{ "labelLang" : "hun", "responseDate" : "2024-03-29 01:26", "content" : { "otype" : "JournalArticle", "mtid" : 30991553, "status" : "VALIDATED", "published" : true, "comment" : "Funding Agency and Grant Number: Feist-Weiller Cancer Center (FWCC); Center for Cardiovascular Diseases and Sciences; Center for Molecular and Tumor Virology; Biomedical Research Foundation; LSU Health Shreveport Foundation\n Funding text: the Feist-Weiller Cancer Center (FWCC); Grant sponsor: the Center for Cardiovascular Diseases and Sciences; Grant sponsor: the Center for Molecular and Tumor Virology; Grant sponsor: Biomedical Research Foundation; Grant sponsor: LSU Health Shreveport Foundation\nDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, United States \n Feist Weiller Cancer Center, LSUHSC, Shreveport, LA, United States \n Overton Brooks VA Medical center, Shreveport, LA, United States \n Cited By :5 \n Export Date: 31 July 2020 \n CODEN: IJCNA \n Correspondence Address: De Benedetti, A.; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences CenterUnited States; email: adeben@lsuhsc.edu \n Chemicals/CAS: bicalutamide, 90357-06-5; discoidin domain receptor; discoidin domain receptor 1; discoidin domain receptor 2; mammalian target of rapamycin complex 1; mammalian target of rapamycin complex 2; NIMA related kinase 1; protein kinase Mer; protein serine threonine kinase; serine threonine protein kinase ULK1; serine/threonine protein kinase WNK1; thioridazine, 130-61-0, 50-52-2; Androgen Antagonists; Androgens; NEK1 protein, human; NIMA-Related Kinase 1; Protein-Serine-Threonine Kinases; Receptors, Androgen; Thioridazine; TLK1 protein, human \n Funding details: Biomedical Research Foundation, BRF \n Funding details: LSU Health Shreveport \n Funding details: U.S. Department of Defense, DOD, W81XWH-17-1-0417 \n Funding details: Feist-Weiller Cancer Center, FWCC \n Funding details: Biomedical Research Foundation, BRF \n Funding details: LSU Health Shreveport \n Funding details: Feist-Weiller Cancer Center, FWCC, W81XWH-17-1-0417 \n Funding text 1: Additional Supporting Information may be found in the online version of this article. V.S. and P.K.J. contributed equally to this work. Conflict of interest: No potential conflicts of interest were disclosed. Grant sponsor: U.S. Department of Defense; Grant number: W81XWH-17-1-0417; Grant sponsor: a FWCC bridge award and DoD-PCRP grant; Grant number: W81XWH-17-1-0417; Grant sponsor: the Feist-Weiller Cancer Center (FWCC); Grant sponsor: the Center for Cardiovascular Diseases and Sciences; Grant sponsor: the Center for Molecular and Tumor Virology; Grant sponsor: Biomedical Research Foundation; Grant sponsor: LSU Health Shreveport Foundation DOI: 10.1002/ijc.32200 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. History: Received 25 Jul 2018; Accepted 29 Jan 2019; Online 9 Feb 2019 Correspondence to: Arrigo De Benedetti, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport Tel.: 318-675-5668, E-mail: adeben@lsuhsc.edu \n Funding text 2: We thank Paula Polk and the Research Core Facility-Genomics and the Histopathology Core at LSU Health-Shreveport, which is supported in part by the LSU Health Shreveport Foundation, the Biomedical Research Foundation, the Center for Molecular and Tumor Virology, the Center for Cardiovascular Diseases and Sciences, and the Feist-Weiller Cancer Center (FWCC). This work was supported primarily by a FWCC bridge award and DoD-PCRP grant W81XWH-17-1-0417 to A. De Benedetti.\nDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, United States \n Feist Weiller Cancer Center, LSUHSC, Shreveport, LA, United States \n Overton Brooks VA Medical center, Shreveport, LA, United States \n Cited By :9 \n Export Date: 18 January 2021 \n CODEN: IJCNA \n Correspondence Address: De Benedetti, A.; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences CenterUnited States; email: adeben@lsuhsc.edu \n Chemicals/CAS: bicalutamide, 90357-06-5; discoidin domain receptor; discoidin domain receptor 1; discoidin domain receptor 2; mammalian target of rapamycin complex 1; mammalian target of rapamycin complex 2; NIMA related kinase 1; protein kinase Mer; protein serine threonine kinase; serine threonine protein kinase ULK1; serine/threonine protein kinase WNK1; thioridazine, 130-61-0, 50-52-2; Androgen Antagonists; Androgens; NEK1 protein, human; NIMA-Related Kinase 1; Protein-Serine-Threonine Kinases; Receptors, Androgen; Thioridazine; TLK1 protein, human \n Funding details: Biomedical Research Foundation, BRF \n Funding details: LSU Health Shreveport \n Funding details: U.S. Department of Defense, DOD, W81XWH-17-1-0417 \n Funding details: Feist-Weiller Cancer Center, FWCC \n Funding details: Biomedical Research Foundation, BRF \n Funding details: LSU Health Shreveport \n Funding details: Feist-Weiller Cancer Center, FWCC, W81XWH-17-1-0417 \n Funding text 1: Additional Supporting Information may be found in the online version of this article. V.S. and P.K.J. contributed equally to this work. Conflict of interest: No potential conflicts of interest were disclosed. Grant sponsor: U.S. Department of Defense; Grant number: W81XWH-17-1-0417; Grant sponsor: a FWCC bridge award and DoD-PCRP grant; Grant number: W81XWH-17-1-0417; Grant sponsor: the Feist-Weiller Cancer Center (FWCC); Grant sponsor: the Center for Cardiovascular Diseases and Sciences; Grant sponsor: the Center for Molecular and Tumor Virology; Grant sponsor: Biomedical Research Foundation; Grant sponsor: LSU Health Shreveport Foundation DOI: 10.1002/ijc.32200 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. History: Received 25 Jul 2018; Accepted 29 Jan 2019; Online 9 Feb 2019 Correspondence to: Arrigo De Benedetti, Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport Tel.: 318-675-5668, E-mail: adeben@lsuhsc.edu \n Funding text 2: We thank Paula Polk and the Research Core Facility-Genomics and the Histopathology Core at LSU Health-Shreveport, which is supported in part by the LSU Health Shreveport Foundation, the Biomedical Research Foundation, the Center for Molecular and Tumor Virology, the Center for Cardiovascular Diseases and Sciences, and the Feist-Weiller Cancer Center (FWCC). This work was supported primarily by a FWCC bridge award and DoD-PCRP grant W81XWH-17-1-0417 to A. De Benedetti.", "unhandledTickets" : 0, "deleted" : false, "lastRefresh" : "2022-11-05T22:48:02.298+0000", "lastModified" : "2019-12-12T04:05:13.163+0000", "created" : "2019-12-12T04:05:12.370+0000", "creator" : { "otype" : "Admin", "mtid" : 10013822, "link" : "/api/admin/10013822", "label" : "WoS admin-2 -1 (WoS import 3, admin)", "familyName" : "WoS admin-2", "givenName" : "-1", "published" : true, "oldId" : 10013822, "snippet" : true }, "lastDuplumSearch" : "2022-11-05T22:23:38.507+0000", "validated" : "2019-12-12T04:05:12.455+0000", "validator" : { "otype" : "Admin", "mtid" : 10013822, "link" : "/api/admin/10013822", "label" : "WoS admin-2 -1 (WoS import 3, admin)", "familyName" : "WoS admin-2", "givenName" : "-1", "published" : true, "oldId" : 10013822, "snippet" : true }, "core" : false, "citation" : true, "publicationPending" : false, "type" : { "otype" : "PublicationType", "mtid" : 24, "link" : "/api/publicationtype/24", "label" : "Folyóiratcikk", "code" : 24, "otypeName" : "JournalArticle", "listPosition" : 1, "published" : true, "oldId" : 24, "snippet" : true }, "subType" : { "otype" : "SubType", "mtid" : 10000059, "link" : "/api/subtype/10000059", "label" : "Szakcikk (Folyóiratcikk)", "name" : "Szakcikk", "nameEng" : "Article", "docType" : { "otype" : "PublicationType", "mtid" : 24, "link" : "/api/publicationtype/24", "label" : "Folyóiratcikk", "code" : 24, "otypeName" : "JournalArticle", "listPosition" : 1, "published" : true, "oldId" : 24, "snippet" : true }, "listPosition" : 101, "published" : true, "oldId" : 10000059, "snippet" : true }, "category" : { "otype" : "Category", "mtid" : 1, "link" : "/api/category/1", "label" : "Tudományos", "published" : true, "oldId" : 1, "snippet" : true }, "languages" : [ { "otype" : "Language", "mtid" : 10002, "link" : "/api/language/10002", "label" : "Angol", "name" : "Angol", "nameEng" : "English", "published" : true, "oldId" : 2, "snippet" : true } ], "firstAuthor" : "Singh, Vibha", "authorships" : [ { "otype" : "PersonAuthorship", "mtid" : 89367815, "link" : "/api/authorship/89367815", "label" : "Singh, Vibha", "listPosition" : 1, "share" : 0.0, "first" : true, "last" : false, "corresponding" : false, "familyName" : "Singh", "givenName" : "Vibha", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 89367816, "link" : "/api/authorship/89367816", "label" : "Jaiswal, Praveen Kumar", "listPosition" : 2, "share" : 0.0, "first" : false, "last" : false, "corresponding" : false, "familyName" : "Jaiswal", "givenName" : "Praveen Kumar", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 89367817, "link" : "/api/authorship/89367817", "label" : "Ghosh, Ishita", "listPosition" : 3, "share" : 0.0, "first" : false, "last" : false, "corresponding" : false, "familyName" : "Ghosh", "givenName" : "Ishita", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 89367818, "link" : "/api/authorship/89367818", "label" : "Koul, Hari K.", "listPosition" : 4, "share" : 0.0, "first" : false, "last" : false, "corresponding" : false, "familyName" : "Koul", "givenName" : "Hari K.", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 89367819, "link" : "/api/authorship/89367819", "label" : "Yu, Xiuping", "listPosition" : 5, "share" : 0.0, "first" : false, "last" : false, "corresponding" : false, "familyName" : "Yu", "givenName" : "Xiuping", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 89367820, "link" : "/api/authorship/89367820", "label" : "De Benedetti, Arrigo ✉", "listPosition" : 6, "share" : 0.0, "first" : false, "last" : true, "corresponding" : true, "familyName" : "De Benedetti", "givenName" : "Arrigo", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true } ], "title" : "Targeting the TLK1/NEK1 DDR axis with Thioridazine suppresses outgrowth of androgen independent prostate tumors", "identifiers" : [ { "otype" : "PublicationIdentifier", "mtid" : 16257018, "link" : "/api/publicationidentifier/16257018", "label" : "DOI: 10.1002/ijc.32200", "source" : { "otype" : "PlainSource", "mtid" : 6, "link" : "/api/publicationsource/6", "label" : "DOI", "type" : { "otype" : "PublicationSourceType", "mtid" : 10001, "link" : "/api/publicationsourcetype/10001", "label" : "DOI", "mayHaveOa" : true, "published" : true, "snippet" : true }, "name" : "DOI", "nameEng" : "DOI", "linkPattern" : "https://doi.org/@@@", "publiclyVisible" : true, "published" : true, "oldId" : 6, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "10.1002/ijc.32200", "realUrl" : "https://doi.org/10.1002/ijc.32200", "published" : false, "snippet" : true }, { "otype" : "PublicationIdentifier", "mtid" : 16257017, "link" : "/api/publicationidentifier/16257017", "label" : "WoS: 000472571300018", "source" : { "otype" : "PlainSource", "mtid" : 1, "link" : "/api/publicationsource/1", "label" : "WoS", "type" : { "otype" : "PublicationSourceType", "mtid" : 10003, "link" : "/api/publicationsourcetype/10003", "label" : "Indexelő adatbázis", "mayHaveOa" : false, "published" : true, "snippet" : true }, "name" : "WoS", "nameEng" : "WoS", "linkPattern" : "https://www.webofscience.com/wos/woscc/full-record/WOS:@@@", "publiclyVisible" : true, "published" : true, "oldId" : 1, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "000472571300018", "realUrl" : "https://www.webofscience.com/wos/woscc/full-record/WOS:000472571300018", "published" : false, "snippet" : true }, { "otype" : "PublicationIdentifier", "mtid" : 17089037, "link" : "/api/publicationidentifier/17089037", "label" : "Scopus: 85062352846", "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" : "85062352846", "realUrl" : "http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85062352846", "published" : false, "snippet" : true }, { "otype" : "PublicationIdentifier", "mtid" : 17089021, "link" : "/api/publicationidentifier/17089021", "label" : "PubMed: 30737777", "source" : { "otype" : "PlainSource", "mtid" : 17, "link" : "/api/publicationsource/17", "label" : "PubMed", "type" : { "otype" : "PublicationSourceType", "mtid" : 10003, "link" : "/api/publicationsourcetype/10003", "label" : "Indexelő adatbázis", "mayHaveOa" : false, "published" : true, "snippet" : true }, "name" : "PubMed", "nameEng" : "PubMed", "linkPattern" : "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=@@@&dopt=Abstract", "publiclyVisible" : true, "published" : true, "oldId" : 17, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "30737777", "realUrl" : "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=30737777&dopt=Abstract", "published" : false, "snippet" : true } ], "journal" : { "otype" : "Journal", "mtid" : 2005, "link" : "/api/journal/2005", "label" : "INTERNATIONAL JOURNAL OF CANCER 0020-7136 1097-0215", "pIssn" : "0020-7136", "eIssn" : "1097-0215", "reviewType" : "REVIEWED", "noIF" : false, "sciIndexed" : true, "scopusIndexed" : true, "lang" : "FOREIGN", "hungarian" : false, "published" : true, "oldId" : 2005, "snippet" : true }, "volume" : "145", "issue" : "4", "firstPage" : "1055", "lastPage" : "1067", "firstPageOrInternalIdForSort" : "1055", "pageLength" : 13, "publishedYear" : 2019, "abstractText" : "Standard therapy for advanced Prostate Cancer (PCa) consists of antiandrogens, which provide respite from disease progression, but ultimately fail resulting in the incurable phase of the disease: mCRPC. Targeting PCa cells before their progression to mCRPC would greatly improve the outcome. Combination therapy targeting the DNA Damage Response (DDR) has been limited by general toxicity, and a goal of clinical trials is how to target the DDR more specifically. We now show that androgen deprivation therapy (ADT) of LNCaP cells results in increased expression of TLK1B, a key kinase upstream of NEK1 and ATR and mediating the DDR that typically results in a temporary cell cycle arrest of androgen responsive PCa cells. Following DNA damage, addition of the TLK specific inhibitor, thioridazine (THD), impairs ATR and Chk1 activation, establishing the existence of a ADT > TLK1 > NEK1 > ATR > Chk1, DDR pathway, while its abrogation leads to apoptosis. Treatment with THD suppressed the outgrowth of androgen-independent (AI) colonies of LNCaP and TRAMP-C2 cells cultured with bicalutamide. Moreover, THD significantly inhibited the growth of several PCa cells in vitro (including AI lines). Administration of THD or bicalutamide was not effective at inhibiting long-term tumor growth of LNCaP xenografts. In contrast, combination therapy remarkably inhibited tumor growth via bypass of the DDR. Moreover, xenografts of LNCaP cells overexpressing a NEK1-T141A mutant were durably suppressed with bicalutamide. Collectively, these results suggest that targeting the TLK1/NEK1 axis might be a novel therapy for PCa in combination with standard of care (ADT).", "subjects" : [ { "otype" : "Classification", "mtid" : 12215, "link" : "/api/classification/12215", "label" : "Klinikai orvostan", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2019, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : null, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2022-11-05", "oaFree" : false, "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, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10984585, "link" : "/api/sjrrating/10984585", "label" : "sjr:Q1 (2019) Scopus - Cancer Research INTERNATIONAL JOURNAL OF CANCER 0020-7136 1097-0215", "listPos" : 37, "rankValue" : 0.24, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 1306, "link" : "/api/classificationexternal/1306", "label" : "Scopus - Cancer Research", "published" : true, "oldId" : 1306, "snippet" : true }, "ranking" : "Q1", "calculation" : "DIRECT", "published" : true, "snippet" : true } ], "ratingsForSort" : "Q1", "mtaRatingsForSort" : "B nemzetközi", "hasCitationDuplums" : false, "directInstitutesForSort" : "", "ownerAuthorCount" : 3, "ownerInstituteCount" : 8, "directInstituteCount" : 0, "authorCount" : 6, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/30991553", "label" : "Singh Vibha et al. Targeting the TLK1/NEK1 DDR axis with Thioridazine suppresses outgrowth of androgen independent prostate tumors. (2019) INTERNATIONAL JOURNAL OF CANCER 0020-7136 1097-0215 145 4 1055-1067", "template" : "