tbuckley/cabot-search huggingface dataset:
Abstract 4909: Artificial intelligence (AI) chatbots and their reponses to most searched Spanish cancer questions
Authors: En Cheng, Jesus D. Anampa, Carolina Bernabe-Ramirez, Juan Lin, Xiaonan Xue, Alyson B. Moadel-Robblee, Edward Chu
Journal: Cancer Research (2025)

Abstract Background: AI chatbots are predominantly trained on English contents. They perform well in answering English cancer questions, but their performance in other languages (such as Spanish) is unknown. Spanish-speaking patients are also concerned that they must use the paywall versions to get better responses, which may exacerbate existing cancer disparities. Methods: We evaluated the responses of AI chatbots to most searched Spanish cancer questions. Using Google Trends (1/1/2020-1/1/2024), we identified the top 5 most searched Spanish cancer questions related to the top 3 common cancers in US Hispanics/Latinos. We selected 6 popular AI chatbots (free and paywall versions of ChatGPT, Claude, and Gemini) and then generated 90 Spanish responses. Board-certified oncologists speaking native Spanish assessed the quality using DISCERN Instrument (score from 1 [low quality] to 5 [high quality]), actionability using Patient Education Materials Assessment Tool (score from 0 [no clear action suggestions] to 100% [clear action suggestions]), readability using Fernández Huerta Reading Grade Level (score from 1 [1st grade] to 13 [college]). Results: The quality of overall AI chatbot responses was moderate (mean [95% CI]: 3.5 [3.4-3.6]). The actionability was low (mean [95% CI]: 35.6% [30.8%-40.3%]), and the readability was high-school level (mean [95% CI]: 9.2 [8.8-9.6] grade). The performance of quality, actionability, and readability did not differ by free and paywall versions (P &amp;gt;0.05). Conclusions: AI chatbots provided moderately accurate information for most searched Spanish cancer-related questions. The responses were not readily actionable and written at the high-school level, which was not concordant with the American Medical Association’s recommendation (6th grade or lower). The performance did not improve by using the paywall versions. Relevance: To reduce cancer disparities in health literacy, AI chatbots need improvement in responding to Spanish cancer questions. Citation Format: En Cheng, Jesus D. Anampa, Carolina Bernabe-Ramirez, Juan Lin, Xiaonan Xue, Alyson B. Moadel-Robblee, Edward Chu. Artificial intelligence (AI) chatbots and their reponses to most searched Spanish cancer questions [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 4909.
Abstract 5491: High throughput bioluminescent homogenous assay to monitor N6-methyladenoisne (m6A)
Authors: Said A. Goueli, Dareen Mikheil, Kevin Hsiao, WeiWei An, Matt Larsen
Journal: Cancer Research (2025)

Abstract N6-methyladenosine (m6A) is a modified nucleoside derived from adenosine, distinguished by the presence of a methyl group at the N6 position. This structural modification enables m6A to play unique roles in cellular signaling, gene expression regulation, and metabolic processes, positioning it as a crucial player in cellular function and disease pathology. Its involvement ushered the beginning of the field of in epitranscriptomics, particularly N6-methyladenosine (m6A)-related pathways, which modulate mRNA stability, translation, and splicing have lent tremendous significance to this form of RNA modification. There are about 7000 mRNAs with m6A modifications and they are highly conserved. Non-coding RNA is mainly regulated by m6A methyltransferase and demethylase, which plays an important biological role in the occurrence and development of tumors. Recent studies suggest that m6A and its derivatives could serve as potential biomarkers for disease diagnosis and as therapeutic targets. Recognizing how important the early detection of m6A is, we have developed an assay that monitors the concentration of m6A so it can be used for screening of m6A-RNA from patients with cancer such as liver cancer. The assay relies on new concept of novel nanoluciferase (nanoluc) complementation where a small peptide (SmBiT) linked to m6A through a linker (m6A tracer) can be recognized by an anti m6A antibody that is linked to a nanoluc complementary fragment (LgBiT) resulting in a bioluminescence upon the addition of nanoluc substrate. The presence of m6A-RNA that is generated in the reaction with RNA substrate, S-adenosylmethionine (SAM) and METTL 3/14 complex can be detected with this assay. Using MTTL3/14 complex we show that SAM is an excellent substrate for this enzyme with a Km of 240nM. The assay does not recognize Adenosine, AMP, ADP, or ATP in the reaction. We will show data in support of this technology to monitor the presence of m6A in methylated RNA. The assay is homogenous, HTS formatted and can be completed in less than one hour. Thus, this assay provides valuable contributions for investigating modulators of the MTTL3/14 complex or FTO demethylating enzymes and facilitates the search for novel therapeutics. Citation Format: Said A. Goueli, Dareen Mikheil, Kevin Hsiao, WeiWei An, Matt Larsen. High throughput bioluminescent homogenous assay to monitor N6-methyladenoisne (m6A) [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 5491.
Abstract 5842: A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma model
Authors: Kempaiah Rayavara, Subeena Sood, Majed Matar, Jessica Kim, John Henderson, Jeff Sparks, Meredyth Kinsella, Olivia Signer, Joseph Rogers, Chelsey Bellmon, Khursheed Anwer
Journal: Cancer Research (2025)

Abstract Cancer vaccine approaches targeting neoantigens are gaining credence due to their specificity for tumors while sparing healthy tissues. Cancer vaccines based on DNA technology are attractive anti-cancer therapeutic tools due to their ability to elicit an effector T-cell-based immune responses. We report the development of a novel DNA-based cancer vaccine that relies on the delivery of a plasmid DNA vector encompassing immune epitopes of multiple neoantigens delivered with a novel synthetic DNA delivery system with the aim to elicit a broader immune response against cancer. The formulated vaccine was also investigated in combination with different adjuvants to maximize the anti-cancer responses. The vaccine vector encoding the immunogenic epitopes of multiple melanoma neoantigens and flanked by signal peptide at N-terminus and an MHC-targeted domain at the C-terminus end was formulated with a functionalized novel synthetic polymer with or without the adjuvants Poly I:C, diABZI, a STING agonist, or a mouse IL-12 plasmid. Mice were implanted subcutaneously with 0.5 x 106 B16F10 tumor cells on Day 0 and vaccinated intramuscularly with the DNA formulations on Day 2, 9, 16 and 23, and monitored for tumor growth and survival . For cellular responses, mice were injected intramuscularly with the DNA formulations on Day 0, 21, 42 and sacrificed 7 days later for cellular immune response by ELISPOT assay. Vaccination with formulated DNA alone yielded a significant inhibition (60%, p&amp;lt;0.01) of tumor growth and improved survival. Addition of Poly I:C, diABZI, or IL-12 plasmid further augmented the tumor inhibition to 90%(p&amp;lt;0.0001), 94%(p&amp;lt;0.0001), and 88% (p&amp;lt;0.0001), respectively, and improved the survival outcome. All animals in the adjuvant groups also lived longer. The anti-tumor efficacy results are supported by the onset of robust T-cell responses in all treatment groups supporting the involvement of immune activation in the action of this novel DNA vaccine that does not require a virus or device and can be manufactured rapidly with a simple and cost-effective manufacturing process critical for the viability of cancer vaccines. Citation Format: Kempaiah Rayavara, Subeena Sood, Majed Matar, Jessica Kim, John Henderson, Jeff Sparks, Meredyth Kinsella, Olivia Signer, Joseph Rogers, Chelsey Bellmon, Khursheed Anwer. A novel formulated neoantigen DNA vaccine with promising anticancer efficacy in B16F10 mouse melanoma 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 5842.
Abstract 5218: RGS4+aSMA+CAF subsets promote tumor immune escape by regulating the formation of immune-exhaustive mesenchymal networks
Authors: Huiping Chen, Wenfeng Zeng
Journal: Cancer Research (2025)

Abstract Solid tumors consist of tumor cells and the tumor microenvironment (TME), a dynamic system comprising various immune cells, mesenchymal cells, cytokines, microvesicles, extracellular matrix, and vascular lymphatic networks. The recruitment of lymphocytes into tumors is essential for effective anti-tumor immunity and successful immunotherapy. The tumor stroma serves as the initial site for effector immune cell infiltration, and the mesenchymal network directly influences immune cell function. Cancer-associated fibroblasts (CAFs) are the largest proportion of TME intrinsic stromal cells, with significant heterogeneity and multiple origins, and perform different biological functions. CAFs can not only induce PD-L1 expression in tumor cells, but also promote PD-L1 expression in TME immune cells through the release of cytokines and vesicles, thereby facilitating tumor immune escape. In this study, we found that in some breast cancer patients, PD-L1 in tumor stroma was abundantly expressed and associated with immunosuppression and poor prognosis, and the distribution of tumor stromal PD-L1 was also closely related to the activation status of CAFs. Furthermore, we performed high-throughput RNA sequencing on PD-L1low and PD-L1high stroma cells, respectively. We found a CAF subset in high PD-L1 expression group, which was characterized by immune exhaustion and hyperactivation. Notably, Regulator of G protein signaling 4 (RGS4) pathways were significantly upregulated in this subset. Furthermore, we confirmed that RGS4 induces fibroblasts to adopt a PD-L1 immunodepleting phenotype and establishes an immune-exhaustive mesenchymal network that modulates anti-tumor immunity. In addition, we validated in humanized murine models that targeting RGS4 significantly enhances the efficacy of immunotherapy in animal models. The spatial heterogeneity of PD-L1 expression in TME is a primary factor contributing to the limited efficacy of PD-L1/PD-1 antibody therapies. Currently, numerous studies aim to enhance the immune response by inhibiting or degrading PD-L1. A comprehensive understanding of the molecular mechanisms governing PD-L1's spatial distribution could fundamentally enhance its clinical application. This study explored the mechanism governing the spatial distribution difference of PD-L1, and provided more possibilities for the development of targeted intervention in CAFs. Citation Format: Huiping Chen, Wenfeng Zeng. RGS4+aSMA+CAF subsets promote tumor immune escape by regulating the formation of immune-exhaustive mesenchymal networks [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 5218.
Abstract 4170: Glucose transporter 2-transported glucosamine inhibits glycolysis in cancer cells through competition with glucose for hexokinase 2
Authors: Se Yong Park, Ki-Hoon Song, Ju-Hee Kang, Jung Ho Hwang, Seung Hyun Oh
Journal: Cancer Research (2025)

Abstract Anticancer effects of glucosamine, a glucose derivative with a similar structure to glucose, have been discovered, but the molecular mechanisms are not yet fully understood. Since glucosamine and glucose not only have similar structures but also are catalyzed by the same enzyme, hexokinase (HK), in this study, we delved into determining whether the anticancer effect of glucosamine involves the inhibition of glycolysis by competition with glucose. Whole-genome screening analysis showed that many of the gene pathways controlled by glucosamine were directly and indirectly involved in glycolysis. In vitro experiments revealed that as more glucose was added, the anticancer effect of glucosamine decreased. Also, we found that glucosamine was transported into cells mainly through glucose transporter (GLUT) 2 which was responsible for the anticancer effects of glucosamine. In addition, we found that cancer cells with low expression level of HKII show high sensitivity to glucosamine, and a HK inhibitor, 3-bromopyruvate, enhanced the anticancer effect of glucosamine. Under hypoxic conditions, activated hypoxia-inducible factor 1α (HIF-1α) inducing glucose uptake and glycolysis hampered glucosamine-induced cell death, and HIF1A knockdown or HK inhibitors restored glucosamine’s anticancer effects. These findings demonstrate that glucosamine is an efficient glycolysis inhibitor and that GLUT2 and HKII play important roles as biomarkers for determining sensitivity to glucosamine. Moreover, our results suggest that the anticancer effect of glucosamine may be more efficient when administered in combination with other glycolytic agents or inhibitors targeting HIF-1α. Citation Format: Se Yong Park, Ki-Hoon Song, Ju-Hee Kang, Jung Ho Hwang, Seung Hyun Oh. Glucose transporter 2-transported glucosamine inhibits glycolysis in cancer cells through competition with glucose for hexokinase 2 [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 4170.
Abstract 3195: Advancing CAR T clinical development with high-parameter CyTOF technology
Authors: Ling Wang, Shakir Hasan, Stephen Li, Michael Cohen, Deeqa Mahamed, Christina Loh
Journal: Cancer Research (2025)

Abstract Adoptive immunotherapy using chimeric antigen receptor (CAR) T cells is considered a recent revolutionary treatment in cancer therapy. CAR T therapy has achieved great success in hematological B cell malignancies. However, it has faced significant challenges in solid tumors due to various factors, such as complex tumor microenvironments, restricted trafficking, impersistent antitumor activity and toxicities. A better understanding of CAR T biology will accelerate development of CAR T therapies with improved antitumor efficacy, durability and decreased toxicities. High-parameter flow cytometry has been a powerful tool to functionally characterize CAR T cells at multiple stages of clinical development, from product characterization during manufacturing to longitudinal evaluation of the infused product in patients. However, fluorescence-based cytometry faces significant challenges with signal overlap and autofluorescence, limiting sensitivity and the number of targets that can be detected in CAR T cells. Consequently, rare cell populations are poorly resolved and functional readouts of CAR T cells are unreliable. CyTOF technology overcomes these limitations with low signal overlap and no autofluorescence. Further, CyTOF technology enables a streamlined and flexible workflow in clinical research using freezing antibody cocktails and stained cell samples. Here, we present a 40-plus-marker CyTOF panel to simultaneously analyze phenotypic and functional protein expression in CAR T cells from in vitro co-culture with tumor cells. CD19 CAR T cells were expanded in vitro and co-cultured with Nalm6 cells at different E:T ratios for 2-5 days. A high-parameter CyTOF panel including over 40 surface, cytoplasmic and nuclear markers was used to stain CAR T cells. Samples co-cultured at different time points were stained, barcoded, frozen and simultaneously acquired on a CyTOF XT system at a later date. The cytotoxicity, activation, proliferation, differentiation and exhaustion of CAR T cells were evaluated. Comprehensive profiling revealed that CAR T cells became activated, proliferated and produced cytokines in in vitro co-culture with tumor cells and showed reduced cytotoxicity and exhaustive phenotype after an extended period of expansion. Overall, we demonstrate that the high-parameter CyTOF panel enables deep functional characterization of CAR T cells by simultaneous detection of surface, cytoplasmic and nuclear markers, supporting the continuous clinical development of CAR T products. Citation Format: Ling Wang, Shakir Hasan, Stephen Li, Michael Cohen, Deeqa Mahamed, Christina Loh. Advancing CAR T clinical development with high-parameter CyTOF technology [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 3195.
Abstract 2548: Elucidating the significance of senescent tumor microenvironment in progression of pancreatic adenocarcinoma
Authors: Ankita Semwal, Anjali Aggarwal, Vinit Sharma, Mayank Sharma, Rajesh Gupta, Ritambhra Nadda
Journal: Cancer Research (2025)

Abstract Background: Oncogenes, oxidative stress, DNA damage response are typical stimulators for cellular senescence in tumor microenvironment (TME). The recent literature emphasizes on the dual nature of senescence where its tumor-promoting effects can outweigh the initial tumor-suppressive effects, especially when senescent cells accumulate and are not efficiently cleared. This study aims to see whether senescence in TME plays any role as contributing factor for the progression and relapse in pancreatic adenocarcinoma. Methodology: In 30 pancreatic adenocarcinoma tissue specimens, senescence was assessed by lysosomal mass quantification, immuno-staining of DNA damage foci, gene expression of cell cycle arrest markers and SASP factors profiling by ELISA. The relevant transcripts of metastasis, stemness and Wnt signaling were evaluated by gene and protein expression. In-vitro Doxorubicin induced senescence model (Panc-1 cells) was created and evaluated for validation of results. Results: The senescence was markedly elevated in tumor tissue, demonstrated by increased positivity of SA-β-gal, Ɣ-H2AX foci, cell cycle arrest markers (p16, p53, p21), pro-inflammatory cytokine (IL-10&amp;gt;0.0547*). The accumulated senescence was found significantly correlated with increased expression of invasiveness markers (Vimentin, and N-cadherin) stemness (Sox2, Oct4, Nanog). The co-localization of Ɣ-H2AX and Sox2 as seen in immunofluorescence microscopy concludes the presence of senescence along with stemness. Genes of Wnt signaling cascade (Wnt2&amp;lt;0.0039**; c-Myc&amp;lt; 0.0039**) which are involved in both senescence and stemness were significantly raised in pancreatic adenocarcinoma. Conclusion: Our findings highlight the critical role of metabolically active senescent cells in remodeling tumor microenvironment through secretory factors and presence of active stemness within. The senescence has positive influence on tumor promoting features like invasion, metastasis and tumor proliferation. Selective elimination of senescence can be a promising therapeutic implication considering the balance between beneficial and harmful effects of senescence in cancer treatment. Citation Format: Ankita Semwal, Anjali Aggarwal, Vinit Sharma, Mayank Sharma, Rajesh Gupta, Ritambhra Nadda. Elucidating the significance of senescent tumor microenvironment in progression of pancreatic adenocarcinoma [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 2548.
Abstract 5192: Next-generation NSCLC drug development powered by PDCs and PDOs: Mimicking real responses
Authors: Sewon Park, Min Hak Lee, Ju-hyeon Lee, Mi Ran Yun, Min Hee Hong, Sun Min Lim, Jii Bum Lee, Byoung Chul Cho
Journal: Cancer Research (2025)

Abstract Purpose: Patient-derived cells (PDCs) and organoids (PDOs) derived from pleural effusion or ascites closely mimic the biological characteristics of individual patients. In cancer research, PDCs and PDOs serve as powerful tools for replicating tumor-specific mutations, overcoming the limitations of traditional cell lines, which fail to capture the heterogeneity and complexity of human tumors. Due to their ability to predict preclinical drug efficacy more accurately, PDCs and PDOs are increasingly utilized in therapy development. This study aims to demonstrate the potential of PDCs and PDOs as effective platforms for screening novel therapeutic strategies for non-small cell lung cancer (NSCLC). Experimental design: Malignant effusions were samples were tested for malignancy, processed, observed by light microscopy, and cultured. The establishment of a PDC was considered complete when it was free of normal cells, maintained known patient tumor mutation, and recapitulated patient’s response. Also, mutations that cell harbors are confirmed by Sanger sequencing, Whole exome sequencing, or RNA-sequencing. Results: Total of 54 PDCs and 171 PDOs were established from NSCLC patients, including models harboring various EGFR, KRAS and BRAF mutations and EML4-ALK or ROS1-CD74 fusions. Particularly the 8 models of PDC and 7 models of PDO harbor mutations which are well known for resistance mechanisms to EGFR-TKIs (T790M, C797S/C797G, MET amplification). Also, some models of PDCs were harboring uncommon EGFR mutations(EGFR G719S, L861Q, S768I etc.).For example, YUO-139 and YU-1092 are patient derived models that harbors uncommon EGFR mutation G719S and L861Q respectively. The models response to afatinib sensitively. IC50 of YUO-139 and YU-1092 to afatinib were 2.1 nM and 23.8 nM respectively. These models were evaluated for novel strategies for targeting uncommon EGFR mutations. Another example is YUO-143, which harbors EGFR mutations E19del/T790M/C797S and was derived from a patient resistant to gefitinib and mavelertinib. YUO-143 was used in the development of the 4th gen TKI, BLU-945, and showed an IC50 of 43 nM. Conclusions: Patient-derived models could serve as a crucial tool in developing novel therapeutic strategies and next-generation drugs for NSCLC. Citation Format: Sewon Park, Min Hak Lee, Ju-hyeon Lee, Mi Ran Yun, Min Hee Hong, Sun Min Lim, Jii Bum Lee, Byoung Chul Cho. Next-generation NSCLC drug development powered by PDCs and PDOs: Mimicking real responses [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 5192.