tbuckley/cabot-search huggingface dataset:
Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis
Authors: Bisheng Cheng, Jilin Wu, Ke Chen, Weijia Li, Jianghua Yang, WenTai Shangguan, Lin Yang, Wenxue Huang, Cunzhen Ma, Zhuohang Li, Boyuan Sun, Qiong Wang, Hai Huang, Peng Wu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating CD8 + T-cell function, implying that 5α-reductase inhibitors (5-ARIs), which lower androgen activity, could enhance antitumor immunity and improve clinical outcomes in patients receiving immunotherapy. This study retrospectively investigates the impact of a history of 5-ARI use (≥12 months) on the efficacy of ICIs in mRCC. Methods We conducted a multicenter retrospective cohort study of 185 patients with mRCC who received ICIs. Patients were stratified based on their history of 5-ARI use. Baseline characteristics included age, body mass index, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, programmed death-ligand 1 (PD-L1) expression levels, tumor stage, and metastasis sites. The primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Cox proportional hazards models. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Key immunological insights were gained through single-cell RNA sequencing analysis of tumor samples. Results Patients with a history of 5-ARI use demonstrated improved ORR (59.8% vs 39.8%, p=0.0075) and DCR (87.0% vs 78.7%, p=0.1747) compared with those without. The median PFS and OS were significantly longer in the 5-ARI group, with HRs of 0.64 (95% CI: 0.47 to 0.86, p=0.0085) for PFS and 0.65 (95% CI: 0.47 to 0.90, p=0.0271) for OS. Subgroup analysis further indicated enhanced ICI efficacy with 5-ARI use across age, IMDC risk scores, and PD-L1 expression levels. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion (CD8 Tex), and lower programmed cell death protein-1 expression in CD8 Tex cells, suggesting an immunologically favorable modification of the tumor. Conclusion A history of 5-ARI use is associated with improved responses to ICI therapy in mRCC, potentially through AR-related modulation of CD8 + T-cell activity and favorable alterations in the immune microenvironment. These findings support further investigation into androgen-targeted approaches as adjunctive strategies in immunotherapy for RCC.
Targeting pyroptosis reverses KIAA1199-mediated immunotherapy resistance in colorectal cancer
Authors: Lisha Li, Lei Zhao, Diwei Zhou, Yuanhang Yu, Peiyi Zhang, Jinge Zheng, Zhenyu Lin, Dandan Yu, Jinghua Ren, Jing Zhang, Pengfei Zhou, Dejun Zhang, Tao Zhang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Despite advancements in treatment modalities, several patients with colorectal cancer (CRC) remain unresponsive to immune checkpoint inhibitor therapy. Pyroptosis, an inflammatory programmed cell death process, holds substantial promise for tumor immunotherapy. In this study, we explored the use of pyroptosis to overcome immunotherapy resistance in CRC. Methods We used a pyroptosis-related gene panel to construct an immunotherapy efficacy evaluation model and validated its performance by immunohistochemical staining of CRC patient samples. Pyroptosis and its underlying mechanisms were examined both in vitro and in vivo using PCR, western blotting, lactate dehydrogenase release assay, ELISA, co-immunoprecipitation, immunohistochemistry, fluorescence cell assays, microscopic imaging, flow cytometry analysis and bioinformatics approaches. Results We established a model to define high or low levels of pyroptosis in CRC, revealed that low pyroptosis led to immunotherapy resistance, and identified KIAA1199 as a characteristic protein of low pyroptosis CRC. We further demonstrated that KIAA1199 contributes to low pyroptosis, resulting in resistance to immunotherapy. Mechanistically, KIAA1199 bound to and stabilized DNA methyltransferase-1 (DNMT1), thereby inhibiting GSDME-mediated pyroptosis. Importantly, our study highlighted that decitabine reversed KIAA1199-mediated immunotherapy resistance by enhancing pyroptosis to restore IL-1B release and CD8 + T cell infiltration. Conclusions We found a critical role of KIAA1199 in promoting immunotherapy resistance by suppressing pyroptosis via the DNMT1/GSDME pathway in CRC. Decitabine has emerged as a promising therapeutic agent for reversing KIAA1199-mediated immunotherapy resistance by enhancing pyroptosis. Our findings provide valuable insights for enhancing the efficacy of immunotherapy in patients with CRC who exhibit resistance to conventional immunotherapy approaches.
Novel post-translational modification learning signature reveals B4GALT2 as an immune exclusion regulator in lung adenocarcinoma
Authors: Pengpeng Zhang, Dingli Wang, Guangyao Zhou, Shuai Jiang, Ge Zhang, Lianmin Zhang, Zhenfa Zhang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment efficacy evaluation. While post-translational modifications are known to influence tumor progression, their prognostic value in LUAD remains largely unexplored. Methods We developed a post-translational modification learning signature (PTMLS) using machine learning techniques, analyzing data from 1231 LUAD patients across seven global cohorts. The signature’s efficacy in predicting immunotherapy response was evaluated using 12 immunotherapy cohorts spanning multiple cancer types (n=1201). An in-house LUAD tissue cohort (n=171) was used to validate beta-1,4-galactosyltransferase 2’s (B4GALT2’s) prognostic significance. The role of B4GALT2 in immune exclusion was investigated through in vivo and in vitro experiments. Results The established PTMLS exhibited exceptional predictive capabilities in LUAD patient outcomes, surpassing the efficacy of 98 existing LUAD prognostic indicators. The system’s predictive value was validated across diverse malignancy categories for immunotherapeutic response assessment. From a biological perspective, significant correlations were observed between PTMLS and immunological parameters, whereby elevated PTMLS levels were characterized by attenuated immune responses and immunologically cold neoplastic features. Within the PTMLS framework, B4GALT2 was identified as a crucial molecular component (r=0.82, p&lt;0.05), and its heightened expression was linked to unfavorable clinical outcomes in LUAD cases, particularly in specimens exhibiting CD8-depleted phenotypes. The spatial distribution patterns between B4GALT2 and immune cell populations, specifically CD8+ T lymphocytes and CD20+ B lymphocytes, were elucidated through multiplexed immunofluorescence analysis. Laboratory investigations subsequently established B4GALT2’s regulatory influence on LUAD cellular expansion in both laboratory cultures and animal models. Significantly, suppression of B4GALT2 was found to enhance CD8+ T lymphocyte populations and their functional status, thereby potentiating anti-programmed cell death protein 1 immunotherapeutic efficacy in animal studies. This phenomenon was characterized by reduced CD62L+CD8 T lymphocyte levels alongside elevated GZMB+/CD44+/CD69+CD8 T cell populations. Conclusion The developed PTMLS system represents an effective instrument for individualized prognostic evaluation and immunotherapy stratification in both LUAD and diverse cancer populations. The identification of B4GALT2 as a previously unrecognized oncogenic factor involved in immune exclusion presents a novel therapeutic avenue for LUAD treatment and immunotherapy optimization.
Targeting mesothelin-CD24 axis repolarizes tumor-associated macrophages to potentiate PD-1 blockade therapy in high-grade serous ovarian cancer
Authors: Yujing Zhong, Yiying Wang, Chenyang Wang, Kankan Cao, Xueling Wang, Xuyao Xu, Moran Yang, Guodong Zhang, Haiou Liu, Jiaqi Lu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background High-grade serous ovarian cancer (HGSOC) is a highly aggressive malignancy marked by an immunosuppressive tumor microenvironment that hinders effective immune responses. A key feature of this environment is the extensive infiltration of myeloid cells, which contributes to immune evasion. This study explored how mesothelin (MSLN), a tumor-associated antigen, modulates the expression of CD24, an emerging target for immune modulation, and its role in promoting immune evasion in HGSOC. Understanding these underlying mechanisms is crucial for enhancing the efficacy of immune checkpoint blockade (ICB) therapies and improving outcomes in patients with HGSOC. Methods We analyzed the expression of MSLN in HGSOC samples and examined its correlation with clinical outcome. In vitro and in vivo models were used to explore how MSLN influences CD24 expression and the polarization of tumor-associated macrophages (TAMs). We also investigated the role of MSLN in the activation of Wnt/β-catenin signaling and its impact on T-cell function and antitumor immunity. The effects of Msln knockdown on CD24 expression and the response to anti-programmed cell death protein-1 (PD-1) therapy were evaluated in syngeneic mouse models. Results MSLN expression was found to be significantly elevated in HGSOC, with high MSLN levels correlating with poor prognosis and resistance to ICB. MSLN upregulated CD24 and promoted the protumorigenic polarization of TAMs, contributing to T-cell dysfunction. Mechanistically, MSLN activated Wnt/β-catenin signaling, which in turn enhanced CD24 expression. This activation forms a positive feedback loop that further promotes MSLN transcription. In contrast, Msln knockdown reduced CD24 expression, relieved cytotoxic T-cell suppression, and significantly improved the efficacy of anti-PD-1 therapy in syngeneic models. Conclusions This study elucidates the critical role of MSLN in immune evasion in HGSOC and its underlying mechanisms. Targeting MSLN in combination with ICB is a promising strategy to enhance the efficacy of immunotherapy and improve patient outcomes in HGSOC.
Seminal Vesicle Involvement of Waldenström Macroglobulinemia on 18F-FDG PET/CT
Authors: Li Bin, Huiting Liu, Xue Liu, Cailiang Gao
Journal: Clinical Nuclear Medicine (2025)

A 57-year-old man was admitted to the hospital with recurrent pain in the lower abdomen for more than half a month. Computed tomography urography and MRI of the prostate gland suggested neoplastic lesions in bilateral seminal vesicle glands. An 18 F-FDG PET/CT examination revealed multiple hypermetabolic nodules and masses in the prostate and bilateral seminal vesicle gland area. Later histopathology confirmed Waldenström macroglobulinemia with bilateral seminal vesicle gland involvement.
Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies
Authors: Ashkan Pouyan, Masoud Ghorbanlo, Masoud Eslami, Majid Jahanshahi, Ehsan Ziaei, Ali Salami, Khatere Mokhtari, Koorosh Shahpasand, Najma Farahani, Tohid Emami Meybodi, Maliheh Entezari, Afshin Taheriazam, Kiavash Hushmandi, Mehrdad Hashemi
Journal: Molecular Cancer (2025)

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor in adults, characterized by a poor prognosis and significant resistance to existing treatments. Despite progress in therapeutic strategies, the median overall survival remains approximately 15 months. A hallmark of GBM is its intricate molecular profile, driven by disruptions in multiple signaling pathways, including PI3K/AKT/mTOR, Wnt, NF-κB, and TGF-β, critical to tumor growth, invasion, and treatment resistance. This review examines the epidemiology, molecular mechanisms, and therapeutic prospects of targeting these pathways in GBM, highlighting recent insights into pathway interactions and discovering new therapeutic targets to improve patient outcomes.
Early-life growth and emotional, behavior and cognitive outcomes in childhood and adolescence in the EU child cohort network: individual participant data meta-analysis of over 109,000 individuals
Authors: Romy Gonçalves, Sophia Blaauwendraad, Demetris Avraam, Andrea Beneíto, Marie-Aline Charles, Ahmed Elhakeem, Joaquin Escribano, Louise Etienne, Gonzalo García-Baquero Moneo, Ana Gonçalves Soares, Jasmin de Groot, Veit Grote, Dariusz Gruszfeld, Kathrin Guerlich, Monica Guxens, Barbara Heude, Berthold Koletzko, Aitana Lertxundi, Manuel Lozano, Hanan El Marroun, Rosie McEachan, Angela Pinot de Moira, Gillian Santorelli, Katrine Strandberg-Larsen, Muriel Tafflet, Chloe Vainqueur, Elvira Verduci, Martine Vrijheid, Marieke Welten, John Wright, Tiffany C Yang, Romy Gaillard, Vincent W V Jaddoe
Journal: The Lancet Regional Health - Europe (2025)
Early Perfusion [123I]FP-CIT SPECT Imaging With a 360-degree CZT Camera in Dementia With Lewy Bodies
Authors: Antoine Verger, Laetitia Imbert, Diego Cecchin
Journal: Clinical Nuclear Medicine (2025)

Dementia with Lewy bodies (DLB) can be diagnosed through a combination of clinical criteria, the loss of dopaminergic neuron terminals in presynaptic [123I]FP-CIT SPECT dopaminergic imaging, and diffuse [18F]FDG PET hypometabolism, which typically affects also the visual cortex. A 360-degree CZT SPECT systems offer advantages in terms of count sensitivity, and both contrast and energy resolution for perfusion and dopaminergic imaging as compared with conventional SPECT systems. As it happens for PET imaging protocols, a dual-time-window protocol with CZT SPECT imaging was used for a suspected DLB patient to capture both perfusion and dopaminergic states.
Metastasis of Urothelial Carcinoma to the Wrist
Authors: Hamidreza Ghorbani, Amin Saber Tanha, Naime Ataei, Reza Ataei, Ali Zare
Journal: Clinical Nuclear Medicine (2025)

A 65-year-old man presented with painless hematuria and a bladder mass, diagnosed as high-grade papillary urothelial carcinoma following transurethral resection. Considering negative metastasis workup, he was scheduled for radical cystectomy. During follow-up, he reported chronic wrist pain. A whole-body 99m Tc-Methylene diphosphonate (MDP) scan showed focal uptake in the wrist, misinterpreted as arthritis and overlooked as inconsequential. Three months later, x-ray imaging revealed a lytic wrist lesion, later confirmed as metastatic carcinoma through biopsy. Immunohistochemical analysis supported the diagnosis, highlighting the importance of careful interpretation of imaging findings in patients with bladder cancer.
Traditional Chinese medicine in lung cancer treatment
Authors: Zhichao Xi, Rongchen Dai, Yufei Ze, Xue Jiang, Mengfan Liu, Hongxi Xu
Journal: Molecular Cancer (2025)

Lung cancer remains a major global health challenge and one of the leading causes of cancer-related deaths worldwide. Despite significant advancements in treatment, challenges such as drug resistance, side effects, metastasis and recurrence continue to impact patient outcomes and quality of life. In response, there is growing interest in complementary and integrative approaches to cancer care. Traditional Chinese medicine (TCM), with its long history, abundant clinical experience, holistic perspective and individualized approach, has garnered increasing attention for its role in lung cancer prevention and management. This review provides a comprehensive overview of the advances in TCM for lung cancer treatment, covering its theoretical foundation, treatment principles, clinical experiences and evidence supporting its efficacy. We also provide a systematic summary of the preclinical mechanisms, through which TCM impacts lung cancer, including the induction of cell death, reversal of drug resistance, inhibition of metastasis and modulation of immune responses. Additionally, future prospects for TCM in lung cancer treatment are discussed, offering insights into its expanded application and integration with modern medicine to address this challenging disease.
Racial Differences in ctDNA Profiles, Targeted Therapy Use, and Outcomes in Metastatic Breast Cancer
Authors: Emily L. Podany, Lorenzo Foffano, Lorenzo Gerratana, Arielle J. Medford, Katherine Clifton, Shaili Tapiavala, Marko Velimirovic, Marla Lipsyc-Sharf, Carolina Reduzzi, Adrian Bubie, Annika Putur, Foluso O. Ademuyiwa, Fabio Puglisi, William J. Gradishar, Cynthia X. Ma, Aditya Bardia, Massimo Cristofanilli, Andrew A. Davis
Journal: JAMA Network Open (2025)

Importance Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment. Objectives To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups. Design, Setting, and Participants This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included. Exposures Targeted treatment use. Main Outcomes and Measures The main outcomes were differences in circulating tumor DNA profiles and use of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors between Black and White patients with metastatic breast cancer. Results The study sample included 1327 women with mBC (mean [SD] age, 58.0 [12.8] years; 140 Black and 1057 White). Black patients had a significantly higher rate of GATA3 single-nucleotide variants (odds ratio, 2.31; 95% CI, 1.17-4.54; P = .02) and CCND2 copy number variants (odds ratio, 4.63; 95% CI, 1.79-11.97; P = .002) on multivariate analysis. These differences were validated in a population-based evidence cohort of 27 224 patients. Black patients with PIK3CA single-nucleotide variants were significantly less likely to receive PI3K inhibitors than White patients (1 of 17 [5.9%] vs 45 of 156 [28.8%]; P = .04), whereas there was no difference in use of CDK4/6 and mTOR inhibitors, which do not require a targetable alteration. Black patients had a shorter overall survival from the time of circulating tumor DNA testing compared with White patients. Conclusions and Relevance This cohort study of patients with mBC found somatic differences, shorter overall survival, and targeted treatment disparities in PI3K inhibitor use in Black compared with White patients despite equal incidence of PIK3CA alterations. Researchers should consider these differences when designing future research and interventions to address the striking and persistent outcomes gap between Black and White patients with mBC.
Social and Financial Costs of Neonatal Intestinal Failure
Authors: Vikram K. Raghu, Sirine Belaid, Susan Gutierrez, Pamela Holzer, Shelby Orris, Scott Rothenberger, Tracey Presel, Kimberly Ackerman, Feras Alissa, Dale King, Jennifer Woo Baidal, Jeffrey A. Rudolph, Geoffrey Bond, George V. Mazariegos, Simon P. Horslen, Kenneth J. Smith
Journal: JAMA Network Open (2025)

Importance Neonatal short bowel syndrome with intestinal failure is rare, and observational studies are limited to small cohorts. Health disparities exist in long-term management with little known about the initial hospitalization. Objective To identify children with neonatal short bowel syndrome with intestinal failure and to determine whether race, ethnicity, and neighborhood opportunity are associated with length of stay during their initial hospitalizations. Design, Setting, and Participants This cross-sectional study of children with neonatal short bowel syndrome and intestinal failure was conducted between 2004 and 2020, with validation and analysis performed from July 2022 to April 2024. Children were identified from the Pediatric Health Information System database, which included administrative data from 50 freestanding US children’s hospitals. Children were included on the basis of a diagnosis code of postsurgical malabsorption and billed charges for a neonatal intensive care unit stay and sustained parenteral nutrition use. Exposures Race and ethnicity were included as a single variable with categories of Hispanic, non-Hispanic Black, non-Hispanic White, other (Asian and multiracial, combined because of low numbers), and unknown according to hospital report. Child Opportunity Index quintile ranged from very low (lowest quintile) to very high (highest quintile). Main Outcomes and Measures The primary outcome was length of stay measured in number of days from admission to discharge. The χ 2 analysis was used to examine unadjusted associations between categorical variables, and Wilcoxon rank-sum test was used for continuous variables. Results A total of 2267 children with neonatal short bowel syndrome with intestinal failure were identified (997 female [44%]; 410 Hispanic [18%]; 481 non-Hispanic Black [21%]; 690 non-Hispanic White [30%]; 231 other [10%]; 455 unknown [20%]), with 629 (28%) living in areas with very low Child Opportunity Index. The median (IQR) length of stay for the initial admission was 150 (112-200) days, with a median (IQR) cost of $528 628 ($374 040-$766 446). In multivariable analysis, non-Hispanic Black children remained in the hospital for 16 days longer than their non-Hispanic White counterparts (95% CI, 7-25 days; P &amp;amp;lt; .001). Child Opportunity Index was not significantly associated with length of stay when controlling for race and ethnicity. Conclusions and Relevance In this cross-sectional study, children with neonatal short bowel syndrome with intestinal failure experienced long initial hospital stays, incurring high costs, with non-Hispanic Black children disproportionately affected. Interventions targeting safe and efficient transition to home are needed to address both efficacy and equity for these children.
Deescalation Perils in Inflammatory Breast Cancer
Authors: Wendy A. Woodward
Journal: JAMA Network Open (2025)

Audree Tadros, MD; Brian Diskin, MD; Varadan Sevilimedu, MBBS, DrPH; Amy Xu, MD, PhD; Perri Vingan, MD; Jonas Nelson, MD; Yoshiko Iwai, MD, MS; Monica Morrow, MD; Oluwadamilola M. Fayanju, MD, MA, MPHS
Consumer Confidence in the Responsible Use of Digital Health Data After the COVID-19 Pandemic
Authors: Ravi Gupta, Meghana Sharma, Nandita Mitra, Carolyn C. Cannuscio, Raina M. Merchant, David A. Asch, David Grande
Journal: JAMA Network Open (2025)

This study compares 2020 and 2022 surveys to identify changes in how respondents view use of their health information by public and private organizations, including by political leaning.