tbuckley/cabot-search huggingface dataset:
Abstract 3208: Immunomodulatory potential of mormodica balsamina crude extract as an immune checkpoint inhibitor on human cancer cells using chicken egg chorioallantoic membrane model
Authors: Portia Pheladi Raphela-Choma, Mpho Suzan Choene, Lesetja Raymond Motadi
Journal: Cancer Research (2025)

Abstract The chorioallantoic membrane (CAM) is widely used as an in vivo model for the evaluation of tumorigenesis. Immune checkpoint molecules play a critical role in the immune system, respond to various infections, and protect against tissue damage. The purpose of this study was to investigate the immunomodulatory potential of Mormodica balsamina (MMB) crude extract in colorectal cancer cells using the CAM model. Human colon cancer cells were transplanted onto the CAM membrane of fertilized eggs, resulting in tumor development. The crude extract was injected intravenously into the chicken egg at different dosages. Comparative studies of the effect of MMB crude extract on colon cancer xenografts were conducted. The crude extract exhibited efficacy in inhibiting tumor progression and metastasis. The proteins (PDL1 and LAG3) were lowly expressed to inhibit cancer proliferation and promote apoptosis. In conclusion, the chicken egg tumor model has shown to be valuable in testing medicinal plants as therapies for human colon cancers. The crude extract may have the potential to be used as a drug target in future studies. Citation Format: Portia Pheladi Raphela-Choma, Mpho Suzan Choene, Lesetja Raymond Motadi. Immunomodulatory potential of mormodica balsamina crude extract as an immune checkpoint inhibitor on human cancer cells using chicken egg chorioallantoic membrane 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 3208.
Abstract 4832: Differential roles of histone lactylation in regulating CD8 T cell effector functions and exhaustion
Authors: Deblina Raychaudhuri, Pratishtha Singh, Bidisha Chakraborty, Aminah Tannir, Swadhin Meher, Sangeeta Goswami
Journal: Cancer Research (2025)

Abstract CD8 T cells undergo metabolic reprogramming upon activation to meet the increased energy demands associated with their cytotoxic functions. A hallmark of CD8 T cell activation is the upregulation of glycolysis, accompanied by increased lactate production. Lactylation, a post-translational modification of histones, derived from lactate, has garnered attention, though its specific role in CD8 T cell biology remains unclear. We have recently demonstrated the enrichment of histone lactylation marks, specifically H3K18-lactylation (H3K18la) and H3K9-lactylation (H3K9la), in human and murine CD8 T cells. Integrating ChIP-sequencing and RNA-sequencing data, we delineated the role of histone lactylation as transcriptional regulators of key genes essential for CD8 T cell-mediated cytotoxicity and effector functions. Importantly, our results, obtained from both in vitro experiments and in vivo disease models demonstrated that H3K18la and H3K9la exert differential effects across various CD8 T cell populations intricately tied to the metabolic profiles of distinct CD8 T cell subsets. Effector CD8 T cells, characterized by elevated glycolytic activity, exhibited correspondingly high levels of histone lactylation. In contrast, terminally exhausted CD8 T cells, where both glycolysis and mitochondrial metabolic pathways are impaired, displayed a marked reduction in histone lactylation. These cells were instead predominantly regulated by histone acetylation. Notably, co-immunoprecipitation assays revealed distinct epigenetic readers that specifically recognized histone lactylation marks, differentiating them from those binding to histone methylation or acetylation modifications. Modulating histone lactylation marks through metabolic and epigenetic interventions significantly altered CD8 T cell effector functions, including anti-tumor responses in preclinical models. Cumulatively, our findings demonstrated that histone lactylation, driven by intrinsic metabolic processes, regulates key aspects of CD8 T cell metabolism and function. Further, we identified distinct epigenetic mechanisms by which selective targeting of H3K18la and/or H3K9la can be leveraged to modulate CD8 T cell phenotype and functionality. Citation Format: Deblina Raychaudhuri, Pratishtha Singh, Bidisha Chakraborty, Aminah Tannir, Swadhin Meher, Sangeeta Goswami. Differential roles of histone lactylation in regulating CD8 T cell effector functions and exhaustion [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 4832.
Abstract 5382: Comprehensive characterization of renal cell carcinomas identifies metabolic reprogramming of the tumor microenvironment associated with disease progression
Authors: Kirsteen H. Maclean, Lakshmi Chandramohan, Qingyan Au, Harry Nunns, Jiong Fei, Erinn Parnell, Anna Juncker-Jensen
Journal: Cancer Research (2025)

Abstract Background: Renal cell carcinoma (RCC) is one of the most frequent urological cancers with the most common histological subtype being clear cell renal cell carcinoma (ccRCC), an immunologically and histologically diverse tumor which is associated with a poor clinical outcome as up to 40% of ccRCC patients develop metastases. While significant progress has been made in the development of immunotherapy for ccRCC, there are still many unanswered questions about the mechanisms of immune evasion and resistance, and the development of predictive biomarkers for optimal treatment strategies for individual patients. Recently, it has become clear that cellular metabolism may play a significant role in the immune response to ccRCC tumors, affecting both the ability of T-cells to function and the overall composition of the tumor microenvironment (TME). This remodeled TME leads to changes in nutrients and metabolites that can promote an immunosuppressive environment and prevent lymphocyte activation and recruitment, eventually promoting T-cell exhaustion. Methods: We performed transcriptomic and spatial profiling of 16 ccRCC patient samples across all clinical TNM stages (Stages I-IV) to define the changes in metabolic processes and infiltrating immune cells with advancing disease. Specifically, we included the spatial MultiOmyx™ IF multiplexing assay (NeoGenomics Laboratories, Inc.) using the new MO2.0 workflow with enhanced whole slide capability coupled to the NanoString nCounter® Metabolic Pathways Panel to investigate metabolic reprogramming, cellular stress, and the relationship to the composition of the TME in advancing disease progression in ccRCC. Results and Conclusions: We identified significant changes associated with the TME, especially immunosuppressive immune cells in advanced disease, coupled to the identification of several metabolism-related genes that correlated with immune infiltrates in ccRCC. Identifying and understanding these metabolic alterations within the different staging of RCC will help in designing new targeted therapies and improving diagnostic tools to better care for patients with this disease. Citation Format: Kirsteen H. Maclean, Lakshmi Chandramohan, Qingyan Au, Harry Nunns, Jiong Fei, Erinn Parnell, Anna Juncker-Jensen. Comprehensive characterization of renal cell carcinomas identifies metabolic reprogramming of the tumor microenvironment associated with disease progression [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 5382.
Abstract 5742: Synthesis of substituted benzimidazole tetrahydropyridines as anti-breast cancer agents
Authors: Kinfe Ken Redda, Madhavi Gangapuram, Absera W. Haile, Suresh Eyunni
Journal: Cancer Research (2025)

Abstract Breast cancer is the most common type of cancer worldwide. In 2023, the World Health Organization (WHO) reported that 2.3 million women were diagnosed with breast cancer, leading to 670, 000 deaths. Furthermore, the incidence rates of breast cancer have been rising at 3% each year. Overexpression of COX-2 in breast cancer tissues is associated with poor prognosis, including higher tumor grade, increased metastatic potential, and resistance to therapy. Selective COX-2 inhibitors have demonstrated potential in reducing tumor growth in preclinical and some clinical studies. These inhibitors may also enhance the effectiveness of chemotherapy and radiotherapy. The benzimidazole nucleus is a valuable subunit for the development of pharmaceuticals and biologically relevant molecules. Tetrahydropyridine (THP)analogs are compounds with diverse biological activities, including analgesics, anti-inflammatory agents, and chemotherapeutic agents. Our previous research findings indicated that the THP derivatives exhibited COX-2 inhibition and demonstrated anti-inflammatory effects in rat paw edema assays. The pharmacological activities of THP derivatives depend on the nature of the substituents in the THP ring system. The incorporation of a benzimidazole moiety may enhance the biological activity of these THP derivatives. Thus, the design and synthesis of novel series of benzimidazole-THP derivatives with potential anticancer and anti-inflammatory activities were initiated. In the current investigation, we synthesized numerous analogs maintaining the N-(5-(1H-benzo[d]imidazol-2-yl)-3, 6-dihydropyridin-1(2H)-yl)benzamide/benzene sulfonamide having modifications on the phenyl ring. We expect that these structural modifications would affect the compounds electron density, lipophilicity and the compounds steric configurations. The starting material 2-(pyridin-3-yl)-1H-benzo[d]imidazole was obtained by the reaction of nicotinic acid, 1, 2-phenyldiamine and polyphosphoric acid by stirring in an oil bath at 180o C for 2 h. N-Amination of substituted 2-(pyridin-3-yl)-1H-benzo[d]imidazole by an aminating agent O-(mesitylsulfonyl)hydroxylamine (MSH), followed by ylide formation and further reduction yielded the desired substituted N-(5-(1H-benzo[d]imidazol-2-yl)-3, 6-dihydropyridin-1(2H)-yl)benzamide derivatives. Final compounds were analyzed via NMR spectroscopy, IR and elemental analysis. The analogs were evaluated for through docking studies. Two products showed significant anti-inflammatory and anti-breast cancer activities. Citation Format: Kinfe Ken Redda, Madhavi Gangapuram, Absera W. Haile, Suresh Eyunni. Synthesis of substituted benzimidazole tetrahydropyridines as anti-breast cancer agents [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 5742.
Abstract 6365: A novel methylation-based classifier to identify cancer signal of origin using blood based testing
Authors: Elmira Forouzmand, Yupeng He, Rachel Gittelman, Alan Selewa, Meromit Singer, Jill Tsai, Theresa Hoang, Jack Tung, Victoria M. Raymond, Amirali Talasaz, Darya Chudova
Journal: Cancer Research (2025)

Abstract Background: Accurate prediction of the cancer signal of origin (CSO) is crucial for blood-based cancer detection in order to guide subsequent diagnostic workups and select the appropriate therapeutic regimes. Here, we present feasibility data from a novel, methylation-based classifier which is able to differentiate the histological origin of 12 cancer types from a single blood-based screening assay. Method: We developed an algorithm on Guardant Infinity®, a next-generation sequencing platform evaluating cell free DNA from plasma samples, to predict the CSO of 12 cancer types (bladder, breast, colorectal, esophageal, kidney, liver, lung, ovarian, pancreatic, prostate, stomach, and uterine/endometrial). This algorithm uses two steps to predict CSO based on the DNA methylation signature of plasma cell-free molecules from &amp;gt;2000 cancer-specific differentially methylated genomic regions. First, a regression model (multi-cancer classifier) was trained using 701 cancer samples across 17 distinct cancer types and 10, 413 non-cancer samples to identify cancer samples with sufficient tumor-derived methylation signal. Next, a methylation-based CSO classifier was used to determine the CSO of samples called positive by the multi-cancer classifier. The CSO classifier was trained on 13, 856 cancer samples from 12 supported cancer types and 4, 142 non-cancer samples, and assessed on 1, 464 advanced cancer samples that were called cancer positive by the cancer detection classifier in the hold out set. Results: Among the 1464 detected cancer samples, 88.2% (1291 / 1464) were correctly classified by the CSO classifier with the top prediction, and 93.6% (1370 / 1464) were correctly classified with the top two predictions. To estimate the real-world performance of this algorithm, the accuracy of the CSO classifier for different cancer types were weighted by the cancer incidence rate in the US population and then aggregated. These adjusted accuracies of the top CSO prediction and top 2 CSO predictions are 88.5% and 93.0%, respectively. Conclusion: Herein, we demonstrate the capability of a novel, methylation-based algorithm to predict CSO with high sensitivity and accuracy from a plasma-based sequencing platform. Further clinical validation in early cancer detection and disease monitoring is needed. Citation Format: Elmira Forouzmand, Yupeng He, Rachel Gittelman, Alan Selewa, Meromit Singer, Jill Tsai, Theresa Hoang, Jack Tung, Victoria M. Raymond, Amirali Talasaz, Darya Chudova. A novel methylation-based classifier to identify cancer signal of origin using blood based testing [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 6365.
Abstract 6927: Novel ferrocene and naphthalene-based analogs block HRH1-signaling to inhibit colon cancer growth
Authors: Affan Ahmad Ansari, Dileepkumar Veeragoni, Ahraar Azaz, Sangita Bhattacharya, Hindole Ghosh, Bernhard Biersack, Prasad Dandawate
Journal: Cancer Research (2025)

Abstract Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide, with over 1.8 million incidences and 900, 000 deaths annually. CRC persists as a significant clinical challenge, detailing a 5-year survival rate of 14% for patients with distant metastases. CRC exhibits high genetic heterogeneity, which supplements a rich mutational landscape that gives rise to aggressive phenotypes. Therefore, there is a pressing need to identify novel and effective therapeutics to target CRC alongside identifying niche molecular pathways that contribute to pathogenesis. Here, we report the identification and formulation of novel histamine receptor 1 (HRH1) antagonists that inhibit CRC cell growth. Ferrocene (Fc) analogs are interesting due to their excellent lipophilicity, redox nature and anticancer activity. We synthesized a series of Fc and naphthalene-based compounds and tested them against colorectal cancer (CRC) cells HCT-116 and DLD-1. Compounds C10 and C12 inhibited the growth of CRC cells (IC50 = 0.5-1 mM), colony formation and induced apoptosis by downregulating bcl2 and mcl1 levels. We identified that both C10 and C12 bind to histamine receptor 1 (HRH1) using molecular docking studies. HRH1 is overexpressed in CRC cells and tissues compared to noncancerous colonic tissue. Further, histamine treatment activated ERK and GSK3β phosphorylation time-dependently in CRC cells, suggesting the receptor's functionality. Moreover, preincubation of C10 and C12 with CRC cells inhibited histamine-induced ERK and GSK3β phosphorylation, suggesting that C10 and C12 block HRH1 to inhibit histamine signaling. Further, a cellular thermal shift assay (CETSA) showed protection from thermal denaturation in C10 and C12 treated groups, suggesting a protein stabilization and potential binding of C10 and C12 with HRH1. Finally, C10 and C12 treatment (20 mg/kg, i.p., once daily, 21 days) reduced tumor volume and weight in HCT116-xenograft growth in NSG mice. In conclusion, we discovered novel HRH1 antagonists to inhibit colon cancer growth. Citation Format: Affan Ahmad Ansari, Dileepkumar Veeragoni, Ahraar Azaz, Sangita Bhattacharya, Hindole Ghosh, Bernhard Biersack, Prasad Dandawate. Novel ferrocene and naphthalene-based analogs block HRH1-signaling to inhibit colon cancer growth [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 6927.
Abstract 5749: Determination of the mTOR inhibitor temsirolimus and its active metabolite sirolimus in human blood, plasma, cerebrospinal fluid, and brain tumor tissue using a validated LC-MS/MS assay
Authors: Gerold S. Kaplan, Tigran Margaryan, Nader Sanai, Artak Tovmasyan
Journal: Cancer Research (2025)

Abstract Temsirolimus is an FDA approved mTOR (mammalian target of rapamycin) inhibitor that is presently under investigation in multiple clinical trials for various cancers, including for recurrent high-grade glioma. Here, we report A robust, sensitive, and extremely rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of total concentrations of temsirolimus and its active metabolite sirolimus in human blood, plasma, brain tumor and cerebrospinal fluid (CSF) samples. The method was validated for the simultaneous determination of both analytes over a concentration range of 1-1000 nM within a total run time of 2.6 min. Simple one-step protein precipitation with methanol was employed to extract analytes from biomatrices. Chromatographic separation of analytes was achieved on Kinetex™ EVO C18 (50 × 2.1 mm, 1.7 µm) column using gradient elution with mobile phases of 5 mM ammonium formate and methanol at a flow rate of 0.5 mL/min and an injection volume of 5 µL. Detection was performed with a Sciex QTRAP 6500+ mass spectrometer, utilizing multiple reaction monitoring mode to register the precursor-to-product ion transitions under positive electrospray ionization. The maximum coefficient of variation for both intra- and inter-day precision was 12.3%, with accuracy ranging from 85.6% - 114.2% in all matrices. Combined temsirolimus and sirolimus samples were determined to be stable at room temperature (RT) in whole blood and brain homogenate for at least 4 hours and in plasma for at least 1 hour. At -80±15°C in a freezer, samples in plasma, brain homogenate, and whole blood were stable for at least 132 days. Stock and working solution stability was also evaluated to be stable for at least 4 hours (RT) and 113 days (-20°C nominal for stock solutions and 4°C for working solutions). The validated method is currently employed in a clinical trial evaluating the efficacy of super-selective intra-arterial infusion for the CNS delivery of temsirolimus in recurrent high-grade glioma patients (NCT05773326) to determine temsirolimus and sirolimus pharmacokinetics in blood, brain tumor, plasma, and CSF. Citation Format: Gerold S. Kaplan, Tigran Margaryan, Nader Sanai, Artak Tovmasyan. Determination of the mTOR inhibitor temsirolimus and its active metabolite sirolimus in human blood, plasma, cerebrospinal fluid, and brain tumor tissue using a validated LC-MS/MS assay [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 5749.
Abstract 5710: Anticancer effects of 2,3-<i>bis</i>(bromomethyl)-quinoxaline 1,4-dioxide on uterine cancer
Authors: Kaitlyn Mayo, Kennedy Szabo, Calli A. Davison-Versagli
Journal: Cancer Research (2025)

Abstract Uterine cancer will claim an estimated 17, 610 lives in the United States in the year 2024. Lack of funding and focus have resulted in little advancement in treatment options for uterine cancer patients. Consequently, uterine cancer incidence and mortality have consistently increased since the 1990’s in the United States. Thus, further investigation and development of uterine cancer therapies is needed. The Peroxiredoxins (I-VI) family of enzymes is responsible for eliminating reactive oxygen species throughout the cell and has been studied in multiple organisms and diseases, including cancer. The compound 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide (Conoidin A) is a Peroxiredoxin II inhibitor that has been studied in the parasite, Toxoplasma gondii. It inhibits the enzymatic activity of Peroxiredoxin II when studied in vitro by covalently binding to cysteine. Recent reports identify Peroxiredoxin II as a potential therapeutic target for cancer therapies and indicate that Peroxiredoxin II down-regulation promotes cancer cell death. Thus, the purpose of these studies was to evaluate Conoidin A as a potential therapeutic for uterine cancer. Here, we report that concentrations of 100 μM, 75 μM, and 50 μM of Conoidin A decreased growth of the uterine cancer cell line, HEC-1-A, after 24 hours as measured using crystal violet assays. Conoidin A concentrations of 100 μM, 75 μM, and 50 μM compromised anchorage-independent growth of HEC-1-A cells in soft agar assays. Furthermore, p53 up-regulation (p53+) correlates with poor prognosis in uterine cancer patients. To determine if Conoidin A is capable of decreasing growth of p53+ tumors, increasing Conoidin A concentrations were tested on the p53+ cell line, C-33a, using crystal violet assays. Preliminary studies found Conoidin A abolishes C-33a growth at concentrations of 100 μM, 75 μM, and 50 μM after 24 hours of treatment. These data identify Conoidin A as a potential therapeutic for uterine cancer, including p53+ tumors. Furthermore, these studies establish Peroxiredoxin II as a novel therapeutic target for this disease. Citation Format: Kaitlyn Mayo, Kennedy Szabo, Calli A. Davison-Versagli. Anticancer effects of 2, 3-bis(bromomethyl)-quinoxaline 1, 4-dioxide on uterine cancer [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 5710.