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Sökning: onr:"swepub:oai:lup.lub.lu.se:20b113cf-8830-4de6-8689-68a215af300b" > Entinostat Enhances...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004900naa a2200577 4500
001oai:lup.lub.lu.se:20b113cf-8830-4de6-8689-68a215af300b
003SwePub
008231130s2023 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/20b113cf-8830-4de6-8689-68a215af300b2 URI
0247 a https://doi.org/10.1158/1078-0432.CCR-23-17952 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Solta, Annau Medical University of Vienna4 aut
2451 0a Entinostat Enhances the Efficacy of Chemotherapy in Small Cell Lung Cancer Through S-phase Arrest and Decreased Base Excision Repair
264 1c 2023
300 a 16 s.
520 a PURPOSE: Acquired chemoresistance is a frequent event in small cell lung cancer (SCLC), one of the deadliest human malignancies. Histone deacetylase inhibitors (HDACi) have been shown to synergize with different chemotherapeutic agents including cisplatin. Accordingly, we aimed to investigate the dual targeting of HDAC inhibition and chemotherapy in SCLC.EXPERIMENTAL DESIGN: The efficacy of HDACi and chemotherapy in SCLC was investigated both in vitro and in vivo. Synergistic drug interactions were calculated based on the HSA model (Combenefit software). Results from the proteomic analysis were confirmed via ICP-MS, cell-cycle analysis, and comet assays.RESULTS: Single entinostat- or chemotherapy significantly reduced cell viability in human neuroendocrine SCLC cells. The combination of entinostat with either cisplatin, carboplatin, irinotecan, epirubicin, or etoposide led to strong synergy in a subset of resistant SCLC cells. Combination treatment with entinostat and cisplatin significantly decreased tumor growth in vivo. Proteomic analysis comparing the groups of SCLC cell lines with synergistic and additive response patterns indicated alterations in cell-cycle regulation and DNA damage repair. Cell-cycle analysis revealed that cells exhibiting synergistic drug responses displayed a shift from G1 to S-phase compared with cells showing additive features upon dual treatment. Comet assays demonstrated more DNA damage and decreased base excision repair in SCLC cells more responsive to combination therapy.CONCLUSIONS: In this study, we decipher the molecular processes behind synergistic interactions between chemotherapy and HDAC inhibition. Moreover, we report novel mechanisms to overcome drug resistance in SCLC, which may be relevant to increasing therapeutic success.
650 7a TEKNIK OCH TEKNOLOGIERx Industriell bioteknikx Medicinsk bioteknik0 (SwePub)209082 hsv//swe
650 7a ENGINEERING AND TECHNOLOGYx Industrial Biotechnologyx Medical Biotechnology0 (SwePub)209082 hsv//eng
653 a Humans
653 a Small Cell Lung Carcinoma/drug therapy
653 a Cisplatin
653 a Lung Neoplasms/pathology
653 a Proteomics
653 a Apoptosis
653 a Histone Deacetylase Inhibitors/pharmacology
653 a DNA Repair
653 a Cell Line, Tumor
7001 a Boettiger, Kristiinau Medical University of Vienna4 aut
7001 a Kovács, Ildikóu National Korányi Institute for Tuberculosis and Pulmonology, Hungary4 aut
7001 a Lang, Christianu Medical University of Vienna4 aut
7001 a Megyesfalvi, Zsoltu Medical University of Vienna4 aut
7001 a Ferk, Franziskau Medical University of Vienna4 aut
7001 a Mišík, Miroslavu Medical University of Vienna4 aut
7001 a Hoetzenecker, Konradu Medical University of Vienna4 aut
7001 a Aigner, Clemensu Medical University of Vienna4 aut
7001 a Kowol, Christian Ru University of Vienna4 aut
7001 a Knasmueller, Siegfriedu Medical University of Vienna4 aut
7001 a Grusch, Michaelu Medical University of Vienna4 aut
7001 a Szeitz, Beátau Semmelweis University4 aut
7001 a Rezeli, Melindau Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)elma-mrl
7001 a Dome, Balazsu Medical University of Vienna4 aut0 (Swepub:lu)ba1464do
7001 a Schelch, Karinu Medical University of Vienna4 aut
7102 a Medical University of Viennab National Korányi Institute for Tuberculosis and Pulmonology, Hungary4 org
7730 t Clinical cancer research : an official journal of the American Association for Cancer Researchg 29:22, s. 4644-4659q 29:22<4644-4659x 1078-0432
8564 u http://dx.doi.org/10.1158/1078-0432.CCR-23-1795x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/20b113cf-8830-4de6-8689-68a215af300b
8564 8u https://doi.org/10.1158/1078-0432.CCR-23-1795

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