bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB073: NCI’s broad-use collections: Accelerating discovery process by improving access to individual-level genomics and other -omics data
Authors: Pruitt Freddie L. , Feolo Michael , Jagu Subhashini , Auvil Jaime Guidry 
Published: April 2023

Abstract
Genomic data sharing increases our understanding of factors that influence health and diseases by enabling additional research questions from secondary data users, increasing statistical power through combining multiple data sources, facilitating reproducibility and validation of research results, and supporting innovation with the development of research tools and methodologies. Research using large-scale genomic and other-omics data is no longer limited by storage space or slow downloading speed for individual datasets. Innovations like cloud infrastructure enable computing over many datasets at multiple locations at once. These developments have increased the need for faster, more efficient processes for data access and sharing. To support scientific exploration and meet the demand for analysis of biomedical data, the National Cancer Institute (NCI) has created two large collections of the broad-use studies within the database of Genotypes and Phenotypes (dbGaP). These collections comply with the consent of the study (data use limitations) for how secondary access to studies are determined. NCI’s Collection of Datasets for General Research Use comprises 284 studies with individual-level data sets, and permits approved users to explore broad research interest, including methods and tool development. NCI’s Collection of Datasets for Health, Medical, and Biomedical (HMB) Research Purposes is comprised of 65 studies of individual-level that are permitted for research interests specific to any health, medical, or biomedical research only. The HMB collection could be used for methods and tool development; research interests involving ancestry/populations studies must be dependent on a health/medical condition. Through these collections, investigators will have the potential to add access to 349 datasets to their approved research projects or submit a new project request for access to the broad-use collections. As new genomic studies are registered by NCI for release through dbGaP, they will be automatically added to these collections. NCI anticipates through the implementation of these broad-use collections a requestor could have access to approximately 70% of NCI’s studies in controlled-access repositories.The streamlined access to broad-use datasets expedites data sharing and potentially accelerates the discovery process. This approach reduces redundancies for obtaining controlled-access data.
Citation Format: Freddie L. Pruitt, Michael Feolo, Subhashini Jagu, Jaime Guidry Auvil. NCI’s broad-use collections: Accelerating discovery process by improving access to individual-level genomics and other -omics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB073.
Abstract LB076: A novel spatial trajectory inference method for detecting regional breast cancer progression from spatial transcriptomics data
Authors: Pham Duy , Nguyen Quan 
Published: April 2023

Abstract
Spatial transcriptomics is a rapidly emerging field that allows for the study of gene expression within a tissue sample. This technology has the potential to provide valuable insights into the molecular mechanisms underlying cancer progression and could be particularly useful in identifying specific regional cancer progression. By studying the regional spatial trajectory of cancer progression, we can develop more targeted therapies and better predict the likelihood of metastasis. Additionally, analyzing gene expression patterns in specific regions of the tissue can reveal the molecular mechanisms driving cancer growth in those areas, potentially uncovering new therapeutic targets.
In this study, we created a spatial trajectory analysis method, named as stLearn - PSeudo-Time-Space (PSTS) algorithm, to investigate specific regional cancer progression. Spatial trajectory analysis is a statistical method that allows for the identification of patterns of transitional gene expression over time and space within a tissue sample. In detail, this method incorporates spatial features, such as tissue sub-structure locations and gene expression changes, to model the trajectory from a single snapshot of transcriptomics data. Also, we evaluated the effectiveness of PSTS by utilizing the cancer progression model in human breast cancer samples.
Using this approach, we were able to identify specific regions within the breast tissue that displayed distinct progression branching trajectories patterns of transitional gene expression associated with ductal carcinoma in situ and invasive ductal carcinoma. These regions were found to be characterized by a high level of cellular diversity and were associated with aggressive forms of breast cancer.
The results of this study suggest that spatial transcriptomics and spatial trajectory analysis could be a powerful tool for identifying specific regional cancer progression and may help to inform the biomarkers for the development of targeted therapies for breast cancer.
Overall, this study highlights the potential of spatial transcriptomics and spatial trajectory analysis to provide valuable insights into the molecular mechanisms underlying cancer progression and could have significant implications for the diagnosis and treatment of cancer.
Citation Format: Duy Pham, Quan Nguyen. A novel spatial trajectory inference method for detecting regional breast cancer progression from spatial transcriptomics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB076.
Abstract LB089: ACE2016: an off-the-shelf EGFR-targeting γδ2 T cell therapy against EGFR-expressing solid tumors
Authors: Li Hao-Kang , Wu Tai-Sheng , Leng Pei-Ru , Kuo Yi-Chiu , Cheng Zih-Fei , Lee Chia-Yun , Lin Yan-Liang , Tang Sai-Wen , Hsiao Shih-Chia 
Published: April 2023

Abstract
Introduction: CAR-αβT therapies have been shown to improve clinical outcomes in hematological malignancies; however, solid tumors still remain as challenges to CAR-αβT therapies due to tumor microenvironment, limited tumor infiltration or antigen escape. Previous research findings indicate γδ2 T cells are involved in tumor surveillance by responding to phosphoantigen overexpressed by most of cancers. The antibody cell conjugation (ACC) technology has the advantage to link cancer-targeting antibodies on cell surface of immune cells without genetic modification. This study applies ACC technology to generate an off-the-shelf EGFR-targeting γδ2 T cell therapy ACE2016, and presents the promising potency of ACE2016 against EGFR-expressing cancer cells.
Methods: γδ2 T cells were expanded from healthy donor PBMCs and αβ T cell population were depleted. Both γδ2 T cells and αEGFR were covalently conjugated to selected DNA aptamers that enable DNA hybridization to generate EGFR-targeting γδ2 T cells, ACE2016. The characteristics and antibody conjugation of ACE2016 was evaluated by flow cytometry, and in vitro cytotoxicity and in vivo anti-tumor potency was investigated using luminescence-based cytotoxicity assay and the orthotopical model with EGFR-expressing cancer cells, respectively.
Results: ACE2016 showed nearly 100 % of αEGFR antibody conjugation and exhibited EGFR-specific binding activity. These features conferred ACE2016 with enhanced in vitro cytotoxicity against EGFR-expressing cancer cells compared to unconjugated γδ2 T cells, while ACE2016 and γδ2 T cells showed no significant difference of anti-tumor potency against EGFR-negative cancer cells. Further characterization studies demonstrated that co-cultured with target cells significantly activated ACE2016 along with enhanced degranulation and cytokine production without measurable IL-6 secretion. Moreover, ACE2016 suppressed EGFR-expressing breast cancer cells in vivo in the orthotopic xenograft model without weight loss or toxicological observations.
Conclusion: ACE2016, an EGFR-targeting γδ2 T cell product, was successfully generated as an effective off-the-shelf treatment for EGFR-expressing solid tumors. This study provides the evidence for the in vitro and in vivo efficacy of ACE2016 against EGFR-expressing cancer cells to support the clinical application against EGFR-expressing tumors.
Citation Format: Hao-Kang Li, Tai-Sheng Wu, Pei-Ru Leng, Yi-Chiu Kuo, Zih-Fei Cheng, Chia-Yun Lee, Yan-Liang Lin, Sai-Wen Tang, Shih-Chia Hsiao. ACE2016: an off-the-shelf EGFR-targeting γδ2 T cell therapy against EGFR-expressing solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB089.
Abstract LB130: Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Valcarcel David , Molero Antonieta , Zamora Lurdes , Palomo Laura , Acha Pamela , Manzanares Ana , Solé Francesc , Esteller Manel 
Published: April 2023

Abstract
Epigenetic alterations, such as DNA methylation aberrations, are a hallmark of human cancer. This observation has led to the assessment of hypomethylating agents (HMAs) as potential drugs to treat oncological patients, being considered the clinical approval of these pharmacological compounds in the therapy of myeloid malignancies as one of the main achievements of this scientific field. A good example is myelodysplastic syndrome (MDS), a pre-leukemia disorder that can evolve into acute myeloid leukemia (AML), where very few therapeutic options were available until the introduction of HMAs. However, it remains unsolved how we can predict if an MDS patient will response or not to the epigenetic drug and for how long. Using the great analytical power of the newly developed single-cell technologies, we have herein tackled this issue. To study the evolution of the clonal molecular and cellular architecture MDS upon the treatment with HMAs, we performed single-cell DNA sequencing (scDNA-seq) of an amplicon panel for 53 genes commonly mutated in myeloid malignancies and single-cell protein sequencing (scProt-seq) of 45 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype. We sequenced hundreds of thousands of cells from these MDS patients where paired bone marrow samples were obtained at the time of diagnosis and at the end of at least six cycles of azacitidine treatment. Our study has unveiled that the co-occurrence of particular truncating or stop codon mutations in the same myeloid progenitor cell; the multibranched dynamics of the mutant clones; and the persistence of particular cell lineages with distinct mutational profiles (such as non-classical monocytes and CD8+ effector T-cells) can predict the clinical response of MDS patients to HMA therapy.
Citation Format: Ignacio Campillo-Marcos, Marta Casado-Pelaez, Veronica Davalos, Gerardo Ferrer, Caterina Mata, Elisabetta Mereu, David Valcarcel, Antonieta Molero, Lurdes Zamora, Laura Palomo, Pamela Acha, Ana Manzanares, Francesc Solé, Manel Esteller. Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB130.
Abstract LB153: Inhibiting BRD4 as a proposed alternative therapeutic strategy for HPV16-associated head and neck squamous cell carcinoma
Authors: Suresh Dhruthi , Mohanty Chitrasen , Wang Albert R. , Kendziorski Christina , Iyer Gopal 
Published: April 2023

Abstract
Integration of Human Papilloma Virus (HPV) 16 into human genomes is an integral event for cancer progression in Head and Neck Squamous Cell Carcinoma (HNSCC). There is a need to differentiate treatment for HPV-16 integrated HNSCC from other subtypes. We hypothesize that by inhibiting Bromodomain Extra Terminal (BET) protein BRD4, a transcriptional co-regulator of host and viral genes can advance treatment in patients with the integrated subtype of HPV16 associated HNSCC. Through small molecule inhibition and knockdown of BRD4 in seven model HPV-16 integrated cell lines, we demonstrated that BRD4 down-regulates the expression of viral genes E6, E7, independent of viral E2 type of integration. Given that E6 expression is mediated by BRD4, E6-p53 interactions was abrogated as revealed through increased expression of p53. Furthermore, BRD4 inhibition caused downregulation of c-Myc. This result also suggests the function of BRD4 in the regulation of proteins in cell cycle regulation, including E2F1 and p21. BRD4 inhibition was also shown to delay DNA damage response (DDR) by reducing the expression of RAD51 in 6 out of 7 cell lines. RNA-sequencing results give further insight regarding the downregulation of genes involved in DDR – RAD51, BRCA1 and BRCA2 in all cell lines. RNA-sequencing data also gives us an understanding of the implication of BRD4-inhibition in other genes involved in cell cycle regulation. Knockdown of BRD4 done through small hairpin RNA (shRNA) constructs phenocopied the effects shown through inhibition of BRD4. Additionally, treating the above-mentioned cell lines with BRD4 inhibitor (JQ1) followed by radiation showed further downregulation of viral oncogenes E6, and E7. This suggests that combining radiation and JQ1 treatment can be a viable combination treatment. De-escalating radiation treatment with BRD4 inhibition has potential to be an effective combination treatment for HPV16 integrated HNSCC.
Citation Format: Dhruthi Suresh, Chitrasen Mohanty, Albert R. Wang, Christina Kendziorski, Gopal Iyer. Inhibiting BRD4 as a proposed alternative therapeutic strategy for HPV16-associated head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB153.
Abstract LB155: In vivo imaging of vascular pathology in mouse orthotopic glioma model using functional ultrasound
Authors: Rytkönen Jussi , Lehtimäki Kimmo , Stenius Taina-Kaisa , Immonen Riikka , Suhonen Ari , Shatillo Artem 
Published: April 2023

Abstract
Neovascularization together with aberrant vasculature is a hallmark of glioblastomas. Understanding tumor vasculature can have a pivotal role in planning therapeutics approaches. The objective of this study was to investigate morphological, vasculature and blood flow changes induced by aggressive tumor growth, using in vivo imaging - magnetic resonance imaging (MRI) and functional ultrasound (fUS) imaging in a mouse model of orthotopic glioma. Female NMRI nude mice were xenografted orthotopically with U-87 MG, a human glioblastoma, cells (5 × 104) at the age of 8 weeks. Four weeks after implantation the mice we anesthetized with isoflurane and scanned with 11.7 T small animal MRI (Bruker) for tumor volumetry. Thereafter, the mice were imaged with Iconeus One imaging system (Iconeus, Paris, France) for structural information of brain vasculature and relative cerebral blood volume (rCBV) changes. High resolution vascular imaging was performed after intravenous injection of microbubble contrast agent (SonoVue, sulphur hexafluoride microbubbles). The average tumor size was 58.8 ± 27.6 mm3 (mean ± SD, n=7) four weeks after implantation. Aberrant vasculature could be visualized with structural fUS imaging as and the necrotic core of the tumor could be observed. A reduced rCBF was observed in ipsilateral hemisphere on the relative power doppler signal timeseries as a lower amplitude and faster decay compared to contralateral side. As a summary, in vivo fUS imaging is a noninvasive tool to visualize vascular changes induced by aggressive brain tumor growth which are not detectable with conventional imaging methods (CT, MRI, PET, SPECT) and can provide a novel readout for efficacy studies.
Citation Format: Jussi Rytkönen, Kimmo Lehtimäki, Taina-Kaisa Stenius, Riikka Immonen, Ari Suhonen, Artem Shatillo. In vivo imaging of vascular pathology in mouse orthotopic glioma model using functional ultrasound [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB155.
Abstract LB160: Mdm2 regulates metastasis and associated cellular processes through modulation of Sprouty4 in a p53-independent manner
Authors: de Queiroz Rafaela Muniz , Efe Gizem , Guzman Asja , Hashimoto Naoko , Kawashima Yusuke , Tanaka Tomoaki , Rustgi Anil K. , Prives Carol 
Published: April 2023

Abstract
Mdm2 and its homologue MdmX form an E3-ligase complex that is best understood as the major regulator of p53. Yet Mdm2 and MdmX have functions in cells that are independent of their ability to degrade p53. Amongst the functions regulated by Mdm2 is cell migration, although the molecular mechanism(s) involved have not been well characterized. We show, in a p53 null model, that either siRNA knockdown of Mdm2 or MdmX as well as pharmacological inhibition of the Mdm2/X complex E3-ligase can reduce migration of cells grown as monolayer or invasion of cells from pre-formed spheroids into collagen-based matrices. This is consistent with our observation that Mdm2 ablation or inhibition leads to decreased cell spreading and attachment of cells to the extracellular matrix. In line with these findings, we found that modulation of Mdm2, MdmX or the Mdm2/X complex impacts focal adhesion (FA) formation, a main step in cell attachment, spreading and migration. Physiologically, Mdm2 silencing leads to decreased metastatic burden in mouse models. Mechanistically, we have discovered that Mdm2 modulates the RNA levels of Sprouty4 and that Sprouty4 is needed for the effects of Mdm2 knockdown on cell migration, FA formation and metastasis. Taken together, we have discovered a pathway by which Mdm2, through the activity of the Mdm2/X complex, mitigates FA formation, migration and ultimately metastasis by regulation of Sprouty4 independently of p53. Our findings suggest that blocking Mdm2 or the Mdm2/X complex might be a potential target to prevent metastasis.
Citation Format: Rafaela Muniz de Queiroz, Gizem Efe, Asja Guzman, Naoko Hashimoto, Yusuke Kawashima, Tomoaki Tanaka, Anil K. Rustgi, Carol Prives. Mdm2 regulates metastasis and associated cellular processes through modulation of Sprouty4 in a p53-independent manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB160.
Abstract LB169: Machine learning-based approach for glioblastoma drug repurposing on real-world patient data
Authors: Lin Ko-Hong , Kim Yejin , Lee Dung-Fang , Jiang Xiaoqian 
Published: April 2023

Abstract
Glioblastoma (GBM) is the most aggressive and deadly type of brain cancer. The poor survival rate of GBM is often attributed to the low therapeutic efficiency of current front-line therapy, treatment resistance, and high recurrence rate. Sizeable clinical data of cancer patients preserve a great potential for drug discovery and drug repurposing research, enabling comprehensive screening of treatment effects among frequently-prescribed medications. To efficiently characterize potent drug candidates and develop novel treatment strategies for GBM, we designed a machine-learning-based pipeline that predicts repurposable drug combinations from large-scale patient claims data. Our pipeline first identified pseudo-randomized drug-user and non-user cohorts from heterogeneous clinical records and balanced the confounding effects using the Inverse Probability of Treatment Weighting (IPTW) method. Next, our model computed the averaged treatment effect on the treated (ATT) values to determine the treatment effects of our candidates. Our methodology identified several promising drug combinations that have been found to be effective in inhibiting GBM in cell line experiments. This research was conducted by integrating computational and experimental approaches to identify drug combinations, providing a promising strategy for the development of new treatments for GBM.
Citation Format: Ko-Hong Lin, Yejin Kim, Dung-Fang Lee, Xiaoqian Jiang. Machine learning-based approach for glioblastoma drug repurposing on real-world patient data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB169.
Abstract LB172: Improved T-cell and B-cell receptor repertoire profiling and immunophenotyping for biomarker discovery
Authors: Chenchik Alex , Makhanov Mikhail , Liu Tianbing , Hu Dongfang , Diehl Paul , Kobzik Lester 
Published: April 2023

Abstract
T-cell receptor (TCR) and B-cell receptor (BCR) repertoire profiling, also referred to as adaptive immune receptor repertoire (AIRR) profiling, holds great potential for the understanding of disease mechanisms and for the development of new treatments in infectious disease, autoimmunity, and immuno-oncology. This potential could be greatly improved by combining information about receptor clonotypes with immunophenotypes of T- and B- cells. A new technology we developed that combines profiling of all human TCR and BCR variable regions with phenotypic characterization of immune cells using the same workflow could be particularly useful. The TCR and BCR immunophenotyping method proposed involves RT-PCR amplification and sequencing of the CDR3 regions of the TCR and BCR genes, and subsequently determining the expression levels of the most informative T- and B-cell phenotyping genes. Preliminary results show that this method allows for comprehensive profiling of all seven TCR and BCR chains from a single sample, in a highly reproducible manner, directly from micro-samples including cancer tissue, whole blood, sorted cells and more. Bioinformatic analysis of the next-generation sequencing (NGS) data from the TCR and BCR clonotypes profile combined with RNA expression profiling of the same samples results in a richer data set that includes the identification of major immune cell subtypes and their activation status. Data from human cancer tissue and whole blood samples will be presented.
Citation Format: Alex Chenchik, Mikhail Makhanov, Tianbing Liu, Dongfang Hu, Paul Diehl, Lester Kobzik. Improved T-cell and B-cell receptor repertoire profiling and immunophenotyping for biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB172.