Cts-Clinical and Translational Science最新文献

{"title":"Dosage Regimen Optimization of Ertapenem Against ESBL-Producing Enterobacterales Infection in Critically Ill Patients Using Monte Carlo Simulation","authors":"Apirat Muangkasem,&nbsp;Wichit Nosoongnoen,&nbsp;Suthida Sririttha,&nbsp;Teerapong Aramruang,&nbsp;Preecha Montakantikul","doi":"10.1111/cts.70274","DOIUrl":"https://doi.org/10.1111/cts.70274","url":null,"abstract":"<p>Extended-spectrum beta-lactamase (ESBL)-producing <i>Enterobacterales</i> infections are associated with high mortality rates. Ertapenem is recommended as one of the first-line drugs due to its efficacy against these pathogens. However, physiological changes in critically ill patients may influence drug pharmacokinetics. Thus, this study aims to optimize the ertapenem dosage regimen for critically ill patients in both efficacy and neurotoxicity. The previously reported population pharmacokinetic model and drug-albumin binding model were used for Monte Carlo simulation. A total of 10 ertapenem dosage regimens were performed in 10,000 simulated critically ill patients with varying degrees of renal function and serum albumin. A PTA of achieving 100% for time of free drug above the minimum inhibitory concentration (<i>f</i>T&gt;MIC) was assessed for efficacy. A PTA of achieving a total drug ≥ 11.77 mg/L was determined for neurotoxicity. A usual recommended dosing of 1 g every 24 h can ensure a PTA &gt; 80% for efficacy only in patients having a creatinine clearance of 30–59 mL/min with unlikely neurotoxic risk (a PTA &lt; 2%). Moreover, the study highlights the need for an individualized ertapenem dosage regimen based on renal function in critically ill patients, as ertapenem in divided doses might be more optimal for both efficacy and safety compared to once daily dosing in patients with creatinine clearance ≥ 60 mL/min. Further randomized controlled trials are needed to confirm these dose recommendations.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Survey Study of Roadblocks in Translational Science","authors":"Fasiha Kanwal,&nbsp;Christopher I. Amos,&nbsp;Katherine H. Sippel,&nbsp;Claudia Neuhauser,&nbsp;Ariel Harrison,&nbsp;Mary E. Dickinson,&nbsp;Charles Minard,&nbsp;Bettina M. Beech","doi":"10.1111/cts.70259","DOIUrl":"https://doi.org/10.1111/cts.70259","url":null,"abstract":"<p>Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks in a comment box. The survey was disseminated in August 2022 to faculty and staff with active research protocols at Baylor College of Medicine and the University of Houston. In total, 227 respondents completed the survey. Their disciplines were basic science (29.5%), translational research (52.9%), clinical research (55.5%), community-engaged research (9.7%), and educational research (9.7%). Respondents identified (1) lack of access to trained research coordinators, (2) lack of understanding about different resources that facilitate research, (3) complex regulatory environment and delays, (4) fragmented infrastructure for administrative and fiscal processes, and (5) inadequate funding for pilot projects to foster new research. Other roadblocks included lack of established community stakeholder partnerships, inadequate access to medical record data, and limited biostatistical support. We identified leading roadblocks to research from the perspectives of scientists and staff conducting clinical and translational research. Operational innovations addressing these roadblocks can accelerate the pace of translation.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Elinzanetant on Simulated Driving Performance in Healthy Women: A Randomized Phase I Study","authors":"Klaus Francke,&nbsp;Stefan Klein,&nbsp;Jennifer Burke,&nbsp;Marcus-Hillert Schultze-Mosgau,&nbsp;Gary Kay","doi":"10.1111/cts.70282","DOIUrl":"https://doi.org/10.1111/cts.70282","url":null,"abstract":"<p>Elinzanetant is a dual neurokinin–1 and –3 receptor antagonist in development for treating vasomotor symptoms associated with menopause. Its central nervous system action and bedtime dosing could produce next-morning residual effects that impact safety when driving. We therefore conducted a randomized, double-blind, placebo- and active-controlled, four-period, crossover study to assess the effect of elinzanetant on next-morning simulated driving performance. Sixty-four healthy women aged 40–65 years with regular sleep patterns were randomized to receive elinzanetant 120 mg, elinzanetant 240 mg, zopiclone 7.5 mg, or placebo for 5 days in one of four sequences. The primary endpoint assessed participant's ability to maintain a consistent position within the lane, measured using standard deviation of lateral position (SDLP). Secondary assessments included lane exceedance, cornering speeds, and treatment-emergent adverse events (TEAEs), among others. The least squares mean SDLP for both doses of elinzanetant on Day 2 and Day 6 were significantly below the non-inferiority margin of 4.4 cm (<i>p</i> &lt; 0.0001). Small increases in SDLP with both doses versus placebo were observed on Day 2 but not on Day 6. Secondary assessments were not significantly different to placebo, apart from lane exceedances and cornering speed threshold exceedances. TEAEs were reported in 84% of participants; most were mild, and there was no increase in TEAE frequency with the 240 mg dose. Our study demonstrated no clinically relevant next-morning residual effects following bedtime elinzanetant dosing and confirmed the elinzanetant benefit: risk balance was not adversely impacted by somnolence or fatigue the following morning.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06219902</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Whole-Brain Radiotherapy Dose on the Occurrence of Otitis Media and Mastoiditis in Patients With Lung Cancer With Brain Metastasis","authors":"Xudong Zhang,&nbsp;Ying Huang,&nbsp;Hongfei Li,&nbsp;Yuntong Pei,&nbsp;Fanyang Kong,&nbsp;Qian Zhang,&nbsp;Yadong Song,&nbsp;Yunji Wang,&nbsp;Guowen Li","doi":"10.1111/cts.70269","DOIUrl":"https://doi.org/10.1111/cts.70269","url":null,"abstract":"<p>This study aims to investigate the incidence of acute mastoiditis in patients with brain metastases undergoing whole-brain radiotherapy (WBRT). A retrospective analysis was conducted on patients with brain metastases who received different doses of WBRT. The incidence of acute mastoiditis within 6 months post-radiotherapy was observed. Patients were divided into four groups based on the radiation dose: 25, 30, 36 and 40 Gy. The incidence of mastoiditis in each group was statistically analyzed. A total of 209 patients were followed up, with no cases lost to follow-up, and the follow-up time was 6 months. The results showed that the number of patients with middle ear mastoiditis was 6 (24%) in group A, 101 (67%) in group B, 12 (80%) in group C and 15 (83%) in group D, and there was a statistically significant difference between the four groups (<i>χ</i>² = 22.525, <i>p</i> &lt; 0.001). The incidence of acute mastoiditis in patients with brain metastases post-WBRT is positively correlated with the radiation dose. Higher doses not only increase the risk of mastoiditis but also potentially lead to more severe damage to the middle ear and mastoid regions. Therefore, careful dose management and preventive measures are recommended in WBRT planning to reduce the risk of such complications.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging In Silico and Artificial Intelligence Models to Advance Drug Disposition and Response Predictions Across the Lifespan","authors":"Kyunghee Yang,&nbsp;Daniel Gonzalez,&nbsp;Jeffrey L. Woodhead,&nbsp;Pallavi Bhargava,&nbsp;Murali Ramanathan","doi":"10.1111/cts.70272","DOIUrl":"https://doi.org/10.1111/cts.70272","url":null,"abstract":"<p>Incorporating inter-individual differences in drug disposition and responses is essential for ensuring the safe and effective use of drugs in real-world patients. Despite ongoing efforts, lower participation of children, older individuals, pregnant and breastfeeding women, postmenopausal women, and people with disease states and disabilities in drug clinical trials is frequent, and it requires multifaceted strategies and tools to evaluate drug exposure and responses in broad populations. The availability of modeling and simulation tools, such as physiologically based pharmacokinetic (PBPK) and quantitative systems pharmacology/toxicology (QSP/QST) modeling, enables the application of virtual populations that reflect the differences in drug disposition and responses for disease states and different stages of the lifespan. These models integrate clinical trial and real-world data (RWD) to predict drug exposure, efficacy, and safety. Additionally, machine learning (ML) and artificial intelligence (AI) offer powerful tools for analyzing large datasets and identifying key physiological determinants of drug response across the lifespan. This review discusses the application of <i>in silico</i> and AI models to advance the prediction of drug exposure and responses across the lifespan, including examples of virtual populations in PBPK and QSP/QST models. A case study on QST modeling for drug-induced liver injury (DILI) in postmenopausal women is presented, along with opportunities and challenges in applying AI for modeling physiological determinants of drug dosing in individuals ranging in age from 12 to &gt; 80 years old in drug development.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pharmacokinetic Study of Zavegepant Nasal Spray in Healthy Adults Comparing Conventional Venous Blood Sampling With Patient-Centric Microsampling","authors":"Mohamed H. Shahin,&nbsp;Ogert Fisniku,&nbsp;Ding Ding,&nbsp;Katty Wan,&nbsp;Sergey Dubrovin,&nbsp;Kyle Matschke,&nbsp;Olga Kavetska,&nbsp;Robert Fountaine,&nbsp;Jing Liu","doi":"10.1111/cts.70199","DOIUrl":"https://doi.org/10.1111/cts.70199","url":null,"abstract":"<p>This Phase 1, non-randomized, open-label, 2-period study compared the pharmacokinetics (PK) of zavegepant nasal spray, using samples collected via patient-centric microsampling (PCS) devices, with those collected through venous phlebotomy (NCT05948085). Fourteen healthy participants received a single intranasal dose of 10 mg zavegepant on Days 1 and 2. Blood samples for PK analysis were collected at 0.5, 1, 2, 4, 8, and 12 h post dose on Day 1 using the Tasso-Plus device (<i>n</i> = 7; produces serum samples), Tasso-M20 (<i>n</i> = 7; produces dried blood samples), and venous phlebotomy (<i>n</i> = 14). PK parameters were calculated using non-compartmental methods. Natural log-transformed areas under the plasma/serum concentration-time profile from time zero to the time of the last quantifiable concentration (AUC_last) and maximum serum/plasma concentration (C_max) of zavegepant were analyzed using a mixed-effects model, with blood collection as a fixed effect and participant as a random effect. Of the two PCS devices assessed, the results of the Tasso-Plus device showed successful bridging with venous phlebotomy sampling. For Tasso-Plus versus venous phlebotomy, 39 of 41 (95.1%) data pairs met concentration correlation criteria (difference within 20% of the mean), median zavegepant concentration-time profiles were comparable, and 90% confidence intervals for geometric mean ratios for AUC_last and C_max were wholly within the range of bioequivalence acceptance (80%–125%). The results of this study confirm that it is feasible to use serum derived from Tasso-Plus collection of whole capillary blood as a reliable PCS approach for PK analysis of zavegepant.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Vaccine Hesitancy or Hesitancies? A Latent Class Analysis of Pediatric Patients’ Parents”","authors":"","doi":"10.1111/cts.70277","DOIUrl":"https://doi.org/10.1111/cts.70277","url":null,"abstract":"<p>Willis DE, Narcisse MR, James L, Selig JP, Ason M, Scott AJ, Cornett LE, McElfish PA. Vaccine Hesitancy or Hesitancies? A Latent Class Analysis of Pediatric Patients’ Parents. Clinical and Translational Science. 2025;18(1):e70042. https://doi.org/10.1111/cts.70042.</p><p>In the article cited above, the correct grant number for the Community Engagement Alliance (CEAL) Against COVID-19 Disparities was missing.</p><p>This part of the funding statement should have read, “This work is supported by the Community Engagement Alliance (CEAL) Against COVID-19 Disparities (NIH 10T2HL156812-01 and OT2HL158287)…”</p><p>We apologize for this error.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Roles for Modeling and Simulation and Real-World Evidence to Inform Challenges in Clinical Trial Diversity Planning","authors":"Ananth Kadambi,&nbsp;Elke H. J. Krekels,&nbsp;Antal Martinecz,&nbsp;Geoff Fatzinger,&nbsp;Hannah M. Jones,&nbsp;Artak Khachatryan,&nbsp;Karen Rowland Yeo,&nbsp;Fran Brown","doi":"10.1111/cts.70276","DOIUrl":"https://doi.org/10.1111/cts.70276","url":null,"abstract":"<p>Due to the highly controlled settings of clinical trials, enrolled subjects may not be fully representative in age, gender, ethnicity, medical status, or socioeconomic background of the variety of patients who will ultimately receive a medication. This disconnect can lead to post-approval challenges, the most substantial of which could include changes in drug label, dosing, or withdrawal due to severe safety risks that were only observed post-approval. To mitigate these risks and improve the likelihood of approval of safe and effective treatments for patients in the real-world setting from both a medical and socioeconomic perspective, recent regulatory guidance has highlighted a critical role for the inclusion of appropriately diverse populations in clinical trials. To achieve this, there is an increasing need for approaches to facilitate sponsors' ability to generate regulatory-acceptable diversity plans. While epidemiological data may serve as the foundation for diversity planning, researchers are increasingly turning toward modeling and simulation (M&amp;S) approaches to optimize study planning and increase the knowledge gained from study data. Additionally, real-world evidence (RWE) generation is receiving increased attention in the regulatory setting, but prior research has only begun to scratch the surface of the value these approaches can bring to trial diversity planning. Herein, we summarize the strategic value of M&amp;S and RWE-based approaches in the context of trial diversity planning, highlighting unmet needs, prior thought leadership, and recent case examples with the goal of providing readers insight into their diversity planning at different stages of the drug development lifecycle.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics Used in Identifying Novel Correlates of Disease in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Diego Paine-Cabrera,&nbsp;Lisa K. Harvey,&nbsp;Michele T. Pritchard,&nbsp;John Thyfault,&nbsp;Antonio Artigues,&nbsp;Udayan Apte,&nbsp;Voytek Slowik","doi":"10.1111/cts.70271","DOIUrl":"https://doi.org/10.1111/cts.70271","url":null,"abstract":"<p>Metabolic dysfunction-associated liver disease (MASLD) is a leading cause of liver disease in children. There is a paucity of data on potential biomarkers and therapeutic targets, especially in pediatric MASLD. We used mass spectrometry (MS)-mediated proteomics followed by enzyme-linked immunosorbent assay (ELISA) to identify potential biomarkers and therapeutic targets in pediatric MASLD. Serum samples were collected from pediatric subjects without (<i>n</i> = 56) and with MASLD (<i>n</i> = 72). Initial screen using MS-based proteomics identified 6 upregulated (adenosine deaminase 2, sex hormone-binding globulin (SHBG), inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1), fructose-bisphosphate aldolase A, type II cytoskeletal 2 epidermal keratine, N-acetylmuramoyl-L-alanine amidase) and 3 downregulated (alcohol dehydrogenase 4 (ADH4), fructose-bisphosphate aldolase B (ALDOB), serum albumin) proteins in the MASLD group. Confirmatory studies using ELISA were performed for the 2 strongest upregulated proteins (SHBG and ITIH1) and two top downregulated proteins (ADH4 and ALDOB). Correlation of ELISA results with clinical data revealed that SHBG had strong associations with BMI, ALT, and HgbA1c (<i>p</i> &lt; 0.05). ADH4 had strong associations with BMI and HgbA1c (<i>p</i> &lt; 0.05). ITIH1 and ALDOB had no strong correlations with common clinical parameters of MASLD. Area under ROC Curve revealed statistically significant ability of SHBG (494 nmol/L, sensitivity = 98%, specificity 80%) and ADH4 (2.14 ng/mL, sensitivity = 65%, specificity = 66%) to diagnosis MASLD (<i>p</i> &lt; 0.05). MS with confirmation ELISA identified SHBG and ADH4 as potential biomarkers of pediatric MASLD.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Organoid-Derived Exosomal microRNA as Liquid Biopsy for Colorectal Cancer: A Multicenter Cross-Sectional Study","authors":"Atsuhiro Sasaki,&nbsp;Masatake Kuroha,&nbsp;Masaki Tosa,&nbsp;Seiichi Takahashi,&nbsp;Shinya Oomori,&nbsp;Eiki Nomura,&nbsp;Tatsuya Kikuchi,&nbsp;Motoyuki Onodera,&nbsp;Yuichiro Sato,&nbsp;Teruko Miyazawa,&nbsp;Hirofumi Chiba,&nbsp;Naonobu Yokoyama,&nbsp;Jun Kusaka,&nbsp;Daisuke Okamoto,&nbsp;Tomoyuki Handa,&nbsp;Mikako Sugimura,&nbsp;Masahiro Iwabuchi,&nbsp;Keiichiro Hiramoto,&nbsp;Hidekazu Shirota,&nbsp;Hideya Iwaki,&nbsp;Hiroshi Nagai,&nbsp;Yusuke Shimoyama,&nbsp;Takeo Naito,&nbsp;Rintaro Moroi,&nbsp;Hisashi Shiga,&nbsp;Yoichi Kakuta,&nbsp;Yoshitaka Kinouchi,&nbsp;Atsushi Masamune","doi":"10.1111/cts.70270","DOIUrl":"https://doi.org/10.1111/cts.70270","url":null,"abstract":"<p>Exosomal microRNAs (miRNAs) are candidates for liquid biopsies. Organoid culture systems enable long-term expansion of the colon epithelium. This study evaluated exosomal miRNAs from colorectal cancer organoids for liquid biopsy. Organoids were established from normal colon and colorectal cancer tissues. Exosomes were isolated from conditioned media. miRNAs were extracted from exosomes and compared using microarray analysis. Exosomal miRNAs expression levels in the sera of healthy patients and patients with colorectal cancer were compared at a single institution. The multicenter study was validated using miRNAs upregulated in the serum of colorectal cancer patients, along with exosomal miRNAs reported to be upregulated in colorectal adenoma organoids and sera. A total of 44 exosomal miRNAs were commonly expressed in both normal colorectal epithelial cells and colorectal cancer organoids, whereas 59 were exclusively expressed in colorectal cancer organoids. In a single-center cohort study, two exosomal miRNAs (miR-4284 and miR-5100) were upregulated in the serum of colorectal cancer patients. In a multicenter study, four exosomal miRNAs (miR-4284, miR-5100, miR-1246, and miR-1290) were upregulated in the serum of patients with colorectal cancer. The combination of these four exosomal miRNAs had comparable diagnostic performance to carcinoembryonic antigen, with an area under the curve of 0.75 (95% confidence interval: 0.65–0.83) versus 0.79 (95% confidence interval: 0.70–0.87). Combining the four miRNAs with carcinoembryonic antigen improved diagnostic accuracy, with an area under the curve of 0.82 (95% confidence interval: 0.74–0.89). Exosomal miRNAs derived from colorectal cancer organoids can serve as diagnostic biomarkers for colorectal cancer.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}