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Sökning: WFRF:(Hellberg Maria) > Cisplatin and oxali...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004818naa a2200577 4500
001oai:DiVA.org:umu-18621
003SwePub
008090219s2009 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:118085755
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-186212 URI
0247 a https://doi.org/10.1093/jnci/djn4182 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1180857552 URI
040 a (SwePub)umud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Hellberg, Victoriau Karolinska Institutet4 aut
2451 0a Cisplatin and oxaliplatin toxicity :b importance of cochlear kinetics as a determinant for ototoxicity
264 c 2008-12-30
264 1a Cary :b Oxford University Press,c 2009
338 a print2 rdacarrier
520 a BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.METHODS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.RESULTS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.
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 mammalian thioredoxin reductase
653 a sulfur-containing compounds
653 a guinea pig
653 a molecular mechanisms
653 a monohydrated complex
653 a cerebrospinal fluid
653 a active site
653 a cell-death
653 a pharmacokinetics
653 a apoptosis
7001 a Wallin, Inger4 aut
7001 a Eriksson, Sofiu Karolinska Institutet4 aut
7001 a Hernlund, Emma4 aut
7001 a Jerremalm, Elin4 aut
7001 a Berndtsson, Mariau Karolinska Institutet4 aut
7001 a Eksborg, Staffanu Karolinska Institutet4 aut
7001 a Arnér, Elias SJ4 aut
7001 a Shoshan, Mariau Karolinska Institutet4 aut
7001 a Ehrsson, Hans4 aut
7001 a Laurell, Göranu Karolinska Institutet,Umeå universitet,Öron- näs- och halssjukdomar,Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden4 aut0 (Swepub:umu)gala0001
7102 a Karolinska Institutetb Öron- näs- och halssjukdomar4 org
7730 t Journal of the National Cancer Instituted Cary : Oxford University Pressg 101:1, s. 37-47q 101:1<37-47x 0027-8874x 1460-2105
8564 u https://academic.oup.com/jnci/article-pdf/101/1/37/7669988/djn418.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-18621
8564 8u https://doi.org/10.1093/jnci/djn418
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:118085755

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