tbuckley/cabot-search huggingface dataset:
Abstract 6781: Effect of Qingre Lishi Huoxue prescription on pyroptosis and the expression of related proteins caspase-3/GSDME in esophageal cancer cells
Authors: Fuchun Si, Gao Si
Journal: Cancer Research (2025)

Introduction: Esophageal carcinoma (EC) is one of the most common malignant tumors posing a threat to human's health, with a high disease incidence and the highest death rate in China. This study aims to screen out the Chinese herbs with strong inhibitory effects on the proliferation of four kinds of EC cells EC9706, EC-1, TE-1 and Eca109 from 300 Chinese herbs, and study the effect of Qingre Lishi Huoxue Prescription(QRLSHXP) on the proliferation and on pyroptosis-related proteins such as Caspase-3 and GSDME of four EC cells. Methods: The MTT assay was used to assess the effects of 300 Chinese herbs alcohol extracts on the proliferation of the four esophageal cancer cell lines. Based on efficacy and safety profiles, selected herbs were combined to formulate a prescription. Dose-response relationships were determined. Cell morphology changes were observed under an inverted microscope. DNA damage was assessed using TUNEL staining. Lactate dehydrogenase (LDH) release was measured to evaluate cell membrane integrity. Cell death was analyzed using Annexin V/PI staining and flow cytometry. Western blotting and ELISA were performed to detect the expression levels of pyroptosis-related proteins and cytokines. Results: Eight herbs significantly inhibited all four esophageal cancer cell lines in the initial screening. Toxic herbs were excluded. Four herbs—Sanye Danshen, Jiuguanxue, Shanchagen, and Huaxuedan—were chosen to create the Qingre Lishi Huoxue Prescription (QRLSHXP). This prescription inhibited the proliferation of the cancer cells in a dose- and time-dependent manner.QRLSHXP treatment induced severe cellular swelling, rupture, and content leakage in EC cells. TUNEL staining revealed increased DNA double-strand breaks, indicating enhanced DNA damage. Elevated LDH levels in supernatants suggested compromised membrane integrity. Flow cytometry showed a significant rise in Annexin V/PI double-positive cells, confirming cell death. Western blot analysis indicated increased Cleaved-Caspase-3 and GSDME-N expression, with unchanged total GSDME levels. ELISA results demonstrated significantly higher IL-1β and IL-18 levels in treated groups. Conclusion: QRLSHXP effectively inhibited the proliferation of EC cells and induced pyroptosis, which was likely associated with the activation of the Caspase-3/GSDME pathway. Citation Format: Fuchun Si, Gao Si. Effect of Qingre Lishi Huoxue prescription on pyroptosis and the expression of related proteins caspase-3/GSDME in esophageal cancer 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 6781.
Abstract 5979: Identification of DNA methylation based prognostic subtype and signature in epithelial ovarian cancer
Authors: Wei Geng, Wei Liu, Lei Liu, Yuxin Chen, Dong Yang, Linqing Chai, Caiyun Huang, Lian Li
Journal: Cancer Research (2025)

Abstract Background: Epithelial ovarian cancer (EOC) is a heterogeneous disease that exhibits different histological types, clinical characteristics, and molecular features. DNA methylation plays a crucial role in the development and progression of cancer and has been utilized for subtyping various tumors. This study focuses on classifying EOC based on DNA methylation and aims to characterize the disease through an integrated analysis of genomic, transcriptomic, and clinical data. Methods: Genome-wide DNA methylation profiling was performed on 137 EOC tumor tissues using Infinium MehylationEPIC array. Prognosis-related differentially methylated positions (DMPs) were identified through multivariate Cox proportional hazards regression models, and non-negative matrix factorization (NMF) approach was used to classify different subtypes. A prognosis prediction model was constructed using LASSO regression and nomogram was constructed. Results: Four methylation-based subtypes (MS1-MS4) were identified using 774 DMPs, showing significant differences in prognosis (P = 2.413 × 10-9).The MS1 group showed the best prognosis and the most favorable response to paclitaxel in combination with platinum-based chemotherapy. MS2 is characterized as an immune-excluded phenotype, while MS3 represents a metabolic subtype with a moderate prognosis as determined through differentially expressed genes and functional enrichment analysis. In contrast, MS4, recognized as a hypermethylated subtype, has the poorest prognosis and is marked by the highest methylation levels among the four subtypes. A four-DMP signature was developed to predict prognosis and methylation subtype, thereby enhancing clinical utility. Conclusion: Together, this study identified a novel molecular subtype of EOC, elucidating the heterogeneity of EOC from an epigenetic perspective and providinga new strategy for personalized treatment options for EOC patients. Citation Format: Wei Geng, Wei Liu, Lei Liu, Yuxin Chen, Dong Yang, Linqing Chai, Caiyun Huang, Lian Li. Identification of DNA methylation based prognostic subtype and signature in epithelial ovarian 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 5979.
Abstract 7389: Examining ovarian cancer disparities: The influence of demographics, insurance coverage, and travel distance on survival outcomes
Authors: Sejong Bae
Journal: Cancer Research (2025)

Abstract Background: Ovarian cancer continues to be a devastating disease despite advancements in medicine. Significant disparities in care and outcomes exist, particularly among marginalized populations, due to limited healthcare access and the considerable impact of travel distance. Patients in remote or underserved areas often face delays in diagnosis and treatment, adversely affecting survival rates. This study underscores the critical need for ongoing research into early detection methods and personalized treatment strategies, aiming to enhance survival rates and quality of life for ovarian cancer patients while addressing barriers to equitable healthcare access. Methods: For the national-level analysis, data from the National Cancer Database (NCDB) was utilized, focusing on ovarian cancer patients in the East South-Central region treated at Academic/Research programs, diagnosed between 2004 and 2017, with a minimum of five years of follow-up. At the local level, data was sourced from the Tumor Registry at the O’Neal Comprehensive Cancer Center. Travel distance in the O'Neal data was determined using zip codes and categorized into tertiles—short, intermediate, and long distances. Multivariable logistic regression models were employed to identify factors associated with five-year mortality, adjusting for distance, demographics, cancer stage, and insurance status at the national level. Results: Both national and local analyses revealed that being Black, older age, and having a higher cancer stage were associated with poorer odds of survival. Nationally, Medicaid recipients (vs. those with private insurance) had worse survival odds. Travel distance was not significantly associated with five-year mortality in the South at the national level. However, data from O’Neal showed that among ovarian cancer patients diagnosed from 2006-2015, longer travel distance was associated with lower five-year mortality compared to those with shorter travel distances to the treatment center. Discussion: Ovarian cancer remains a lethal disease with significant disparities, affecting Black patients, older individuals, and Medicaid recipients the most. While travel distance did not impact survival rates nationally, the O'Neal data revealed an unexpected association between longer travel distances and better survival rates, likely due to access to specialized care. These findings highlight the urgent need for equitable healthcare access and continued research to improve early detection and treatment strategies. Citation Format: Sejong Bae. Examining ovarian cancer disparities: The influence of demographics, insurance coverage, and travel distance on survival outcomes [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 7389.
Abstract 7390: Differences in cancer and all cause mortality among non Hispanic Black American adults by nativity and duration of U.S. residence: Findings from the 1997-2018 NHIS-NDI record linkage study
Authors: Aminu K. Abubakar, Phoung T. Nguyen, Mahbubur Rahman
Journal: Cancer Research (2025)

Abstract Background: Non-Hispanic Black (NHB) Americans bear a high burden of cancer and all-cause mortality. Previous studies show that foreign-born individuals generally have lower cancer mortality rates, though declines are more pronounced among U.S.-born NHBs. This study examined differences in cancer and all-cause mortality risk between U.S.-born and foreign-born NHB adults as well as by duration of U.S. residence among the foreign-born. Method: We used pooled data from the 1997-2018 National Health Interview Survey, linked to the National Death Index with follow-up through December 31, 2019, including 90, 487 adult NHB participants. Cox regression models were used to estimate hazard ratios by place of birth and duration of residence in the U.S. after adjusting for sociodemographic and health behavior factors. Result: The intra-racial disparity in cancer mortality has been continuously observed over the past several decades among NHBs by their place of birth (foreign-born versus US-born). Multi-pronged research strategies are needed to understand this disparity as well as to plan appropriate interventions to address this gap among NHB. Citation Format: Aminu K. Abubakar, Phoung T. Nguyen, Mahbubur Rahman. Differences in cancer and all cause mortality among non Hispanic Black American adults by nativity and duration of U.S. residence: Findings from the 1997-2018 NHIS-NDI record linkage study [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 7390.
Abstract 7388: Trends of diagnosis disclosure among individuals with plasma cell disorders
Authors: Akshay Dalvi, Maria Malik, Andriy Derkach, Ana Sahagun, Jorge A. Martinez, Gia Merlo, Jennifer Ahlstrom, Jay R. Hydren, Saad Z. Usmani, Susan Chimonas, Robin Ortiz, Urvi Shah
Journal: Cancer Research (2025)

Abstract Multiple myeloma, along with precancerous conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, represent the most common plasma cell disorders (PCDs) around the world. Coping with such disorders is often a challenging prospect for patients, and the disclosure or withholding of information pertaining to the patient’s diagnosis or prognosis may have a significant impact on the patient’s perception of their care. We hypothesize that patient perceptions of diagnosis disclosure will be largely positive due to the various psychosocial benefits conferred by the sharing of information with friends and family. In order to investigate these diagnosis disclosure patterns among individuals with PCDs and determine areas for interventions that utilize social support strategies to help patients navigate their diagnosis, we invited participants with PCDs through the HealthTree Cure Hub to complete a 34-question online survey regarding their disclosure trends (n= 510). Participants generally reported sharing their diagnosis with at least one person (98%), with the most common responses being a spouse, domestic partner or significant other (60%) and friend(s) (10%). Most participants that chose to disclose their diagnosis experienced a positive impact in their coping (79%) and became closer with others (55%), whereas patients who chose not to disclose their diagnosis generally reported feeling more isolated in their relationships (56%). Despite some reports of certain negative experiences associated with sharing a PCD diagnosis, the majority of participants expressed no regrets over sharing their diagnosis (87%). Based on these findings, patients generally perceive sharing their diagnosis among their primary social networks to be beneficial to their coping. Oncologists may also be advised to promote the utilization of social support to navigate a PCD diagnosis. Citation Format: Akshay Dalvi, Maria Malik, Andriy Derkach, Ana Sahagun, Jorge A. Martinez, Gia Merlo, Jennifer Ahlstrom, Jay R. Hydren, Saad Z. Usmani, Susan Chimonas, Robin Ortiz, Urvi Shah. Trends of diagnosis disclosure among individuals with plasma cell disorders [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 7388.
Abstract 6077: PLT012, a humanized CD36-blocking antibody, is effective for unleashing anti-tumor immunity and against liver metastasis
Authors: Yi-Ru Yu, Sheue-Fen Tzeng, Zheng Meng, Jaeoh Park, Lana Kandalaft, Yun-Han Lin, Chin-Hsien Tsai, Ping-Chih Ho
Journal: Cancer Research (2025)

Abstract Tumor cells employ various mechanisms to evade immune surveillance, including metabolic modulation of the tumor microenvironment (TME). Lipid metabolic stress in the TME leads to upregulation of CD36 in tumor-infiltrating immune cells, impairing anti-tumor immunity by enhancing the survival and suppressive activity of regulatory T cells (Tregs) and promoting ferroptosis and exhaustion in CD8+ T cells. Here, we developed PLT012, a humanized anti-CD36 IgG4 antibody targeting the lipid-binding domain of CD36, with a remarkable safety profile and favorable pharmacokinetics demonstrated in cynomolgus monkey models. Moreover, PLT012 significantly reduces tumor growth and reprograms the immune landscape, enhancing CD8+ T cell effector functions while reducing Treg-mediated suppression. In both immunotherapy-sensitive and resistant hepatocellular carcinoma (HCC) models, PLT012 alone or in combination with PD-L1 blockade induces robust anti-tumor immunity. Importantly, in a syngeneic liver metastasis model, PLT012 decreases immunosuppressive populations, enhances effector T cell responses, and reduces ICI resistance. Notably, ex vivo studies with human HCC samples further confirm PLT012’s capacity to remodel the immune microenvironment. Taken together, these findings position PLT012 as a first-in-class immunotherapy targeting CD36, addressing critical challenges in HCC and liver metastasis treatment. Citation Format: Yi-Ru Yu, Sheue-Fen Tzeng, Zheng Meng, Jaeoh Park, Lana Kandalaft, Yun-Han Lin, Chin-Hsien Tsai, Ping-Chih Ho. PLT012, a humanized CD36-blocking antibody, is effective for unleashing anti-tumor immunity and against liver metastasis [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 6077.
Abstract 4294: SMCHD1 is a synthetic lethal strategy for cancers with a cancer-testis antigen gene expression signature
Authors: Victor Quereda, Youyou Zhang, Diana Klimaszewska, Stefano Tonin, Theodore Groth, Yanhua Rao, Michael T. McCabe, Benjamin Schwartz, Markus Queisser, Rachel Buxton, Thomas J. Berrodin, Simon Peace
Journal: Cancer Research (2025)

Abstract SMCHD1 is a component of the structural maintenance of chromosomes (SMC) protein family involved in epigenetic gene silencing of the X chromosome and other autosomal chromosome regions. SMCHD1 encodes an ATPase domain and binds chromatin at both N- and C-term domains to facilitate long-range chromatin interactions. However, the exact mechanism by which it elicits transcriptional silencing remains unknown. We have identified a selective dependency on SMCHD1 in cell lines exhibiting a gene expression signature characterized by high expression of multiple cancer testis antigen (CTA) genes. This CTA signature is observed in multiple cancers with &amp;gt;60% prevalence in Chronic Myeloid Leukemia. Importantly, SMCHD1’s effect on cell growth was independent of its ATPase activity, and a knock-in degron tag phenocopied SMCHD1 KO indicating that the proliferative advantage offered by SMCHD1 might be due to structural SMCHD1 function unrelated with its enzymatic ATPase role. Finally, SMCHD1 depletion led to the upregulation of multiple genes, including a cluster of CTA genes, in sensitive cell lines with the CTA-positive signature, while CTA-negative cell lines remained unaffected. These data confirm that SMCHD1 is a potential therapeutic target for patients with elevated CTA expression, and provides insight to what therapeutic modality would be most effective. Citation Format: Victor Quereda, Youyou Zhang, Diana Klimaszewska, Stefano Tonin, Theodore Groth, Yanhua Rao, Michael T. McCabe, Benjamin Schwartz, Markus Queisser, Rachel Buxton, Thomas J. Berrodin, Simon Peace. SMCHD1 is a synthetic lethal strategy for cancers with a cancer-testis antigen gene expression signature [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 4294.
Abstract 7408: Factors influencing false positive low-dose computed tomography-based lung cancer screening in an urban, safety-net system
Authors: Rutu Rathod, Urooj Wahid, Asha Kandathil, Mary Gwin, Sheena Bhalla, Song Zhang, Andrea Semlow, Vijaya Natchimuthu, Sarah Malone, George Oliver, David H. Johnson, Megan A. Mullins, David Gerber, Rasmi Nair
Journal: Cancer Research (2025)

Abstract Background: False-positive results from low-dose computed tomography (LDCT)-based lung cancer screening can result in unnecessary follow-up tests, increased patient anxiety, and higher healthcare costs. We evaluated the prevalence of false-positive LDCT results and assessed factors associated with these LDCT results within an integrated, urban safety-net healthcare system serving a diverse and underserved population. Design: Retrospective cohort study. Setting: Electronic health records data from Parkland Health, an integrated safety-net provider in Dallas, Texas (January 1, 2017-May 31, 2022), with a 1-year follow-up period through May 31, 2023. Outcome: False-positive LDCT was defined as positive screen (lung RADS 3, 4A, 4B or 4X) followed by a negative completed work-up or no diagnosis of lung cancer after 12-month follow-up. Analysis: Univariable and multivariable logistic regression models were used to assess the associations between patient characteristics (patient age, sex, race/ethnicity, preferred language, insurance status, comorbidity score, smoking status and smoking pack-years) and a false-positive LDCT. Results: A total of 2525 LDCTs were included from 2029 patients. Of these, lung cancer was diagnosed in 12 patients (0.6%), and 394 (19.4%) were classified as false-positive. Median age was 62 years, 59% were men, 49% were non-Hispanic Black, 16% were Hispanic, and the median pack-years were 40. In both univariable and multivariable analyses, age was significantly associated with false positive LDCT results. Patients aged 65-70 years (OR=1.81, 95% CI: 1.06-3.10) and &amp;gt;70 years (OR=2.02, 95% CI: 1.15-3.54) had higher odds of false-positive results compared to those aged 50-54 years. Conclusion: In our integrated safety-net healthcare system, approximately one in 5 patients had a false-positive LDCT result, and age was a significant contributor. Patients aged 65 years and older were more likely to experience false-positive findings, suggesting that age-related factors may influence the diagnostic accuracy of LDCT. Future studies are needed to replicate these findings and further minimize unnecessary follow-up interventions, particularly in older populations. Citation Format: Rutu Rathod, Urooj Wahid, Asha Kandathil, Mary Gwin, Sheena Bhalla, Song Zhang, Andrea Semlow, Vijaya Natchimuthu, Sarah Malone, George Oliver, David H. Johnson, Megan A. Mullins, David Gerber, Rasmi Nair. Factors influencing false positive low-dose computed tomography-based lung cancer screening in an urban, safety-net system [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 7408.
Abstract 7407: Generalizability of an AI-based mammogram risk score (MRS) for breast cancer among racially and ethnically diverse women
Authors: Shu JIang, Debbie L. Bennett, Peter Kraft, Graham A. Colditz
Journal: Cancer Research (2025)

Abstract Breast cancer remains the most common cancer diagnosed among women worldwide. While risk prediction models hold great promise for enhancing preventive breast cancer management, a major challenge lies in accurately identifying women at elevated risk across diverse racial and ethnic groups. Mammogram risk scores (MRS), an AI-driven feature summarizing mammographic texture, have shown potential to accurately classify 5-year breast cancer risk in racially diverse populations.1 However, similar prediction performance across groups does not necessarily ensure the model's generalizability. To address this, we analyzed data from two large North American cohorts—Emory and British Columbia—encompassing over 226, 000 racially diverse women, including Non-Hispanic White (NHW), Non-Hispanic Black (NHB), East Asian, South Asian, and Indigenous women. We assessed the distribution of MRS by race and ethnicity and observed little variation in median MRS between the two cohorts overall, among race and ethnicity groups within each cohort, or between cohorts within race and ethnicity (where such comparisons were feasible). We further examined the association between MRS and breast cancer risk both overall and stratified by race/ethnicity. Statistically significant associations were found, with hazard ratios (HR) per standard deviation increase in MRS ranging from 2.03 (95% CI: 2.00-2.06) to 2.15 (95% CI: 1.93-2.40) after adjusting for age. This significant association was consistent across racial/ethnic groups: NHB (2.12, 95% CI: 1.92-2.51), East Asian (2.10, 95% CI: 2.02-2.18), South Asian (2.09, 95% CI: 1.72-2.49), and Indigenous women (2.19, 95% CI: 1.65-2.79). Prediction accuracy, as assessed using the 5-year AUC, also showed no statistically significant differences by race/ethnicity within each cohort. Our findings indicate no clinically meaningful differences in MRS performance across these groups, suggesting broad applicability. The MRS could be effectively used in clinical practice to estimate age-specific breast cancer incidence, including for individuals with mixed ancestry or self-reported identities commonly encountered in real-world settings. 1. Jiang S, Debbie B, Rosner B, Tamimi R, Colditz G. Development and validation of dynamic 5-year breast cancer risk model using repeated mammograms. JCO Clinical Cancer Informatics, In press. 2024. Citation Format: Shu JIang, Debbie L. Bennett, Peter Kraft, Graham A. Colditz. Generalizability of an AI-based mammogram risk score (MRS) for breast cancer among racially and ethnically diverse women [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 7407.