Academic Journal
Relations between strain and gender dependencies of irinotecan toxicity and UGT1A1, CES2 and TOP1 expressions in mice.
| العنوان: | Relations between strain and gender dependencies of irinotecan toxicity and UGT1A1, CES2 and TOP1 expressions in mice. |
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| المؤلفون: | Ahowesso C., PICCOLO, Enza, Li X. M., Dulong S., Hossard V., La Sorda R., Filipski E., TINARI, Nicola, Delaunay F., IACOBELLI, Stefano, Lévi F. |
| المساهمون: | Ahowesso, C., Piccolo, Enza, Li, X. M., Dulong, S., Hossard, V., La Sorda, R., Filipski, E., Tinari, Nicola, Delaunay, F., Iacobelli, Stefano, Lévi, F. |
| سنة النشر: | 2010 |
| المجموعة: | ARUd'A - Archivio Istituzionale della ricerca dell'università Chieti-Pescara (IRIS) |
| مصطلحات موضوعية: | Cancer, Gender, Irinotecan, Personalized medicine, Phase II metabolism, Toxicity |
| الوصف: | Irinotecan hydrochloride (CPT-11) can display severe toxicities in individual cancer patients. CPT-11 is bio-activated through CES, detoxified through UGT1A1 and inhibits TOP1. CPT-11 toxicity and UGT1A1, CES2 and TOP1 mRNAs and UGT1A1 protein were determined in male and female C57BL/6, B6D2F1 and B6CBAF1, as potential models for tailoring CPT-11 delivery. CPT-11 was administered intravenously (40-90 mg/kg/day for 4 days at 7h after light onset). The relations between dose and lethal toxicity or body weight loss were steep and similar in C57BL/6 (lethality, p=0.001; weight loss, p=0.002) and B6D2F1 (p=0.01; p=0.03, respectively), but weak in B6CBAF1. Females displayed less toxicity than males (p<0.001). Mean mRNA expression of UGT1A1 was highest in B6CBAF1 (p=0.039) and in females (p<0.001). Both CES2 and TOP1 varied according to strain and gender (p<0.001). The three gene expression data explained the most severe toxicity of CPT-11 in male B6D2F1, but displayed inconsistent relations with toxicity in the other groups. Mean UGT1A1 protein expression was highest in males as compared to females, and so by approximately 8-fold in C57BL/6 as compared to B6D2F1 (p<0.0001). Genetic background and gender significantly altered the molecular prediction of irinotecan toxicity by UGT1A1, CES2 and TOP1 mRNA expressions. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/19931604; info:eu-repo/semantics/altIdentifier/wos/WOS:000275615300016; volume:192; issue:3; firstpage:395; lastpage:401; numberofpages:7; journal:TOXICOLOGY LETTERS; https://hdl.handle.net/11564/271164; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-75549090022 |
| DOI: | 10.1016/j.toxlet.2009.11.017 |
| الاتاحة: | https://hdl.handle.net/11564/271164 https://doi.org/10.1016/j.toxlet.2009.11.017 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.4CE57789 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.toxlet.2009.11.017 |
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