bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1451: Cognition-mediated transcriptomic signature associated with androgen deprivation therapy in prostate cancer
Authors: Verma Shiv Shankar , Shankar Eswar , Singh Vaibhav , Krishna Vijay , Gupta Sanjay 
Published: April 2023

Abstract
Androgen deprivation therapy (ADT) is the mainstay treatment for non-metastatic and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment results in adverse side-effects in patients including depression, memory loss, cognitive decline, and dementia. We aimed to identify critical molecules that could provide link between brain-related changes and pathological mechanisms responsible for cognitive decline in prostate cancer patients on ADT protocol. For these studies, gene expression data (GSE150807 and GSE151083) of human prostate cancer cells exposed to enzalutamide emulating ADT protocol was used to identify differential expression of genes at the transcript level. RNA sequencing analysis identified 9409 and 7757 differentially expressed genes (DEGs) in LNCaP and C4-2B enzalutamide exposed cells at p-value &lt; 0.0005 and FDR&lt; 0.05. In both cell lines, neuronal receptor signaling pathway was significantly overrepresented at 0.05 FDR-adjusted p-value (q-value). The genes associated with neuronal receptor signaling pathway belong to the ligand-gated ion channel and G-protein coupled receptors. Validation studies using brain glial cells treated with enzalutamide showed significant upregulation (p-value 0.001) of GABRB1, GABRA3, GABBR2 (GABA receptors/ligand-gated ion channel), BDNF (brain-derived neurotrophic factor), IFNB1 (interferon beta 1), NR3C1 (nuclear receptor subfamily 3 group c member/glucocorticoid receptor), ATGR1 (type-1 angiotensin II receptor), GRIN1 (glutamate ionotropic receptor NMDA type submit 1/ligated-gated ion channel), GRIN2D (glutamate ionotropic receptor NMDA type submit 2D/ligated-gated ion channel). In brain neuronal cells, enzalutamide exposure resulted in increased expression of NR3C1 whereas GABA/ligand-gated ion channel and others were downregulated and/or statistically non-significant. Further analysis using DisGenET (cytoscape) highlighted ATGR1, GABRB1, GRIN1, GRIN2D, and NR3C1 association with neuronal diseases including cognition disorder, forgetfulness, depressive mood, and others. The results of our study provide the first proof of evidence linking cognitive decline, depression, memory loss, and other neurological disorder more likely to develop in prostate cancer patients undergoing long-term androgen deprivation therapy.
Citation Format: Shiv Shankar Verma, Eswar Shankar, Vaibhav Singh, Vijay Krishna, Sanjay Gupta. Cognition-mediated transcriptomic signature associated with androgen deprivation therapy in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1451.
Abstract 1459: Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B
Authors: Awah Chidiebere U. , Mun Joo Sun , Boylu Baris , Paragodaarachchi Alooka , Ochu Chika , Zhang Junfei , Mastui Hiroshi , Ogunwobi Olorunseun 
Published: April 2023

Abstract
c-MYC is a master transcription factor overexpressed in more than 70% of human cancers including breast cancers (TNBC), lung cancers, brain tumors, prostate cancers, lymphomas, pediatrics cancers, pancreatic cancers, colorectal cancers, and ovarian cancers. Yet there is no clinically approved drug that directly targets it. The lack of direct clinically approved inhibitors of c-MYC is a significant biological and clinical question that needs urgent attention, especially in the context of aggressive cancers such as MYC driven triple negative breast cancer. In the USA, TNBC accounts for 10.34% of breast cancers, in China the rate is at 14%, and in African Americans the rate is 40%. We engineered the stable polyU sequences on the 3’UTR of c-MYC into unstable forms and specifically destabilized and degraded c-MYC transcript and protein and controlled primary tumor and metastasis in vivo. We developed three c-MYC destabilizing constructs that were effective in TNBC. They specifically destabilized c-MYC transcript, degraded c-MYC protein and the transcription factors STAT5A/B with increased expression of active caspase 3/7 leading to cancer cell death. In vivo, we delivered nanocage complexed with the MYC destabilizing constructs into TNBC mice bearing tumor and achieved reduction of primary tumor volume by 60-80%, 80% reduction in secondary tumor metastasis and very significant survival outcome (p&lt;0.0001). Mechanistically, the destabilization of c-MYC degraded c-MYC and its super enhancer interacting partner, STAT5A/B, in primary tumors and metastatic tumors. Taken together, we have developed a novel therapy for TNBC and uncovered c-MYC super enhancer STAT5A/B interaction as the target
Citation Format: Chidiebere U. Awah, Joo Sun Mun, Baris Boylu, Alooka Paragodaarachchi, Chika Ochu, Junfei Zhang, Hiroshi Mastui, Olorunseun Ogunwobi. Nanocage delivered engineered destabilized 3UTR ARE of cMYC inhibits triple negative breast cancer growth and metastasis in vivo by targeting cMYC and downregulating STAT5A5B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1459.
Abstract 1524: Effect of a chimeric antibody targeting CXCL1 in bladder cancer
Authors: Kim Nari , Furuya Hideki , Murakami Kaoru , Rosser Charles J. 
Published: April 2023

Abstract
Introduction and Objectives: Chemokine (C-X-C motif) ligand 1 (CXCL1) plays a crucial role in tumor initiation, promotion, and progression in bladder cancer (BCa) development. Previously, we reported on a monoclonal murine antibody (HL2401) towards CXCL1 which was capable of inhibiting growth in both in vitro and in vivo models. Herein, we have developed a chimeric anti-CXCL1 antibody, which is partially human (cHL2401). In this study, we tested the effect of cHL2401 on tumor growth and angiogenesis in both in vitro and in vivo models.
Methods: We developed chimeric anti-human CXCL1 antibody (cHL2401), and then tested for the following: ability to inhibit in vitro angiogenesis, ability to inhibit cellular proliferation, and tumor growth in cell line-derived xenograft model.
Results: We first performed the tube formation assay to evaluate the effect on angiogenesis. cHL2401 significantly inhibited tube formation in HUVEC, suggesting that cHL2401 inhibits angiogenesis. The inhibitory effect was better than bevacizumab (FDA-approved drug, anti-VEGF antibody). Next, we performed the cell proliferation assay to evaluate the effect on tumor growth in vitro. cHL2401 significantly inhibited the cell proliferation of T24 and 253J cell lines highly expressing CXCL1. Finally, we tested the effect of cHL2401 on tumor growth in an animal model. Both 8 and 32 mg/kg (i.p., twice weekly) significantly inhibited the tumor growth. The final volume of control tumor was 224.5 mm3, while those of 8 and 32 mg/kg were 102.9 and 93.08, respectively.
Conclusions: The chimeric antibody, cHL2401 contains human constant domains and mouse variable domains of mouse HL2401 antibody. Species-matched chimeric antibodies reduce anti-species immune responses in animal models. In this study, we tested whether the effects of mouse HL2401 that we have reported were induced by neutralizing CXCL1 by antibody. Taken together, the results suggest that neutralizing CXCL1 by antibody could be a promising therapeutic agent in BCa.
Citation Format: Nari Kim, Hideki Furuya, Kaoru Murakami, Charles J. Rosser. Effect of a chimeric antibody targeting CXCL1 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1524.
Abstract 1527: KY-CLC-mouse, a common light chain bi-specific antibody discovery platform
Authors: Peng Hao , Hao Feng , Wu Guojin , He Feng , Ning Jinying 
Published: April 2023

Abstract
Bi-specific antibody (BsAb) is an attractive therapeutic antibody format for treating different diseases. The matching of light chains is the central issue of BsAb manufacturing. Here we developed a Common Light Chain mouse named KY-CLC-mouse. KY-CLC-mouse has no λ light chain expression with an identical κ light chain. This identical κ light chain was modified from a light chain that frequently appeared in mice and paired with different heavy chains. This light chain had good solubility and stability. It was also easy to humanize without post-translation modifications within CDRs. And the CDRs were modified to decrease immunogenicity. The mouse was validated by developing different monoclonal antibodies against various antigens with an identical light chain and high affinity. Mouse monoclonal antibodies against PD1, LAG-3, PD-L1, CD47, cMET, and EGFR were generated from the hybridoma of KY-CLC-mouse, with KD ranging from 0.1nM to 10nM. Humanized antibodies were derived from the above antibodies with high affinity. BsAb binding two of the above targets were generated by Knob-into-Hole (KiH) technology, such as fully humanized PD1xLAG-3 and CD47xPD-L1 BsAb. PD1xLAG-3 BsAb was simultaneously bound to PD1 and LAG-3 with a blockade of binding to their ligands, PD-L1 and MHCII. CD47xPD-L1 BsAb was simultaneously bound to CD47 and PD-L1 and inhibited their binding to ligands, SIPRα and PD1. Both BsAbs had typical mouse PK with a half-life longer than seven days. The above results indicated that KY-CLC-mouse is an efficient platform for discovering therapeutic antibodies with a common light chain.
Citation Format: Hao Peng, Feng Hao, Guojin Wu, Feng He, Jinying Ning. KY-CLC-mouse, a common light chain bi-specific antibody discovery platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1527.
Abstract 1528: 6B5, an anti-human B7-H3 therapeutic antibody that enhances antibody-dependent cellular cytotoxicity and inhibits tumor growth in B7-H3-humanized mice
Authors: Chen Yunyun , Li Jiangmei , Guo Yanan , Hu Wenqi , Mao Ting , Hui Li , An W. Frank , Yang Yi , Li Feng 
Published: April 2023

Abstract
B7-H3 (CD276) is a type I transmembrane protein belonging to the B7 family of immune-regulatory ligands. Initially reported as a costimulatory signal of human T cells, increasing evidence suggests that it may also have coinhibitory function. TLT-2 has been identified as a potential cognate receptor for B7-H3, but others may exist. Overexpression of B7-H3 protein is found in a variety of human cancers, including lung adenocarcinomas, neuroblastomas, gliomas, and pancreatic tumors—and is associated with poor prognosis and survival. While B7-H3 can promote T cell activation and anti-tumor responses in the context of CD3 stimulation, its coinhibitory function inhibits T and NK cell activity in the tumor microenvironment. We generated 6B5, a fully human B7-H3 monoclonal antibody, from murine B7-H3 knock-out RenMab™ mice, which contain the full human immunoglobulin variable domain. 6B5 is cross-reactive with rodent and cynomolgus monkey B7-H3. It displays higher affinity for tumor cell lines than Enoblituzumab. 6B5 has no staining on normal human tissues. In vitro antibody-dependent cellular cytotoxicity (ADCC) against H520 squamous cell carcinoma cells was potentiated by 6B5 relative to Enoblituzumab and, critically, did not exhibit the hook effect at high dosage. In vivo efficacy of 6B5 in humanized B7-H3 mice bearing murine EL4 lymphomas was comparable to Enoblituzumab. ADCC enhancement in vivo was comparable to afucosylation or five-point mutations. Epitope mapping revealed non-overlapping B7-H3 binding epitopes of 6B5 and Enoblituzumab. Taken together, these data suggest that 6B5 is a promising therapeutic anti-human B7-H3 IgG monoclonal antibody that may find clinical application in a range of cancers, including current refractory types.
Citation Format: Yunyun Chen, Jiangmei Li, Yanan Guo, Wenqi Hu, Ting Mao, Li Hui, W. Frank An, Yi Yang, Feng Li. 6B5, an anti-human B7-H3 therapeutic antibody that enhances antibody-dependent cellular cytotoxicity and inhibits tumor growth in B7-H3-humanized mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1528.
Abstract 1722: KRAS, BRAF, BRCA1 and EGFR mutation-specific panels using hydrogel-based 3D in vitro tumor models
Authors: Xue Bin , Schüler Julia , Harrod Christopher , Bomya Zoji , Hribar Kolin C. 
Published: April 2023

Abstract
Mutation-targeting therapies have become a transformative technology and in many ways a new paradigm for cancer treatment for patients. The early development of Erlotinib for non-small cell lung cancer paved the way for EGFR treatment, irrespective of tumor indication subtype. And the more recent launch of Sotorasib for KRASG12C mutation has marked a turning point for the once undruggable mutation. The advent of gene specific-treatments requires a reconfiguration of preclinical models which more effectively represent the said mutation in populations of diverse backgrounds and tumor indications. 3D models which have the ability to recreate the key hallmarks of cancer - such as growth, invasion, immune infiltration and suppression, stromal transformation, drug diffusion, as well as gene mutational signatures - are of exceptional interest to drive rapid and scalable compound efficacy screening. Here, we developed four 3D in vitro tumor panels carrying mutations in one of the following genes - KRAS, EGFR, BRCA1, and BRAF - as well as wildtype models for comparison. The tumors were grown in a hydrogel matrix in 96-well plates with stromal fibroblasts and screened with the standard of care (e.g. Sotorasib for KRASG12C, Erlotinib for EGFRmut, the PARP inhibitor Olaparib for BRCAmut, and Vemurafenib for BRAFV600E) and other known therapeutic compounds that target their respective mutations. The utility of a 3D hydrogel matrix and fibroblasts in the panels’ models were key in recreating the stromal compartment of the tumor microenvironment. Endpoints were determined within four days of treatment, including tumor size reduction and tumor killing, via high-content image analysis. The Panels’ robustness as demonstrated by the reproducible results in independent experiments suggests they can be utilized at in vitro pharmacology stages and earlier in Hit and Lead finding screens.
Citation Format: Bin Xue, Julia Schüler, Christopher Harrod, Zoji Bomya, Kolin C. Hribar. KRAS, BRAF, BRCA1 and EGFR mutation-specific panels using hydrogel-based 3D in vitro tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1722.
Abstract 189: Developing a patient-derived organoid biobank, suitable for large scale drug screenings
Authors: Fielmich Lars-Eric , Buijs Annemarie , Mori Daniele , Viergever Bas , Draoui Nihed , Schepers Anna , Costa e Silva Mariana M. , Scholtus Mathijs , Mahmoudi Tokameh , Zuiverloon Tahlita , Derksen Merel , Gavine Paul , Boj Sylvia F. , Meijer Richard , Kranenburg Onno , Arts Janine , Vries Robert 
Published: April 2023

Abstract
Conventional models for preclinical drug screening offer poor predictive value for patient response, causing high attrition rates of new agents in the clinic. HUB’s proprietary Patient-Derived Organoid (PDO) Technology enables long-term expansion of primary patient material to generate ‘mini organs in a dish’ that can be used as patient avatars, thus bringing every “patient in the lab®”. We present the world’s first NMIBC PDO biobank comprising 50 PDO models from transurethral resection of bladder (TURB) biopsies collected at three hospitals. Clinical and pathological characterization of the PDOs confirmed the representation in the biobank of a range of tumor stages and differentiation grades, as well as patient treatment and follow-up. The genomic analyses of PDOs revealed mutations in known BC driver genes and genomic instability, a hallmark of cancer. Finally, transcriptomic analyses confirmed gene expression profiles familiar to BC and characterized gene fusions. Next, we successfully screened the biobank on a panel of two reference compounds for the treatment of bladder cancer and seven candidate drugs, indicating potential new leads for further development of some of the compounds. The work presented here shows the feasibility of building PDO biobanks representing a specific patient population, suitable for improving the drug development pipeline for the next generation of cancer drugs.
Citation Format: Lars-Eric Fielmich, Annemarie Buijs, Daniele Mori, Bas Viergever, Nihed Draoui, Anna Schepers, Mariana M. Costa e Silva, Mathijs Scholtus, Tokameh Mahmoudi, Tahlita Zuiverloon, Merel Derksen, Paul Gavine, Sylvia F. Boj, Richard Meijer, Onno Kranenburg, Janine Arts, Robert Vries. Developing a patient-derived organoid biobank, suitable for large scale drug screenings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 189.
Abstract 1900: Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609)
Authors: Urbanic James J. , Shaw Edward G. , Takita Cristiane , Wright Jean L. , Ip Edward H. , Lu Lingyi , Baez-Diaz Luis , Brown Doris R. , Strasser Jon , Baglan Kathy , Palmer Mark , Thakrar Anu , Curtis Amarinthia E. , Lesser Glenn , Hu Jennifer J. 
Published: April 2023

Abstract
Background: Adjuvant radiotherapy (RT) following surgery significantly improves breast cancer survival. However, some patients, particularly minorities, develop early adverse skin reactions (EASRs) or skin toxicities that negatively impact the quality of life (QOL). We assess RT-related EASRs and QOL using clinician-reported outcomes (CROs) and patient-reported outcomes (PROs) in a large multi-racial/ethnic breast cancer population.
Methods: This prospective study recruited 1,000 breast cancer patients undergoing RT through the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base between 2011 and 2013. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria for CROs and Skindex-16 (SD-16) for PROs.
Results: This study included 405 non-Hispanic whites (NHW), 277 black/African Americans (AA), 241 HW, 62 Asian/Pacific Islanders (ASPI), and 15 others. About 42% and 15% of patients developed RT-induced ONS grade 3+ and 4+ skin toxicities, respectively. RT-induced EASRs differed significantly by race/ethnicity at mid-RT, 1-month, and 2-month post-RT, but not at the end of RT. Total SD-16 scores differ by race/ethnicity at pre-RT, 1-month, and 6-month post-RT, but not at the end of RT. Overall, PROs have a moderate but significant correlation with CROs at the end of RT.
Conclusion: RT-induced EASRs differed significantly by race/ethnicity. There was a moderate but significant correlation between PROs and CROs. However, PROs delineated a broader spectrum in capturing the impact of RT on patients’ QOL, which highlights the importance of integrating PROs in accessing RT-induced EASRs, particularly in minorities with worse RT-induced EASRs.
Trial Registration: NCT01407770 (09/02/2011)
Citation Format: James J. Urbanic, Edward G. Shaw, Cristiane Takita, Jean L. Wright, Edward H. Ip, Lingyi Lu, Luis Baez-Diaz, Doris R. Brown, Jon Strasser, Kathy Baglan, Mark Palmer, Anu Thakrar, Amarinthia E. Curtis, Glenn Lesser, Jennifer J. Hu. Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1900.
Abstract 2072: Computational modeling of metabolic variations in tumor microenvironment
Authors: Guo Tingbo , Zhu Haiqi , Wang Xiao , Wang Jia , Zhou Xinyu , Wei Yuhui , Dang Pengtao , Zhang Chi , Cao Sha 
Published: April 2023

Abstract
Dysregulation of metabolic pathways is a hallmark of cancer. Despite a plethora of knowledge on the core components of metabolic pathways we have gained, there are still major gaps in our understanding of the integrated behavior and metabolic heterogeneity of cells in the context of their microenvironment. Essentially, metabolic behavior can be determined by different factors and vary dramatically from cell to cell due to their high plasticity, driven by the need to cope with various dynamic metabolic requirements. Large amount of single-cell, spatial or tissue multi-omics data obtained from disease tissue has been proven to be endowed with the potential to deliver information on a cell functioning state and its underlying phenotypic switches.We have recently developed single-cell flux estimation analysis (scFEA) to predict sample-wise metabolic fluxome by using single-cell or bulk transcriptomics data. We further developed a web portal scFLUX.org, empowered by our scFEA method, expanding the analytic ability to both human and mouse metabolic networks. We also developed a probabilistic model named Michaelis-Menten-based Flux Estimation Analysis (mmFEA) for statistical inference of flux changes between conditions or cell types based on matched or unmatched gene expression data, metabolomics data, and partially observed kinetic parameters. These methods provide the following unmet capabilities to study metabolic variations in cancer: (1) reconstruction of cell or tissue specific and subcellular-resolution metabolic network, (2) estimation of cell-/sample-wise metabolic flux by considering metabolic imbalance, metabolic exchange between cells, and shifted redox, pH and energy balance in disease microenvironment, (3) a systematic evaluation of functional impact of variations in gene expression, genetic/epigenetic variations, metabolite availability and network structure on the context specific metabolic network and flux, (4) estimate the impact of each gene on flux by using a first-order derivative, (5) perturbation analysis to predict how alterations in enzymes or metabolites may affect the metabolic flux, and (6) identification of the samples and sub-network of a distinct metabolic shift.The methods were validated on matched scRNA-seq, metabolomics and fluxomics data. We demonstrated the function of this computational framework on pan-cancer transcriptomics and proteomics data, and single cell and spatial transcriptomics data.
Citation Format: Tingbo Guo, Haiqi Zhu, Xiao Wang, Jia Wang, Xinyu Zhou, Yuhui Wei, Pengtao Dang, Chi Zhang, Sha Cao. Computational modeling of metabolic variations in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2072.