bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1031: Targeting genomic biomarker in voided urine for prostate cancer detection
Authors: Thakur Mathew L. , Tomar Vivek S. , Dale Emma , Gomella Leonard G. , Navarro Hector T. , Kolesnikov Oleksandr , Leong Joon Yau , Dahlgren Olivia , Trabulsi Edouard J. 
Published: March 2024

Abstract
Introduction: Prostatic cancer (PCa) is the second most prevalent disease in men globally. In 2020 it lead to &gt;14 million new cases and &gt;375,000 deaths worldwide. Despite numerous detection methods, detecting PCa reliably and non-invasively continues to be challenging. PCa malignant cells (MC) express VPAC (combined for Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Peptide) in high density. A VPAC specific PACAP analogues (Kd=3.1 × 10−8M) developed in our laboratory was conjugated with a fluorophore and named TP4303. The goal was to assess if TP4303 will image PCa-MC shed in voided urine and present severity of PCa as grade group (GG).
Method: Consenting PCa patients (N=110) scheduled for radical prostatectomy provided voided urine. Urine was cyto-centrifuged. Cells on glass slide were fixed, incubated with TP4303, washed, treated with DAPI (4,6-diamidodino-2-phenylindole), cover slip placed and analyzed with Zeiss Axio Observer microscope, coupled with ZENN Microscopy software. The software determined percentage of PCa MC shed by each patient. The results were corroborated as per GG, determined by post-surgical histopathology and analyzed statistically.
Results:TP4303 imaged PCa in all subjects. The percent MC shed in urine increased from 13.1±14.4% for GG1 to 25.3±21.07% for GG3 (p=0.05) to 50.5±26.7% for GG5 (p=0.002). Similarly, the fluorescence intensity increased from 43.8±2.2 for GG1 to 48.8±7.0 for GG3 (p=0.01) to 51.5±14.4 for GG5 (p=0.15).
Conclusions: The data strongly suggests that TP4303 may not only detect PCa reliably and noninvasively, but may also predict the severity of PCa.
Supported by NIH: NC5R01CA249921
Citation Format: Mathew L. Thakur, Vivek S. Tomar, Emma Dale, Leonard G. Gomella, Hector T. Navarro, Oleksandr Kolesnikov, Joon Yau Leong, Olivia Dahlgren, Edouard J. Trabulsi. Targeting genomic biomarker in voided urine for prostate cancer detection [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 1031.
Abstract 1055: ORF1p expression from LINE-1 occurs in clear cell ovarian carcinoma precursors and is detectable in patients’ plasma samples
Authors: de Santiago Pamela R. , Sato Sho , Zhuravlev Yelena , Rendulich Hannah S. , Taylor Marty S. , Wu Connie , Dougher Meaghan C. , Schwartz Lauren , Walt David R. , Burns Kathleen H. , Drapkin Ronny 
Published: March 2024

Abstract
Long interspersed element 1 (LINE-1) retrotransposons are repetitive genomic sequences able to move across the genome by an autonomous “copy and paste” mechanism. Given the mutagenic potential of LINE-1, benign cells restrict its expression, although the molecular mechanisms involved are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) accounts for ~5-10% of ovarian cancers and is believed to arise from endometriosis. Women have a poor prognosis when it presents at an advanced stage, which emphasizes the need for a better understanding of the disease. In the present study, we found that ~85% of CCOC tumors express ORF1p, one of two proteins encoded by LINE-1. We show that CCOC cell lines retain ORF1p expression and release it into the extracellular media. By using single molecule array (Simoa) assays, we detected ORF1p in patient plasma, proposing ORF1p as a non-invasive biomarker for this disease. Finally, we found that LINE-1 retrotransposon de-repression is an early event in CCOC, as ORF1p is enhanced during the transition from typical to atypical endometriosis and that is retained in the invasive cancer.
Citation Format: Pamela R. de Santiago, Sho Sato, Yelena Zhuravlev, Hannah S. Rendulich, Marty S. Taylor, Connie Wu, Meaghan C. Dougher, Lauren Schwartz, David R. Walt, Kathleen H. Burns, Ronny Drapkin. ORF1p expression from LINE-1 occurs in clear cell ovarian carcinoma precursors and is detectable in patients’ plasma samples [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 1055.
Abstract 1246: Erg-driven prostate cancer emerges from a basal subset of cells with luminal transcriptomic features
Authors: Ladewig Erik , Feng Weiran , Leslie Christina , Sawyers Charles 
Published: March 2024

Abstract
Translocations of the ETS family transcription factor ERG are found in nearly 150,000 newly diagnosed prostate cancers (PCas) each year in the United States underscoring the importance of defining the mechanism by which ERG promotes prostate epithelial transformation. A consequence of nearly all ERG translocations is the aberrant expression of ERG in prostate luminal cells under transcriptional control of TMPRSS2. Multiple lines of evidence implicate ERG translocations as an initiating event in prostate cancer. ERG expression is seen in prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy; expression in cancers is typically uniform; and, in the context of PI3K pathway activation, ERG is sufficient to induce cancers in mice. Yet, despite extensive research the mechanism by which ERG initiates prostate cancer is unclear. To gain insight into how ERG translocations cause prostate cancer, we performed both transcriptional profiling (scRNA-seq) and chromatin accessibility via Assay for Transposase-Accessible Chromatin using sequencing (snATAC-seq) in single cells of an autochthonous mouse model at an early stage of disease initiation. Surprisingly, we observed in prostate epithelial cells broadly expressing ERG enhanced proliferation primarily in a hybrid subpopulation of cells having basal identity but with luminal morphology and cytokeratin expression. Through a series of lineage tracing and primary prostate epithelial transplantation experiments, we confirmed tumor initiating activity resided within a subpopulation of basal cells expressing luminal genes (e.g., Tmprss2 and Nkx3-1). A trajectory analysis from single-cell Chromatin accessibility indicated Erg+ cells began to lose basal (Trp63) accessibility and gained in STAT/NFAT TFs while retaining the ability to rapidly differentiate into luminal cells that reflect the lineage of ERG-positive cancers. These findings help resolve a preexisting debate about the cell of origin of ERG-driven prostate cancer and narrow the focus for future mechanistic studies to a basal-luminal subpopulation of tumor initiating cells.
Citation Format: Erik Ladewig, Weiran Feng, Christina Leslie, Charles Sawyers. Erg-driven prostate cancer emerges from a basal subset of cells with luminal transcriptomic features [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 1246.
Abstract 1248: The BRD8/p53 epigenetic switch re-establishes tumor suppression in glioblastoma
Authors: Sun Xueqin Sherine , Mills Alea A. 
Published: March 2024

Abstract
Glioblastoma (GBM) is the most common and deadly adult primary brain malignancy. Median survival is just 12-14 months, with only about 5% of GBM patients surviving 5 years after diagnosis. This picture has not substantially improved over decades and there is an urgent need to discover more specific and effective treatments for this deadly malignancy. We discovered the bromodomain-containing chromatin regulator BRD8 as essential to GBM lacking p53 mutations (TP53WT), which make up ~71% of cases (1). BRD8 maintains malignancy by crippling p53-mediated tumor suppression in a way distinct from previously described mechanisms: it reprograms the p53 network through the EP400 histone acetyltransferase complex and by bromodomain-directed occupancy of the histone variant H2AZ at p53-induced targets, enforcing a repressive chromatin state that prevents p53-mediated transactivation. Importantly, targeting BRD8 in TP53WT GBM remodels chromatin by evicting H2AZ and enhancing chromatin accessibility, enabling p53 to bind and transactivate its targets. This chromatin remodeling cascade (referred to as the “BRD8/p53 epigenetic switch”) re-establishes p53 activity in TP53WT GBM, normalizing gene expression, evoking cell cycle arrest, inhibiting gliomagenesis, and prolonging survival in xenograft models of TP53WT GBM. Our recent work: (i) reveals that BRD8 opposes p53 function in non-malignant brain cells; (ii) shows that the bromodomain of BRD8 is unique amongst the bromodomain-containing protein family, as it is the only one that selectively reprograms the p53 network; and (iii) demonstrates that targeting BRD8 works synergistically with MDM2 inhibition. Our findings present a previously unappreciated mechanism by which cancer cells side-step p53, indicate that targeting BRD8 re-establishes p53-mediated tumor suppression in TP53WT GBM, highlight unique features of the bromodomain of BRD8, and propose therapies using co-inhibition of BRD8 and MDM2 as a dual-level tactic for boosting up p53. Thus, our work sheds light on new principles of chromatin biology and offers new promise for treating patients with this devastating malignancy.
(1)Sun et al., 2023 Nature 613 (7942):195-202.
Citation Format: Xueqin Sherine Sun, Alea A. Mills. The BRD8/p53 epigenetic switch re-establishes tumor suppression in 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 1248.
Abstract 1257: CHD5 suppresses glioblastoma by inhibiting MYC
Authors: Sun Xueqin Sherine , Mills Alea 
Published: March 2024

Abstract
Fundamentally, cancer is a disease caused by genetic and epigenetic alterations that converge to reprogram gene expression networks, leading to unrestrained proliferation. Glioblastoma (GBM) is the most prevalent and aggressive primary brain cancer, median survival being approximately one year and the 5-year survival rate being only 5%. Despite decades of effort, this devastating picture has not appreciably improved and effective therapies have been elusive for GBM patients. A better understanding of GBM biology is essential for developing more effective therapies. Although several genetic alterations have been implicated in gliomagenesis, driving genetic factors responsible for GBM are still obscure, and the interplay between genetic alterations and epigenetic dysregulation is largely undocumented during the gliomagenic process. Here, we show that CHD5 — a gene mapping to the 1p36 chromosomal region that is notoriously deleted in many cancers, is recurrently deleted in over 20% of GBM cases and is further downregulated through epigenetic means. To delineate how CHD5 loss promotes gliomagenesis, we established a glioma-prone mouse model harboring conditional alleles of Pten, Trp53, and Chd5. We developed an engineered mouse neural stem cell (NSCs)-based strategy to elicit glioma formation, as NSCs are the major cell-of-origin for GBM. We show that Chd5 loss significantly impairs NSCs differentiation while promoting proliferation, transformation, and gliomagenesis in vivo. Mechanistically, Chd5 forms a Chd3-containing but Chd4-independent NuRD complex that directly binds the Myc promoter and super enhancers to govern Myc expression in normal NSCs, with the Snf2 domain of Chd5 playing the most critical chromatin regulating role in the context of GBM. Chd5 loss triggers the remodeling of chromatin, enhances accessibility, and augments Myc expression, leading to the formation of highly aggressive glioma. Furthermore, reactivating CHD5 in human GBM xenograft models significantly extends survival. This work demonstrates the tumor suppressive role of CHD5 in gliomagenesis, providing therapeutic insights for cancers with 1p36 deletions. In parallel, this work presents a powerful strategy for rapidly interrogating gene function during gliomagenesis using engineering NSCs, and the generation of novel mouse models with classic clinical features of GBM, offering new approaches for elucidating GBM biology that can inform on therapeutic opportunities for treating patients with GBM.
Citation Format: Xueqin Sherine Sun, Alea Mills. CHD5 suppresses glioblastoma by inhibiting MYC [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 1257.
Abstract 1292: ProTALKS: A community outreach project founded by a graduate of the CaRE2 Community Scientist Research Advocacy training program, Mrs. Lynn Jones-Turpin
Authors: Jones-Turpin Lynn , Guzman Ileana , Hensel Brooke , Webb Fern 
Published: March 2024

Abstract
ProTALKS was created and led by a community member committed to reducing prostate cancer health disparities. ProTALKS stands for Prostate Cancer Outreach, Opinions, and Opportunities and is designed to increase awareness of prostate cancer prevention, research, and treatment as well as highlight the health disparities observed in Black communities. According to the Florida Department of Health, prostate cancer incidence and mortality rates among Black men living in Duval County are higher compared to men of other races and ethnicities. Therefore, there is a need for programs like ProTALKS that focus on early detection strategies and promoting community resources. In collaboration with the Prostate Health Education Network (PHEN), The American Legion Post 197, and Florida Blue, ProTALKS has increased access to services such as prostate cancer screening and evidence-based information. Community events implemented by ProTALKS bring together oncologists, researchers, key community leaders, health educators, and providers to educate and promote positive health behavior changes among high-risk communities. In addition to hosting health fairs, ProTalks has hosted grilling competitions and community awareness walks to further educate the community about prostate cancer prevention, screening, and research. ProTALKS also shares information through the local newspaper, The Jacksonville Free Press, The Lynn & Friends radio show, and social media platforms. Since its start in 2021, with support from the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center, ProTALKS has implemented more than 10 community events with over 1,000 community members from Jacksonville, Florida. ProTALKS, in collaboration with CaRE2, continues to disseminate information about cancer screening, the importance of clinical trial participation, and donating biospecimens for cancer research. Although ProTALKS has been successful in its mission, there have been challenges throughout its implementation. For example, one challenge has been increasing the number of community members attending events and using appropriate marketing techniques to promote ProTALKS’ activities. Future implications to avoid challenges include recruiting more volunteers, and partnering with other community organizations in Duval County.
Citation Format: Lynn Jones-Turpin, Ileana Guzman, Brooke Hensel, Fern Webb. ProTALKS: A community outreach project founded by a graduate of the CaRE2 Community Scientist Research Advocacy training program, Mrs. Lynn Jones-Turpin [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 1292.
Abstract 1310: Social determinants of migrant health factors impacting prostate cancer care and survivorship among sub-Saharan African immigrant men diagnosed with prostate cancer
Authors: Kaninjing Ernest , Asiedu Gladys , Van Voorhis Kaitlin , Young Mary Ellen , Erefah Ebenezer , Agboola Emmanuel , Odedina Folakemi , Dronca Roxana , Ashing Kimlin , Rotimi Solomon , Ngufor Che , Merriweather Arnola , McCall John , Hill Anthony 
Published: March 2024

Abstract
Background: Sub-Saharan African Immigrants (SSAI) represent one of the fastest-growing segments of the immigrant population in the United States (US). Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. Despite these growing numbers, little is published about the extent to which SSAIs adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the Social Determinants of Health (SDOH) among this population relative to their migration experiences and their influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options.
Methods: This qualitative study employed grounded theory and the social determinants of migrant heath framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. In-depth interviews were conducted with 8 survivors who live in the states of Florida and Minnesota.
Findings: Some participants reported limited access to care and financial challenges paying for drugs. In terms of coping with diagnosis and treatment, most of the participants relied on their faith, a positive outlook about survivorship and support of family members. Some participants relied on the coaching and support of a loved one who experienced prostate cancer in the past. Erectile dysfunction severely impacted the sexual life of most participants as they experienced difficulty getting an erection.
Conclusion: Participants expressed the benefit of belonging to support groups with other survivors for social and emotional support. As the number of immigrants from sub-Saharan continue to rise, so too will the demand for culturally tailored care to address and reduce disparities in survivorship among this sub-population.
Citation Format: Ernest Kaninjing, Gladys Asiedu, Kaitlin Van Voorhis, Mary Ellen Young, Ebenezer Erefah, Emmanuel Agboola, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnola Merriweather, John McCall, Anthony Hill. Social determinants of migrant health factors impacting prostate cancer care and survivorship among sub-Saharan African immigrant men diagnosed with prostate 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 1310.
Abstract 1313: Racial disparities in colorectal cancer incidence across US ethnic groups: A comprehensive analysis
Authors: Chaudhuri Anathbandhu , Gray Rosianna 
Published: March 2024

Abstract
Colorectal cancer (CRC) ranks as the third most prevalent global cancer and the fourth leading cause of cancer-related deaths. Racial disparities in CRC within the United States pose a significant public health concern, affecting incidence, mortality rates, and screening rates. This study investigates the impact of racial disparities on CRC incidence across various US states, utilizing CRC data from the National Cancer Institute (NCI) at the Centers for Disease Control and Prevention (CDC). Analysis with GraphPad Prism 5 software and Student's t-test reveals a consistent trend of higher CRC incidence in males compared to females, irrespective of ethnicity. Notably, the Black and American Indian ethnic groups demonstrate the highest CRC incidences among all races, especially in individuals aged 65 and above. Certain states, including Iowa and Mississippi for Black populations, and Alaska, Minnesota, Montana, Oklahoma, and South Dakota for American Indian populations, exhibit significantly elevated CRC incidences compared to the national average. County-specific analysis in Alabama reveals varying CRC incidence rates across ethnic groups, with higher rates in specific counties, such as Clarke County for Black males. Limited reports for American Indian, Asian Pacific, and Hispanic ethnic groups indicate potential disparities in access to testing, awareness, and funding for CRC detection and prevention. This study concludes that Black and American Indian males and females experience a higher incidence of colorectal cancer, possibly influenced by genetic factors or other variables contributing to CRC development. The observed disparities are multifaceted, arising from a combination of social, economic, and healthcare system factors. Addressing these complexities is crucial for mitigating CRC disparities and promoting equitable healthcare access and outcomes. Additional research, including molecular screening studies, is essential to substantiate disparities in cancer-related health and enhance public health and cancer awareness within the community.
Key Words: Cancer, Colorectal Cancer, Health Care, Racial Disparities
Citation Format: Anathbandhu Chaudhuri, Rosianna Gray. Racial disparities in colorectal cancer incidence across US ethnic groups: A comprehensive 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 1313.