Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"Ultrasound-Responsive Serotonylation and Hallmark Pathway Gene Signatures Reveal Tumor Microenvironment Vulnerabilities and Prognostic Subtypes in Colorectal Cancer.","authors":"Xiaohui Zhang, Xuguang Cao, Xinyao Su, Wei Hu, Shuoshuo Hou, Xiaohua Zhou, Hongbao Yang, Hongjian Ji","doi":"10.1177/10849785261422976","DOIUrl":"10.1177/10849785261422976","url":null,"abstract":"<p><strong>Background: </strong>Focused ultrasound, low-intensity focused ultrasound, and microbubble-enhanced sonoporation are examples of ultrasound-based cancer therapies that have shown promise as biophysical modalities for enhancing drug penetration, immunogenic cell death, and targeted delivery of radiopharmaceuticals in solid tumors. The molecular factors controlling ultrasonic therapy receptivity, however, are still not well understood. Because of the significant variability of the tumor microenvironment (TME), colorectal cancer (CRC) necessitates biomarker-guided techniques to enhance ultrasound-based therapy regimens.</p><p><strong>Methods: </strong>To investigate serotonylation-related and hallmark-pathway-related genes that might influence ultrasound-responsive cellular pathways, such as extracellular matrix (ECM) remodeling, mechanotransduction, and immune activation, the authors combined bulk RNA-sequencing (RNS-seq) (TCGA-COAD), single-cell RNA-seq (GSE132465), and spatial transcriptomics (GSE280313) datasets. Nine prognostic genes were found using survival analysis and differential expression screening. To create a prognostic classifier with translational relevance for ultrasonic therapies, the authors used non-negative matrix factorization clustering, single-cell functional scoring, spatial deconvolution, and 101 machine-learning models.</p><p><strong>Results: </strong>Of the 2475 serotonylation-hallmark genes found, 784 exhibited differential expression in tumor and normal tissues. CRC was divided into six molecular subgroups with different TME symptoms and survival patterns by nine important prognostic genes (<i>PCOLCE2, TIMP1, FJX1, FABP4, CALB2, NAT1, CDKN2A, FSTL3,</i> and <i>INHBB</i>). Elevated stromal activation, epithelial-mesenchymal transition signals, macrophage infiltration, and ECM stiffness were seen in high-risk clusters; these variables are known to affect cavitation thresholds, ultrasonic energy absorption, and treatment response. Strong prognostic accuracy was demonstrated by the final RSF-SuperPC model (concordance index 0.72-0.85 across validation cohorts). Strong enrichment in mechanotransduction, oxygen metabolism, and immune chemotaxis pathways-pathways previously demonstrated to regulate ultrasound-triggered drug delivery and immune activation-was revealed by functional studies.</p><p><strong>Conclusions: </strong>This multiomics integration reveals a serotonylation-hallmark gene signature that represents microenvironmental characteristics, such as matrix stiffness, stromal density, and immune infiltration, that are pertinent to ultrasound-based CRC therapy. These biomarkers could direct patient classification for radiopharmaceutical, immunotherapy, and ultrasound-enhanced medication delivery. This work supports future clinical trial stratification frameworks and offers a mechanistic basis for precision ultrasound oncology.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"873-888"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Evaluation of Ultrasound-Enhanced Radiotracer Uptake for Radioligand Therapy in Metastatic Prostate Cancer.","authors":"Yangbing Liang, Qingguo Wu, Yiwen Liang, Hanchu Ji","doi":"10.1177/10849785261431192","DOIUrl":"10.1177/10849785261431192","url":null,"abstract":"<p><strong>Background: </strong>Low-intensity pulsed ultrasound (LIPUS) may noninvasively enhance intratumoral delivery of radiopharmaceuticals, but clinical data are scarce. The authors prospectively evaluated whether adding LIPUS to prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) improves uptake and outcomes in metastatic prostate cancer while maintaining safety.</p><p><strong>Methods: </strong>A total of 42 men with PSMA PET-positive metastatic prostate cancer received up to six cycles of ¹⁷⁷Lu-PSMA-617. Before each infusion, LIPUS (1 MHz, 0.5-2.0 W/cm², 10 min) was applied to one dominant metastasis. Baseline and postcycle-1 PSMA PET/CT measured percent change in SUV_max (ΔSUV_max) for the sonicated lesion versus a matched nonsonicated reference lesion. Patients were classified as high (ΔSUV_max ≥20%) or low enhancement. Prostate-specific antigen (PSA) response, progression-free survival (PFS), and toxicity were recorded.</p><p><strong>Results: </strong>LIPUS was feasible in all patients without treatment interruptions. Sonicated lesions showed higher uptake (median ΔSUV_max + 32%) than reference lesions (+3%; <i>p</i> < 0.001). High-enhancement patients had more PSA_50 responses (71% vs. 33%) and longer PFS (11.5 vs. 5.3 months; hazard ratio 0.35). Adverse events were mainly Grades 1-2 local discomfort and typical ¹⁷⁷Lu-PSMA toxicities; no Grade ≥3 LIPUS-related events occurred.</p><p><strong>Conclusions: </strong>US-enhanced RLT appears safe and can increase intratumoral radiotracer uptake, translating into improved biochemical control and PFS in metastatic prostate cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"941-951"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-Mediated Modulation of circRNA hsa_circ_0004870 as a Prognostic and Therapeutic Biomarker in Pancreatic Cancer.","authors":"Chunyang Lv, Xiaodong Fan, Gaoyuan Wang, Haijian Sun, Dexuan Chen, Tong Shen, Taiyang Zhu, Cunbing Xia, Hong Zhu, Yongkang Zhu","doi":"10.1177/10849785251412134","DOIUrl":"https://doi.org/10.1177/10849785251412134","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer remains one of the most fatal tumors, with a 5-year survival rate of less than 10%, owing mostly to late-stage detection and inadequate treatment efficiency. The pressing need for novel diagnostic and therapeutic approaches has sparked interest in genetic biomarkers and ultrasound-based precision therapies. Circular RNAs (circRNAs) have recently been identified as intriguing regulatory molecules with diagnostic, prognostic, and therapeutic applications.</p><p><strong>Methods: </strong>A comprehensive study of transcriptome and clinical datasets revealed that <i>hsa_circ_0004870</i> is significantly elevated in pancreatic cancer tissues and is linked with poor patient outcomes. Functional tests, including colony formation, cell counting kit-8, flow cytometry, wound healing, and Transwell invasion studies, were used to evaluate its biological roles. Bioinformatic predictions, along with dual-luciferase reporter assays, revealed the <i>hsa_circ_0004870/miR-3124-3p/TRIM24</i> regulatory axis. <i>In vivo</i> xenograft research and immunohistochemistry analyses supported these findings. In addition, the authors developed an ultrasound-mediated biophysical modulation model to investigate the potential therapeutic control of this axis.</p><p><strong>Results: </strong><i>hsa_circ_0004870</i> was highly overexpressed in pancreatic cancer cells, which increased proliferation, migration, and invasion. It acts as a competitive endogenous RNA, sequestering <i>miR-3124-3p</i>, resulting in increased <i>TRIM24</i> and tumorigenic behavior. <i>In vivo</i>, silencing <i>hsa_circ_0004870</i> reduced tumor development significantly. Combining these findings with developments in ultrasound-targeted gene and molecular delivery technology suggests that ultrasound-mediated manipulation of the <i>hsa_circ_0004870</i> axis might provide a precise and noninvasive therapeutic method to overcome resistance and enhance localized cancer management.</p><p><strong>Conclusions: </strong><i>hsa_circ_0004870</i> was overexpressed in pancreatic cancer cells, resulting in enhanced proliferation, migration, and invasion. It works as a competitive endogenous RNA, sequestering <i>miR-3124-3p</i>, leading to enhanced <i>TRIM24</i> and tumorigenic behavior. <i>In vivo</i>, suppressing <i>hsa_circ_0004870</i> dramatically decreased tumor growth. Combining these findings with advances in ultrasound-targeted gene and molecular delivery technology, it appears that ultrasound-mediated manipulation of the <i>hsa_circ_0004870</i> axis could provide a precise and noninvasive therapeutic method for overcoming resistance and improving localized cancer management.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":"41 10","pages":"904-919"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149277230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of Fibrosis-4 in Male Patients with Alcohol-Related Hepatocellular Carcinoma: Implications for Ultrasound-Based Therapeutic Strategies.","authors":"Chang Guo, Wu-Cai Yang, Bin-Xia Chang, Chun-Yan Wang, Yi-Ming Fu, Jian-Jun Wang, Wen-Chang Wang, Xu-Yang Li, Yi-Fan Guo, Meng-Wen He, Dong Ji","doi":"10.1177/10849785251398953","DOIUrl":"10.1177/10849785251398953","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is still the largest cause of cancer-related death globally, with alcohol-related HCC (AR-HCC) being a particularly difficult subtype with poor clinical results. Noninvasive biomarkers, such as the fibrosis-4 (FIB-4) index, may provide significant prognostic information that might aid in guiding new interventional techniques, such as ultrasound-based treatments.</p><p><strong>Methods: </strong>The authors performed a retrospective cohort analysis on male AR-HCC patients diagnosed between January 2008 and December 2018. Clinical data and survival outcomes were obtained from electronic medical records, with HCC diagnosed as the baseline. The major endpoint was 12-month mortality. Multivariate logistic regression and limited cubic spline analysis were used to assess the relationship between FIB-4 and mortality risk.</p><p><strong>Results: </strong>Among 786 AR-HCC patients (mean age 57 years), 90.1% reported a history of alcohol usage for more than 10 years. The Barcelona Clinic Liver Cancer staging showed 42.8% in stage 0/A, 45.9% in stage B/C, and 11.3% in stage D. Deceased individuals had substantially higher FIB-4 levels (<i>p</i> < 0.05). Logistic regression demonstrated that higher FIB-4 was independently related with increased mortality, and spline analysis revealed a linear risk increase with a threshold of 5.61.</p><p><strong>Conclusion: </strong>Elevated FIB-4 (≥5.61) predicts worse mortality in AR-HCC, indicating its potential relevance in stratifying patients for ultrasound-based cancer therapy. The level of fibrosis may impact both therapeutic response and procedural risk. Routine incorporation of FIB-4 into clinical processes may aid precision decision-making in choosing AR-HCC patients most likely to benefit from ultrasound-guided or ultrasound-enhanced biotherapeutic.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"895-903"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Driven Ultrasound Identifies Rare Triphasic Colon Cancer and Unlocks Candidate Genomic Mechanisms via Ultrasound Genomic Techniques.","authors":"Xianqiao Li, Shukai Wang, Ulf Dietrich Kahlert, Tianchi Zhou, Kexin Xu, Wenjie Shi, Xiaofei Yan","doi":"10.1177/10849785251370718","DOIUrl":"10.1177/10849785251370718","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer is a heterogeneous disease, and rare subtypes like triphasic colon cancer are difficult to detect with standard methods. Artificial intelligence (AI)-driven ultrasound combined with genomic analysis offers a promising approach to improve subtype identification and uncover molecular mechanisms.</p><p><strong>Methods: </strong>The authors used an AI-driven ultrasound model to identify rare triphasic colon cancer, characterized by a mix of epithelial, mesenchymal, and proliferative components. The molecular features were validated using immunohistochemistry, targeting classical epithelial markers, mesenchymal markers, and proliferation indices. Subsequently, ultrasound genomic techniques were applied to map transcriptomic alterations in conventional colon cancer onto ultrasound images. Differentially expressed genes were identified using the <i>edgeR</i> package. Pearson correlation analysis was performed to assess the relationship between imaging features and molecular markers.</p><p><strong>Results: </strong>The AI-driven ultrasound model successfully identified rare triphasic features in colon cancer. These imaging features showed significant correlation with immunohistochemical expression of epithelial markers, mesenchymal markers, and proliferation index. Moreover, ultrasound genomic techniques revealed that multiple oncogenic transcripts could be spatially mapped to distinct patterns within the ultrasound images of conventional colon cancer and were involved in classical cancer-related pathway.</p><p><strong>Conclusions: </strong>AI-enhanced ultrasound imaging enables noninvasive identification of rare triphasic colon cancer and reveals functional molecular signatures in general colon cancer. This integrative approach may support future precision diagnostics and image-guided therapies.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"867-872"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteogenomic Biomarker Profiling for Predicting Radiolabeled Immunotherapy Response in Resistant Prostate Cancer.","authors":"Benchun Yan, Yuqiu Gao, Yulong Zou, Long Zhao, Zhiping Li","doi":"10.1177/10849785251366066","DOIUrl":"10.1177/10849785251366066","url":null,"abstract":"<p><p>Treatment resistance prevents patients with preoperative chemoradiotherapy or targeted radiolabeled immunotherapy from achieving durable response, which presents a major challenge in the prostate cancer (PCa) area. A novel integrative framework combining a machine learning workflow with proteogenomic profiling was used to identify predictive ultrasound biomarkers and classify patient response to radiolabeled immunotherapy in high-risk PCa patients who are treatment resistant. The deep stacked autoencoder (DSAE) model, combined with Extreme Gradient Boosting, was designed for feature refinement and classification. The Cancer Genome Atlas and an independent radiotherapy-treated cohort have been utilized to collect multiomics data through their respective applications. In addition to genetic mutations (whole-exome sequencing), these data contained proteomic (mass spectrometry) and transcriptomic (RNA sequencing) data. Maintaining biological variety across omics layers while reducing the dimensionality of the data requires the use of the DSAE architecture. Resistance phenotypes show a notable relationship with proteogenomic profiles, including DNA repair pathways (Breast Cancer gene 2 [BRCA2], ataxia-telangiectasia mutated [ATM]), androgen receptor (AR) signaling regulators, and metabolic enzymes (ATP citrate lyase [ACLY], isocitrate dehydrogenase 1 [IDH1]). A specific panel of ultrasound biomarkers has been confirmed in a state deemed preclinical using patient-derived xenografts. To support clinical translation, real-time phenotypic features from ultrasound imaging (e.g., perfusion, stiffness) were also considered, providing complementary insights into the tumor microenvironment and treatment responsiveness. This approach provides an integrated platform that offers a clinically actionable foundation for the development of radiolabeled immunotherapy drugs before surgical operations.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"932-940"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-Guided Microbubble-Assisted Delivery of Radiopharmaceutical Agents for Gastric Tumor Control.","authors":"Changyong Zhao, Qiqi Shen, Lei Qin","doi":"10.1177/10849785261426673","DOIUrl":"10.1177/10849785261426673","url":null,"abstract":"<p><strong>Background: </strong>Radiopharmaceutical therapy uses drugs with radioactive isotopes for targeted cancer treatment. However, its effectiveness in gastric cancer is often limited by poor tumor penetration, heterogeneous intratumoral distribution, and off-target radiation exposure. Ultrasound-guided microbubble-assisted delivery offers a noninvasive means to increase vascular permeability and enhance tumor-specific radiopharmaceutical uptake.</p><p><strong>Methods: </strong>This study developed and evaluated an ultrasound-guided microbubble delivery system to enhance intratumoral radiopharmaceutical accumulation, therapeutic efficacy, and safety in gastric cancer. Ligand-functionalized, radiopharmaceutical-loaded microbubbles were administered intravenously in an orthotopic gastric tumor model. Tumors were localized by real-time ultrasound imaging and then exposed to focused ultrasound to induce controlled microbubble cavitation. Biodistribution was analyzed using positron emission tomography imaging. Tumor growth was monitored by serial ultrasound, and therapeutic response was assessed with histopathology and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Radiation safety was determined by organ-specific biodosimetry.</p><p><strong>Results: </strong>Microbubble activation significantly increased intratumoral uptake to 8.4-1.2%ID/g, compared with 3.0 - 0.6%ID/g for conventional delivery (<i>p</i> < 0.001). Tumor-to background ratios improved approximately 2.6-fold, and tumor volumes decreased by 58% relative to controls. Apoptotic indices reached 41.8 - 6.3% in treated tumors versus < 15% in controls; off-target organ uptake remained < 2.0% ID/g.</p><p><strong>Conclusions: </strong>Ultrasound-guided, microbubble-assisted radiopharmaceutical administration increased tumor-specific absorption, slowed tumor development, and decreased systemic exposure, indicating a promising treatment strategy for gastric cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"920-931"},"PeriodicalIF":1.7,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Adverse Drug Effects for Three Radiopharmaceuticals: A Descriptive Analysis from WHO-VigiAccess.","authors":"Yiheng Jin, Kunlun Gui, Kaixin Chen, Xiaowu Wang, Xinlong Wan, Shugen Qu","doi":"10.1177/10849785261446231","DOIUrl":"10.1177/10849785261446231","url":null,"abstract":"<p><strong>Background: </strong>Radiopharmaceuticals are being used more frequently to treat neuroendocrine tumors and advanced prostate cancer; however, their clinical application is associated with adverse drug reactions (ADRs) that may affect patient safety. Real-world data from spontaneous reporting systems such as the World Health Organization's (WHO's)-VigiAccess can aid in assessing safety after the drugs have been marketed.</p><p><strong>Materials and methods: </strong>A retrospective descriptive analysis was conducted using ADR reports from the WHO-VigiAccess database up to November 2024. Reports related to lutetium (¹⁷⁷Lu) dotatate (Lutathera^®), lutetium (¹⁷⁷Lu) vipivotide tetraxetan (Pluvicto^®), and radium (²²³Ra) dichloride (Xofigo^®) were extracted and analyzed with respect to patient demographics, geographic distribution, and ADRs classified by MedDRA System Organ Class and Preferred Terms. Descriptive statistics were used to compare safety profiles.</p><p><strong>Results: </strong>A total of 17,743 ADR reports were analyzed. Lutathera was predominantly associated with gastrointestinal disorders and skin or subcutaneous tissue reactions. In contrast, Pluvicto demonstrated a higher frequency of general systemic disorders and a disproportionately higher number of fatal outcomes, a finding consistent with its indication for the treatment of advanced prostate cancer. Xofigo was primarily linked to hematological and musculoskeletal toxicities. In addition to 169 ADRs that were common to all three agents, distinct drug-specific reaction patterns were also observed.</p><p><strong>Conclusions: </strong>WHO-VigiAccess data reveal clearly differentiated ADR profiles among Lutathera, Pluvicto, and Xofigo. These results highlight the necessity for individualized risk assessment, careful monitoring, and further prospective investigations to optimize the safe clinical application of radiopharmaceuticals.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"851-862"},"PeriodicalIF":1.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemoglobin-Based Oxygen Carriers Promoted the Antitumor Effect of ¹⁷⁷Lu-PSMA-617 by Enhancing DNA Repair Capacity of Immune Cells.","authors":"Danyue Qu, Chenyi Shao, Xinyuan Ji, Yichi Huang, Chen Tian, Jiaze Li, Hu Zhou, Yilei Shi, Hong Wang, Jiaxin Liu, Yu Zhao","doi":"10.1177/10849785261448523","DOIUrl":"10.1177/10849785261448523","url":null,"abstract":"<p><p><i><b>Purpose:</b></i> Targeted radionuclide therapy with ¹⁷⁷Lu-PSMA-617 prolongs radiographical progression-free survival in prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC), yet 13% of patients develop symptomatic skeletal events. The authors hypothesized that hemoglobin-based oxygen carriers (HBOCs) could potentiate ¹⁷⁷Lu-PSMA-617 by reprogramming bone marrow (BM) immunity.<i>Methods:</i>Using PSMA-expressing xenografts, they demonstrated that concomitant HBOC administration significantly reduced tumor volume without increasing systemic toxicity. To dissect the underlying mechanism, the authors performed high-resolution single-cell RNA sequencing of murine BM.<i>Results:</i>HBOC treatment markedly expanded mature neutrophils, plasmacytoid dendritic cells, classical monocytes, natural killer T cells, and mature B cells, while concomitantly upregulating DNA damage repair genes such as <i>Parp9</i>, <i>Dtx3l</i>, and <i>Smchd1</i> within these subsets. Gene set enrichment analysis confirmed significant activation of DNA damage response pathways, implying enhanced cellular radioresistance and improved tolerance to β-particle irradiation.<i>Conclusions:</i> Thus, HBOCs improve ¹⁷⁷Lu-PSMA-617 antitumor efficacy indirectly via immune-subset expansion and DNA-repair reinforcement, offering a clinically feasible and safe strategy to optimize combination protocols for patients with mCRPC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"794-810"},"PeriodicalIF":1.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Tumor Classification and Severity Identification Using Deep Convolutional Spiking U-Net Lyrebird Neural Network and Alpha Piecewise Linear-Fuzzy.","authors":"Hemanand Chittapragada, Saggurthi Ramesh, Anumula Kalyan Kumar, M S Radha Manga Mani, Sivaramaiah Yenugu","doi":"10.1177/10849785261431191","DOIUrl":"10.1177/10849785261431191","url":null,"abstract":"<p><p><i>Purpose:</i> To develop a robust framework that accurately classifies brain tumors and provides an estimation of their severity using an artificial intelligence approach to solve issues related to multimodal MRIs (Magnetic Resonance Imaging), such as resolution variability, misalignment and heterogeneity.<i>Methodology:</i> An intelligent Deep Convolutional Spiking U-Net Lyrebird Neural Network combined with an Alpha-Piecewise Linear-Fuzzy (CSULALF) model. Lyrebird Optimization (LBO) will improve parameter tuning and convergence of the Deep Convolutional Spiking U-Net. The Alpha-Piecewise Linear-Fuzzy logic will evaluate tumor severity through a combination of clinical indicators and imaging features.<i>Findings:</i> The proposed framework demonstrates improved performance over existing methods using traditional methods to handle multimodal inconsistencies and extract discriminative spatiotemporal features. The CSULALF model achieved an accuracy rate of 99.35% and a recall of 99.36%, demonstrating high capability for classification and prediction of severity.<i>Research Limitations:</i> The proposed framework exhibit decreased performance level for data that is skewed or noisy. There is an additional computational overhead associated with multimodal image processing and optimization methods, which could affect scalability.<i>Practical Implications:</i>The system enables reliable and automated clinical decision-making, improving diagnostic precision and supporting effective treatment planning in real world healthcare environments.<i>Originality:</i>This work presents a novel method that integrates spiking neural networks, Lyrebird Optimization, and Alpha-Piecewise Linear-Fuzzy, resulting in an explainable and unified approach to analyzing multimodal brain tumor imaging.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"824-831"},"PeriodicalIF":1.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}