bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6114: Trends in hematological cancer subtype mortality by educational attainment and sex in the United States, 2000-2020
Authors: Marlow Emily C. , Islami Farhad , Jemal Ahmedin 
Published: March 2024

Abstract
Objective: To examine mortality trends for hematological cancer subtypes (leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and myeloma) by educational attainment and sex in the United States.
Methods: Using data on 1,082,234 U.S. deaths from 2000-2020, age-standardized death rates were calculated by sex and educational attainment (high school/GED or less, some college, and 4 years of college or more). Annual percentage change (APC) and 95% confidence intervals (CI) for mortality rates were generated using Joinpoint regression.
Results: For all hematological cancer subtypes, mortality rates were largest among males and those with the least education for all study years. In general, decreasing trends were observed in recent years for non-Hodgkin’s lymphoma, myeloma, and leukemia mortality rates. Non-Hodgkin’s lymphoma mortality rates, for example, decreased among males and females in 2009-2020 (APC: -2.0%; 95%CI: -2.4%, -1.5% and APC: -2.8%; 95%CI -3.2%, -2.3%). As another example, non-Hodgkin’s lymphoma mortality rates among most educated males decreased in 2000-2012 (APC: -1.8%; 95%CI: -2.2%, -1.3%) followed by a steeper decline in 2012-2020 (APC: -3.7%; 95%CI: -4.4%, -2.9%); a similar pattern was observed among most educated females (APC: -1.6%; 95%CI: -2.2%, -1.0% in 2000-2011 and APC: -4.1%; 95%CI: -4.9%, -3.4% in 2011-2020). Trends in Hodgkin’s lymphoma death rates however differed by educational attainment. For example, mortality rates among least educated males increased in 2000-2009 (APC: 1.7%; 95%CI: 0.8%, 2.5%) and remained unchanged in 2009-2020 (APC: -0.3%; 95%CI: -0.9%, 0.3%). Rates among least educated females also increased in 2000-2020 (APC: 0.4%; 95%CI: 0.1%, 0.7%). In contrast, mortality rates declined for most educated males from 2010-2020 (APC: -1.9%; 95%CI: -2.6%, -1.2%) and most educated females from 2011-2020 (APC: -3.5%; 95%CI: -4.8%, -2.2%).
Conclusion: Hematological cancer mortality rates were highest among males and those with least education. In general, mortality rates have declined in recent years for non-Hodgkin’s lymphoma, myeloma, and leukemia for males and females among all educational attainment groups, while Hodgkin’s lymphoma has shown a slight increasing trend among least educated males and females.
Citation Format: Emily C. Marlow, Farhad Islami, Ahmedin Jemal. Trends in hematological cancer subtype mortality by educational attainment and sex in the United States, 2000-2020 [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 6114.
Abstract 6118: Sex-related disparity in immune checkpoint inhibitor benefit for patients with esophageal squamous cell carcinoma: A systematic review and meta-analysis
Authors: Zhang Chaoqi , Wu Peng , Liu Jingjing , Li Dongyu , Sun Nan , He Jie 
Published: March 2024

Abstract
Sex-related dimorphism in cancer incidence and immune response is widely recognized, yet the impact of an individual's sex on the effectiveness of Immune Checkpoint Inhibitors (ICIs) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains poorly understood. In this study, we conducted a comprehensive meta-analysis to evaluate the heterogeneity of ICIs in patients with advanced ESCC. We collected studies from PubMed, MEDLINE, Embase, and Scopus, spanning from the inception of the databases to September 30, 2023. These studies focused on phase III randomized trials comparing first-line ICIs (PD-1/PD-L1) plus chemotherapy with chemotherapy alone for advanced or metastatic ESCC. Additionally, we reviewed abstracts and presentations from AACR, ASCO, ESMO, and WCLC. Inclusion criteria mandated the reporting of overall survival (OS) data stratified by sex and nonselective baseline PD-L1 expression. The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The analysis included 6 randomized clinical trials comprising 3603 ESCC patients, of whom 3090 (85.8%) were male and 513 (14.2%) were female. A significant OS benefit was observed for ICIs plus chemotherapy in all patients (HR, 0.68; 95% CI, 0.62-0.74; P &lt; 0.001). Similarly, ICIs plus chemotherapy correlated with a significantly prolonged OS in males (HR, 0.67; 95% CI, 0.61-0.74, P &lt; 0.001). However, there was no significant OS benefit observed in females with ICIs plus chemotherapy (HR, 0.79; 95% CI, 0.58-1.09; P = 0.148). Females had a tendency toward less benefit than males (pooled HR, 1.18; 95% CI, 0.89-1.57; P = 0.245). Our findings suggest that there is no statistically significant association between patient sex and the efficacy of ICIs for ESCC patients. Importantly, we report, for the first time, a lack of survival benefit with the ICI plus chemotherapy regimen in the first-line setting compared to chemotherapy alone in female ESCC patients.
Citation Format: Chaoqi Zhang, Peng Wu, Jingjing Liu, Dongyu Li, Nan Sun, Jie He. Sex-related disparity in immune checkpoint inhibitor benefit for patients with esophageal squamous cell carcinoma: A systematic review and meta-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 6118.
Abstract 6132: Exploring genomic complexity in lung cancer at the Tijuana/California border: A real-world perspective through liquid biopsy comprehensive genomic profiling
Authors: Guadarrama-Orozco Jorge Alberto , Ramirez-Puente Jennifer , Dominguez-Gonzalez Elizabeth 
Published: March 2024

Abstract
Objective: This study explores the application of liquid biopsy with next-generation sequencing (NGS) in profiling the genomic landscape of lung cancer patients from the Tijuana/California Border region. Specifically, we employ blood-based comprehensive genomic profiling (CGP) to assess the complexity of the genomic profile in these patients.
Materials and Methods: From April 2019 to November 2023, 37 lung cancer patients from Tijuana underwent profiling using the FoundationOne®Liquid CDx (F1LCDx®) assay, focusing on circulating tumor DNA (ctDNA). The assay, which spans 324 cancer-related genes and genomic signatures, provides insights into tumor fraction (TF) and blood-based tumor mutational burden (bTMB). Variants were classified based on the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT).
Results: A notable 88.6% of patients exhibited at least one detectable alteration in plasma. The most frequently mutated genes were TP53 (51.3%), EGFR (16.2%), DNMT3A (13.5%), and KRAS (10.8%). Tumor mutational burden (TMB) was assessable in 9 out of 37 patients, with values ranging from 0 to 10 mut/Mb. According to ESCAT classification, 63.1% of samples revealed potentially actionable alterations (Tier I-II), while an additional 24.1% harbored alterations for which approved drugs are available in other cancer types (Tier III).
Conclusion: Liquid biopsy NGS emerges as a viable and valuable strategy for guiding personalized therapy. Given restricted accessibility to new drugs or clinical trials in Mexico, the use of blood-based CGP may enhance the identification of druggable alterations, thereby increasing the likelihood of accessing targeted drugs or enrolling in clinical trials.
Citation Format: Jorge Alberto Guadarrama-Orozco, Jennifer Ramirez-Puente, Elizabeth Dominguez-Gonzalez. Exploring genomic complexity in lung cancer at the Tijuana/California border: A real-world perspective through liquid biopsy comprehensive genomic profiling [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 6132.
Abstract 6153: Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma
Authors: Zhu Jingjing , Wu Ke , Liu Shuai , Masca Alexandra , Zhong Hua , Yang Tai , Ghoneim Dalia H. , Surendran Praveen , Liu Tanxin , Yao Qizhi , Liu Tao , Fahle Sarah , Butterworth Adam , Alam Md A. , Vadgama Jaydutt V. , Deng Youping , Deng Hong-Wen , Wu Chong , Wu Yong , Wu Lang 
Published: March 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on two selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. Our dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.
Citation Format: Jingjing Zhu, Ke Wu, Shuai Liu, Alexandra Masca, Hua Zhong, Tai Yang, Dalia H. Ghoneim, Praveen Surendran, Tanxin Liu, Qizhi Yao, Tao Liu, Sarah Fahle, Adam Butterworth, Md A. Alam, Jaydutt V. Vadgama, Youping Deng, Hong-Wen Deng, Chong Wu, Yong Wu, Lang Wu. Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma [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 6153.
Abstract 6161: Investigating the relationships between race and socioeconomic status on the biology of ER+ breast cancer
Authors: DeWitt Jerry Tyler , Oropeza Elena , Haricharan Svasti 
Published: March 2024

Abstract
Black women in the US have worse health care options, poorer educational opportunities, and decreased income quality which collectively contribute to an overall lower socioeconomic status (SES) compared to white women. Furthermore, although the incidence of estrogen receptor positive (ER+) breast cancer is similar for Black and white women in the US, Black patients have significantly worse outcomes. The field has traditionally focused on systemic factors such as SES to explain outcome disparities. Consequently, differences in the molecular biology between tumors from Black and White women remains a gap in knowledge in the field. Recent studies have found that Black cancer patients have a unique gene expression profile that may modulate treatment response. However, how SES contributes to these differences in molecular biology and whether these differences in SES alter treatment response remain unknown. One challenge to addressing these questions is that existing datasets significantly underrepresent Black women and are not sufficiently annotated to understand the complex interplay between molecular biology and SES. Here, we present analysis of RNA expression datasets from 60 ER+ patient tumors (38 Black, 22 White), with corresponding SES and patient outcome annotations which suggest that the ECM and TIME of ER+ breast cancer are influenced by race and factors of SES including BMI and community poverty burden. We further provide evidence that these alterations in the TME may also associate with worse patient outcomes.
Citation Format: Jerry Tyler DeWitt, Elena Oropeza, Svasti Haricharan. Investigating the relationships between race and socioeconomic status on the biology of ER+ 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 6161.
Abstract 6282: Novel androgen related gene network in prostate cancer cell model
Authors: McDonald Alex L. , Snow Spencer , Ho Shuk-mei , Leung Yuet-kin 
Published: March 2024

Abstract
Prostate cancer stands as the foremost cause of cancer-related deaths among men in the United States, with the primary treatment being androgen receptor (AR) antagonists relying on current androgen signaling knowledge. Most of this knowledge is derived from next-generation sequencing experiments, but the oversight of splice variants and highly similar sequences in multiple loci can hinder a comprehensive understanding. In an effort to unveil the complete androgen receptor transcriptional program, we employed a novel sequencing analysis protocol. Using a R1881-LNCaP model, we identified 212 upregulated and 92 downregulated genes, of which a notable one-third (68 upregulated and 39 downregulated) had not been previously associated with androgen. Among these novel transcripts, 5.6% lacked splice variants, while 16.3% exhibited one or more splice variants, including 3.8% from seven unique gene families. Recognized androgen-regulated genes, such as ORM1, STEAP4, NPPC, ORM2, and KLK3, were validated as upregulated, while GRB10, FN1, PPFIA2, and PLA2G2A were confirmed as downregulated in this in-vitro model. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) data, we found that 13% of the genes contained at least one androgen response element within 5 kb upstream or downstream. Further validation through real-time PCR confirmed the expression levels of 90% of the selected genes (18). Ingenuity Pathway Analysis revealed two major regulators (ESRRA and ARFGEF2) in causal networks likely interacting with the novel genes. Intriguingly, 57.1% of ESRRA-involved genes contained at least one ESRRA binding site in a ChIP-seq dataset. Although ESRRA is known to activate androgen biosynthesis in castration-resistant prostate cancer, its interaction with AR and co-regulation of androgen signaling remain unknown. Ongoing studies involve the characterization of these networks in prostate cancer cell lines, examining anchorage-independent capacity, invasion, migration, proliferation, and progression. Data collection and comparison will ascertain whether the signaling is driven by mutated AR, and the role of ARv7 will be elucidated through gene lockdown experiments.
Citation Format: Alex L. McDonald, Spencer Snow, Shuk-mei Ho, Yuet-kin Leung. Novel androgen related gene network in prostate cancer cell model [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 6282.
Abstract 6290: Effects of a circuit, interval-based exercise program on vascular function among cancer survivors
Authors: Christopher Cami N. , Kang Dong-Woo , Gonzalo-Encabo Paola , Wilson Rebekah L. , Normann Amber J. , Norris Mary K. , Dieli-Conwright Christina M. 
Published: March 2024

Abstract
Background: Cancer survivors are at an increased risk of cardiovascular comorbidity, including atherosclerosis, hypertension, and heart failure, due to negative impacts of cancer treatments on vascular function. Exercise is recommended in recent cardio-oncology rehabilitation guidelines and has been shown to improve vascular function in clinical populations; however, its effects on vascular function are understudied in clinical oncology settings.
Purpose: This pilot study examined whether a circuit, interval-based exercise intervention can improve vascular function, assessed by brachial artery flow-mediated dilation (baFMD) and carotid intima media thickness (cIMT) in breast, prostate, and colorectal cancer survivors.
Methods: Overweight or obese (BMI&gt;25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors were randomized to exercise (n=60) or usual care (n=30). Survivors in the 4-month exercise intervention trained three times/week, in a circuit, interval-based supervised moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) program. cIMT and baFMD were measured at baseline and post-intervention via an ultrasound. Paired t-tests and repeated-measures analysis of variance were run to assess within- and between-group differences.
Results: The study sample included breast (n=38), prostate (n=24), colorectal (n=28) cancer survivors who were 63.2 ± 10.8 years old, completed chemotherapy and/or radiation (75%) and were obese (87%). Post-intervention, baFMD significantly increased in the exercise group compared to the control group (between-group mean difference: 6.3%; 95% CI: [1.9 to 9.3], p=0.001). There was also a significant reduction in cIMT in the exercise group compared to the control group (between-group mean difference: -0.039mm, 95% CI: [-0.080 to -0.009], p=0.002).
Conclusions: Our findings in this pilot study support that a circuit, interval-based aerobic and resistance exercise intervention may improve vascular function in breast, prostate, and colorectal cancer survivors. Future studies are recommended to understand how exercise interventions can be utilized clinically to improve cardiovascular disease risk and co-morbidity among cancer survivors.
Citation Format: Cami N. Christopher, Dong-Woo Kang, Paola Gonzalo-Encabo, Rebekah L. Wilson, Amber J. Normann, Mary K. Norris, Christina M. Dieli-Conwright. Effects of a circuit, interval-based exercise program on vascular function among cancer survivors [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 6290.
Abstract 6335: Armoring CAR-T therapy with PD-1 blockade: a powerful strategy for enhancing anti-tumor effects in pancreatic cancer
Authors: Zhang Zhixiang , Huang Jingwei , Zhao Zhifeng , Wang Xiangyi , he Cnhui , Yang Sen , Gu Qingyang 
Published: March 2024

Abstract
Chimeric antigen receptor-modified T cells (CAR-T) have been widely applied in the treatment of hematological malignancies and are currently under investigation for their potential effectiveness against solid tumors. Nevertheless, the effectiveness of CAR-T in treating solid tumors remains unsatisfactory due to a range of factors, including CAR-T cell infiltration and heterogeneity. The efficacy of CAR-T therapy is substantially influenced by the tumor microenvironment. This is particularly evident when PD-L1 is activated through CAR-T, leading to the inhibition of CAR-T cell activity via the PD-1 pathway. In this study, we engineered a CAR-T therapy that targets mesothelin and concurrently expresses a membrane-bound PD-1 receptor. This design blocks the PD-1 on CAR-T cells, effectively counteracting the suppression of CAR-T function mediated by PD-L1. We observed a substantial upregulation of PD-L1 on AsPC-1 tumor cells after 4 hours of IFN-γ stimulation in vitro. CAR-T cells engineered to co-express PD-1 antibody (aMSLN-28BBZ-mPD-1) exhibited similar short-term cytotoxicity and cytokine secretion profiles to those of the traditional third-generation CAR-T (aMSLN-28BBZ). Notably, aMSLN-28BBZ-mPD-1 displayed significantly improved long-term target cell killing. Furthermore, in an in vivo model of pancreatic cancer, aMSLN-28BBZ-mPD-1 demonstrated enhanced anti-tumor activity when compared to the traditional aMSLN-28BBZ, as supported by RNAscope analysis and immunofluorescence assays of tumor tissues. These analyses revealed a marked upregulation of PD-L1 expression and enhanced CAR-T cell infiltration in the aMSLN-28BBZ-mPD-1 treatment group. In summary, our study demonstrates that co-expression of a membrane-bound PD-1 antibody overcomes PD-L1 mediated CAR-T suppression, as observed in both in vitro and in vivo. This innovative strategy underscores its therapeutic potential and value in treating solid tumors. Keywords: CAR-T, PD-1, Tumor Microenvironment, Pancreatic Cancer
Citation Format: Zhixiang Zhang, Jingwei Huang, Zhifeng Zhao, Xiangyi Wang, Cnhui he, Sen Yang, Qingyang Gu. Armoring CAR-T therapy with PD-1 blockade: a powerful strategy for enhancing anti-tumor effects in pancreatic 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 6335.
Abstract 6353: AM105: A novel bispecific antibody with Anti 4-1BB affibodies and EGFR antibody
Authors: Kim Dong-Wook , Lee Hyun-Jong , Kim Seong Yeol , Yoon Min , Lee Youngha , Hwang In-Sik , Lee Yoon , Kim Jong-Hoon , Lee Jong-Seo 
Published: March 2024

Abstract
T cell engaging bispecific antibodies have emerged as promising treatments for hematologic malignancies. While most antibodies are CD3-based, offering therapeutic benefits, they are often associated with severe side effects and limited efficacy in solid tumors. To address these challenges, we present AM105, a groundbreaking anti 4-1BB affibodies based bispecific antibody designed to target EGFR. We carefully engineered AM105 with distinct binding affinities for EGFR (KD = 1.8 nM) and 4-1BB (KD = 60 nM), favoring EGFR binding. Affibody specificity was confirmed through a cross-reactivity test with proteins of TNF-receptor superfamily and 21 cell lines expressing 4-1BB or not. In cytotoxicity assays, AM105 exhibited superior tumor cell killing compared to cetuximab, particularly in EGFR-expressing cell lines. Notably, AM105 displayed remarkable efficacy in cell lines harboring RAS and/or BRAF mutations, traditionally unresponsive to EGFR-targeting treatments. In vivo experiments utilizing humanized 4-1BB mice demonstrated AM105's exceptional tumor cell elimination compared to cetuximab. The anti-tumor effects persisted even in the face of new tumor cell introductions, suggesting the induction of T cell memory function. Our findings collectively establish AM105 as a potent therapeutic agent with strong anti-tumor T cell activity. The unique 4-1BB based Affibodies (AffiMab format) of AM105 holds promise for addressing the limitations of current bispecific antibodies, positioning it as a potential breakthrough in cancer immunotherapy.
Citation Format: Dong-Wook Kim, Hyun-Jong Lee, Seong Yeol Kim, Min Yoon, Youngha Lee, In-Sik Hwang, Yoon Lee, Jong-Hoon Kim, Jong-Seo Lee. AM105: A novel bispecific antibody with Anti 4-1BB affibodies and EGFR antibody [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 6353.