| 1. |
- Erondu, Ngozi, et al.
(författare)
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Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults
- 2006
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 4:4, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. We tested the hypothesis that blockade of the NPY5R will lead to weight loss in humans using MIK-0557, a potent, highly selective, orally active NPY5R antagonist. The initial series of experiments reported herein, including a multiple-dose positron-emission tomography study and a 12 week proof-of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52 week, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although statistically significant at 52 weeks, the magnitude of induced weight loss was not clinically meaningful. These observations provide the first clinical insight into the human NPY-energy homeostatic pathway and suggest that solely targeting the NPY5R in future drug development programs is unlikely to produce therapeutic efficacy.
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| 2. |
- Kataoka, Masako, et al.
(författare)
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Ultrafast Dynamic Contrast-enhanced MRI of the Breast : How Is It Used?
- 2022
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Ingår i: Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine. - : Japanese Society for Magnetic Resonance in Medicine. ; 21:1, s. 83-94
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Forskningsöversikt (refereegranskat)abstract
- Ultrafast dynamic contrast-enhanced (UF-DCE) MRI is a new approach to capture kinetic information in the very early post-contrast period with high temporal resolution while keeping reasonable spatial resolution. The detailed timing and shape of the upslope in the time-intensity curve are analyzed. New kinetic parameters obtained from UF-DCE MRI are useful in differentiating malignant from benign lesions and in evaluating prognostic markers of the breast cancers. Clinically, UF-DCE MRI contributes in identifying hypervascular lesions when the background parenchymal enhancement (BPE) is marked on conventional dynamic MRI. This review starts with the technical aspect of accelerated acquisition. Practical aspects of UF-DCE MRI include identification of target hypervascular lesions from marked BPE and diagnosis of malignant and benign lesions based on new kinetic parameters derived from UF-DCE MRI: maximum slope (MS), time to enhance (TTE), bolus arrival time (BAT), time interval between arterial and venous visualization (AVI), and empirical mathematical model (EMM). The parameters derived from UF-DCE MRI are compared in terms of their diagnostic performance and association with prognostic markers. Pitfalls of UF-DCE MRI in the clinical situation are also covered. Since UF-DCE MRI is an evolving technique, future prospects of UF-DCE MRI are discussed in detail by citing recent evidence. The topic covers prediction of treatment response, multiparametric approach using DWI-derived parameters, evaluation of tumor-related vessels, and application of artificial intelligence for UF-DCE MRI. Along with comprehensive literature review, illustrative clinical cases are used to understand the value of UF-DCE MRI.
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