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Sökning: onr:"swepub:oai:DiVA.org:uu-421048" > Targeting aggressiv...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004736naa a2200517 4500
001oai:DiVA.org:uu-421048
003SwePub
008201006s2020 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4210482 URI
0247 a https://doi.org/10.1177/17588359209378912 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Byrgazov, Konstantinu Oncopeptides AB, Luntmakragatan 46, SE-11137 Stockholm, Sweden.;St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.4 aut
2451 0a Targeting aggressive osteosarcoma with a peptidase-enhanced cytotoxic melphalan flufenamide
264 c 2020-07-29
264 1b SAGE PUBLICATIONS LTD,c 2020
338 a electronic2 rdacarrier
520 a Background: Low survival rates in metastatic high-grade osteosarcoma (HGOS) have remained stagnant for the last three decades. This study aims to investigate the role of aminopeptidase N (ANPEP) in HGOS progression and its targeting with a novel lipophilic peptidase-enhanced cytotoxic compound melphalan flufenamide (melflufen) in HGOS. Methods: Meta-analysis of publicly available gene expression datasets was performed to determine the impact ofANPEPgene expression on metastasis-free survival of HGOS patients. The efficacy of standard-of-care anti-neoplastic drugs and a lipophilic peptidase-enhanced cytotoxic conjugate melflufen was investigated in patient-derived HGOSex vivomodels and cell lines. The kinetics of apoptosis and necrosis induced by melflufen and doxorubicin were compared. Anti-neoplastic effects of melflufen were investigatedin vivo. Results: ElevatedANPEPexpression in diagnostic biopsies of HGOS patients was found to significantly reduce metastasis-free survival. In drug sensitivity assays, melflufen has shown an anti-proliferative effect in HGOSex vivosamples and cell lines, including those resistant to methotrexate, etoposide, doxorubicin, and PARP inhibitors. Further, HGOS cells treated with melflufen displayed a rapid induction of apoptosis and this sensitivity correlated with high expression ofANPEP. In combination treatments, melflufen demonstrated synergy with doxorubicin in killing HGOS cells. Finally, Melflufen displayed anti-tumor growth and anti-metastatic effectsin vivo. Conclusion: This study may pave the way for use of melflufen as an adjuvant to doxorubicin in improving the therapeutic efficacy for the treatment of metastatic HGOS.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
653 a aminopeptidase
653 a chemotherapy
653 a melflufen
653 a metastasis
653 a osteosarcoma
7001 a Andersson, Claesu Uppsala universitet,Cancerfarmakologi och beräkningsmedicin4 aut0 (Swepub:uu)cland109
7001 a Salzer, Benjaminu St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.4 aut
7001 a Bozsaky, Evau St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.4 aut
7001 a Larsson, Rolfu Uppsala universitet,Cancerfarmakologi och beräkningsmedicin4 aut0 (Swepub:uu)rolflars
7001 a Gullbo, Joachimu Oncopeptides AB, Luntmakragatan 46, SE-11137 Stockholm, Sweden.4 aut
7001 a Lehner, Manfredu St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.4 aut
7001 a Lehmann, Fredriku Oncopeptides AB, Luntmakragatan 46, SE-11137 Stockholm, Sweden.4 aut
7001 a Slipicevic, Anau Oncopeptides AB, Luntmakragatan 46, SE-11137 Stockholm, Sweden.4 aut
7001 a Kager, Leou Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria.;CCRI, Vienna, Austria.4 aut
7001 a Fryknäs, Mårtenu Uppsala universitet,Cancerfarmakologi och beräkningsmedicin4 aut0 (Swepub:uu)mafry516
7001 a Taschner-Mandl, Sabineu St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.4 aut
7102 a Oncopeptides AB, Luntmakragatan 46, SE-11137 Stockholm, Sweden.;St Anna Childrens Canc Res Inst CCRI, Vienna, Austria.b Cancerfarmakologi och beräkningsmedicin4 org
7730 t THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGYd : SAGE PUBLICATIONS LTDg 12q 12x 1758-8340x 1758-8359
8564 u https://doi.org/10.1177/1758835920937891y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1473616/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u https://journals.sagepub.com/doi/pdf/10.1177/1758835920937891
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421048
8564 8u https://doi.org/10.1177/1758835920937891

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