tbuckley/cabot-search huggingface dataset:
Abstract 519: Targeting MYC as a novel therapeutic strategy for an epigenetic-driven cancer: NUT Carcinoma
Authors: Carmen Escudero-Iriarte, Joel Castro, Iker Beniavides-Puy, Natalia S. Tissera, Jessica Querol-Paños, Irene Agustí, Jonathan R. Whitfield, Maria Vieito, Lara Nonell, Teresa Macarulla, Irene Braña, Laura Soucek, Tian V. Tian
Journal: Cancer Research (2024)

Abstract Epigenetic dysregulation is widespread in cancer, playing a pivotal role in shaping cell function and contributing to the process of oncogenic transformation. NUT Carcinoma (NC) is an exceptionally rare and aggressive cancer lacking effective treatment, with a dismal prognosis - NC patients typically survive less than seven months after the initial diagnosis. NC is characterized by the presence of chromosomal rearrangements involving the gene encoding for the testis-specific NUT protein and a ubiquitous gene encoding an epigenetic regulator, BRD4 in most cases. Previous studies have demonstrated the role of the BRD4-NUT fusion protein in generating clusters of acetylated histones, namely “megadomains,” throughout NC cell chromatin. These NUT-containing fusion proteins are involved in NC oncogenesis by altering the epigenetic and transcriptional landscapes, promoting cell proliferation while impeding cell differentiation. Indeed, several downstream targets, including P63, SOX2, and MYC, have been identified to be modulated by NUT fusion proteins, independently of the fusion partners. This study focuses on a novel therapeutic approach targeting MYC for NC treatment. We conducted a comprehensive preclinical study of OMO-103, a MYC inhibitor currently undergoing clinical evaluation, using various NC patient-derived cell lines. Through cell viability assays, cell cytometry, western blotting, RNA-seq data analysis in vitro, as well as in vivo drug efficacy evaluation in NC xenografts, we delved into the effects of OMO-103 on NC cells. Our findings reveal that OMO-103 effectively inhibits NC cell growth both in vitro and in vivo. It induces cell apoptosis, differentiation, and cell cycle arrest in vitro, and when tested in xenografts in vivo, OMO-103 reduces tumor growth and enhances mouse survival, particularly when combined with a chemotherapy regimen. This study presents a promising therapeutic strategy for an incurable and aggressive cancer type. Citation Format: Carmen Escudero-Iriarte, Joel Castro, Iker Beniavides-Puy, Natalia S. Tissera, Jessica Querol-Paños, Irene Agustí, Jonathan R. Whitfield, Maria Vieito, Lara Nonell, Teresa Macarulla, Irene Braña, Laura Soucek, Tian V. Tian. Targeting MYC as a novel therapeutic strategy for an epigenetic-driven cancer: NUT Carcinoma [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 519.
Abstract 5473: Combined inhibition of MDM2 and PARP lead to a synergistic anti-tumoral response in p53 wild-type rhabdomyosarcoma
Authors: Guillem Pons, Gabriel Gallo-Oller, Lia García-Gilabert, Patricia Zarzosa, Júlia Sansa-Girona, Natalia Navarro, Paula Cabré-Fernández, Miguel F Segura, Josep Sánchez de Toledo, Soledad Gallego, Lucas Moreno, Josep Roma
Journal: Cancer Research (2024)

Abstract Targeting MDM2-p53 interaction to enhance p53 activity represents an attractive antitumoral strategy for p53 wild-type tumors. However, early-phase clinical trials in hematological and solid cancers have shown limited efficacy of MDM2 inhibitors highlighting the necessity for exploring more effective combinations with additional agents. In this study, we provide results from a 22-drug combination screening demonstrating the therapeutic potential of combining Siremadlin (MDM2 inhibitor) and Olaparib (PARP inhibitor) for treating p53 wild-type rhabdomyosarcoma (RMS). Cell survival, cell death and apoptosis analysis revealed synergistic effects when combining Siremadlin and Olaparib in vitro. Combination of both drugs resulted in a significant increase of p53 activity as evidenced by p53 accumulation and K382 acetylation along with an increased expression of p53 targets. Finally, combination of both drugs resulted in significant reduction of tumor growth and increased overall survival outperforming individual treatments and control groups. In summary, our study demonstrates, for the first time, the synergistic effect of the combination between Siremadlin and Olaparib in the inhibition of p53 wild-type RMS tumor growth in vitro and in vivo. These findings advocate for the exploration of this drug combination in clinical trials and underscore the need for further investigation in tumors sharing similar molecular features. Citation Format: Guillem Pons, Gabriel Gallo-Oller, Lia García-Gilabert, Patricia Zarzosa, Júlia Sansa-Girona, Natalia Navarro, Paula Cabré-Fernández, Miguel F Segura, Josep Sánchez de Toledo, Soledad Gallego, Lucas Moreno, Josep Roma. Combined inhibition of MDM2 and PARP lead to a synergistic anti-tumoral response in p53 wild-type rhabdomyosarcoma [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 5473.
Tuberculosis in people of Ukrainian origin in the European Union and the European Economic Area, 2019 to 2022
Authors: Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke van der Werf, Christoph Lange
Journal: Eurosurveillance (2024)

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.
Abstract 1389: Understanding the differential role of an IL-6 family cytokine in varying subtypes of breast cancer patients for novel therapeutic intervention
Authors: Cody L. Wolf, Ken Tawara, Cheryl L. Jorcyk
Journal: Cancer Research (2024)

Abstract In the United States, it is estimated that over 295,000 women will be diagnosed with breast cancer, and over 43,000 breast cancer deaths in 2023. Mortality in breast cancer is due in large part due to distant metastasis to organs such as the bone, lung, liver, and brain. Our laboratory has identified that the IL-6-family cytokine oncostatin M (OSM) plays a crucial role in initiating metastasis by secreting pro-metastatic molecules such as VEGF, LOXL2 and IL-6, and increasing circulating tumor cell numbers and metastases to bone and lung in vivo. More recent work within our lab has identified unique roles for OSM in varying subtypes of breast cancer patients, particularly between estrogen receptor positive (ER+) and ER- patients. It is well known that patients with ER- breast cancer, specifically triple negative breast cancer (TNBC; ER- PR- HER2-), have limited therapeutic options. However, the divergent role OSM plays in ER+ and ER- breast cancer and the mechanism by which this occurs has yet to be fully understood. Thus, we aimed to fully elucidate the difference between OSM in ER+ versus ER- breast cancer. RNA sequencing analysis on OSM-treated human ER+ cells and ER- TNBC cells discovered significant differences in gene expression between both cell lines upon treatment with OSM, including alteration in DNA-replication and cell cycle pathway genes. Afterwards to evaluate the correlation between OSM and DNA synthesis and this role on metastasis, we evaluated the role of a novel anti-OSM therapeutic and its correlation with decreased metastasis. This research aims to elucidate the unique role OSM plays in ER+ and ER- breast cancer and will provide a molecular understanding of how this occurs and will provide detailed information on which patients will benefit most from anti-OSM therapeutics. Citation Format: Cody L. Wolf, Ken Tawara, Cheryl L. Jorcyk. Understanding the differential role of an IL-6 family cytokine in varying subtypes of breast cancer patients for novel therapeutic intervention [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 1389.
Abstract 7447: Understanding survivorship: A national survey of post-treatment experiences in Black prostate cancer survivors
Authors: Dottington Fullwood, Daniel Lee, Veronika Panagiotou, Samantha B. Siegel, Mariel Molina, Folakemi T. Odedina
Journal: Cancer Research (2024)

Abstract Prostate cancer, impacts over 3.1 million survivors, poses persistent challenges in post-treatment care, creating uncertainties regarding the best course of follow-up actions for leading productive lives. Unfortunately, these concerns, especially among ethnically diverse Black men, are frequently overlooked. The post-treatment journey for Black prostate cancer survivors is dependent on how they navigate survivorship to determine how it impacts their quality of life and emotional wellbeing. This study evaluated the post-treatment cancer experience and gauge satisfaction with care among a cohort of Black survivors (n = 45). Utilizing data from the 2023 National Coalition for Cancer Survivorship State of Survivorship Study (n = 1303), conducted between May 9th to June 6th, 2023, the research specifically targets self-identified Black males, constituting 10% of the study population and spanning an age range from 18 to 80 years. Results revealed that oncologists (44%) managed post-treatment care more than primary care physicians (30%). While conversation about follow-up care monitoring cancer tests regularly occurred (68%), while topics such as quality of life (27%), mental and emotional health (21%), and post-treatment survivorship care plans (9%) received minimal attention. Although most survivors felt generally informed about side effects (62% very informed), less than half felt their health care team was very helpful in dealing with them. Symptoms reported by survivors included feeling overly tired (47%), depression, anxiety, and mental health impacts (40%), and uncertainty about the cancer status (34%). Survivors engaging in diverse integrative treatments, including such practices as prayer and exercise, represented 29% and 28%, respectfully. Notably, 80% and 60% of individuals utilizing these modalities reported finding them effective during the post-treatment care phase. The journey from the point of prostate cancer diagnosis to post-treatment can impose a significant mental and physical toll on survivors. To address the emotional and psychological challenges associated with a diagnosis and post-treatment, survivors adopting integrative oncology modalities and exercise prescriptions to cope are crucial. These strategies may help survivors maintain a positive outlook and achieve optimal post-treatment health, with a focus on providing tailored resources that cater to the unique needs of Black survivors. Citation Format: Dottington Fullwood, Daniel Lee, Veronika Panagiotou, Samantha B. Siegel, Mariel Molina, Folakemi T. Odedina. Understanding survivorship: A national survey of post-treatment experiences in Black prostate 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 7447.
Abstract 6081: DNA integrity and preanalytical handling of endocervical samples for use in liquid biopsy-based diagnostics and monitoring of gynecological cancer
Authors: Jacob Malchau Lauesgaard, Therese Carlsson, Anna Linder, Sara Schumacher, Karin Sundfeldt
Journal: Cancer Research (2024)

Abstract Background: Liquid biopsies from the gynecological tract can be useful for analysis of cell free DNA (cfDNA) (1, 2, 3). Sampling procedure and optimal preanalytical handling are poorly investigated. In this study, we aimed to evaluate how the profile and integrity of DNA, sampled from the female genital tract, were affected by preanalytical handling. Methods: Biobanked/archival (stored at -80℃ after 48h at room temperature (RT)) and freshly obtained clinical samples were analyzed together with standardized in vitro samples. Archival and in vitro samples were preserved in methanol-based solution, imitating clinical handling of endocervical samples which are initially stored at RT for 48h before further handling. The fragmentation profile of archival and in vitro samples was analyzed. Time series of in vitro samples at RT and 4℃, with extraction at 6-hour intervals from 0 to 96h, were performed. The fresh clinical samples were collected from the endocervix in methanol-based solution and from the vagina in a solution designed to preserve DNA and placed at 4℃ resp RT. Extraction was performed within 4h and at 48h. Results: Accumulation of short DNA fragments were observed in the archival samples and in the in vitro samples, indicating that fragmentation was initiated prior to 48h. Time series showed that the quantity of short DNA fragments gradually increased with time at both RT and 4℃ but at a slower rate in 4℃. At RT the percentage of fragments between 100-350bp increased 12-fold (0.39% vs 4.75%, p=0.002). The freshly obtained endocervical samples showed a similar significant increase in short fragments in samples stored at RT compared with samples stored at 4℃ (p= 0.02 for 100-230bp; p= 0.007 for 230-350bp; p= 0.03 for 100-2500bp) at 4h-48h. Conclusion: Pre-analytical handling of endocervical samples can be optimized. Lowering temperature from RT to 4℃ immediately haltered DNA fragmentation. Citation Format: Jacob Malchau Lauesgaard, Therese Carlsson, Anna Linder, Sara Schumacher, Karin Sundfeldt. DNA integrity and preanalytical handling of endocervical samples for use in liquid biopsy-based diagnostics and monitoring of gynecological 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 6081.
Abstract 906: Large-scale surface protein abundance prediction from single-cell transcriptomes with a zero-shot model and its applications to cancer research
Authors: Ruoqiao Chen, Bin Chen, Jiayu Zhou
Journal: Cancer Research (2024)

Abstract We develop SPIDER, a zero-shot model which can predict the abundance for a large scale (&amp;gt;2,000) of surface proteins from single-cell transcriptomes in various contexts. This is to overcome the challenges in current single-cell protein abundance quantification tools (e.g., flow cytometry, CITE-seq) and computational models (e.g., totalVI, Seurat, cTPnet), where routinely only &amp;lt;300 surface proteins can be quantified or predicted. Comprehensive benchmarking on four external validation sets shows that the prediction accuracy of SPIDER outperforms other state-of-the-art methods including Seurat, totalVI, and cTPnet, with a prediction accuracy elevated as much as 42.5% in new contexts. We further conduct case studies in cancers by applying SPIDER to predict the abundance of &amp;gt;2,500 surface proteins on scRNA-seq datasets of hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (RCRLM), where the predicted surface protein abundance data is analyzed to demonstrate the broad downstream applications of SPIDER including facilitating cell type annotation, disease biomarker/target identification, and cell-cell interaction (CCI) inference. For instance, in these datasets we find that SPIDER can reveal (novel) disease biomarkers that are overlooked by solely observing transcript expression, such as CD44/PIK3IP1 in hepatocytes/γδ2 T cells as a positive/negative HCC biomarker, demonstrating the capability of SPIDER to compensate for the limitations in the RNA modality. In conclusion, we propose the SPIDER model which can provide valuable information on the abundance of a large scale of surfaceomes in single cells, and can be further used to gain new insights into cancers via promoting cell type annotation, disease biomarker/target identification, and CCI inference. Citation Format: Ruoqiao Chen, Bin Chen, Jiayu Zhou. Large-scale surface protein abundance prediction from single-cell transcriptomes with a zero-shot model and its applications to cancer research [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 906.
Abstract 5628: Aberrant 3'UTR processing regulates a tumor suppressor network in AML
Authors: Eric Wang, Cuijuan Han, Alexander Calderon, Abimbo Lawal, Sakthi Harini Rajendran, Sadik Karma, Nidhi Hariramani, Iannis Aifantis, Aristotelis Tsirigos
Journal: Cancer Research (2024)

Abstract Differentiation blockade is a hallmark of acute myeloid leukemia (AML). While inactivating mutations in tumor suppressor genes (TSGs) have been well-studied, non-genetic mechanisms that impair TSGs to promote myeloid differentiation and influence drug response remain poorly understood. In this study, we performed genome-wide loss-of-function CRISPR/Cas9 screens to identify suppressors of myeloid differentiation. These screens converged on the zinc finger transcriptional repressor, ZBTB7A whose ablation restricted myeloid maturation and promoted a dysregulated inflammatory state to protect leukemic cells from undergoing differentiation. Moreover, genetic deletion of ZBTB7A or its paralog, ZBTB7B impeded leukemia differentiation and conferred resistance to differentiation-inducing agents. Mechanistically, we found that leukemia cells hijack 3’UTR processes to reduce mRNA expression of the tumor suppressor gene paralogs ZBTB7A and ZBTB7B. These findings provide a molecular framework of altered 3’UTR regulation that orchestrate a tumor suppressive function and promote resistance to AML differentiation-based therapies. Citation Format: Eric Wang, Cuijuan Han, Alexander Calderon, Abimbo Lawal, Sakthi Harini Rajendran, Sadik Karma, Nidhi Hariramani, Iannis Aifantis, Aristotelis Tsirigos. Aberrant 3'UTR processing regulates a tumor suppressor network in AML [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 5628.
Abstract 3436: Circadian rhythm dysregulation with risk of gastrointestinal cancers: A large-scale prospective analysis
Authors: Yi Kang, Shinghei Mok, Xiaoyu Zong, Yin Cao
Journal: Cancer Research (2024)

Abstract Introduction: The incidence of multiple gastrointestinal (GI) cancers has been rising among younger adults with unknown etiology. Circadian rhythm dysregulation due to increasing exposures to artificial lighting, irregular work hours, and frequent travel, has been recently linked with multiple diseases. Disruption of the circadian clock drives Apc LOH to hyperactivate Wnt signaling and enhances MYC-dependent glycolytic metabolism to accelerate colorectal cancer progression. However, the association between circadian rhythm dysregulation, quantified by relative amplitude (RA)–a parameter derived from rest-activity patterns, and risk of colorectal and other GI cancers has not been evaluated in epidemiologic studies. Methods: We prospectively examined the associations between RA and risk of incident GI cancers among 87,653 UK Biobank participants who wore an Axivity AX3 triaxial accelerometer over 7 days (2013-15) with follow-up to 2021. RA was derived and averaged across all valid days, using the difference between the mean activity levels during the most active 10-hour period and the least active 5-hour period. Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: During 512,074 person-years, 1,079 incident GI cancer cases occurred. After multivariable adjustment, lower RA was associated with an increased risk of overall GI cancer (RR per SD [standard deviation] = 1.12, 95% CI 1.04-1.21, P for trend = 0.01). Compared to individuals in the highest tertile (T1), those with RA in the lowest tertile (T3) had a 25% increased risk of overall GI cancer (RR = 1.25, 95% CI 1.05-1.50). The positive associations with GI cancers were mainly driven by gastric cancer (RR per SD = 1.33, 95% CI 1.02-1.74, P for trend= 0.04) and colon cancer (RR per SD = 1.13, 95% CI 1.00-1.28, P for trend = 0.03). Conclusion: In this large-scale, prospective analysis of accelerometer data, circadian rhythm dysregulation was associated with subsequent risk of GI cancers, primarily gastric and colon cancer. To our knowledge, this is among the first population-based studies reporting the positive link between circadian rhythm dysregulation with cancer risk. Citation Format: Yi Kang, Shinghei Mok, Xiaoyu Zong, Yin Cao. Circadian rhythm dysregulation with risk of gastrointestinal cancers: A large-scale prospective 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 3436.