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- Aksnes, M., et al.
(författare)
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Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals
- 2023
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Ingår i: Neurobiology of Aging. - 0197-4580. ; 131, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-& beta;42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging. & COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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- Maison-Blanche, Pierre, et al.
(författare)
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An open-label study to investigate the cardiac safety profile of cabazitaxel in patients with advanced solid tumors
- 2014
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 73:6, s. 1241-1252
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Tidskriftsartikel (refereegranskat)abstract
- This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade a parts per thousand yen3 cardiovascular adverse events. Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (-0.012 [95 % CI -0.017; -0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade a parts per thousand yen3 cardiac adverse events were observed; Grade a parts per thousand yen3 hypotension and lymphocele occurred in two patients and one patient, respectively. These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.
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