{ "labelLang" : "hun", "responseDate" : "2024-03-28 14:02", "content" : { "otype" : "JournalArticle", "mtid" : 31907362, "status" : "APPROVED", "published" : true, "comment" : "Departments of Obstetrics and Gynecology and Nephrology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China \n Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States \n Ministry of Education Key Laboratory of Diagnostic Medicine, The School of Laboratory Diagnostic Medicine, Chongqing Medical University, Chongqing, China \n Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266061, China \n Department of Spine Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, China \n Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China \n Department of Neurosurgery, The Affiliated Zhongnan Hospital, Wuhan University, Wuhan, 430072, China \n Department of Surgery Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, United States \n Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, United States \n Cited By :1 \n Export Date: 9 March 2021 \n Correspondence Address: He, T.-C.; Molecular Oncology Laboratory, 5841 South Maryland Avenue, United States; email: tche@uchicago.edu \n Correspondence Address: Qi, H.; Department of Obstetrics and Gynecology, China; email: qihongbo728@163.com \n Funding details: P30CA014599 \n Funding details: National Institutes of Health, NIH, CA226303, T32 GM00-7281 \n Funding details: National Center for Advancing Translational Sciences, NCATS, UL1 TR000430 \n Funding text 1: The authors wish to thank Dr. Ernest Lengyel of The University of Chicago for providing human ovarian cancer cell lines OVCAR8, HeyA8, and the paclitaxel (PTX)-resistant HeyA8-MDR. The reported work was supported in part by research grants from the National Institutes of Health (CA226303 to TCH). WW was supported by the Medical Scientist Training Program of the National Institutes of Health (T32 GM00-7281). This project was also supported in part by The University of Chicago Cancer Center Support Grant (P30CA014599) and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430. TCH was supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund. 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true }, "published" : false, "snippet" : true } ], "title" : "The inhibition of BRAF activity sensitizes chemoresistant human ovarian cancer cells to paclitaxel-induced cytotoxicity and tumor growth inhibition", "identifiers" : [ { "otype" : "PublicationIdentifier", "mtid" : 18513099, "link" : "/api/publicationidentifier/18513099", "label" : "Scopus: 85099362377", "source" : { "otype" : "PlainSource", "mtid" : 3, "link" : "/api/publicationsource/3", "label" : "Scopus", "type" : { "otype" : "PublicationSourceType", "mtid" : 10003, "link" : "/api/publicationsourcetype/10003", "label" : "Indexelő adatbázis", "mayHaveOa" : false, "published" : true, "snippet" : true }, "name" : "Scopus", "linkPattern" : "http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@", "publiclyVisible" : true, "published" : true, "oldId" : 3, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "85099362377", "realUrl" : 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While ovarian cancer is highly heterogeneous in histological subtypes and molecular genetic makeup, epithelial ovarian cancer is the most common subtype. The clinical outcomes of ovarian cancer largely depend on early detection and access to appropriate surgery and systemic therapy. While combination therapy with platinum-based drugs and paclitaxel (PTX) remains the first-line systemic therapy for ovarian cancer, many patients experience recurrence and die of progressive chemoresistance. Thus, there is an unmet clinical need to overcome recurrent disease due to resistance to chemotherapies of ovarian cancer. Here, we investigated whether BRAF inhibitors (BRAFi) could sensitize PTX-resistant ovarian cancer cells to PTX, and thus would overcome the resistance to chemotherapies. We found that BRAF and several members of the RAS/MAPK pathways were upregulated upon PTX treatment in ovarian cancer cells, and that BRAF expression was significantly elevated in the PTX-resistant ovarian cancer cells. While the BRAFi vemurafenib (VEM) alone did not cause any significant cytotoxicity in PTX-resistant ovarian cancer cells, VEM significantly enhanced PTX-induced growth inhibition and apoptosis in a dose-dependent manner. Furthermore, VEM and PTX were shown to synergistically inhibit tumor growth and cell proliferation of PTX-resistant human ovarian cancer cells in vivo. Collectively, these findings strongly suggest that BRAFi may be exploited as synergistic sensitizers of paclitaxel in treating chemoresistant ovarian cancer. © 2020 E-Century Publishing Corporation. All rights reserved.", "keywords" : [ { "otype" : "Keyword", "mtid" : 14530, "link" : "/api/keyword/14530", "label" : "Combination chemotherapy", "published" : true, "oldId" : 14530, "snippet" : true }, { "otype" : "Keyword", "mtid" : 16728, "link" : "/api/keyword/16728", "label" : "targeted therapy", "published" : true, "oldId" : 16728, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1060770, "link" : "/api/keyword/1060770", "label" : "Ovarian cancer", "published" : true, "oldId" : 1060770, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1131609, "link" : "/api/keyword/1131609", "label" : "Chemoresistance", "published" : true, "oldId" : 1131609, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1349698, "link" : "/api/keyword/1349698", "label" : "Vemurafenib", "published" : true, "oldId" : 1349698, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1535920, "link" : "/api/keyword/1535920", "label" : "Paclitaxel (PTX)", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1701056, "link" : "/api/keyword/1701056", "label" : "paclitaxel resistance", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2285057, "link" : "/api/keyword/2285057", "label" : "BRAF inhibitor (BRAFi)", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2021, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : null, "missingAuthor" : false, "oaType" : "GOLD", "oaCheckDate" : "2022-07-29", "oaFree" : false, "oaLink" : "http://www.ajtr.org", "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 1, "citedCount" : 1, "references" : [ { "otype" : "Reference", "mtid" : 18869582, "link" : "/api/reference/18869582", "label" : "1. 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