Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan
| العنوان: | Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan |
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| المؤلفون: | Yin Huang, Yingtong Lv, Jiaqing Chen, Wei Li, Zunjian Zhang, Fengguo Xu, Yiqiao Gao, Xu Wang |
| المصدر: | Acta Pharmaceutica Sinica B, Vol 9, Iss 1, Pp 157-166 (2019) Acta Pharmaceutica Sinica. B |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Smt, sensitive for myelosuppression toxicity, Metabolite, C, control group, RSD, relative standard deviation, NSgt, non-sensitive for gastrointestinal toxicity, pFDR, false-discovery-rate-adjusted P value, Logistic regression, CPT-11, irinotecan, OPLS-DA, orthogonal partial least-squares-discriminant analysis, chemistry.chemical_compound, VIP, variable importance in the projection, 0302 clinical medicine, GCA, glycocholic acid, Medicine, DBIL, direct bilirubin, Complicating toxicity, General Pharmacology, Toxicology and Pharmaceutics, CA, cholic acid, 0303 health sciences, AUC-ROC, area under receiver operating characteristic, Gastrointestinal toxicity, BHB, β-hydroxybutyric acid, UFLC, ultrafast liquid chromatography, MSTFA, N-methyl-N-trifluoroacetamide, Diarrhea, S, sensitive group, 030220 oncology & carcinogenesis, T, CPT-11 treated group, Toxicity, medicine.symptom, Phe, phenylalanine, Lys, lysine, Sgt, sensitive for gastrointestinal toxicity, medicine.drug, Original article, medicine.medical_specialty, Trp, tryptophan, FDR, false discovery rate, IBIL, indirect bilirubin, Irinotecan, 03 medical and health sciences, Metabolomics, Internal medicine, NS, non-sensitive group, Adverse effect, 030304 developmental biology, PCA, principal component analysis, business.industry, lcsh:RM1-950, IT-TOF/MS, ion trap/time-offlight hybrid mass spectrometry, NSmt, non-sensitive for myelosuppression toxicity, Precision medicine, QC, quality control, lcsh:Therapeutics. Pharmacology, DCA, deoxycholic acid, chemistry, Individual differences, PLS-DA, partial least-squares-discriminant analysis, Prediction, business, Biomarkers |
| الوصف: | Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine. Graphical abstract Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to screen the exclusive biomarkers in predose serums. Based on the pharmacometabolomic analysis, two prediction models were constructed to predict gastrointestinal toxicity and myelosuppression of CPT-11 simultaneously, followed by verification of relevant chemotherapeutic toxicity evaluation indexes.fx1 |
| اللغة: | English |
| تدمد: | 2211-3835 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55052975da7aee65ba1d4f6ad669e41f http://www.sciencedirect.com/science/article/pii/S2211383518304453 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....55052975da7aee65ba1d4f6ad669e41f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113835 |
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