm light and 5-ALA at a concentration of 50μM. A similar, albeit slightly less profound, effect was observed in G7 cells, with a viability decrease of more than 53%. These outcomes, meticulously quantified through the MTT viability assay (n=4), were reinforced by statistical significance, as indicated by p-values falling below 0.05 and, lower 0.001. Furthermore, clonogenic assays employing G7 cells provided an additional layer of evidence, demonstrating a substantial inhibition of clonogenic potential following PDT treatment with 410 nm light and 5-ALA. Immunohistochemistry techniques, particularly focusing on the cleaved caspase-3 marker, in both Ox5 core and G7 cells, underscoring the mechanistic basis of the observed cell death. In stark contrast, the conventional standard of care, involving TMZ monotherapy, was tested, and the results across four biological replicates were less significant. The relative viability of Ox5 and G7 cells exhibited no statistical significance, with p-values exceeding 0.05, implying a limited impact of this regimen on cell viability. Moreover, clonogenic assays conducted under the standard of care protocol (TMZ+/-Radiotherapy) unveiled the persistence of colonies, even at higher radiation doses of 4 and 6 Gy.In summary, PDT, specifically when implemented with 410 nm light and 5-ALA, represents a breakthrough strategy that leads to substantial cell death in both Ox5 and G7 cells. This compelling alternative therapy shines a hopeful light on the horizon of GBM treatment, providing a potentially transformative approach that can augment the current standard of care.
Citation Format: Nazar Vasyliv, Karin Williams. Photodynamic therapy improves therapeutic management of 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 7593.
Abstract 7620: Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder cancer
Authors: Romero Pedro J. , Desponds Emma , Croci Davide , Wosika Victoria , Hadadi Noushin , Cost Sara Fonseca , Ciarloni Laura , Ongaro Marco , Zdimerova Hana , Leblond Marine M. , Hosseinian-Ehrensberger Sahar , Verdeil Grégory 
Published: March 2024

Abstract
Muscle-invasive bladder cancer (MIBC) accounts for 25% of bladder cancer cases. Despite the broader usage of immune checkpoint blockade targeting the PD-1/PD-L1 axis, the response rate and survival of patients remain low for this disease. Redirecting swiftly these patients toward alternative therapeutic strategies upon immunotherapy failure should be a priority. So far, no marker allows to precisely determine early outcome to the treatment.Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical response to immunotherapy. In this study, we used next generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed at identifying biomarkers associated with immunotherapy response and to assess the potential application of simple non-invasive blood biomarkers as therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICI. Interestingly, a common lymphocytic activation signature can be identified in both compartments associated with the efficient response to immunotherapy, including a blood specific CD8+ T cell activation/proliferation signature which predicts immunotherapy response.
Citation Format: Pedro J. Romero, Emma Desponds, Davide Croci, Victoria Wosika, Noushin Hadadi, Sara Fonseca Cost, Laura Ciarloni, Marco Ongaro, Hana Zdimerova, Marine M. Leblond, Sahar Hosseinian-Ehrensberger, Grégory Verdeil. Immuno-transcriptomic profiling of blood and tumor tissue identifies gene signatures associated with immunotherapy response in metastatic bladder cancer [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 7620.
Abstract 789: GrafGen: Distance-Based Inference of Population Ancestry for Helicobacter pylori Genomes
Authors: Wheeler William , Wang Difei , Zhao Isaac , Jin Yumi , Rabkin Charles S. 
Published: March 2024

Abstract
BACKGROUND: The 1.67 megabase H. pylori genome contains ~143,000 biallelic single-nucleotide polymorphisms (SNP) with minor allele frequency &gt; 1%. Confounding by population stratification is a major source of bias requiring adjustment in genome-wide association studies (GWAS). Previous model- and distance-based methods for bacterial genomes yield varying results depending upon which strains are included for comparison in analyses. We therefore developed a robust classification of H. pylori ancestry to facilitate generalizable inferences about disease associations. METHODS: GrafGen is an R software package adapted from the GrafPop tool for human ancestry (Jin et al., 2017; Jin et al., 2019). The underlying classification algorithm compares SNPs of an individual genome with frequencies in reference populations to estimate subject ancestry and ancestral proportions based on calculated genetic distances. Outputs incorporate visualization tools that provide natural geometric interpretation of population structure. RESULTS: Training data were obtained from the H. pylori Genome Project (HpGP), a global survey of 1011 H. pylori genomes collected across 51 countries (Thorell et al., 2023). Based on genetic distances, HpGP sequences clustered into nine mutually exclusive populations designated by their predominant geographic source. Previously published population assignments for a test set of 255 sequences obtained from GenBank mapped to specific GrafGen classifications (Table). GrafGen assignments based on randomly selected sets of 14,300 and 1430 SNPs were &gt;97% and &gt;90% identical, respectively, to those based on all 143,000 SNPs. CONCLUSIONS: GrafGen's universal categorization of H. pylori ancestry has utility for bacterial GWAS. The software code is publicly available for research on this important pathogen. Theoretically, the same algorithm can be implemented to infer ancestry of any single chromosome haploid species that has sufficient sequence data for references.
Citation Format: William Wheeler, Difei Wang, Isaac Zhao, Yumi Jin, Charles S. Rabkin. GrafGen: Distance-Based Inference of Population Ancestry for Helicobacter pylori Genomes [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 789.