bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 263: Automating next generation sequencing workflows for custom hyb panels: high quality library preparation and target enrichment on the Biomek NGeniuS System
Authors: Roseman Nicole , Tucker Laura , Criscuolo Francesco , Lewis Lynette , Liu Li , Buit Tyler , Mandair Jasmeen , Smith Zachary , Cortes Calvin 
Published: April 2023

Abstract
This study investigates a custom 2Mb xGen Hyb panel designed against mutated gene targets implicated in several cancers using an end-to-end assay workflow on the Biomek NGeniuS platform. Automation in laboratories is advantageous to generate reproducible next generation sequencing (NGS) sample libraries, however, assay automation differs from instrument vendor to vendor but also from lab to lab with different deck layouts of the same instrument. These differences require a significant amount of optimization to design the workflow and begin generating NGS libraries. In addition to this optimization, some research, e.g., cancer research utilizes low input and/or degraded samples such as cfDNA from plasma or FFPE biopsies. Integrated DNA Technologies (IDT) and Beckman Coulter - Life Sciences together provide a walk away NGS automation solution for these research samples directly upon instrument installation with no optimization required by combining Beckman Coulter’s Biomek NGeniuS with IDT’s xGen cfDNA & FFPE DNA Library Prep kit and xGen Hybridization Capture. This trio provides a solution for laboratories to minimize technician hands-on time, error reduction, and rework while improving flexibility. IDT’s xGen cfDNA & FFPE DNA Library Prep kit utilizes novel chemistry to maximize sample input conversion, suppress adapter-dimer formation, and facilitate consensus analysis. IDT’s xGen Hybridization Capture products maintain high library diversity, obtain high on-target, and provide consistent and uniform sequencing coverage regardless of panel size. We demonstrate performance of this complete workflow with a custom 2Mb xGen Hyb panel yielding high library complexity, high on-target coverage, and capture uniformity. The combination of IDT’s xGen library preparation solutions on the NGeniuS Biomek platform provides a reliable and consistent solution that can be instantly downloaded from the portal straight to analysis of precious low input and degraded samples.
Citation Format: Nicole Roseman, Laura Tucker, Francesco Criscuolo, Lynette Lewis, Li Liu, Tyler Buit, Jasmeen Mandair, Zachary Smith, Calvin Cortes. Automating next generation sequencing workflows for custom hyb panels: high quality library preparation and target enrichment on the Biomek NGeniuS System [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 263.
Abstract 2645: A high-throughput platform for targets screening by membrane protein library
Authors: Li dan , Xiong Junyi , Ning Jinying , Hao Feng 
Published: April 2023

Abstract
The specificity of antibodies, CAR-T cells and other biologic therapeutics to their binding targets is important to evaluate drug quality. The non-specific binding may lead serious toxic side effects. Therefore, specificity detection is an important step in the evaluation process of drug development. At present, the non-specific binding of antibody drugs is often verified only after serious adverse reactions founding in clinical trials, which may result in drug safety accidents and the abandonment of previous studies. To address the need for antibody target deconvolution and receptor identification, we developed a novel approach “AB5000”. AB5000 is an excellent solution for antibody specificity screening which enable early off-target screening and can de-risk the antibody drug development program. The AB5000 makes use of the full coverage membrane protein, representing over 5465 unique human membrane proteins including receptors, transporters, enzymes, miscellaneous and other membrane protein. Gene vector was transfected into target cells. Each membrane protein introduces a C-terminal epitope tag, allowing confirmation of protein expression and cellular location. To provide the highest level of sensitivity, we use luciferase reporter cell line system which is more rapid, simple and highly sensitive than flow cytometry or other binding assays. The AB5000 has widely application in testing the specificity of antibodies, deconvolution of orphan antibodies and ligands, detection of CAR-T proteins. The AB5000 represents a rapid, comprehensive, and highly sensitive platform for identifying the membrane protein targets of a wide variety of antibodies, protein ligands, and functional interactions. It is a promising powerful tool for biotherapeutic modalities development.
Citation Format: dan Li, Junyi Xiong, Jinying Ning, Feng Hao. A high-throughput platform for targets screening by membrane protein library [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 2645.
Abstract 268: Antitumor CD4+ T cells reprogram tumor metabolism to drive progressive tumor regression
Authors: Brandle Caitlin , Okoko Ogacheko D. , Gazi Md Yeashin , Wang Xin , Kehinde-Ige Mercy , Shi Huidong , Zhou Gang 
Published: April 2023

Abstract
Adoptive cell therapy has revolutionized the landscape of cancer immunotherapy, exhibiting unprecedented success in treating various types of cancer. Substantial investigative efforts have been devoted to gaining a deeper understanding of the ways in which adoptively transferred T cells eliminate tumors and to discovering strategies that enhance T cell functionality in the tumor microenvironment. We have established an experimental mouse model in which adoptive transfer of tumor-specific CD4+ T cells leads to eradication of established tumors. Using this model, we previously reported on the profound disruption of tumor metabolism induced by adoptive T cell therapy. However, the detailed mechanisms that enable tumor-reactive CD4+ T cells to alter tumor metabolism remain largely undefined. In the current study, we aimed to identify the key metabolic enzymes and pathways targeted by antitumor CD4+ T cells that lead to progressive tumor regression. Utilizing next-generation sequencing strategies, including bulk and single-cell RNA sequencing, we examined the metabolic changes cancer cells undergo in response to treatment, and the immune cell compositions in the tumor microenvironment. Additionally, we performed an in vivo CRISPR knockout screen to identify the metabolic genes that either sensitize tumor cells to adoptive cell therapy or contribute to tumor resistance. Results from our study may also illuminate potential targets in cancer metabolism that can be exploited using small-molecule inhibitors when adoptive cell therapy is not feasible.
Citation Format: Caitlin Brandle, Ogacheko D. Okoko, Md Yeashin Gazi, Xin Wang, Mercy Kehinde-Ige, Huidong Shi, Gang Zhou. Antitumor CD4+ T cells reprogram tumor metabolism to drive progressive tumor regression [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 268.
Abstract 2708: Nano-immunotherapy: efficacy of nanoconjugate QN-247 in a triple negative breast cancer (TNBC) mouse model
Authors: Arshad Tariq , Fait Stephen , Gammon Guy , Hertig Andrew , Sarno Mark J. 
Published: April 2023

Abstract
Introduction and Purpose: Triple-negative breast cancer (TNBC) accounts for 12% of breast cancers (BC) in the US and 15% worldwide. It lacks expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared to other types of BC, it is more aggressive and has higher risks of recurrence. In the metastatic setting, survival outcomes are much worse than other BC subtypes, with a 5-years survival rate of 8-16%. There is an urgent need to develop better treatment options for TNBC patients. We have developed a novel therapeutic, QN-247, by conjugating an anti-proliferative DNA aptamer to gold nanospheres. The aptamer-gold nanosphere construct shows increased half-life and cytotoxic effects relative to the aptamer alone. QN-247 inhibits nucleolin, a key regulatory protein overexpressed in triple-negative breast cancer (TNBC) cells, thereby reducing their proliferation.
Description of Experimental Procedures: A subcutaneous, TNBC model (MDA-MB-231 xenograft) in nude mice was used in this efficacy study. When tumor volumes reached sufficient size (85 mm3), QN-247 test compound, aptamer alone, and vehicle control was administered daily (QD) at 1 mg/kg via intraperitoneal injection for 12 days. Tumor volumes and body weights were measured regularly through day 20. Nine animals were included in each treatment group. Summary of DataA statistically significant reduction in mean tumor volumes of QN-247 treated mice compared to the vehicle control and aptamer alone was observed. Tolerability of the QN-247 treatment was excellent with no evidence of toxicity.
Statement of Conclusions: This study demonstrates that QN-247 exerts a powerful anti-tumor effect. Additional preclinical mouse xenograft tumor models will be treated with QN-247 to study its effect on other cancers.
Citation Format: Tariq Arshad, Stephen Fait, Guy Gammon, Andrew Hertig, Mark J. Sarno. Nano-immunotherapy: efficacy of nanoconjugate QN-247 in a triple negative breast cancer (TNBC) mouse model [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 2708.
Abstract 2717: A potent and highly tumor-selective KRAS inactivator for tumor targeting
Authors: Liu Shihui , Zuo Zehua , Liu Jie 
Published: April 2023

Abstract
Cancer driver mutations in the RAS-RAF-MEK-ERK pathway occur in 46% of all human cancers. This has inspired the successful development of many small molecule inhibitors of BRAF and MEK. However, development of RAS small molecule inhibitors has not been successful in large part due to the lack of a sufficiently large and deep hydrophobic pocket in RAS proteins to allow for small molecule binding. Notably, in this regard, many bacterial pathogens have evolved potent protein toxins to disrupt the RAS-RAF-MEK-ERK pathway. Fortunately, these naturally designed potent toxins, such as anthrax toxin, Fortunately, these potent, naturally designed toxins, such as anthrax toxin and DUF5, can be structurally modified to achieve high tumor specificity. DUF5 (amino acids Glu3581-Gln4089) is a toxin effector domain of MARTX (a multifunctional-autoprocessing repeats-in-toxin) from Vibrio vulnificus. DUF5 was recently identified to be a specific and potent endopeptidase that cleaves and inactivates RAS. To address the above critical unmet medical needs, in this work, we have generated an anthrax toxin/DUF5-based, highly tumor-selective RAS inactivator and evaluated its anti-tumor activity in a variety of tumor models. This tumor-selective RAS inactivator can specifically bind to the major anthrax toxin receptor CMG2 on tumor cells and tumor stromal cells, and strictly relies on the simultaneous presence of two distinct tumor-associated proteases, MMPs and urokinase, to gain entry into tumor cells and tumor stromal cells to proteolytically inactivate RAS signaling, achieving potent selective targeting. Our data show that our tumor-selective RAS inactivator displays potent cytotoxicity to cancer cells whose survival depends on oncogenic RAS signaling. Our engineered toxin displayed potent in vivo antitumor activity to a range of tumors with oncogenic RAS mutations in syngeneic and human xenograft mouse tumor models. Therefore, we have developed a tumor-selective, safe, and highly potent RAS inactivator that has high potential for targeting tumors with oncogenic RAS mutations.
Citation Format: Shihui Liu, Zehua Zuo, Jie Liu. A potent and highly tumor-selective KRAS inactivator for tumor targeting [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 2717.
Abstract 2748: Identifying therapeutic mechanism of action and new potential patient populations using PRISM
Authors: Nguyen Ellen , Nair Shiker , Davis John , Masciotti Antonella , Mochi Connor , Finn John , Ponsi Cole , Engel Brienne , Mapa Claudine , Kocak Mustafa , Ronan Melissa , Rees Matthew G. , Roth Jennifer A. 
Published: April 2023

Abstract
Our multiplexed cell viability platform, PRISM (profiling relative inhibition simultaneously in mixtures), enables screening of potential cancer therapeutics at an unprecedented scale. We routinely assess the effects of perturbations against more than 900 cancer cell lines concurrently through the use of unique oligonucleotide barcodes stably transduced into individual cancer cell lines. Following barcode transduction, individual cell lines are pooled together in groups of 20-25 based on growth rate similarity, then thawed into 384-well assay-ready plates containing compounds of interest. After 5 days of growth, isolated mRNA is used to detect transcribed barcode abundance of each individual cancer cell line to measure relative viability. We leverage the baseline cellular features (e.g., gene expression, cell lineage, mutation, copy number, metabolomics, proteomics, genome-wide RNAi and CRISPR dependencies) of each cell line to interpret viability profiles, enabling identification of drivers of differential sensitivity and potential biomarkers of compound response. Critically, the scale and throughput of PRISM has enabled the generation of large, publicly available datasets and the rapid characterization of emerging therapeutic targets and classes (e.g., isoform-selective RAS inhibitors and degraders). Although the read-out of PRISM is relative cell line viability, the platform can be used to answer a multitude of scientific questions. For example, PRISM data can be used to identify potential patient populations who would most benefit from treatment with a specific compound, uncover unexpected off-target toxicities, and validate mechanism of action hypotheses on a more holistic scale. Ultimately, PRISM offers a large-scale and comprehensive platform for the testing and validation of anti-cancer compounds to aid in the search for new oncology therapeutics.
Citation Format: Ellen Nguyen, Shiker Nair, John Davis, Antonella Masciotti, Connor Mochi, John Finn, Cole Ponsi, Brienne Engel, Claudine Mapa, Mustafa Kocak, Melissa Ronan, Matthew G. Rees, Jennifer A. Roth. Identifying therapeutic mechanism of action and new potential patient populations using PRISM [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 2748.
Abstract 275: Harnessing chemerin signaling as a novel therapeutic vulnerability in ccRCC
Authors: Wang Dazhi , Welford Scott , Brugarolas James , Tan Sze K. 
Published: April 2023

Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, accounting for 70-80% of the cases. While surgical resection of early-stage tumors remains the standard care for patients, advanced ccRCC, metastatic or recurrent, portends a 5-year survival rate of only 12%, primarily due to insensitivity toward conventional chemotherapy. ccRCC is identifiable histologically by its dramatic lipid storage phenotype, similar to adipocytes; yet the role of lipid metabolism in ccRCC is poorly understood. One of the well-established risk factors for ccRCC is obesity and given that adipose tissue is known to produce a variety of pro-adipogenic signaling molecules (called adipokines), we hypothesized that adipokine signaling might be involved in the etiology of ccRCC. We recently identified a pro-tumorigenic adipokine protein, chemerin (RARRES2), that is positively correlated with tumor aggressiveness. Suppression of chemerin via either monoclonal antibody or siRNA led to reduction in lipid storage and significant tumor growth impairment in both in vitro and in vivo models by inducing ferroptosis. We next investigated the signaling mechanisms of chemerin and have found that chemerin drives downstream cellular activities and lipid deposition through either of the two receptors, GPR1 and CMKRL1. We further demonstrated that chemerin signals to both receptors to drive the expression adipose triglyceride lipase (ATGL) that frees up fatty acid from lipid depositions. In addition, Chemerin/CMKLR1 signaling axis further drives the activation of SREBP-mediated lipogenesis pathway. By using a small molecule antagonist specific for CMKRL1, α-NETA, we could suppress ccRCC tumor growth by inhibiting intracellular lipid droplet formation both in vitro and in vivo through the activation of ATGL-mediated lipolysis pathway and suppression of SREBP-mediated lipogenesis pathway. We have therefore shown the possibility of targeting Chemerin/CMKLR1 axis both genetically and pharmacologically to suppress the growth of ccRCC by increasing ferroptosis. Overall, our studies have identified chemerin/CMKLR1 axis as a promising therapeutic target that weakens ccRCC by modulating its lipid metabolic profiles and validated such vulnerability by using a more clinically relevant PDX orthotopic model. Further mechanistic investigations revealed overlapping yet distinct pathways downstream of chemerin that could potentially yield combinational strategies to treat ccRCC patients.
Citation Format: Dazhi Wang, Scott Welford, James Brugarolas, Sze K. Tan. Harnessing chemerin signaling as a novel therapeutic vulnerability in ccRCC [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 275.
Abstract 2784: JW-1-283 inhibits melanoma tumor growth via the stabilization of p53 pathway
Authors: Xie Yang , Hartman Kelli , Wu Zhongzhi , Li Wei 
Published: April 2023

Abstract
Melanoma is the most lethal skin cancer, with the increasing incidence in the past decade. Despite the significant advancements in immune therapy and targeted therapy, the overall prognosis for metastatic melanoma remains unsatisfactory. TP53 is a tumor suppressor, but its wildtype is inactivated in about 90% of melanoma. Since activated p53 can promote cancer cell apoptosis and thus effectively inhibit tumor growth and tumor metastasis, reactivation of p53 is considered a promising strategy for cancer therapy. Herein, we report a recently developed small molecule compound, JW-1-283, targeting the interactions between MDM2 E3 ubiquitin-protein ligase and p53 protein. In vitro, JW-1-283 showed potent cytotoxicity against A375 melanoma cell line (IC50 2.2±0.3 μM) which has wildtype p53, but its potency is substantially reduced in two other melanoma cell lines with either p53 mutation (M14) or p53 null (RPMI-7951) status. Treatment with JW-1-283 significantly dose-dependently reduced the stemness in A375 melanoma cells, as indicated by low numbers of colony formation, impaired tumor sphere formation abilities, and inhibition of cancer cell migration. Mechanistically, JW-1-283 disrupts the p53-MDM2 interaction, prevents p53 and MDM2 degradation in the existence of cycloheximide, and induces p38 and p53 phosphorylation in the apoptotic pathway. Genetic knockdown of p38 by siRNA further confirmed that the stabilized p53 could be subsequently phosphorylated by p38, leading to induced apoptosis as well as S phase cell cycle arrest. In vivo, when A375 tumors grown in NSG mice were treated with 7.5 mg/kg of JW-1-283 intraperitoneally every other day for a consecutive of 16 days, significant inhibition of tumor growth was observed, along with decreased tumor cell proliferation, tumor angiogenesis, and enhanced tumor cell apoptosis. In summary, this work provides the initial proof-of-concept of developing the JW-1-283 scaffold as a potential strategy for advanced melanoma, which inhibits tumor growth by activating the p53 signaling pathway.
Citation Format: Yang Xie, Kelli Hartman, Zhongzhi Wu, Wei Li. JW-1-283 inhibits melanoma tumor growth via the stabilization of p53 pathway [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 2784.
Abstract 2787: Targeting Nrf2 signaling pathway by Keap1-mediated degradation in acquired gemcitabine resistant pancreatic cancer cells
Authors: Lee Sang Kook , Bae Eun Seo , Byun Woong Sub , Ock Chae Won , Kim Won Kyung , Park Hyen Joo 
Published: April 2023

Abstract
Redox status is a main indicator of cancer cell adaptation to chemotherapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the crucial regulators of redox condition and can affected to drug resistance through redox imbalance. The incidence and mortality of pancreatic cancer (PC) have been gradually increasing globally. Although the first line treatment with anticancer agents improves the disease status, acquired drug resistance is major huddles in the treatment failure. Targeting Nrf2 has been suggested as a promising therapeutic approach for the overcoming drug resistance. In the present study, Nrf2 was found to be upregulated in tumor tissues and gemcitabine-resistant PC cells. In addition, Nrf2 knockdown exhibited to recover gemcitabine sensitivity in the gemcitabine-resistant PC cells. To further validate the role of Nrf2 in gemcitabine-resistant cells, the effects of Nrf2 inhibitor, periplocin, were employed. Periplocin exerted the antiproliferative activities by regulating Nrf2 suppression which leads to the increase of reactive oxygen species generation. Furthermore, the downregulation of Nrf2 by periplocin was correlated to Keap1-mediated protein degradation. Docking simulation also confirmed the binding interaction of Nrf2 and Keap1 by periplocin. These findings suggest that targeting the Nrf2 might be a therapeutic strategy for overcoming acquired gemcitabine PC. Keywords: Pancreatic cancer cell, Gemcitabine resistance, Nuclear factor erythroid-2-related factor 2 (Nrf2), Kelch Like ECH Associated Protein 1 (Keap1), protein degradation
Acknowledgements: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A1A01063346).
Citation Format: Sang Kook Lee, Eun Seo Bae, Woong Sub Byun, Chae Won Ock, Won Kyung Kim, Hyen Joo Park. Targeting Nrf2 signaling pathway by Keap1-mediated degradation in acquired gemcitabine resistant pancreatic cancer cells [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 2787.