tbuckley/cabot-search huggingface dataset:
Abstract 977: Metabolomic and proteomic signatures of ultra-processed foods with liver cancer and liver disease
Authors: Longgang Zhao, Yun Chen, Alyssa Clay-Gilmour, Jiajia Zhang, Xuehong Zhang, Susan Steck
Journal: Cancer Research (2025)

Abstract Introduction: Higher intake of ultra-processed foods is associated with increased risk of obesity and type 2 diabetes, but evidence is limited on associations of metabolomics and proteomics with ultra-processed foods and liver diseases. We aimed to evaluate associations of metabolomic and proteomic signatures related to ultra-processed food intake with liver cancer and liver disease. Methods: Data from a total of 173, 840 participants aged 40-69 years from the UK Biobank were analyzed. Ultra-processed food intake was assessed by 24-hour dietary recalls. Metabolites were measured by nuclear magnetic resonance spectroscopy and plasma proteome was profiled using the Olink platform. Liver disease outcomes were ascertained using data from the in-hospital, cancer registry, and death registry including metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and severe liver disease (hepatocellular carcinoma and other severe liver diseases). Elastic net regression with 10-fold cross validation was used to calculate the omics signatures related to ultra-processed food intake. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for ultra-processed food intake and its omics signatures and liver disease outcomes adjusting for multiple potential confounding factors. Results: With a median of 8.9 years follow-up, ultra-processed food intake was positively associated with risk of MASLD (HR Tertile 3 vs. tertile 1 1.42; 95% CI 1.21-1.67), cirrhosis (HR 1.25; 95% CI 1.05-1.48), and severe liver disease (HR 1.52; 95% CI 1.21-1.91) but not with liver cancer (HR 1.30; 95% CI 0.89-1.91). The metabolic signature score of ultra-processed foods was positively associated with risk of MASLD (HR 3.25; 95% CI 2.06-5.14). The proteomic signature score of ultra-processed foods was positively associated with risk of MASLD (HR 1.99; 95% CI 1.04-3.80) and cirrhosis (HR 2.00; 95% CI 1.12-3.60). A total of 34 metabolites and 65 proteins were significantly associated with ultra-processed food intake based on the multivariable-adjusted model and elastic net regression. These metabolites and proteins are linked to biological pathways such as lipids metabolism, oxidative stress, and inflammatory response. Conclusions: Ultra-processed food intake and its metabolic and proteomic signatures are positively associated with risk of adverse liver outcomes. Citation Format: Longgang Zhao, 1 Yun Chen, 1 Alyssa Clay-Gilmour, 2 Jiajia Zhang, 2 Xuehong Zhang, 1 Susan Steck2. Metabolomic and proteomic signatures of ultra-processed foods with liver cancer and liver disease [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 977.
Abstract 1002: BRCA2, ATM, and POT1 genes mutations in Chilean hereditary gastric cancer families
Authors: Graciela Adriana Molina Fuentes, Ana Patricia Estrada-Florez, Paul Lott, Osvaldo Torres, Cedric Adelsdorfer, Alejandro H Corvalán, Luis Carvajal-Carmona
Journal: Cancer Research (2025)

Abstract The purpose of this study is to describe Chilean families having hereditary Gastric Cancer (GC) presenting pathogenic mutations in BRCA 2 (c.4740_4741dup NP_000050.3:p.Glu1581fs), ATM (c.3381_3384del NP_000042.3:p.Gln1128fs) and Protector of Telomers 1 (POT1, 1087C&amp;gt;T:p.Arg363Ter) genes. Only one hereditary diffuse GC (HDGC) Chilean family with a pathogenic CDH1 mutation has been reported, suggesting a low frequency of pathogenic mutation detection in this population. Whole exome sequencing (WES) was performed using the Agilent SureSelect Human All Exome V7 kit and sequenced in a NovaSeq6000 (Illumina, Inc.) S4 150PE aiming 100x. Alignment and variant calling were performed using Illumina Dragen v3.8. Variant calls were re-calibrated using GATK v4 variant recalibration and annotated with Illumina Nirvana and Annovar. Genotypification of the index patient and their family was performed using KASP-PCR. The index patient having a BRCA2 mutation had metastatic HDGC and his mother had asynchronous breast cancer and GC. The family presenting an ATM gene mutation had three GC-affected subjects, the index patient, and both parents. The index patient of the family having a POT1 mutation presented a CG at 47 yr., and two of her children died of CG at 24 yr. All families show an incomplete penetrance and variable expressivity. We are searching for the second hit in the index patient´s tumor samples. This is the first report of a POT1 gene mutation detected in a hereditary GC. POT1 belongs to the shelterin complex that protects telomeres. This mutation affects the binding to the shelterin complex, and it was previously reported in colorectal cancer. Beca Chile Postdoctorado 74190063, CONICYT-FONDAP 15130011 /ANID-FONDAP APOYO 1523A0008, NIH R01CA223978, R21CA199631, U54CA233306, and P30CA093373. Citation Format: Graciela Adriana Molina Fuentes, Ana Patricia Estrada-Florez, Paul Lott, Osvaldo Torres, Cedric Adelsdorfer, Alejandro H Corvalán, Luis Carvajal-Carmona. BRCA2, ATM, and POT1 genes mutations in Chilean hereditary gastric cancer families [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 1002.
Abstract 1051: Predicting stroke as a cause of death in Black cancer patients using ensemble machine learning models
Authors: Raghad Wesamah Alrawashdeh, Nour Wesamah Alrawashdeh
Journal: Cancer Research (2025)

Abstract Objective: No studies have sought to identify the risk factors associated with cerebrovascular diseases (CVD) as a cause of death in black cancer patients. This study aimed to use advanced machine learning techniques to predict CVD mortality in Black cancer patients and to identify significant risk factors. Methods: We utilized The Surveillance, Epidemiology, and End Results 17 registry to predict CVD as a cause of death in Black cancer patients from January 1, 2000, to December 31, 2020. Various machine learning models were employed, including Random Forest, Logistic Regression, XGBoost, LightGBM, and Gradient Boosting. The dataset included features such as age, sex, cancer type, year of diagnosis, and treatment modalities including adjuvant chemotherapy, adjuvant radiotherapy, adjuvant chemoradiotherapy, surgery alone, primary chemotherapy, primary radiotherapy, primary chemoradiotherapy, and no treatment. Data preprocessing involved cleaning, feature selection, and 80-20 stratified train-test splitting. The models were combined into a voting ensemble to leverage their strengths. The performance of each model was evaluated using metrics including accuracy, AUC (macro, micro, weighted), precision, recall, and F1 scores. Feature importance was analyzed to identify the most contributing variables in predicting CVD. Results: A total of 292, 680 black cancer patients were included, with a mean age of 57.36 ± 13.68 years. The cohort comprised 152, 991 males (52.27%) and 139, 689 females (47.73%). Among them, 5, 874 patients (2.01%) died from cerebrovascular diseases, while 286, 806 patients are alive. The voting ensemble model achieved an accuracy of 0.98, with an AUC macro of 0.88, AUC micro of 0.99, and AUC weighted of 0.88. The average precision scores were 0.64 (macro), 0.99 (micro), and 0.98 (weighted). The F1 scores were 0.64 (macro), 0.98 (micro), and 0.97 (weighted). The precision scores were 0.78 (macro), 0.98 (micro), and 0.97 (weighted). Significant predictors of CVD included an earlier year of diagnosis (with patients diagnosed earlier in the study period from 2000 to 2020 having a higher risk of CVD), older age, lack of any cancer treatment, and specific cancer types (notably gastrointestinal and male genital cancers). Conclusions: Our findings suggest that the voting ensemble machine learning model can effectively predict stroke mortality in black cancer patients, with high accuracy and robust performance metrics. Citation Format: Raghad Wesamah Alrawashdeh, Nour Wesamah Alrawashdeh. Predicting stroke as a cause of death in Black cancer patients using ensemble machine learning 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 1051.
Abstract 521: Drug repurposing via ultra-high throughput 3D spheroids screening in rare cancer treatment
Authors: Marybeth G. Yonk, Muhibullah S. Tora, Megan A. Lim, Thais Federici, Haian Fu, Yuhong Du, Bing Yao, Nicholas Boulis, Kecheng Lei
Journal: Cancer Research (2025)

Spinal cord gliomas (SCG) are rare cancers, and relevant pharmaceutical research and treatments are limited. While drug repurposing of FDA-approved compounds has shown promise for orphan diseases, its potential for SCG remains uncertain. Our research team has recently developed an SCG model in minipigs, offering anatomical, immunological, developmental, and genetic similarities to humans, which makes it an ideal model for translational precision medicine. In this study, we used a novel drug repurposing strategy using 3D spheroids from our recently established large animal SCG model as a case study. First, we established a miniaturized 3D cell culture platform for ultra-high-throughput screening (uHTS). After screening the FDA-approved and Bioactive compound library with minipig SCG 3D spheroids, Clofoctol, showed potential as a glioma treatment by targeting genes in the p53 pathway. Evaluation in a xenograft model demonstrated Clofoctol's ability to suppress tumor growth over a 10-day treatment period, followed by immunohistochemistry and RNA-seq. These findings suggested Clofoctol is a promising therapeutic for glioma treatment. Thus, our study shows the feasibility of 3D spheroids uHTS to expedite orphan disease research, providing a strategy for future drug repurposing for rare cancer patients. Citation Format: Marybeth G. Yonk, Muhibullah S. Tora, Megan A. Lim, Thais Federici, Haian Fu, Yuhong Du, Bing Yao, Nicholas Boulis, Kecheng Lei. Drug repurposing via ultra-high throughput 3D spheroids screening in rare cancer treatment [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 521.
Abstract 1031: Cervical cancer awareness program in Rio Grande Valley (RGV) colonias: empowering communities through our cervical cancer prevention action network (CCPAN) program
Authors: Swati Mohan, Bhupendra B. Srivastava, Murali M. Yallapu, Subhash C. Chauhan
Journal: Cancer Research (2025)

Cervical cancer remains a significant health challenge, particularly in underserved communities of US-Mexico trans-border Rio Grande Valley (RGV) region. This region represents remarkably higher cervical cancer health disparities. Thus, to improve awareness about cervical cancer in the RGV Colonias by providing crucial evidence-based information on the prevention, early detection, and available clinical resources is utmost desirable in this RGV region. Towards this, we have established a unique cervical cancer prevention action network (CCPAN) program to cater to this need of the community. Our approach towards the awareness of cervical cancer through community engagement and by explaining what cervical cancer is, its risk factors, symptoms, importance of Human Papillomavirus (HPV) vaccination, and right dose schedule of HPV vaccination in our visits to underserved Hispanic population of RGV Colonias. We also explain etiology and progression of HPV infection through our small dramatic representation, videos and cartoons. Additionally, we provide information to the residents of Colonia about the importance of regular Pap tests and HPV tests in early detection of cervical cancer. Moreover, we also provide patients navigation information to local clinics and healthcare facilities that offer cervical cancer, HPV screenings and HPV vaccinations. We encourage people to get vaccinated, get screened, and spread the word at grass root level in the communities. Through our CCPAN program, we are also developing a database regarding Demographics, Knowledge and Awareness, Screening and Prevention, Attitudes and Beliefs, and Awareness of Local Resources. So far, the data that we have collected is alarming and is very different compared to nationwide data. Our collected data from RGV colonias suggest that communities have very limited information related to cervical cancer (30%), causes of cervical cancer (5%), awareness of HPV vaccine (30%) and timely receiving of HPV vaccine (30%). This situation appears alarming and RGV colonias communities required urgent community support to reduce cervical cancer health disparities in the region. We believe that our unique CCPAN program has very high potential to educate and empower the RGV colonias communities to take proactive steps in preventing cervical cancer, that can ultimately lead to reduce cervical cancer health disparities in the RGV. Citation Format: Swati Mohan, Bhupendra B. Srivastava, Murali M. Yallapu, Subhash C. Chauhan. Cervical cancer awareness program in Rio Grande Valley (RGV) colonias: empowering communities through our cervical cancer prevention action network (CCPAN) program [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 1031.
Abstract 551: The FOXC2 transcription factor inhibitor MC-1-F2 alters the chemosensitivity of B16-F10 melanoma cells
Authors: Baylor F. Jenkins, Kristian M. Hargadon
Journal: Cancer Research (2025)

Abstract Melanoma, the most aggressive form of skin cancer, is highly resistant to diverse classes of chemotherapeutics. The FOXC2 transcription factor, which is dysregulated in many cancers, has been linked with drug resistance in cancers of epithelial origin. We have recently identified a role for FOXC2 in the progression of melanoma. To investigate whether FOXC2 contributes to chemoresistance in this cancer, we have evaluated B16-F10 melanoma cell susceptibility to diverse classes of chemotherapeutic agents following treatment with the FOXC2 inhibitor MC-1-F2. We report increased anti-tumor activity when MC-1-F2 is used in combination with 5-fluorouracil, doxorubicin-HCl, or gemcitabine, highlighting the potential of this inhibitor as a novel chemosensitizing anti-cancer agent. Citation Format: Baylor F. Jenkins, Kristian M. Hargadon. The FOXC2 transcription factor inhibitor MC-1-F2 alters the chemosensitivity of B16-F10 melanoma cells [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 551.
Abstract 1189: MYB-driven extracellular vesicle-associated microRNAs in pancreatic cancer: potential significance in pathobiology and biomarker development
Authors: Shashi Anand, Kunwar Somesh Vikramdeo, Mohammad Aslam Khan, Seema Singh, Moh'd Khushman, Ajay Pratap Singh
Journal: Cancer Research (2025)

Abstract The oncogenic transcription factor MYB is aberrantly expressed in pancreatic cancer (PC), where it plays a key role in tumor progression and metastasis. Our previous studies have demonstrated that MYB supports hypoxic survival through metabolic reprogramming and modulates the cellular secretome, highlighting its potential role in shaping the pancreatic tumor microenvironment (TME). Extracellular vesicles (EV), secreted by nearly all cell types, carry a wide range of biological molecules and serve as crucial mediators of intercellular communication. microRNAs (miRNAs) are among the most abundant EV cargo components, regulating a variety of gene targets through post-transcriptional mechanisms. In this study, we investigated the impact of MYB on EV shedding and EV encapsulated miRNA cargo. EV were isolated from the conditioned media (CM) of endogenous MYB-overexpressing non-targeting sgRNA-transfected control cells (MYBCtrl) and MYB knockout (MYBKO) cells by differential-speed centrifugation and subjected to nanoparticle tracking analysis (NTA), RNA isolation, and next-generation small RNA sequencing (sRNA-seq). NTA revealed that MYBKO cells released a higher number of large EV (LEV) and a reduced number of small EV (SEV) compared to the MYBCtrl PC cells, while no significant differences in medium-sized EV (MEV) were observed. Through sRNA-seq, we identified differential levels of 215 miRNAs in SEV, with 99 miRNAs exhibiting lower and 116 higher levels in MYBKO cells relative to MYBCtrl cells. Gene ontology (GO) and KEGG pathway enrichment analyses of the target genes associated with these differentially-present miRNAs revealed their involvement in various biological processes, including small GTPase-mediated signal transduction, cellular growth, apoptosis, histone modification, axon guidance, immune suppression, and extracellular matrix degradation. Together, these findings suggest a novel role for MYB in stromal remodeling by regulating EV release and biogenesis, as well as influencing the miRNA content of EV in PC cells. This insight could pave the way for the development of targeted therapeutic interventions and novel diagnostic and prognostic biomarkers for pancreatic cancer. Citation Format: Shashi Anand, Kunwar Somesh Vikramdeo, Mohammad Aslam Khan, Seema Singh, Moh'd Khushman, Ajay Pratap Singh. MYB-driven extracellular vesicle-associated microRNAs in pancreatic cancer: potential significance in pathobiology and biomarker development [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 1189.
Abstract 805: Macrophages protect salivary glands from ionizing radiation
Authors: Dimitri Scofield, Cristina Paz, Jasmine Robinson, Kwang Nickel, Randy Kimple
Journal: Cancer Research (2025)

Abstract Background: Radiation-induced xerostomia (RIX) is a common side-effect of radiation therapy in patients with head and neck cancer. Our group has previously demonstrated that MSC(M) injection into irradiated murine SMG tissue results in an improvement in salivary function and improvement in glandular health (% saliva in MSC v PBS groups). which corresponds to alterations in macrophages. Our clinical studies have demonstrated that MSC(M) injection into salivary glands is safe and effective. However, the full mechanism behind this effect remains unknown. We hypothesized that MSC(M)s in the SMG are affectingimpact tissue-resident macrophage activity and/or promotein macrophage traffickingg the influx of new macrophages to mediate improved salivary function. Here we test whether macrophages modulate the response to radiation in our mouse model of RIX and whether MSC(M)s can modulate salivary tissue resident macrophages. Methods: Clodronate liposomes delivered via tail vein injection were used to deplete macrophages in C57/BL6 mice prior to irradiation treatment (15 Gy) of SMGs with 15 Gy. Saliva production was monitoredmonitored, and glands were collected for histology at 3-, 7-, and 60-days post-irradiation. Primary, marrow-derived MSCs (MSC(M)) from C57/B6 male mice were isolated, cultured, and characterized using the immune monitoring 48-plex Luminex assay to characterize the secretion profile of immunomodulatory chemokines. Results: Macrophage depletion was confirmed via flow cytometry of mouse spleens. Clodronate-treated mice produced less saliva than control mice (92% vs 71% percent decrease respectively) consistent with a protective effect of macrophages. Secretome analysis of MSC(M) revealed a robust secretion profile with high levels of macrophage associated proteins including CCL2 (1527 pg/mL), CCL7 (332.18 pg/mL), CXCL1 (311.41 pg/mL), and CCL5 (157.62 pg/mL). These data suggest that MSC(M)s may have the capacity to modulate recruited and tissue-resident SMG macrophages. This is currently being tested. Conclusions: Our data suggests a beneficial role of macrophages in the natural response to radiation in the murine SMG. Previous data from our lab demonstrates a benefit from MSC injection after RT-exposure, and our secretome analysis of these cells show the immunomodulatory capacity of our MSC line. Future experiments must be done evaluating the effectiveness of MSC injection in our immune depleted models to determine whether MSCs are directly impacting the macrophages in the radiation damaged gland. Citation Format: Dimitri Scofield, Cristina Paz, Jasmine Robinson, Kwang Nickel, Randy Kimple. Macrophages protect salivary glands from ionizing radiation [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 805.