{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T23:40:30Z","timestamp":1781307630783,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Funding of the Faculty of Medicine, Ruhr University Bochum (FoRUM Program)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative time points receiving Propofol or Sevoflurane were extracted with polymer-based methods and quantified with a nanoparticle-tracking analysis. Vesicle-associated micro-RNAs were analyzed with a real-time polymerase chain reaction using array cards and single assays for tumor-associated miR-21-5p, miR-15a-5p, miR-17-5p and miR-451a. Plasma extracellular vesicle concentration (suture: fold change (fc) in Propofol at 4.1 \u00b1 3.9 vs. Sevoflurane at 0.8 \u00b1 0.5; p = 0.003) and associated miRNAs increased significantly (+30% post induction, +9% 30 Min surgery) in the Propofol group. Tumor-associated miRNAs increased during surgery in both groups (fc in miR-21-5p: 24.3 \u00b1 10.2, p = 0.029; fc in miR-15a-5p: 9.7 \u00b1 3.8, p = 0.027; fc in miR-17-5p: 5.4 \u00b1 1.7, p = 0.014), whereas antitumor miR-451a increased in the Propofol group only (fc: 2.5 \u00b1 0.6 vs. 1.0 \u00b1 0.2; p = 0.022). Anesthetics influence extracellular vesicles and associated micro-RNAs of bladder cancer patients during surgery. Increased expression of antitumor micro-RNA may be an explanatory approach for decreased tumor cell viability after Propofol.<\/jats:p>","DOI":"10.3390\/cells12202503","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T01:41:21Z","timestamp":1698025281000},"page":"2503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9244-2381","authenticated-orcid":false,"given":"Luisa","family":"Gluth","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crista","family":"Ochsenfarth","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Nam Viet","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Wischermann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Komanek","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-489X","authenticated-orcid":false,"given":"Florian","family":"Roghmann","sequence":"additional","affiliation":[{"name":"Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich H.","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care, Pain and Palliative Care, Marien Hospital Herne, Ruhr-University Bochum, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/S0140-6736(18)30996-6","article-title":"Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): An open-label, randomised, phase 3, non-inferiority trial","volume":"391","author":"Parekh","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00345-006-0117-8","article-title":"Staged based directed surveillance of invasive bladder cancer following radical cystectomy: Valuable and effective?","volume":"24","author":"Donat","year":"2006","journal-title":"World J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/sj.bjc.6605651","article-title":"Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: A systematic review","volume":"102","author":"Peach","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1158\/0008-5472.CAN-16-1536","article-title":"Surgery for Cancer: A Trigger for Metastases","volume":"77","author":"Tohme","year":"2017","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/bja\/aeq164","article-title":"Effect of anaesthetic technique and other perioperative factors on cancer recurrence","volume":"105","author":"Snyder","year":"2010","journal-title":"Br. J. Anaesth."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrclinonc.2014.224","article-title":"Exploiting the critical perioperative period to improve long-term cancer outcomes","volume":"12","author":"Horowitz","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/ALN.0000000000000936","article-title":"Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis","volume":"124","author":"Wigmore","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233.e1","DOI":"10.1016\/j.urolonc.2020.08.024","article-title":"Can anesthetics affect bladder cancer recurrence? Total intravenous versus volatile anesthesia in patients undergoing robot-assisted radical cystectomy: A single institution retrospective analysis","volume":"39","author":"Pfail","year":"2021","journal-title":"Urol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000504807","article-title":"Anesthesia in Combination with Propofol Increases Disease-Free Survival in Bladder Cancer Patients Who Undergo Radical Tumor Cystectomy as Compared to Inhalational Anesthetics and Opiate-Based Analgesia","volume":"98","year":"2020","journal-title":"Oncology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/ALN.0000000000002506","article-title":"Anesthesia and Cancer Recurrence: Context for Divergent Study Outcomes","volume":"130","author":"Sessler","year":"2019","journal-title":"Anesthesiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e12867","DOI":"10.1111\/cpr.12867","article-title":"Effects of propofol on the development of cancer in humans","volume":"53","author":"Xu","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ishikawa, M., Iwasaki, M., Sakamoto, A., and Ma, D. (2021). Anesthetics may modulate cancer surgical outcome: A possible role of miRNAs regulation. BMC Anesthesiol., 21.","DOI":"10.1186\/s12871-021-01294-w"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1007\/s00018-011-0689-3","article-title":"Membrane vesicles, current state-of-the-art: Emerging role of extracellular vesicles","volume":"68","author":"Aradi","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA expression profiles classify human cancers","volume":"435","author":"Lu","year":"2005","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMra1704286","article-title":"Circulating Extracellular Vesicles in Human Disease","volume":"379","author":"Shah","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Harris, P.A., Taylor, R., Minor, B.L., Elliott, V., Fernandez, M., O\u2019Neal, L., McLeod, L., Delacqua, G., Delacqua, F., and Kirby, J. (2019). The REDCap consortium: Building an international community of software platform partners. J. Biomed. Inform., 95.","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.4103\/sja.SJA_559_18","article-title":"The CONSORT statement","volume":"13","author":"Cuschieri","year":"2019","journal-title":"Saudi J. Anaesth."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20360","DOI":"10.3402\/jev.v2i0.20360","article-title":"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research","volume":"2","author":"Witwer","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41585-019-0261-8","article-title":"Extracellular vesicles in urological malignancies: An update","volume":"17","author":"Linxweiler","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12078","DOI":"10.3892\/mmr.2021.12078","article-title":"Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR-145-5p\/TOP2A axis","volume":"23","author":"Du","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/anae.13331","article-title":"Effects of anaesthesia on proliferation, invasion and apoptosis of LoVo colon cancer cells in vitro","volume":"71","author":"Xu","year":"2016","journal-title":"Anaesthesia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"118154","DOI":"10.1016\/j.lfs.2020.118154","article-title":"Isoflurane promotes epithelial-to-mesenchymal transition and metastasis of bladder cancer cells through HIF-1\u03b1-\u03b2-catenin\/Notch1 pathways","volume":"258","author":"Lu","year":"2020","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1097\/ALN.0000000000003440","article-title":"Volatile versus Total Intravenous Anesthesia for Cancer Prognosis in Patients Having Digestive Cancer Surgery","volume":"133","author":"Makito","year":"2020","journal-title":"Anesthesiology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.clinthera.2014.05.010","article-title":"Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells","volume":"36","author":"Oksvold","year":"2014","journal-title":"Clin. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles","volume":"3","author":"Hill","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.3892\/or.2016.5040","article-title":"miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc","volume":"36","author":"Wang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/ALN.0000000000002986","article-title":"Propofol and Sevoflurane Differentially Impact MicroRNAs in Circulating Extracellular Vesicles during Colorectal Cancer Resection: A Pilot Study","volume":"132","author":"Buschmann","year":"2020","journal-title":"Anesthesiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s12967-014-0279-x","article-title":"Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells","volume":"12","author":"Zhang","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"476962","DOI":"10.1016\/j.jneuroim.2019.05.003","article-title":"Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release","volume":"333","author":"Liu","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3542149","DOI":"10.1155\/2017\/3542149","article-title":"Inhibition of Caveolae Contributes to Propofol Preconditioning-Suppressed Microvesicles Release and Cell Injury by Hypoxia-Reoxygenation","volume":"2017","author":"Deng","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113813","DOI":"10.1016\/j.addr.2021.05.023","article-title":"Agony of choice: How anesthetics affect the composition and function of extracellular vesicles","volume":"175","author":"Abel","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1057571","DOI":"10.3389\/fphar.2022.1057571","article-title":"An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"963689720985113","DOI":"10.1177\/0963689720985113","article-title":"Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway","volume":"30","author":"Li","year":"2021","journal-title":"Cell Transplant."},{"key":"ref_38","first-page":"6228","article-title":"Propofol exhibits a tumor-suppressive effect and regulates cell viability, migration and invasion in bladder carcinoma by targeting the microRNA-10b\/HOXD10 signaling pathway","volume":"18","author":"Qi","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_39","unstructured":"Renovato-Martins, M., Gomes, A.C., Amorim, C.S., and Moraes, J.A. (2022). Gastrointestinal Cancers, Exon Publications."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1002\/ijc.32820","article-title":"Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery","volume":"146","author":"Raskov","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tabnak, P., Masrouri, S., Geraylow, K.R., Zarei, M., and Esmailpoor, Z.H. (2021). Targeting miRNAs with anesthetics in cancer: Current understanding and future perspectives. Biomed. Pharmacother., 144.","DOI":"10.1016\/j.biopha.2021.112309"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1161\/HYPERTENSIONAHA.119.13549","article-title":"Extracellular Vesicles: How a Circulating Biomarker Can Double As a Regulator of Blood Pressure","volume":"75","author":"Bagher","year":"2020","journal-title":"Hypertension"},{"key":"ref_43","first-page":"387","article-title":"Micro-RNA profiling in kidney and bladder cancers","volume":"25","author":"Gottardo","year":"2007","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Oeyen, E., Hoekx, L., de Wachter, S., Baldewijns, M., Ameye, F., and Mertens, I. (2019). Bladder Cancer Diagnosis and Follow-Up: The Current Status and Possible Role of Extracellular Vesicles. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040821"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"24668","DOI":"10.18632\/oncotarget.14969","article-title":"MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma","volume":"8","author":"Matsuzaki","year":"2017","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15027078","DOI":"10.4238\/gmr.15027078","article-title":"Propofol inhibits proliferation and accelerates apoptosis of human gastric cancer cells by regulation of microRNA-451 and MMP-2 expression","volume":"15","author":"Peng","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1158\/1535-7163.MCT-12-0802","article-title":"The potential role of miR-451 in cancer diagnosis, prognosis, and therapy","volume":"12","author":"Pan","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Martellucci, S., Orefice, N.S., Angelucci, A., Luce, A., Caraglia, M., and Zappavigna, S. (2020). Extracellular Vesicles: New Endogenous Shuttles for miRNAs in Cancer Diagnosis and Therapy? Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186486"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Campanella, C., Caruso Bavisotto, C., Logozzi, M., Marino Gammazza, A., Mizzoni, D., Cappello, F., and Fais, S. (2019). On the Choice of the Extracellular Vesicles for Therapeutic Purposes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020236"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.ijpharm.2012.07.008","article-title":"A propofol microemulsion with low free propofol in the aqueous phase: Formulation, physicochemical characterization, stability and pharmacokinetics","volume":"436","author":"Cai","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1007\/s11095-006-9092-4","article-title":"Lipid injectable emulsions: Pharmacopeial and safety issues","volume":"23","author":"Driscoll","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3109\/00498259109043207","article-title":"Distribution in female rats of an anaesthetic intravenous dose of 14C-propofol","volume":"21","author":"Simons","year":"1991","journal-title":"Xenobiotica"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s005400070018","article-title":"Pharmacokinetic profile of propofol after a single-dose injection during general anesthesia in Japanese adults","volume":"14","author":"Okada","year":"2000","journal-title":"J. Anesth."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:02Z","timestamp":1760130602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/20\/2503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":53,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cells12202503"],"URL":"https:\/\/doi.org\/10.3390\/cells12202503","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}