tbuckley/cabot-search huggingface dataset:
Abstract 1223: A novel 3D high-throughput screen identified drugs that re-epithelialize colorectal cancer cells and enhance response to chemotherapy
Authors: Sarah J. Harmych, Thomas P. Hasaka, Chelsie K. Sievers, Seung W. Kang, Vivian T. Jones, Zhiguo Zhao, Oleg Kovtun, Claudia C. Wahoski, Ken S. Lau, Robert J. Coffey, Joshua A. Bauer, Bhuminder Singh
Journal: Cancer Research (2025)

Abstract Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype also impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact these morphologic changes are understudied, in part, due the complete failure of typical live/dead 2D high-throughput screens (HTS) to capture morphology or lack of robustness of 3D screens. Here, we designed an HTS using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies. One of these drugs, Azithromycin, increased colony circularity, enhanced E-cadherin membrane localization, and surprisingly, also elevated sensitivity to the chemotherapeutic, Irinotecan. A retrospective study of patient data demonstrated that the combination of Azithromycin with Irinotecan improved the 5-year survival of patients with CRC. These results highlight the importance of morphologic screens to identify novel drug candidates and synergistic mechanisms. Citation Format: Sarah J. Harmych, Thomas P. Hasaka, Chelsie K. Sievers, Seung W. Kang, Vivian T. Jones, Zhiguo Zhao, Oleg Kovtun, Claudia C. Wahoski, Ken S. Lau, Robert J. Coffey, Joshua A. Bauer, Bhuminder Singh. A novel 3D high-throughput screen identified drugs that re-epithelialize colorectal cancer cells and enhance response to chemotherapy [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 1223.
Abstract 945: Live attenuated MMR vaccines modulate tumor immune cell infiltration and synergize with standard of care to prolong survival in preclinical HCC models
Authors: Mulu Z. Tesfay, Aleksandra Cios, Khandoker U. Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Steven Post, Thomas Kelly, Moaven Moaven, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei Basnakian, Nagalo Bolni
Journal: Cancer Research (2025)

The global burden of hepatocellular carcinoma (HCC) continues to rise, driven by increasing metabolic risk factors such as nonalcoholic fatty liver disease, obesity, and type II diabetes. Patients with advanced HCC have limited therapeutic options and a dismal prognosis. While recent advancements in combination therapies—including immune checkpoint blockade (ICB) with anti-PD-1/PD-L1 and anti-CTLA-4 agents and anti-angiogenics—have improved survival for some, up to 80% of patients fail to respond, underscoring an unmet need for new strategies. Emerging data indicate a strong association between increased tumor-infiltrating lymphocytes (TILs) and better responses in ICB-treated HCC, suggesting TIL enhancement as a promising approach. However, HCC’s inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) limit the efficacy of current TIL-promoting strategies. Here, we demonstrate that low-dose intratumoral immunotherapy using the trivalent MMR vaccine—composed of live attenuated measles, mumps, and rubella viruses—modulates TME immune infiltration, increases cytotoxic T cell frequency, and delays tumor growth in multiple murine HCC models. Importantly, intratumoral or systemic MMR administration in combination with dual ICB (anti-mPD-1/anti-mCTLA-4) significantly prolongs survival, promoting tumor-specific and memory immune responses in both subcutaneous and orthotopic HCC models. These findings reveal a unique mechanism of vaccine-induced anti-tumor activity, highlighting MMR as a viable, globally accessible option for enhancing immune responses in advanced HCC therapy. Citation Format: Mulu Z. Tesfay,Aleksandra Cios,Khandoker U. Randal S. Shelton,Bahaa Mustafa,Camila C. Simoes,Steven Post,Thomas Kelly,Moaven Moaven,Lewis R. Roberts,Mitesh J. Borad,Martin J. Cannon,Alexei Basnakian,Nagalo Bolni. Live attenuated MMR vaccines modulate tumor immune cell infiltration and synergize with standard of care to prolong survival in preclinical HCC 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 945.
Abstract 56: Multi-omic profiling of PSMA heterogeneity in prostate cancer liver metastases identifies new metabolomic targets
Authors: Martin K. Bakht, Yasutaka Yamada, Sheng-Yu Ku, Anthony P. Belanger, Quang-De Nguyen, Himisha Beltran
Journal: Cancer Research (2025)

Abstract Background: Prostate-specific membrane antigen (PSMA) is a metabolic enzyme involved in glutamate and folate pathways. Being a cell surface protein, PSMA serves as a theranostic target in castration-resistant prostate cancer (CRPC) with PSMA-radioligand therapy (PSMA-RLT). However, not all patients with PSMA-PET positive tumors respond to PSMA-RLT, partly due to heterogeneous expression of PSMA. We hypothesize that the metabolic features of the tumor microenvironment contribute to PSMA expression and function. Methods: We profiled CRPC autopsy tumors from five patients and a series of orthotopic PSMA-positive metastatic CRPC models using mass spectrometry (MS), H3K27ac ChIP-seq, and spatial whole transcriptomics by Visium CytAssist platform. Results: Spatial transcriptomic mapping indicated enrichment of amino acid transport and biosynthesis pathways in PSMA-suppressed liver metastases versus other sites of disease. Similarly, MS metabolomics revealed elevated levels of neutral amino acids, such as L-Leucine, in liver metastases. H3K27ac ChIP-seq showed that only liver metastatic tumors in the 22Rv1 CRPC model exhibited an H3K27ac peak at the SLC7A5 (LAT1) gene locus, correlating with low PSMA expression, not seen in primary tumors. A PSMA-suppressed 22Rv1 liver metastasis-derived cell line demonstrated sensitivity to LAT1 inhibition (V-9302), suggesting its potential as a therapeutic target. Conclusions: Multi-omic profiling of patient tumors and prostate cancer models point to PSMA-suppression and heterogeneity in liver metastases associated with potentially targetable epigenetic and metabolomic alterations. Citation Format: Martin K. Bakht, Yasutaka Yamada, Sheng-Yu Ku, Anthony P. Belanger, Quang-De Nguyen, Himisha Beltran. Multi-omic profiling of PSMA heterogeneity in prostate cancer liver metastases identifies new metabolomic targets [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 56.
Abstract 3681: A tumor-naive method for estimating tumor fraction using 5-hydroxymethylation cytosine in cell-free DNA
Authors: Ceyda Coruh, Onur Sakarya, Yuhong Ning, Yuan Xue, Michael Cipriano, Kyle Hazen, Alexander W. Wyatt, David Quigley, Felix Feng, Martin Sjostrom, Gulfem Guler, Wayne Volkmuth, Samuel Levy
Journal: Cancer Research (2025)

Abstract Accurate measurement of the tumor fraction (TF) in circulating cell-free DNA (cfDNA) allows estimation of tumor burden non-invasively, potentially useful in guiding treatment decisions, monitoring treatment response, and detecting minimal residual disease. 5-hydroxymethylation of cytosine (5hmC) marks activation of cancer drivers and downstream gene targets, and has been shown to positively correlate with gene expression and gene regulation. Here we trained a machine learning (ML) model to predict TF in a tumor-naive way from 5hmC-enriched sequencing data together with low-pass whole genome sequencing data. In cross-validation the ML model showed excellent performance, showing high correlation (R &amp;gt; 0.8) and low composite absolute error (CAE &amp;lt; 5%) compared to copy-number variation (CNV) based estimates. The high correlation was confirmed in an independent test set which also showed R &amp;gt; 0.8, with only a modest increase in CAE (&amp;lt;10%) using targeted point mutation-based TF estimates as an external reference comparator. Using in silico cancer mixtures that created contrived cfDNA samples targeting concentrations below 10%, our 5hmC-based TF prediction method achieved detection sensitivity of approximately 90% with a specificity of 97%. Finally, we observed that 5hmC-based predicted TF was significantly associated with overall survival (HR = 1.04, p &amp;lt; 0.001) in an independent prostate patient cfDNA cohort when controlling for other covariates. In summary, we find that the 5hmC-based TF estimate is a reliable metric of tumor burden irrespective of tumor mutational status. The 5hmC-based TF estimate may be used either alone or in conjunction with mutation and CNV-based estimates to provide more accurate measures of survival risk and therapy response during treatment. Citation Format: Ceyda Coruh, Onur Sakarya, Yuhong Ning, Yuan Xue, Michael Cipriano, Kyle Hazen, Alexander W. Wyatt, David Quigley, Felix Feng, Martin Sjostrom, Gulfem Guler, Wayne Volkmuth, Samuel Levy. A tumor-naive method for estimating tumor fraction using 5-hydroxymethylation cytosine in cell-free DNA [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 3681.
Consumer insights from a feasibility study on remote and extended use of a novel non-invasive wearable fetal electrocardiogram monitor
Authors: Debjyoti Karmakar, Tarini Paul, Emerson Keenan, Marimuthu Palaniswami, Kaitlin Constable, Erica Spessot, Fiona Brownfoot
Journal: npj Digital Medicine (2025)

Abstract The COVID-19 pandemic accelerated the adoption of telehealth and remote monitoring in obstetric care. This study assessed pregnant patients’ perceptions before and after using a novel non-invasive fetal electrocardiogram (NI-FECG) device. The trial is prospectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTRN12621001260819; submitted June 9th, 2021; approved September 17th, 2021). Seventy participants from 36 weeks’ gestation completed pre- and post-use surveys. Interest in continuous and home fetal monitoring was high (79% and 90%, respectively). Post-use, 89% reported satisfaction; over 90% comfortable wearing and removing the sensor. Extended use was acceptable to 76%, and only 3% reported high skin irritation. Sentiment analysis highlighted themes of reassurance, convenience, and reduced anxiety. Some suggested smaller, wireless design. Analysis by natural language processing and clustering provided deeper insights. Findings support strong interest in at-home fetal monitoring; further refinement and education are needed to enhance acceptability. Future research should assess long-term effects on anxiety and clinical outcomes.
Abstract 1507: Oxidative stress increases the aggressiveness of colorectal cancer by activating the antioxidant transmembrane chloride intracellular channel 1 (tmCLIC1)
Authors: Francesca Cianci, Guido Rey, Carlotta Tacconi, Luca Palloni, Matteo Ranucci, Giulia Bertolini, Luca Roz, Alessandro Fantin, Michele Mazzanti
Journal: Cancer Research (2025)

Abstract Colorectal cancer is the third leading cause of death in developed country, especially in the presence of metastases. Metastatic cancer cells depend on antioxidants like glutathione (GSH) to tackle oxidative stress as they adapt to distinctive environments different from those of the primary tumor. The mechanisms that cause oxidative stress in cancer cells are poorly understood, but it was recently discovered that the Chloride Intracellular Channel 1 (CLIC1) protein supports tumor cell Reactive Species of Oxigen (ROS) overproduction. CLIC1 is a ubiquitous protein from the CLICs family, which is unique in its ability to be metamorphic. In normal cells, CLIC1 protein is expressed as a cytosolic form and binds antioxidant glutathione (GSH). Under the chronic stress typical of cancer cells, CLIC1 undergoes a conformational change, translocating to the plasma membrane (tmCLIC1). This transition releases GSH into the cytoplasm while tmCLIC1 facilitates reactive oxygen species (ROS) overproduction, fostering an aggressive cancer phenotype. Studies reveal a contradiction where cancer cells simultaneously exhibit high levels of both ROS and GSH, which are usually inversely related. In this work, we demonstrate that this paradox is linked to tmCLIC1 activity, where GSH release acts as a defense mechanism, while tmCLIC1 overexpression amplifies ROS production, driving cancer cell proliferation and metastasis. Blocking tmCLIC1 activity has shown a reduction of proliferation, migration, and invasion of metastatic colorectal cancer cells (CRC). The study also demonstrated that forcing non-metastatic CRC cells (SW480) to release GSH using the antioxidant N-Acetyl Cysteine (NAC) enriched cytoplasmic GSH and increased tmCLIC1 expression. This effect, however, was absent in cells where CLIC1 was silenced, proving that GSH release depends on tmCLIC1 activity. These cells were converted from non-aggressive cell lines to metastatic ones in vitro and in vivo. These findings challenge the traditional view of antioxidants in cancer treatment, suggesting that tmCLIC1 inhibition could serve as a novel therapeutic strategy against metastatic colorectal cancer, addressing a pressing societal health concern. Citation Format: Francesca Cianci, Guido Rey, Carlotta Tacconi, Luca Palloni, Matteo Ranucci, Giulia Bertolini, Luca Roz, Alessandro Fantin, Michele Mazzanti. Oxidative stress increases the aggressiveness of colorectal cancer by activating the antioxidant transmembrane chloride intracellular channel 1 (tmCLIC1). [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 1507.
Abstract 637: Single-cell analysis of systemic immune response to sequential radiation and immune checkpoint blockade in metastatic colorectal cancers
Authors: Joshua Brand, Sean G. Kraus, Michael Bassetti, Dustin A. Deming, Huy Q. Dinh
Journal: Cancer Research (2025)

Abstract Immune checkpoint blockade (ICB) has shown significant clinical efficacy in mismatch repair deficient colorectal cancers (CRCs). However, an effective means to use these therapies for mismatch repair proficient (pMMR) CRC has yet to be developed. To enhance the efficacy of ICB for patients with oligometastatic pMMR CRC, we performed a clinical trial evaluating the sequential use of stereotactic body radiotherapy (SBRT), pembrolizumab, surgical resection, and then adjuvant pembrolizumab (NCT02837263). The primary endpoint of 1-year recurrence-free survival (1 yr RFS) was met in 60% of trial participants compared to a historical control of 50%. From this trial, 13 subjects could have blood samples collected for peripheral blood mononuclear cell isolation pretreatment and after operative management. We hypothesize that the systemic immune response changes upon combined treatment and is distinct between responders and non-responders. We performed scRNA-Seq on these samples to compare the circulating immune cell populations with clinical outcomes. Despite a small sample size, integrated bioinformatics analysis identified (i) pre-existing CD8+ T cells were observed with treatment response (p = 0.031) (ii) combined RT and ICB induces changes in myeloid cell phenotypes, including reduced pro-inflammatory monocytes (p = 0.038) and conventional cDC2 (p = 0.030) in subjects without recurrence and increasing pDCs (p = 0.024) in most patients. CD8+ T cells from those recurrence-free subjects showed terminally differentiated effector phenotypes, expressing CX3CR1, GZMB, and KLRG1 before treatment. cDC2s expressed interferon activity markers, including STAT1, IFI44, and IRF7, that presented a more activated state. CD8+ T cell abundance remained stable, with no significant changes before and after treatment. In contrast, myeloid cells showed greater variability, reflecting unique polarization states through differences in cytokine (CCL3, CXCL8), interferon (ISG15, IFI44), and complement (C1QA, C1QB) associated genes. Future work will increase sample size in independent patient cohorts to elucidate the extent to which circulating phenotypes are also identified in tumors. Overall, this study demonstrates pre-existing T cell abundance and changes in myeloid cell phenotypes may be associated with clinical outcomes from combined immunotherapy, which have the potential to serve as predictive biomarkers for therapeutic response. Citation Format: Joshua Brand, Sean G. Kraus, Michael Bassetti, Dustin A. Deming, Huy Q. Dinh. Single-cell analysis of systemic immune response to sequential radiation and immune checkpoint blockade in metastatic colorectal cancers [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 637.
Abstract 622: Age-dependent changes in cell cycle dynamics and hematopoietic responses to chemotherapy
Authors: Jianxing He, Yue Pan, Hao Liu, Ying Huang, Hongsheng Deng, Chao Yang, Qi Cai, Shan Xiong, Huiting Liu, Wenhua Liang
Journal: Cancer Research (2025)

Abstract Background: Precision medicine emphasizes individualized cancer treatment, particularly for elderly lung cancer patients facing unique chemotherapy challenges. Age-related changes in cell cycle dynamics significantly influence therapeutic outcomes, yet their role in optimizing personalized therapies remains underexplored. This study investigates these age-related dynamics to inform personalized therapeutic strategies for elderly lung cancer patients. Methods: Single-cell RNA sequencing data from 166 healthy individuals (aged 25-85 years) were analyzed to explore age-associated changes in cell cycle distribution, differentially expressed genes (DEGs), and enriched pathways. Young (9-11 weeks) and aged (17 months) mice received weekly cisplatin for four cycles. Peripheral blood and hematopoietic stem cells (HSCs) were monitored dynamically for cell cycle phases, DNA damage (γ-H2AX), and vascular leakiness using immunofluorescence. RNA sequencing of HSCs identified DEGs and enriched pathways after treatment cycles. Results: Single-cell analysis revealed a linear decrease in S-phase proportions with age (r=−0.681, p=0.0026) and identified 28 DEGs, including PAXB-AS1, BABAM1, and DONSON, enriched in immune regulation and cell cycle pathways. In murine models, aged mice showed impaired immune recovery, with persistently higher neutrophil proportions (post-cycle 1: 14.75% vs. 6.1%, p&amp;lt;0.05) and lower lymphocyte proportions (post-cycle 1: 65.73% vs. 79.98%, post-cycle 4: 60.5% vs. 63.8%) compared to young mice. Moreover, aged mice exhibited delayed neutrophil recovery (Day 4 vs. Day 2), accompanied by persistent G1-phase arrest in HSCs (Day 4: 86% vs. 82%) and reduced G2/M-phase proportions (Day 4: 3% vs. 6%). RNA sequencing of aged HSCs further revealed significant enrichment in the DNA_DAMAGE_TELOMERE_STRESS_INDUCED_SENESCENCE pathway after four treatment cycles (|NSE| = 1.98, p &amp;lt; 0.05), a pattern absent in young mice. Finally, γ-H2AX flow cytometry confirmed increased DNA damage in aged HSCs, while immunofluorescence demonstrated heightened bone marrow vascular leakiness in aged mice. Conclusion: Aging significantly alters cell cycle dynamics, hematopoietic recovery, and chemotherapy responses, highlighting the need to integrate cell cycle-based insights into personalized treatment strategies. These findings provide a foundation for future research on age-specific therapeutic interventions in lung cancer. Citation Format: Jianxing He,Yue Pan,Hao Liu,Ying Huang,Hongsheng Deng,Chao Yang,Qi Cai,Shan Xiong,Huiting Liu,Wenhua Liang. Age-dependent changes in cell cycle dynamics and hematopoietic responses to chemotherapy [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 622.
Abstract 2526: Development of ultrahigh sensitivity magnetic particle imaging for stem cell tracking
Authors: Yimeng Li, Yu An, Yang Du, Lin Shen, Jie Tian
Journal: Cancer Research (2025)

Abstract In vivo tracking of stem cells is critical to stem cell transplantation and regenerative medicine research. Achieving long-term, non-invasive imaging of transplanted cells demands highly sensitive imaging technology. Magnetic particle imaging (MPI) is an emerging modality capable of visualizing the distribution of superparamagnetic iron oxide nanoparticles (SPIOs). Previous studies have reported that MPI can detect clusters of approximately 2500 SPIO-labeled stem cells. However, more than this sensitivity level is needed to monitor the survival, migration, differentiation, and regeneration of stem cells. To address this limitation, we developed an ultrahigh-sensitivity magnetic particle imaging (US-MPI) device capable of detecting stem cells at scales of hundreds of cells. Through full-chain design and optimization, US-MPI maximizes the capture of SPIO signals from stem cells. Using a commercial SPIO (VivoTrax), mouse mesenchymal stem cells were labeled, and samples with varying cell numbers (ranging from 50 to 1×107) were tested using US-MPI and 9.4 T MRI (uMR 9.4T, United Imaging Life Science Instrument, Wuhan, China) for comparison. US-MPI demonstrated the ability to detect as few as 50 labeled stem cells in vitro and 150 cells in vivo, whereas 9.4 T MRI required at least 1×105 cells for detection in vitro. Thus, US-MPI exhibited a sensitivity 2, 000 times higher than that of 9.4 T MRI. The efficacy of US-MPI for stem cell tracking was further validated in a lipopolysaccharide (LPS)-induced mouse hind limb inflammation model. Eight hours after SPIO-labeled stem cells were injected intravenously, US-MPI detected strong signals on the inflamed limb, which remained significantly higher than those of the healthy limb during a 48-hour monitoring period. Post-mortem Prussian blue staining of inflamed tissues confirmed the presence of blue-stained SPIO particles, verifying that the US-MPI signals originated from labeled stem cells. These results highlight the ultrahigh sensitivity of US-MPI for stem cell tracking, providing a valuable tool for advancing stem cell research. Citation Format: Yimeng Li, Yu An, Yang Du, Lin Shen, Jie Tian. Development of ultrahigh sensitivity magnetic particle imaging for stem cell tracking [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 2526.