| 1. |
- Chen, Zhen, et al.
(författare)
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Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH)
- 2020
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier. - 0960-894X .- 1464-3405. ; 30:21
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC50 value 11 nM at a substrate concentration of 0.5 µM), and without showing time-dependency. The PET tracer [11C]8 (also called [11C]FAAH-1906) was successfully radiolabeled with [11C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [11C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [11C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
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| 2. |
- Li, Cong, et al.
(författare)
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Advanced multimodal imaging in differentiating glioma recurrence from post-radiotherapy changes
- 2020
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Ingår i: Novel therapeutic advances in glioblastoma. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 281-297
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Bokkapitel (refereegranskat)abstract
- Gliomas are the most common malignant primary brain tumor, and their prognosis is extremely poor. Radiotherapy is an important treatment for glioma patients, but the changes caused by radiotherapy have brought difficulties in clinical image evaluation because differentiating glioma recurrence from post-radiotherapy changes including pseudo-progression (PD) and radiation necrosis (RN) remains a challenge. Therefore, accurate and reliable imaging evaluation is very important for making clinical decisions. In recent years, advanced multimodal imaging techniques have been applied to achieve the goal of better differentiating glioma recurrence from post-radiotherapy changes for minimizing errors associated with interpretation of treatment effects. In this review, we discuss the recent applications of advanced multimodal imaging such as diffusion MRI sequences, amide proton transfer MRI sequences, perfusion MRI sequences, MR spectroscopy and multinuclides PET/CT in the evaluation of post-radiotherapy treatment response in glioma patients and highlight their potential role in differentiating post-radiotherapy changes from glioma recurrence.
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| 3. |
- Li, Cong, et al.
(författare)
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The therapeutic and neuroprotective effects of an antiepileptic drug valproic acid in glioma patients
- 2020
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Ingår i: Neuropharmacology of Neuroprotection. - : ELSEVIER. - 9780128208137 ; , s. 369-379
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Bokkapitel (refereegranskat)abstract
- Glioma is the most common primary malignant brain tumor in adults and the patients have poor prognosis despite treatment with surgery, radiotherapy and chemotherapy. The anti-epileptic drug, valproic acid (VPA) as a HDAC inhibitors is often used in glioma patients even if the patients don't have brain tumors associated epilepsy (BAE). Some previous studies have found that VPA not only has anti-epileptic effect, but also has anti-glioma growth effect through enhance radiotherapy sensitivity or other mechanism. Then VPA is reported to improve the survival of glioma patients receiving chemoradiation therapy. In addition, there are limited researches have shown that VPA has a neuroprotective effect in protect normal cells and tissues from the deleterious effects of treatment of glioma, especially radiotherapy. We'll give a brief overview of these effects of VPA in glioma patients.
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| 4. |
- Zhang, Zhiqiang, et al.
(författare)
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Inhibitory effect of Siwei Xiaoliuyin on glioma angiogenesis in nude mice
- 2020
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Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 243-252
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Bokkapitel (refereegranskat)abstract
- Objective: Application of Siwei Xiaoliuyin in glioma mice. Explore the effect of Siwei Xiaoliuyin on angiogenesis of nude mice glioma and its mechanism. Methods: Establish human glioma cell line U87 tumor model. Mice were randomized to the saline group, the conventional dose of Siwei Xiaoliuyin, high dose group of Siwei Xiaoliuyin, TMZ group, combination therapy group, record the tumor volume. Using the method of Weidner counted the microvessel density. ELISA enzyme-linked adsorption method to detect the content of nude mice serum VEGF and ES. The difference was statistically significant (P < 0.05). Results: The tumor volume and MVD of conventional dose group, large dose group, Siwei Xiaoliuyin combined temozolomide group was smaller than the blank group,the difference was statistically significant (P < 0.05). VEGF levels in three groups of nude mice were lower than the blank group and ES content is higher than blank group, the difference was statistically significant (P < 0.05). Conclusion: Siwei Xiaoliuyin can inhibit glioma angiogenesis. Its mechanism of glioma angiogenesis inhibition may be through regulation VEGF and down-regulation of endostatin expression of vascular endothelial growth factor achieved. Down-regulation of endostatin expression of vascular endothelial growth factor achieved.
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| 5. |
- Zhang, Zhiqiang, et al.
(författare)
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New advances on the inhibition of Siwei Xiaoliuyin combined with Temozolomide in glioma based on the regulatory mechanism of miRNA21/221
- 2020
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Ingår i: NOVEL THERAPEUTIC ADVANCES IN GLIOBLASTOMA. - LONDON ENGLAND : Elsevier. - 9780128211144 ; , s. 99-110
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Bokkapitel (refereegranskat)abstract
- Objective: To provide evidence for the mechanism of Chinese medicine to treat glioma. We observe the effects of Si wei xiao xiu yin combined with chemotherapy on the growth of subcutaneous xenografts in nude mice and the expression of miRNA-21 and miRNA-221 in tumor tissues. Methods: The subcutaneous transplantation model of nude mice was established by subcutaneous inoculation of glioma U87 cell suspension. They were randomly divided into saline group, traditional Chinese medicine group, temozolomide group and traditional Chinese medicine combined with temozolomide group to observe the changes in body weight, and the tumor weight, length, short diameter, volume of mice. The relative expression levels of miRNA-21 and miRNA-221 in tumor tissues were detected by qRT-PCR, and the differences between groups were compared. Results: After 28 days of gavage, the tumor growth of the other three groups was slower than that of saline group, and the difference was most significant in the combination group (P = 0.008 < 0.05), besides, the relative expression of the three groups of miRNA-21 and miRNA-221 was significantly inhibited compared with saline group, and the difference was significant in the combination group (F = 8.918, P = 0.010 < 0.05). Conclusion: To some extent, Si wei xiao xiu yin combined with temozolomide can inhibit the growth of subcutaneous xenografts in glioma nude mice. The mechanism may be related to the inhibition of miRNA-21 and miRNA-221 expression.
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