Αρχειοθήκη ιστολογίου

Δευτέρα 22 Αυγούστου 2022

Integrated analysis of probability of type 2 diabetes mellitus with polymorphisms and methylation of SLC30A8 gene: a nested case-control study

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Docetaxel Targets Aggressive Methylation Profiles and Serves as a Radiosensitizer in High-Risk Meningiomas

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Abstract
Background
Meningioma is the most common primary intracranial tumor in adults. A subset of these tumors recur and invade the brain, even after surgery and radiation, resulting in significant disability. There is currently no standard-of-care chemotherapy for meningiomas. As genomic DNA methylation profiling can prognostically stratify these lesions, we sought to determine whether any existing chemotherapies might be effective against meningiomas with high-risk methylation profiles.
Methods
A previously published dataset of meningioma methylation profiles was used to screen for clinically significant CpG methylation events and associated cellular pathways. Based on these results, patient-derived meningioma cell lines were used to test candidate drugs in vitro and in vivo, including efficacy in conjunction with radiotherapy.
Results
We identi fied 981 genes for which methylation of mapped CpG sites was related to progression-free survival in meningiomas. Associated molecular pathways were cross-referenced with FDA-approved cancer drugs, which nominated Docetaxel as a promising candidate for further preclinical analyses. Docetaxel arrested growth in 17 meningioma cell sources, representing all tumor grades, with a clinically-favorable IC50 values ranging from 0.3 nM to 10.7 mM. The inhibitory effects of this medication scaled with tumor doubling time, with maximal benefit in fast-growing lesions. The combination of Docetaxel and radiation therapy increased markers of apoptosis and double-stranded DNA breaks, and extended the survival of mice engrafted with meningioma cells relative to either modality alone.
Conclusions
Global patterns of DNA methylation may be informative for the selection of chemotherapies against meningiomas, and existing drugs may enhance radiation sensitivity in high-risk cases.
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Effects of maxillomandibular advancement on respiratory function and facial aesthetics in obstructive sleep apnoea patients with versus without maxillomandibular deficiency

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The aim of this study was to compare the effects of maxillomandibular advancement (MMA) on respiratory function between obstructive sleep apnoea (OSA) patients with and without maxillomandibular deficiency, and to compare the changes in facial aesthetics after MMA between the two groups. MMA-treated patients who had both baseline and follow-up polysomnography (PSG) data and lateral cephalograms were enrolled in this retrospective study. In addition to PSG and cephalometric data, patient satisfaction with postoperative breathing and facial aesthetics, and overall satisfaction with the treatment were assessed. (Source: International Journal of Oral and Maxillofacial Surgery)
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