bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4671: Efficacy and mechanism of mebendazole for ovarian cancer therapy
Authors: Rai Rajani , Penta Dhanamjai , Dey Debasish , Benbrook Doris M , Wang Lin , Bieniasz Magdalena , Dockery Lauren E 
Published: March 2024

Abstract
Introduction: Ovarian cancer (OvCa) is the most lethal gynecological malignancy. Although most OvCa patients initially respond to frontline platinum-based therapies with approximately 80% of patients experiencing remission, approximately 75% of those women experience a recurrence with only approximately 50% of patients alive 5 years following diagnosis. There is a critical need to develop novel therapeutic agents or methods to overcome chemoresistance and toxicities experienced with conventional chemotherapy regimens used for OvCa patients. Repurposing drugs is a promising strategy to safely and more rapidly evaluate potentially effective treatment regimens. Over the past two decades, Mebendazole (MBZ), an anti-parasitic drug, has gained much attention in oncology due to its favorable biosafety profile and potent anti-cancerous activity seen in several human malignancies. Therefore, we examined the efficiency and mechanism of MBZ against OvCa.
Methods: The in vitro efficacy of MBZ was evaluated in cisplatin-resistant (CPR) and parent (WT/sensitive) OVCAR-8 cell lines as well as in ascites samples collected from chemo-resistant OvCa patients by using 2D and/or 3D cell viability assay and invasion assay. The in vivo efficacy of MBZ was assessed in orthotopic animal models, utilizing CPR-OVCAR8 spheroids, and patient-derived xenograft (PDX) animal models with specimens from chemo-resistant ovarian cancer patients. Molecular mechanisms were investigated through western blot and immunofluorescence analysis.
Result: Our results confirmed that MBZ efficiently decreased cell viability, spheroid size, and the invasion ability of OvCa cell lines and ascites samples. OvCa cells treated with MBZ demonstrated downregulation of proliferation markers and upregulation of apoptosis markers indicating inhibition of cell proliferation and induction of apoptosis. Mechanistically, MBZ inhibited the Wnt/β-catenin signaling pathway by downregulating the expression and nuclear localization of β-catenin and epithelial-mesenchymal transition (EMT) markers. Preclinical studies showed that MBZ at 50 mg/kg/day dose for 28 days significantly reduced tumor growth in PDXs and orthotopic tumor models without any evidence of toxicity.
Conclusion: Collectively, our study strongly supports the therapeutic potential of MBZ against OvCa particularly, which warrants further clinical studies.
Citation Format: Rajani Rai, Dhanamjai Penta, Debasish Dey, Doris M Benbrook, Lin Wang, Magdalena Bieniasz, Lauren E Dockery. Efficacy and mechanism of mebendazole for ovarian cancer therapy [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 4671.
Abstract 4775: Unveiling caveolin-1's crucial role in breast cancer progression and metastasis: A molecular perspective
Authors: Begum Rizwana , Thota Shilpa , Singh Dhirendra Pratap , Chintala Naveen , Pandit Abhishek , Sapkota Biplov , Francis Joseph 
Published: March 2024

Abstract
Background: Breast cancer, particularly its metastatic form, constitutes a significant portion of oncological mortality. Caveolin-1 (Cav-1), a caveolae structural protein, has been implicated in cellular processes such as proliferation, apoptosis, autophagy, and cellular motility (aberrant in breast cancer). With its dual role as a tumor suppressor and promoter, Cav-1's function in breast cancer pathophysiology requires elucidation for potential therapeutic targeting.
Methods: We utilized a syngeneic mouse model to engineer Cav-1 deficient 4T1 murine mammary carcinoma cells which mirror the characteristics of stage IV breast cancer to investigate Cav-1's role in tumor growth and metastasis. We assessed cellular proliferation and lung metastasis, compared with wild-type controls, and performed molecular analyses to evaluate epithelial and mesenchymal marker expression, stemness-related markers, and autophagy-related gene expression.
Results: Cav-1 ablation corresponded with a marked decrease in tumor proliferation and lung metastasis, indicating a suppressive role in tumor progression. Molecular characterization revealed downregulated epithelial markers (E-cadherin, β-catenin), transcription factors (TWIST1/2), and stem cell markers (NANOG, OCT4, SOX2, c-MYC, SALL4), with concurrent upregulation of the mesenchymal marker vimentin. Enhanced expression of autophagy-related genes (Beclin-1, ATG5, ATG16) was also observed, suggesting a disruption in autophagic pathways.
Conclusion: Our findings underscore the critical role of Cav-1 in breast cancer progression, specifically its function in suppressing metastasis and modulating cellular phenotypes. Targeting Cav-1 could represent a novel therapeutic strategy to mitigate breast cancer growth and dissemination. Further research is warranted to explore the therapeutic potential of modulating Cav-1 in breast cancer treatment.
Citation Format: Rizwana Begum, Shilpa Thota, Dhirendra Pratap Singh, Naveen Chintala, Abhishek Pandit, Biplov Sapkota, Joseph Francis. Unveiling caveolin-1's crucial role in breast cancer progression and metastasis: A molecular perspective [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 4775.
Abstract 4788: Noninvasive longitudinal monitoring of residual disease in chemotherapy-treated colorectal cancer patients
Authors: Tang Alison D. , Gupte Rebecca , Cheung Victoria , Qing Tao , Cauwels Austin , Leff Emily , Walter Kimberly , Tabari Ehsan , Lovejoy Alex , Lin Jimmy C. 
Published: March 2024

Abstract
Noninvasive monitoring of cancer shows great promise in assessing therapy response and improving patient outcomes. Recently, various groups have developed methods that detect circulating tumor DNA (ctDNA) in the plasma to measure minimal or molecular residual disease (MRD). Aberrant DNA methylation patterns are a hallmark of cancers, and robust signals can be detected by sensitive ctDNA assays. Here, we present a methylation-based approach for longitudinal monitoring of tumor burden that is tumor-naive, i.e., with no reliance on prior characterization of tumor molecular characteristics. We assess the effectiveness of our approach in a cohort of colorectal cancer (CRC) patients receiving chemotherapy with or without additional targeted agents.
Longitudinal blood samples were collected from patients (n = 57) while on therapy, which averaged 4.9 months, for a total of 239 sample collection time points (median per patient = 5). Based on RECIST status, 16 patients were classified as complete responders (CR) at the end of treatment.
We generated plasma cell free DNA-derived libraries for methylation sequencing targeting regions relevant to CRC. Next, we computed a disease burden score for each sample and related these scores to clinical response (CR vs. non-CR). We trained a classifier on an independent cohort of CRC and healthy donor plasma cfDNA samples, and used this classifier to check for residual disease at the end of treatment for each of our 57 patients. The classifier detected residual disease in only 3/16 CRs (19%) but 35/41 non-CRs (85%).
Two of the non-CR patients were initially assessed as CRs at earlier time points. In both cases, our method successfully detected residual disease at or prior to the CR assessment and consistently showed residual disease in all follow up samples. This suggests improved sensitivity relative to RECIST and highlights the potential of using noninvasive blood tests for continuous monitoring of CRC patients receiving therapy.
Citation Format: Alison D. Tang, Rebecca Gupte, Victoria Cheung, Tao Qing, Austin Cauwels, Emily Leff, Kimberly Walter, Ehsan Tabari, Alex Lovejoy, Jimmy C. Lin. Noninvasive longitudinal monitoring of residual disease in chemotherapy-treated colorectal cancer patients [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 4788.
Abstract 4850: Sex differences in cancer incidence: Prospective analyses in the UK Biobank
Authors: Khan Maira , Papier Keren , Pirie Kirstin , Atkins Joshua , Key Tim , Travis Ruth 
Published: March 2024

Abstract
Background: Exploring the underlying sex differences in cancer incidence and the potential reasons for the differences may provide insights into cancer aetiology. We aimed to examine the differences in incidence of cancer between men and women in the UK Biobank and to assess the extent to which any disparities persisted after accounting of established risk factors for those cancers.
Methods: Prospective analyses were performed in the UK Biobank to examine associations between sex and risk of 15 cancers (and 13 subtypes) common to both sexes using minimal and multivariable-adjusted Cox proportional hazards regression models.
Results: Over an average of 10.5 (SD 2.2) years of follow-up, 46,081 incident cancers were identified in 470,771 individuals (aged 37 to 73 years at recruitment); 24,634 cancers (53.5%) diagnosed in women and 21,447 (46.5%) in men. While some differences in cancer risk between the sexes were attenuated in the comprehensively multivariable-adjusted models, men compared to women remained at greater risk of cancers at eight sites. Compared to women, men had higher risks of oesophageal adenocarcinoma (hazard ratio 5.45; 95% confidence interval, 4.17-7.12), gastric cardia (3.65; 2.48-5.38), bladder (3.47; 2.85-4.24), oral (2.06; 1.69-2.51), liver (1.91; 1.48-2.47), kidney (1.77; 1.51-2.09), rectum (1.7; 1.47-1.96), and leukaemia (1.43; 1.21-1.69); while women had higher risks of cancers of the breast, thyroid (0.36; 0.26-0.49), anus (0.41; 0.26-0.64), gallbladder (0.56; 0.31-0.99), and lung adenocarcinoma (0.72; 0.62-0.84).
Conclusion: Further studies of unexplained sex differences may provide insights into cancer aetiology.
Citation Format: Maira Khan, Keren Papier, Kirstin Pirie, Joshua Atkins, Tim Key, Ruth Travis. Sex differences in cancer incidence: Prospective analyses in the UK Biobank [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 4850.
Abstract 4878: Enhancing non-invasive detection of urothelial carcinoma through combined cytology and methylation profiling of urinary cell-free DNA
Authors: Zhao Huan , Dong Hang , Tang Haoran , Zhang Zhihui , Wei Na , Xu Jingjing , Du Pan , Jia Shidong , Xiao Ting , Guo Huiqin 
Published: March 2024

Abstract
Detection of urothelial carcinoma (UC) faces a significant challenge in sensitivity due to the limitations of existing methodologies such as cytology. Identifying tumors through epigenetics pattern presents a promising advancement in diagnostic precision. This study aims to explore a non-invasive and more sensitive strategy by analyzing urinary cell-free DNA (ucfDNA) methylation profiles in conjunction with traditional urine cytology. The cohort for this study were collected from 20 patients with UC and 17 patients with benign or non-tumor lesions which histopathologic and cytopathologic results were reviewed by pathologist. Additional 16 cancer samples and 40 healthy donor samples were collected from independent research centers. We employed PredicineEPIC, a comprehensive whole-genome methylation assay, to investigate the DNA methylation characteristics in urine samples. The dataset was splited into 1:2 proportions for modeling and validation. The methylation signals were fed to three machine learning algorithms for determining the most effective classification model. Differentiating cancer and benign samples through urinary cytology has high specificity (1.0) but low sensitivity (0.3). Then we examined differentially methylated regions and implemented four most abnormally methylated regions as classify features. We found that the Gradient Boosting Machine (GBM) model achieved optimal performance in the validation set, with an AUC of 0.93, sensitivity of 0.81 (21/26), and specificity of 1.0 (36/36). The combination of methylation- and urine cytology-based models raised 2% prediction accuracy without reducing precision, suggesting that this assay could be applied to augment the cytology testing for UC detection. This study proposes a new and promising approach, leveraging cytology combined with epigenetic profiles of urinary cell-free DNA, for the precise diagnosis of urothelial carcinoma.
Citation Format: Huan Zhao, Hang Dong, Haoran Tang, Zhihui Zhang, Na Wei, Jingjing Xu, Pan Du, Shidong Jia, Ting Xiao, Huiqin Guo. Enhancing non-invasive detection of urothelial carcinoma through combined cytology and methylation profiling of urinary cell-free DNA [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 4878.
Abstract 4943: Benchmarking unpaired single-cell RNA and single-cell ATAC integration
Authors: Chen Jiani , Xiao Wanzi , Zhang Eric , Chen Xiang 
Published: March 2024

Abstract
The integration of single-cell RNA-sequencing (scRNA-seq) and single-cell ATAC-sequencing (scATAC-seq) data offers a unique opportunity to gain a comprehensive view of cellular identity with defining features and to infer gene-regulatory relationships. Despite the emergence of technologies that simultaneously capture both the gene expression and chromatin accessibility of individual cells (paired data), the practical challenges of these approaches (e.g., the unavailability in previous samples and prohibitive cost) have led researchers to turn to the existing trove of single-modality data generated from independent biological samples (unpaired data). Various computational tools have been developed to integrate these unpaired single modality datasets. However, the comparative performance of these tools has not been comprehensively evaluated, and a standard benchmark pipeline is still lacking. To address these challenges, we used pseudo-unpaired scRNA-seq and scATAC-seq data derived from publicly available paired single-cell multi-omics datasets to benchmark 14 publicly available integration methods. The primary goal of unpaired single-cell multi-omics integration is to narrow the omics gap while preserving cell type diversity. We therefore focused on pair-wise cell distance and cluster performance in the joint latent space constructed by various integration tools in our benchmarking pipeline. To ensure the robustness of these computational approaches, we examined their stability across a variety of scenarios, including variations in cell number, cell types, and biological and technical batch effects. A number of the integration methods tested produced promising results. While the widely used Seurat package was recently reported to have the best performance (Lee et al., Genome Biology 2023), other computational tools such as scVI, Cobolt, scJoint, scglue and scBridge performed equally well or better in reducing omics differences and facilitating the identification of cell clusters. Notably, scglue and Cobolt demonstrated strong performance in aligning the same cell from different modalities, and discrete clusters emerged in the joint latent space using scJoint and scBridge. These findings suggest that it may not be strictly necessary to use paired multi-omics data to guide integration to achieve favorable results. Our freely available benchmarking pipeline will empower researchers to identify the optimal data integration methods for their specific data, facilitate the benchmarking of new methods, and contribute to future method development in the field.
Citation Format: Jiani Chen, Wanzi Xiao, Eric Zhang, Xiang Chen. Benchmarking unpaired single-cell RNA and single-cell ATAC integration [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 4943.
Abstract 4977: The prevalence of key oncogenic driver mutations in stage I-III non-small cell lung cancer: Results from the AACR GENIE BPC dataset
Authors: Zu Ke , Ma Jiemin , Chen Cai , Pierce Christine 
Published: March 2024

Abstract
Background: While there is growing interest in targeted therapy for non-small cell lung cancer (NSCLC) in perioperative settings, data on key oncogenic driver mutations is limited in early-stage NSCLC. This real-world database study aims to evaluate the prevalence of select genomic alterations in stage I-III NSCLC.
Methods: From the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) V2.1-consortium dataset, we included adult patients with a confirmed diagnosis of NSCLC who had genomic testing using stage I-III NSCLC tissue samples. Descriptive statistics were used to summarize baseline characteristics and the prevalence of select genomic alterations.
Results: A total of 465 patients were included in this study, of whom 61% were female, 85% were white, 19% were never smokers, and 77% had adenocarcinoma. Less than 2% of the study population had BRAF V600E, HER2 activating mutations, HER2 amplification, MET amplification, HER3 amplification, RET fusion, ALK fusion, or ROS1 fusion. Among genomic alterations with a prevalence of 2% or higher, such as EGFR sensitizing mutations, KRAS G12C, MET exon 14 skipping, STK11, KEAP1, and TP53, some variations in prevalence were observed across baseline patient and disease characteristics such as race, smoking status, and histology (Table 1).
Conclusion: The prevalence of key oncogenic drivers and its relationship to select baseline disease characteristics among patients with early-stage NSCLC are similar to those of advanced NSCLC observed in other real-world clinico-genomic databases.
Table 1. Prevalence of Select Genomic Alterations in Stage I-III NSCLC (N=465) Prevalence of Positive Biomarker Status (%) EGFR KRAS G12C MET Exon 14 Skipping STK11* KEAP1* TP53 Overall 17.6 12.7 4.5 16.0 11.0 52.7 Gender Male 7.1 9.3 5.5 18.5 18.5 59.6 Female 24.5 15.9 3.9 14.3 6.3 48.2 Race White 15.6 14.1 4.5 16.5 12.0 53.7 Black 15.0 5.0 5.0 22.2 11.1 60.0 Asian 44.0 4.0 8.0 8.3 4.2 44.0 Smoking Status Never smoker 41.4 1.2 6.9 4.7 1.2 36.8 Former smoker 13.7 16.0 4.6 17.4 12.9 52.4 Current smoker 5.7 12.9 1.4 23.9 15.4 72.9 Histology Adenocarcinoma 20.1 14.3 4.6 18.1 10.4 46.0 Squamous cell carcinoma 0 2.9 4.4 4.6 14.1 86.8 *The numbers of patients tested for STK11 and KEAP1 were 457 and 445, respectively.
Citation Format: Ke Zu, Jiemin Ma, Cai Chen, Christine Pierce. The prevalence of key oncogenic driver mutations in stage I-III non-small cell lung cancer: Results from the AACR GENIE BPC dataset [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 4977.
Abstract 4979: Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location
Authors: Ozer Muhammet , Goksu Suleyman Y. , Goksu Busra Bacik , Sanford Nina N. , Jones Amy , Verma Nilesh , Kazmi Syed 
Published: March 2024

Abstract
Background: Here, we describe analyses towards identifying and comparing genetic variations between the primary and metastatic sites in early-onset metastatic colorectal cancer patients.
Methods: We selected patients with early-onset metastatic colorectal cancer (under 50 years old) using data from the American Association for Cancer Research Project GENIE (version 14.1). We used the Fisher exact test to compare genetic mutations between the primary tumor and metastatic sites, complemented by the Benjamini-Hochberg adjustment method.
Results: In a total of 1,791 patients with early-onset metastatic colorectal cancer, 27.1% had tumor samples from metastatic sites, while the majority, 72.9%, were from the primary tumor location. The most common mutations found were in the TP53 gene (77.6%), followed by APC (76.0%), KRAS (42.4%), and PIK3CA (19.0%). Notably, the metastatic samples had a significantly higher occurrence of SMAD4 mutations compared to their primary site counterparts (20.8% vs. 14.0%, p&lt;0.001, q&lt;0.001). Conversely, the primary tumor samples exhibited higher frequencies of TCF7L2 and ARID1A mutations (16.9% vs. 10.6%, p&lt;0.001, q&lt;0.001, and 13.0% vs. 6.4%, p&lt;0.001, q&lt;0.001, respectively).
Conclusion: Determining the specific genes responsible for the formation of metastatic tumors is crucial for a deeper understanding of the disease's underlying biology in early-onset metastatic colorectal cancer. Such genomic details are crucial to pave the way to the discovery of potential biomarkers for diagnosis and the development of new cancer therapeutics.
Citation Format: Muhammet Ozer, Suleyman Y. Goksu, Busra Bacik Goksu, Nina N. Sanford, Amy Jones, Nilesh Verma, Syed Kazmi. Genomic profiling of early-onset metastatic colorectal cancer based on tumor sample location [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 4979.
Abstract 5000: Low dose ionizing radiation elicits the extrusion of neutrophil extracellular traps
Authors: Teijeira Alvaro , Martinez-Riaño Ana , Pinci Beatrice , Manzanal Almudena , Molero Paula , Ruiz Maria E. Rodriguez- , Melero Ignacio 
Published: March 2024

Abstract
The majority of cancer patients undergo radiotherapy interventions at some point in their clinical management with unintended irradiation of blood vessels. We show that very low γ-irradiation doses (0.5-1 Gy) of human and mouse neutrophils elicit neutrophil extracellular trap (NET) formation in a manner dependent on oxidative stress, NADPH oxidase activity and autocrine interleukin-8. Radiation-induced NETs interfere with NK- and T-cell cytotoxicity-repelling effector lymphocytes away from tumor cells. As a consequence, pre-injection of irradiation-induced NETs increases the number of successful metastases in mouse tumor models. Increases in circulating NETs are readily detected in series of patients following radiotherapy interventions. Our results reveal new mechanisms whose knowledge may help to improve the efficacy and safety of radiotherapy, especially when used in combination with immunotherapy approaches.
Citation Format: Alvaro Teijeira, Ana Martinez-Riaño, Beatrice Pinci, Almudena Manzanal, Paula Molero, Maria E. Rodriguez- Ruiz, Ignacio Melero. Low dose ionizing radiation elicits the extrusion of neutrophil extracellular traps [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 5000.