Sökning: onr:"swepub:oai:DiVA.org:umu-18621" > Cisplatin and oxali...
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000 | 04818naa a2200577 4500 | |
001 | oai:DiVA.org:umu-18621 | |
003 | SwePub | |
008 | 090219s2009 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:118085755 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-186212 URI |
024 | 7 | a https://doi.org/10.1093/jnci/djn4182 DOI |
024 | 7 | 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 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Hellberg, Victoriau Karolinska Institutet4 aut |
245 | 1 0 | a Cisplatin and oxaliplatin toxicity :b importance of cochlear kinetics as a determinant for ototoxicity |
264 | c 2008-12-30 | |
264 | 1 | a 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 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a 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 | |
700 | 1 | a Wallin, Inger4 aut |
700 | 1 | a Eriksson, Sofiu Karolinska Institutet4 aut |
700 | 1 | a Hernlund, Emma4 aut |
700 | 1 | a Jerremalm, Elin4 aut |
700 | 1 | a Berndtsson, Mariau Karolinska Institutet4 aut |
700 | 1 | a Eksborg, Staffanu Karolinska Institutet4 aut |
700 | 1 | a Arnér, Elias SJ4 aut |
700 | 1 | a Shoshan, Mariau Karolinska Institutet4 aut |
700 | 1 | a Ehrsson, Hans4 aut |
700 | 1 | a Laurell, Göranu Karolinska Institutet,Umeå universitet,Öron- näs- och halssjukdomar,Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden4 aut0 (Swepub:umu)gala0001 |
710 | 2 | a Karolinska Institutetb Öron- näs- och halssjukdomar4 org |
773 | 0 | t Journal of the National Cancer Instituted Cary : Oxford University Pressg 101:1, s. 37-47q 101:1<37-47x 0027-8874x 1460-2105 |
856 | 4 | u https://academic.oup.com/jnci/article-pdf/101/1/37/7669988/djn418.pdf |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-18621 |
856 | 4 8 | u https://doi.org/10.1093/jnci/djn418 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:118085755 |
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