Cancer Biotherapy and Radiopharmaceuticals最新文献

{"title":"CavitoMod-UTMDNet: A Mechanistic Cavitation-Diffusion Framework for Ultrasound-Targeted Microbubble Destruction-Enhanced Liposomal Doxorubicin Delivery in Pancreatic Cancer.","authors":"Yazeed Alashban, Ghada Moh Samir Elhessewi, Mohammed Maray, Ali M Al-Sharafi, Hanadi Alkhudhayr, Rana Alabdan, Nujud Aloshban, Shouki A Ebad","doi":"10.1177/10849785261431195","DOIUrl":"https://doi.org/10.1177/10849785261431195","url":null,"abstract":"<p><p><i>Background:</i> Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest treatment responses since it contains desmoplastic stroma, lacks good vascularity, and has high interstitial fluid pressures, which are the most damaging factors depriving chemotherapy. Liposomal doxorubicin is much better in terms of systemic pharmacokinetics but is not efficient in PDAC due to the significant barrier of nanoparticles-stromal and vascular barriers.<i>Purpose/Hypothesis:</i> In a bid to eliminate these shortcomings, this paper presents CavitoMod-UTMDNet, which is an integrated mechanistic and experimental platform capable of utilizing ultrasound-targeted masterpiece unaffiliating (UTMD) as a means of temporarily improving vascular and stromal permeability and better intratumoral delivery of liposomal doxorubicin.<i>Population/Subjects:</i> The model combines Rayleigh-Plesset cavitation modeling and Fickian diffusion analysis with a two-compartment pharmacokinetic model and systematic in vitro and in vivo validation.<i>Assessment:</i> Passive cavitation detection was used to establish stable cavitation exposure windows within FDA-acceptable mechanical index limits.<i>Statistical Tests:</i> UTMD increased intracellular drug uptake 3.2-3.8fold and reduced IC 0 in PANC-1 and BxPC-3 pancreatic cancer cell lines by around 50% in the presence of a stable cavitation (MI 1.2). UTMD progressively improved the level of intratumor drug delivery in the orthotopic immunodeficient mouse models (NU/NU strain) (2.4-fold) and led to a 54% decrease in tumor volume 21 days later without any trace of hepatic, renal, and cardiac toxicity.<i>Results:</i> There were strong links between cavitation energy density and drug uptake and diffusion depth and therapeutic response as evidence that there is a mechanistic character to UTMD-enhanced actions. It will support the drug development in a better way. CavitoMod-UTMDNet is a combined strategy to maximize ultrasound-enhanced nanocarrier (nanoparticles) delivery using a physics-based reproducible plan to optimize ultrasound-enhanced nanocarrier delivery in PDAC that will see improvement in future translation to image-guided therapeutic strategies.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261431195"},"PeriodicalIF":2.1,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678465","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-Assisted Radiopharmaceutical Investigation of GNL1-Mediated AKT-P53-P21 Axis Activation in Cervical Cancer Progression.","authors":"Yingying Jiang, Jing Ren, Junzhen Tao","doi":"10.1177/10849785261438424","DOIUrl":"https://doi.org/10.1177/10849785261438424","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is a leading cause of cancer death in women worldwide, and the outcomes for advanced or recurrent disease remain poor. Ultrasound-assisted delivery could increase intratumoral uptake of radiopharmaceuticals, but prospective clinical evidence and risk data are limited.</p><p><strong>Methods: </strong>In a single-center pilot (<i>n</i> = 30), patients with advanced cervical cancer underwent paired PET/CT sessions 60 min after identical intravenous radiopharmaceutical injections: control (no ultrasound) and ultrasound-assisted delivery using 1 MHz focused ultrasound (FUS) for 10 min with microbubble cavitation monitoring. Uptake (SUV_max) and tumor-to-background ratio (TBR) were compared within patient; response used RECIST 1.1, and adverse events (AEs) used CTCAE v5.0. Paired biopsies quantified GNL1, phospho-AKT, p53, and p21 (H-score).</p><p><strong>Results: </strong>Ultrasound increased median index-lesion SUV_max by ∼28% (<i>p</i> < 0.001) with improved TBR. The objective response rate was 26.7% and the disease control rate was 76.7%. Median progression-free survival was 8.5 months (95% confidence interval, 6.2-11.8) and the 12-month overall survival was 75% (median not reached). Most AEs were Grades 1-2; 20% were Grade ≥3, with no treatment-related deaths. Post-ultrasound biopsies showed decreased GNL1 and phospho-AKT with increased p53 and p21, and Δp21 correlated with uptake gain.</p><p><strong>Conclusions: </strong>Nonablative FUS can safely enhance radiopharmaceutical uptake in cervical cancer and is associated with biomarker shifts consistent with p53/p21 pathway activation.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261438424"},"PeriodicalIF":2.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641014","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":"Identification of circ_0085616 as an Upregulated and Oncogenic Circular RNA in Cervical Cancer Via the miR-503-5p-Mediated <i>ATXN7L3</i> Activation.","authors":"Lu Lin, Nan Li, Xiaowen Hu, Jing Sun, Yu He","doi":"10.1089/cbr.2020.3865","DOIUrl":"10.1089/cbr.2020.3865","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence enhanced the recognition of circular RNAs (circRNAs) implicated in cancer progression. CircRNA_0085616 (circ_0085616) is a novel circRNA with high expression in cervical cancer (CC); its function and action mechanism are explored during this study.</p><p><strong>Methods: </strong>The measurement of circ_0085616, microRNA-503-5p (miR-503-5p), and Ataxin-7L3 (<i>ATXN7L3</i>) was performed via quantitative real-time polymerase chain reaction. Next, 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and colony formation assays were implemented to analyze the proliferative ability. Cell metastasis was evaluated by using transwell migration and invasion assays. Glycolysis was analyzed by using glucose consumption, lactate and adenosine triphosphate production. Western blot was employed for protein analysis. The target binding was performed by dual-luciferase reporter assay and RNA immunoprecipitation assay. An animal experiment <i>in vivo</i> was conducted by xenografts.</p><p><strong>Results: </strong>Circ_0085616 was heightened and its downregulation blocked cellular proliferation, metastasis, and glycolysis in CC. Then, we found that circ_0085616 had a sponge effect on miR-503-5p and the miR-503-5p inhibitor could ameliorate the effects of circ_0085616 knockdown on CC cells. In addition, miR-503-5p directly targeted <i>ATXN7L3</i> to obstruct CC cell proliferation, metastasis, and glycolytic process. Further, circ_0085616 could enhance <i>ATXN7L3</i> by sequestering miR-503-5p, and the miR-503-5p/<i>ATXN7L3</i> axis was also responsible for circ_0085616 on promoting CC tumorigenesis <i>in vivo</i>.</p><p><strong>Conclusion: </strong>It was obvious that circ_0085616 facilitated the carcinogenic effect on CC via the activation of <i>ATXN7L3</i> by sponging miR-503-5p. Our study may be likely to provide a novel molecular target for CC therapy.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"244-256"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38517748","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":"Choline Kinase Alpha Promoted Glioma Development by Activating PI3K/AKT Signaling Pathway.","authors":"Yourui Zou, Ling Huang, Shengyu Sun, Fangqian Yue, Zhuoqi Li, Yue Ma, Hui Ma","doi":"10.1089/cbr.2021.0294","DOIUrl":"10.1089/cbr.2021.0294","url":null,"abstract":"<p><strong>Objective: </strong>The most commonly reported primary brain tumor in adults is glioma. Choline kinase alpha (<i>CHKA</i>) has been proved to play important roles in glioma. However, the mechanism of <i>CHKA</i> involved remains unclear. Therefore, this study aims to explore the mechanism of <i>CHKA</i> in glioma development.</p><p><strong>Methods: </strong>Immunohistochemistry, qRT-PCR, and Western blot were used to detect the expression of <i>CHKA</i>. Flow cytometry, Cell Counting Kit-8 (CCK-8), transwell, and wound healing assays were performed to evaluate cell apoptosis, proliferation, invasion, and migration, respectively. RNA sequencing was used to explore the differentially expressed genes affected by <i>CHKA</i>. The enrichment analysis of gene ontology (<i>GO</i>) and Kyoto Encyclopedia of Genes and Genomes (<i>KEGG</i>) helped to detect the signaling pathways <i>CHKA</i> affected. Tumor-bearing mice were established and evaluated by TUNEL assay, Ki-67 immunohistochemistry. and hematoxylin and eosin staining.</p><p><strong>Results: </strong><i>CHKA</i> increased in glioma tissues and promoted cell proliferation, invasion, and migration, while inhibiting the glioma cell apoptosis. It was also showed that <i>CHKA</i> promoted glioma development <i>in vivo</i>. <i>GO</i> and KEGG analysis indicated that PI3K/AKT was significantly enriched in <i>CHKA</i> knockdown U251 cells. And <i>CHKA</i> promoted glioma development by activating PI3K/AKT signaling pathway.</p><p><strong>Conclusions: </strong>The authors demonstrated that <i>CHKA</i> was significantly elevated in glioma tissues. Mechanism analysis indicated that <i>CHKA</i> could promote glioma development by activating PI3K/AKT signaling pathway, suggesting that <i>CHKA</i> is promising to be a biomarker and therapeutic strategy for prognostic prediction of patients with glioma.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"270-278"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39898927","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":"LINC00319 Promotes Cervical Cancer Progression Via Targeting miR-147a/IGF1R Pathway.","authors":"Zhe Ma, Yufei Cai, Limei Zhang, Chenchen Tian, Lin Lyu","doi":"10.1089/cbr.2020.3722","DOIUrl":"10.1089/cbr.2020.3722","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is identified as the fourth most common female malignancy worldwide. Recently, Linc00319 was reported to play an important role in the development and progression of cervical cancer. However, little is known about the molecular mechanism and clinical significance of Linc00319 in the carcinogenesis of cervical cancer. This study aims to reveal the biological function and molecular mechanisms of Linc00319 in cell proliferation, invasion, and migration of cervical cancer.</p><p><strong>Materials and methods: </strong>In the current study, gene expression levels of Linc00319, miR-147a, and IFG1R were detected by quantitative real-time PCR in clinical tissue samples and cervical cancer cell lines. Protein levels were also determined by western blot assay in cervical cancer cells. CCK-8, transwell, and wound healing assays were used to test the proliferation, invasion, and migration of cervical cancer cell lines <i>in vitro</i>. Target genes were predicted through bioinformatics methods and then verified by gene engineering technology.</p><p><strong>Results: </strong>The authors' results showed that Linc00319 was upregulated in cervical cancer tissues and cell lines, while Linc00319silencing could inhibit cervical cancer cell proliferation, invasion, and migration. Further investigations showed that Linc00319 interacted with miR-147a and inhibited its expression, unregulated IGF1R to induce progression of cervical cancer.</p><p><strong>Conclusions: </strong>Their research indicated that Linc00319 might play an oncogenic role in cervical cancer and regulate the progression of cervical tumor growth by inhibiting the expression of miR-147a and activating IGF1R-related pathway. The findings suggest a novel molecular biomarker and therapeutic target for cervical tumor and may provide a novel therapeutic strategy for preventing the metastasis of cervical cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"234-243"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38136893","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":"Functional Profiling of Head and Neck/Esophageal Squamous Cell Carcinoma to Predict Cetuximab Response.","authors":"Senthamil R Selvan, Jennifer A Brichetti, Denise B Thurber, Gregory M Botting, Greg P Bertenshaw","doi":"10.1089/cbr.2021.0283","DOIUrl":"10.1089/cbr.2021.0283","url":null,"abstract":"<p><strong>Background: </strong>Cetuximab, an epidermal growth factor receptor (EGFR)-targeting antibody, remains the only Food and Drug Administration-approved targeted therapy for squamous cell carcinoma (SCC) of head and neck/esophagus. However, in clinical trials, cetuximab only benefited a subset of patients and frequently caused toxicity. Predicting which patients respond to cetuximab remains unsolved. The authors sought to identify predictive biomarkers in EGFR signaling and autophagy pathways, which may be impacted by cetuximab under certain treatment conditions.</p><p><strong>Methods: </strong><i>In vitro</i> responses of SCC cell lines to cetuximab under various nutrient conditions were assessed by WST-8 growth assay. Functional profiles of several EGFR signaling biomarkers were investigated by Luminex-based assays and corroborated with immunoblots. Autophagy markers were analyzed with immunoblots.</p><p><strong>Results: </strong><i>In vitro</i> growth response assays identified cetuximab responder and nonresponder cell lines. Optimal growth conditions and growth factors enhanced responses, and even reversed nonresponsiveness in some cell lines. Strong correlation was found between response in growth assays (reference assay) and dynamic changes in p-Erk1/2 and LC3-II (index assays).</p><p><strong>Conclusions: </strong>This study indicates that nutrient modification may enhance cetuximab response in SCC patients. Biomarker results strengthen the hypothesis that dynamic biomarkers can be used to predict patient response to cetuximab. Future studies are warranted to test in more complex samples including patient-derived tumor tissues.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"210-223"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39931409","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":"The Survival Benefit of Pegylated Liposomal Doxorubicin-Based Neoadjuvant Chemotherapy in the Management of Breast Cancer.","authors":"Ruoyang Li, Xuewei Zhao, Yunfei Huang, Chunxiao Li, Lei Liu, Meiqi Wang, Jiaxing Wang, Zhenchuan Song","doi":"10.1089/cbr.2024.0011","DOIUrl":"10.1089/cbr.2024.0011","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the short-term outcomes and prognosis and the cardiac safety of pegylated liposomal doxorubicin (PLD)-based neoadjuvant chemotherapy (NAC) compared with epirubicin-based therapy in breast cancer treatment.</p><p><strong>Methods: </strong>In total, 304 patients diagnosed with stages II and III breast cancer were enrolled that included 97 cases treated with PLD and 207 controls treated with epirubicin in NAC. The effectiveness of the antibreast cancer treatment was evaluated using overall survival (OS) and disease-free survival (DFS) metrics, whereas cardiac toxicity was measured through the left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) assessments.</p><p><strong>Results: </strong>The 5-year DFS and OS rates in the PLD group were 84.5% and 88.7% (with 15 recurrences and 11 deaths), respectively, whereas in the control group, these rates were 72.9% and 79.2% (with 56 recurrences and 43 deaths). Regarding cardiac toxicity, there was no significant difference in ECG abnormalities or LVEF decline between the two groups.</p><p><strong>Conclusions: </strong>The study suggests that PLD-based NAC may provide substantial benefits in terms of DFS and OS, along with a safe cardiac toxicity profile, in patients with stage II-III breast cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"203-209"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186386","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":"MiR-769-5p, Which Targets <i>HDGF</i>, Inhibits Cell Proliferation and Invasion in Nonsmall Cell Lung Cancer.","authors":"Yuejun Sun, Jie Li, Shiying Zheng","doi":"10.1089/cbr.2021.0363","DOIUrl":"10.1089/cbr.2021.0363","url":null,"abstract":"<p><p>MiR-769-5p regulates tumor correlative genes, which plays a critical role in the progression of various types of tumor. However, the precise regulatory mechanism of miR-769-5p on nonsmall cell lung cancer (NSCLC) is unknown. This study was to discover the role and underlying mechanisms of miR-769-5p in NSCLC. MiR-769-5p expression was shown to be reduced, according to our findings. MiR-769-5p overexpression inhibited NSCLC cell proliferation while promoting NSCLC cell apoptosis. Furthermore, NSCLC cell migration and invasion were reduced when miR-769-5p was overexpressed. Furthermore, <i>HDGF</i> was confirmed as a miR-769-5p target gene that was negatively regulated by miR-769-5p. Furthermore, more research revealed that <i>HDGF</i> overexpression reduced the inhibitory effect of miR-769-5p on NSCLC cell biofunction. Finally, miR-769-5p inhibited NSCLC cell proliferation and invasion by targeting <i>HDGF</i>, indicating that NSCLC could benefit from miR-769-5p as a diagnostic and prognostic biomarker.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"224-233"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39870435","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":"Long Noncoding RNA <i>MALAT1</i> Knockdown Inhibits Proliferation, Migration, and Invasion and Promotes Apoptosis in Non-Small-Cell Lung Cancer Cells Through Regulating <i>miR-515-3p</i>/<i>TRIM65</i> Axis.","authors":"Yu Wang, Qigang Zhang","doi":"10.1089/cbr.2020.3730","DOIUrl":"10.1089/cbr.2020.3730","url":null,"abstract":"<p><strong>Background: </strong>Long noncoding RNAs (lncRNAs) and mRNAs (messenger RNAs) have been reported to exert function in non-small-cell lung cancer (NSCLC), but how lncRNAs and mRNAs operate in the regulation of NSCLC is unclear. The purpose of this research was to elucidate the functional mechanism of lncRNA metastasis associated in lung adenocarcinoma transcript 1 (<i>MALAT1</i>) and tripartite-motif protein family member 65 (<i>TRIM65</i>) in NSCLC.</p><p><strong>Materials and methods: </strong>Quantitative real-time polymerase chain reaction and western blot assay were employed to measure gene expression. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were performed to assess cell proliferation and apoptosis, respectively. Also, cell migratory and invasive abilities were detected by transwell assay. The interaction between <i>miR-515-5p</i> and <i>MALAT1</i> or <i>TRIM65</i> was predicted by starBase and then confirmed with the dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or pull-down assay. Besides, mouse xenograft was conducted to analyze the effect of <i>MALAT1</i> knockdown on tumor growth <i>in vivo</i>.</p><p><strong>Results: </strong><i>MALAT1</i> and <i>TRIM65</i> expression was upregulated, and <i>miR-515-5p</i> expression was downregulated in NSCLC tissues and cells. Both <i>MALAT1</i> knockdown and <i>TRIM65</i> depletion suppressed cell proliferation, migration, and invasion and induced apoptosis in NSCLC cells. Interestingly, <i>MALAT1</i> directly inhibited <i>miR-515-5p</i> expression and <i>miR-515-5p</i> decreased <i>TRIM65</i> level through interaction. <i>MALAT1</i> knockdown repressed NSCLC cell growth via modulation of miR-515-5p/<i>TRIM65</i> axis. Furthermore, silencing <i>MALAT1</i> inhibited tumor growth <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Our findings demonstrated that <i>MALAT1</i> depletion inhibited the growth of NSCLC cells by regulating miR-515-5p/<i>TRIM65</i> axis, providing the theoretical basis for the therapy of NSCLC.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"257-269"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39114225","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-Potentiated Targeting of GLS1 by an Oridonin Derivative (R13) in Multiple Myeloma: Therapeutic Efficacy and Safety Considerations.","authors":"Xi Xu, Yan Zhuang, Yu Zhang, Dongmei Tian, Kang Yu","doi":"10.1177/10849785261422297","DOIUrl":"https://doi.org/10.1177/10849785261422297","url":null,"abstract":"<p><strong>Objective: </strong>To create a structurally optimized oridonin derivative (R13) and study its safety profile, molecular mechanism, and ultrasound-enhanced antitumor activity in multiple myeloma (MM), with an emphasis on glutamine metabolism-driven oncogenic signaling.</p><p><strong>Materials and methods: </strong>Using oridonin as the parent nucleus, photocatalytic double-bond addition and esterification processes were used to create R13. Using CCK-8, colony formation, and Transwell assays, the antiproliferative, anticlonogenic, and anti-invasive effects of R13 were assessed in MM cell lines (U266 and KMS-11) both on its own and in response to low-intensity ultrasonic exposure. Key elements of the glutaminase 1-protein kinase B (GLS1-AKT) signaling axis were evaluated for modification using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Stable cell lines with GLS1 knockdown and overexpression were created to confirm target reliance and ultrasound-mediated sensitization. To assess systemic toxicity, organ safety, and <i>in vivo</i> antitumor activity under combination treatment settings, a nude mouse xenograft model was created.</p><p><strong>Results: </strong>In a dose- and time-dependent way, R13 dramatically reduced MM cell proliferation, and colony formation, invasion, and migration; these effects were further enhanced by exposure to ultrasound. Mechanistically, R13 specifically targeted and downregulated GLS1, leading to inhibition of the GLS1-AKT signaling pathway, which is characterized by overexpression of the tumor suppressor PTEN and lower expression of AKT2, AKT3, and GSK-3β without changing the expression of AKT1. The biological benefits of R13 and its ultrasound-enhanced pathway regulation were partially reversed by GLS1 overexpression, indicating GLS1-dependent therapeutic action. R13 therapy significantly slowed the growth of xenograft tumors <i>in vivo</i>, while coadministration with ultrasound increased the anticancer activity. Major organs showed no discernible histopathological damage, suggesting a good safety profile.</p><p><strong>Conclusions: </strong>Through ultrasound-potentiated suppression of GLS1-driven metabolic and AKT signaling pathways, R13, a new oridonin derivative, exhibits strong anti-MM action with little systemic toxicity. These results support the combination of drugs originating from Traditional Chinese Medicine with noninvasive ultrasound techniques to enhance treatment efficacy while preserving safety, and they show R13 as a good option for ultrasound-augmented biotherapy in MM.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":"10849785261422297"},"PeriodicalIF":2.1,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147516941","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}