tbuckley/cabot-search huggingface dataset:
Abstract 2348: Unveiling dichotomies between liver cancer and adjacent normal tissues in Wilson’s disease model
Authors: Ritam Adhikari, Chiranjeev Dash, Rabindra Roy
Journal: Cancer Research (2025)

Abstract Objective: The Long-Evans Cinnamon (LEC) rat is a model for Wilson’s disease (WD) and is associated with chronic inflammation and hepatocellular carcinoma. This study performed a gene expression microarray using total RNA extracted from LEC liver tissue at 84 weeks late chronic hepatitis, tumor-adjacent normal (84 weeks N), and 84 weeks tumor (84 weeks T). Understanding the difference between a tumor and adjacent normal within the same animal can be very intriguing as both are in the same environment, and one becomes and sustains a tumor status, but the other still maintains its normalcy. Experiment: Total RNA was extracted from liver tissue of three LEC rats at 84 weeks N and 84 weeks T and hybridized to the Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix Inc, Santa Clara). GeneGO Pathways software was used to analyze the differentially expressed genes using a cutoff of P-value ≤0.05 and FDR &amp;lt;0.25% and a fold change +/- 2. A volcano plot was generated to visualize significant gene change expression between 84 weeks N vs 84 weeks T. Agglomerative Hierarchical and K-means clustering were used to group similarly expressed genes into clusters and build a hierarchy of clusters. Each cluster obtained from K-means clustering analysis within the up or down-regulated groups were checked for pathway analysis to understand the interplay between biological pathways by QIAGEN Ingenuity® Pathway Analysis (QIAGEN IPA). In addition − log(p) &amp;gt; 1.3, a z-score cut-off͕ ≥ 2 for activation and a z-score cutoff ≤ -2 for inhibition was used to call a pathway activation, and inhibition is significant. Result: The seven most significant pathways that were activated are the S100 Family Signaling Pathway, Extracellular Matrix Organization, Response to Elevated platelet cytosolic Ca2+, HMGB1 Signaling, Sertoli Cell-Sertoli Cell Junction Signaling, Cachexia Sunaina Pathway, and Nicotine Degradation II. Except for Nicotine Degradation II pathway, all other pathways are shown activated in non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) patients previously but shown in the WD model for the first itme. The Nicotine Degradation II pathway is shown to be activated in the NAFLD patient before. Conclusion: To our knowledge, this is the first report where gene expression analysis was done between tumor-adjacent normal and tumor within the same animal in the WD model. Our results identified multiple pathways in the model that could lead us to new diagnostics and therapeutic targets when validated. Citation Format: Ritam Adhikari, Chiranjeev Dash, Rabindra Roy. Unveiling dichotomies between liver cancer and adjacent normal tissues in Wilson’s disease model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2348.
Abstract 2667: Full spectrum profiling flow cytometry to study cancer-associated fibroblast heterogeneity
Authors: Kevin Muñoz Forti, Marta Storl-Desmond, Daniel Martínez, Sayana Issac, Shan Cao, Simon Schwörer
Journal: Cancer Research (2025)

It is now well appreciated that tumor growth depends on the tumor microenvironment (TME) comprising various non-malignant stromal cell types, including cancer-associated fibroblasts (CAFs). Cancer-associated fibroblasts (CAFs) are responsible for secreting the extracellular matrix (ECM) prominent in certain solid tumors such as pancreatic adenocarcinoma (PDAC). Despite our increasing knowledge of CAFs, therapeutic targeting of CAFs is currently not a feasible strategy, as CAFs are highly heterogeneous and extremely plastic, with each CAF population able to adopt both tumor-promoting and -restraining functions. We hypothesize that the plasticity and functional heterogeneity of CAFs can be explained by their flexible metabolism in response to environmental cues and the existence of discrete metabolic states within CAF subpopulations. While metabolic states can be predicted from single-cell transcriptomic data, this does not provide information on metabolic activity and potential, nor does it allow perturbations required for validation. Scalable and tractable methods to assess metabolic activity and CAF heterogeneity in parallel at the single cell level are needed to distinguish numerous existing CAF states do not exist. To address this need, in this work, we developed a strategy to study CAF metabolic activity and phenotypic heterogeneity at the single-cell level. We designed and optimized a 25-plex immunophenotyping panel of CAF and fibroblast markers that can be combined with numerous metabolic probes via Full Spectrum Profiling (FSP) flow cytometry. In addition, we compiled an analysis pipeline to facilitate the analysis of high-dimensional flow cytometry data. Using established 2D and 3D mono- and co-culture assays, we demonstrate the potential of our panel to be multiplexed with chemical probes for cell proliferation, lipid content, lipid uptake, fatty acid oxidation, glucose uptake, cholesterol content, hypoxia, or mitochondrial potential. Deploying our strategy in a KPC organoid-derived murine model of PDAC, we observed subpopulations of CAFs with differing metabolic potentials that are consistent with our predictions from transcriptomic metabolic modeling. With the high throughput and single-cell nature of FSP, our strategy represents a novel and modular tool for studying CAF phenotypic and metabolic heterogeneity. Citation Format: Kevin Muñoz Forti, Marta Storl-Desmond, Daniel Martínez, Sayana Issac, Shan Cao, Simon Schwörer. Full spectrum profiling flow cytometry to study cancer-associated fibroblast heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2667.
Blood pressure reduction and all-cause dementia in people with uncontrolled hypertension: an open-label, blinded-endpoint, cluster-randomized trial
Authors: Jiang He, Chuansheng Zhao, Shanshan Zhong, Nanxiang Ouyang, Guozhe Sun, Lixia Qiao, Ruihai Yang, Chunxia Zhao, Huayan Liu, Weiyu Teng, Xu Liu, Chang Wang, Songyue Liu, Chung-Shiuan Chen, Jeff D Williamson, Yingxian Sun
Journal: Nature Medicine (2025)
Abstract 4855: Metabolic and functional dynamics of T cell activation: bioluminescent assays for immune monitoring and modulation
Authors: Kim Haupt, Kayla Sylvester, Tony Lauer, Natasha Karassina, Jolanta Vidugiriene
Journal: Cancer Research (2025)

Abstract Advancing our understanding of T cell activation and its regulatory pathways is critical for developing effective cancer immunotherapies. This study characterizes T cell health and functional dynamics under diverse activation conditions, highlighting key molecular mechanisms that influence immune responses within the tumor microenvironment. We investigate mTOR and AMPK signaling pathways, as well as the metabolic balance between glycolysis and oxidative phosphorylation, which are integral to T cell function in immunotherapeutic contexts. Using selective inhibitors, we identify modulators that regulate cytokine secretion and T cell metabolic states, revealing media composition as a significant variable affecting immune function. Our methodology leverages a suite of bioluminescent Lumit and Metabolite-Glo assays for sensitive quantification of cytokines and metabolites, enabling precise, non-invasive monitoring while preserving cell integrity. This approach is scalable and adaptable for analyzing diverse activation conditions and high-throughput screening applications. Additionally, our findings correlate these metabolic and functional profiles with cell surface markers assessed by traditional methods, providing a comprehensive framework for immune monitoring. These insights underscore the importance of metabolic and signaling interplay in T cell activation, offering a robust platform for studying immune dynamics and uncovering novel immunomodulatory targets. Our work supports the development of precision strategies to modulate T cell activity and optimize immune responses in cancer therapy. Citation Format: Kim Haupt, Kayla Sylvester, Tony Lauer, Natasha Karassina, Jolanta Vidugiriene. Metabolic and functional dynamics of T cell activation: bioluminescent assays for immune monitoring and modulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4855.
Abstract 2657: Impact of STRN4 knockdown on TNBC migration and survival
Authors: Caroline Rinderle, Jordan Wright, Olivia Mayer, Bruce Bunnell
Journal: Cancer Research (2025)

Abstract Introduction: Striatin 4 (STRN4) is a member of the STRIPAK protein complex, including protein phosphatase 2A (PP2A) and other interacting protein kinases. These proteins interact to play a role in a range of signaling cascades, including MAPK and Hippo signaling. STRN4 has been shown to play a role in several cancer types, as it is a negative prognostic marker of renal, ovarian, and liver cancers. It has also been shown to contribute to liver cancer migration, and its knockdown diminishes pancreatic cell migration and proliferation. However, although STRN4 is associated with a trend of decreased overall survival in breast cancer patients, it is relatively understudied in the context of the disease. Experimental Methods: To better understand the role of STRN4 in breast cancer survival and related processes, an siRNA-mediated knockdown of STRN4 was performed in a patient-derived xenograft-derived triple-negative breast cancer (TNBC) cell line: TU-BcX-4IC (4IC). Using three pre-validated siRNAs (A, B, and C) specific to STRN4 paired with a polymer-based transfection reagent, we knocked down the expression of STRN4. We then monitored the effects of the knockdown on 4IC cell migration and invasion, proliferation, metabolism, and gene expression via Boyden chamber migration assays, colony-forming unit assays, XTT assays, and qRT-PCR, respectively. Results: STRN4 gene expression was significantly diminished 24 hours post-transfection, which was maintained 72 hours post-transfection. However, there was no significant difference in the migration of 4IC cells through a Boyden chamber, and only minor alterations in the expression of epithelial-to-mesenchymal transition markers E-cadherin, Vimentin, CD24, and Jagged1 24, 48 and 72 hours post-knockdown, despite significantly lower expression of STRN4 at these timepoints. However, there was substantially lower colony-forming unit potential and metabolic output in the C siRNA group despite there being no difference between the A and B siRNA groups. Conclusions: Overall, STRN4 knockdown has minimal effects on TNBC cell migration and gene expression 24, 48, and 72 hours after the onset of diminished expression. While this may suggest that STRN4 is not as crucial to TNBC-related processes, much research remains. In the future, we plan to add additional cell lines to the knockdown experimental groups and monitor protein expression during STRN4 knockdown. Citation Format: Caroline Rinderle, Jordan Wright, Olivia Mayer, Bruce Bunnell. Impact of STRN4 knockdown on TNBC migration and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2657.
Abstract 4697: FDA approved non-cardiotoxic hERG1 inhibitor ketoconazole enhances radiation sensitivity in glioblastoma
Authors: Johnathan Rodgers Gochicoa, Tingting Huang, Kelli B. Pointer
Journal: Cancer Research (2025)

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a median survival of less than two years despite multimodal therapy, including surgery, radiation, chemotherapy, and tumor treating fields. GBM's dismal prognosis is largely due to its high recurrence rates. Emerging evidence implicates ion channels in promoting tumor progression and treatment resistance across various malignancies. Specifically, the potassium voltage-gated channel hERG1, encoded by the KCNH2 gene, has been associated with worse patient outcomes in GBM. However, the mechanisms underlying hERG1’s contribution to treatment resistance, particularly radiation resistance, remain poorly understood. Here, we investigated the role of hERG1 in driving radiation resistance in GBM. RNA-sequencing data from 350 GBM patient tumors in The Cancer Genome Atlas (TCGA) were analyzed to assess KCNH2 expression and its correlation with overall survival. Patients were stratified into quartiles by KCNH2 expression, and Kaplan-Meier survival analyses were performed using R Studio (v4.3.1). The human GBM cell line LN-229 was used for in vitro studies. A drug screen determined the IC25 for an FDA-approved, non-cardiotoxic hERG1 inhibitor ketoconazole. Cell viability was assessed after 72 hours of drug treatment. Cells were treated with IC25 concentrations of inhibitors for three days, with radiation (0 Gy or 8 Gy) administered on day two, followed by two additional days of drug treatment. All experiments were performed in triplicate for statistical rigor. KCNH2 expression in the upper quartile was 9.7 times higher than in the lower quartile. Patients in the upper quartile exhibited worse median overall survival compared to those in the lower quartile (11.8 months vs. 12.9 months, p = 0.00053). The IC25 for ketoconazole was 28μM. Ketoconazole combined with radiation decreased cell viability by 54.4% compared to radiation alone (p =0.01) and by 78.8% compared to vehicle control (p &amp;lt; 0.0001). High KCNH2 expression is associated with worse survival outcomes in GBM patients. FDA-approved, non-cardiotoxic hERG1 inhibitor ketoconazole decreased cell viability and enhanced radiation sensitivity in vitro. These findings suggest that combining a non-cardiotoxic hERG1 inhibitor with radiation may represent a promising therapeutic strategy to improve GBM patient outcomes. Citation Format: Johnathan Rodgers Gochicoa, Tingting Huang, Kelli B. Pointer. FDA approved non-cardiotoxic hERG1 inhibitor ketoconazole enhances radiation sensitivity in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4697.
Abstract 1366: Single-cell gene expression profiling of the tumor immune microenvironment (TIME) and its association with immunotherapy response in syngeneic mouse models
Authors: Jia Wang, Minjuan Deng, Bin Jiang, Han Yan, Yu Jiang, Siyuan Wang, Xiao Ding, Pei Zhang, Wei Jin, Zhirong Shen
Journal: Cancer Research (2025)

The TIME, comprised of the extracellular matrix and a milieu of both immune and non-immune cells, plays a critical role in tumor development, disease progression, and response and resistance to immunotherapy. Much of our understanding of the TIME’s immunological features, cellular heterogeneity, and associations with immunotherapy response have come from the use of syngeneic mouse models representing various cancer cell types. To provide further characterization of the TIME in syngeneic mouse lines commonly used for immunogenic drug discovery, Cd45+ single-cell RNA sequencing was performed in 10 syngeneic mouse models representing 7 distinct cancer types (breast mammary carcinoma: 4T1, EMT6, MMTV-PyMT; colon carcinoma: CT26.WT, MC38; glioma: GL261; renal adenocarcinoma: Renca; lung carcinoma: LL2; melanoma: B16F10; and pancreatic adenocarcinoma: Pan02). Further, to unveil cellular subpopulations that correspond to immunotherapy response, anti-PD-1 therapy efficacy studies were performed in the syngeneic models and correlations with the abundances of distinct immune cell populations were explored. Across all syngeneic tumor lines examined, seven major immune cell populations were identified and subpopulations within T cells, NK cells, innate lymphoid cells, and distinct myeloid cells were characterized. Efficacy of anti-PD-1 treatment was positively correlated with a unique population of ISGhigh macrophages. Moreover, an over-representation of neutrophils and proliferating/C1Q+ macrophage subsets was observed in models exhibiting resistance to anti-PD-1 treatment. These findings provide further characterization of these syngeneic lines to aid in rational model selection to facilitate translational relevance. This study also provides further insight into how immune cell composition and abundance within tumors may contribute to immune checkpoint blockade resistance. Citation Format: Jia Wang, Minjuan Deng, Bin Jiang, Han Yan, Yu Jiang, Siyuan Wang, Xiao Ding, Pei Zhang, Wei Jin, Zhirong Shen. Single-cell gene expression profiling of the tumor immune microenvironment (TIME) and its association with immunotherapy response in syngeneic mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1366.
Abstract 6327: Prevention of glioblastoma cell growth by Vialinin A
Authors: Chandu Goli, Roxana Nojoumi, Kota V. Ramana
Journal: Cancer Research (2025)

Glioblastoma is regarded as the most aggressive and common type of primary malignant brain tumor in adults that is characterized by rapid growth of glial cells. It is mainly resistant to therapy and exhibits a universally poor prognosis. Therefore, there is a vital need to explore other alternatives to complement current standard treatment modalities. Recent studies have revealed that Vialinin A, a small antioxidant molecule isolated from the Chinese edible mushroom, has potential antioxidant and anti-inflammatory properties. However, its chemopreventive role is not clear. We now examined the chemopreventive efficacy of this compound in glioblastoma growth and invasion. The different capabilities of Vialinin A and downstream effects, such as cell viability, invasion, migration, and apoptosis induction, were explored in various experiments using human U-87 Glioblastoma cell lines obtained from ATCC. Our results indicate that Vialinin A prevents the growth of glioblastoma cells in a time- and dose-dependent manner. Vialinin A also prevented the invasion and trans-well migration of glioblastoma cells. Further, it also regulated the expression of various pro-apoptotic and anti-apoptotic factors and other inflammatory factors, including Bad, Bax, Bcl-2, cIAP-1, cIAP-2, and procaspase 3. These results suggest that Vialinin A promotes the cancer cell apoptotic pathways to prevent glioblastoma cell growth. Further, we plan to examine how Vialinin A prevents glioblastoma growth in nude mice xenografts. Citation Format: Chandu Goli, Roxana Nojoumi, Kota V. Ramana. Prevention of glioblastoma cell growth by Vialinin A [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6327.
Abstract 4078: Enabling single-cell RNA analysis of hundreds of samples and millions of cells through automated library preparation
Authors: Rosary Nguyen, Swarnagowri Vaidyanathan, Zorine Hlathu, Xueying Zhao, Jamie Moskwa, Ricelle A. Acob, Chelsea Gordon, Larry Wang, Aruna Ayer
Journal: Cancer Research (2025)

Single-cell RNA-seq is a powerful method for studying complex cell populations. As opportunities grow for single-cell multiomics methods in translational research, there is an increased need for high-throughput approaches capable of efficiently capturing and analyzing large numbers of cells and samples simultaneously. Current assays on scRNA-seq platforms have limited throughput due to the low cell recovery and tedious hands-on library preparation steps. Here we demonstrate the feasibility of automating single-cell RNA-seq library preparation with BD Rhapsody cell capture bead libraries on the Hamilton NGS STAR system. To show the range of cell input capabilities of the NGS STAR system, we input BD Rhapsody Cell Capture Beads containing captured molecules from 6,000 to 20,000 cells. To evaluate the repeatability and reproducibility of the platform, we generated a large pool of BD Rhapsody cell-captured beads to test the same sample library across multiple wells, instruments, and runs. Using in-process quality control and sequencing, we confirmed equivalent biological output in terms of library quality, sensitivity, and gene expression correlation (R2 &amp;gt; 0.9) compared to manual bench controls. In addition, we loaded several BD Rhapsody HT Xpress lanes with 100,000 cells and used automated library preparation to compare with manual bench controls. This study demonstrates that BD Rhapsody cell captured beads can be utilized on the Hamilton NGS STAR to generate high quality libraries for sequencing and increase throughput of samples, while reducing hands on time. Processing 48 samples with 100K cells each allows users to prepare libraries for over 4 million cells in a single run. When combined with upstream sample multiplexing, hundreds of samples can be analyzed together, offering significant time savings and reducing variability between samples. This application could be readily extended to other existing multiomics single-cell technologies such as CITEseq assay. For Research-Use Only. Not for use in diagnostic or therapeutic procedures.BD and the BD Logo are trademarks of Becton, Dickinson and Company. © 2024 BD. All rights reserved. NPM-5204. Citation Format: Rosary Nguyen, Swarnagowri Vaidyanathan, Zorine Hlathu, Xueying Zhao, Jamie Moskwa, Ricelle A. Acob, Chelsea Gordon, Larry Wang, Aruna Ayer. Enabling single-cell RNA analysis of hundreds of samples and millions of cells through automated library preparation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4078.