Based on the results of this meta-analysis, it would appear that an algorithm based on serial PCT measurements would allow a more judicious use of antibiotics than currently occurs during the traditional treatment of patients with infections. PCT-guided antibiotic treatment appears to be safe and may also improve clinical outcome.
Alzheimer disease (AD) is characterized by β-amyloid (Aβ) plaques and tau neurofibrillary tangles. There are several PET imaging biomarkers for Aβ including C-PiB andF-florbetapir. Recently, PET tracers for tau neurofibrillary tangles have become available and have shown utility in detection and monitoring of neurofibrillary pathology over time. Flortaucipir F 18 is one such tracer. Initial clinical studies indicated greater tau binding in AD and mild cognitive impairment patients than in controls in a pattern consistent with tau pathology observed at autopsy. However, little is known about the reproducibility of such findings. To our knowledge, this study reports the first data regarding test-retest reproducibility of flortaucipir F 18 PET. Twenty-one subjects who completed the study (5 healthy controls, 6 mild cognitive impairment, and 10 AD) received 370 MBq of flortaucipir F 18 and were imaged for 20 min beginning 80 min after injection and again at 110 min after injection. Follow-up (retest) imaging occurred between 48 h and 4 wk after initial imaging. Images were spatially normalized to Montreal Neurological Institute template space. SUVRs were calculated using AAL (Automated Anatomical Labeling atlas) volumes of interest (VOIs) for parietal, temporal, occipital, anterior, and posterior hippocampal, parahippocampal, and fusiform regions, as well as a posterior neocortical VOI composed of average values from parietal, temporal, and occipital areas. Further, a VOI derived by discriminant analysis that maximally separated diagnostic groups (multiblock barycentric discriminant analysis [MUBADA]) was used. All VOIs were referenced to a subsection of cerebellar gray matter (cere-crus) as well as a parametrically derived white matter-based reference region (parametric estimate of reference signal intensity [PERSI]). test, correlation analyses, and intraclass correlation coefficient were used to explore test-retest performance. Test-retest analyses demonstrated low variability in flortaucipir F 18 SUVR. The SD of mean percentage change between test and retest using the PERSI reference region was 2.22% for a large posterior neocortical VOI, 1.84% for MUBADA, 1.46% for frontal, 1.98% for temporal, 2.28% for parietal, and 3.27% for occipital VOIs. Further, significant correlations ( > 0.85; < 0.001) were observed for all regions, and intraclass correlation coefficient values (test-retest consistency) were greater than 0.92 for all regions. Significant test-retest reproducibility for flortaucipir F 18 was found across neocortical and mesial temporal lobe structures. These preliminary data suggest that flortaucipir F 18 tau imaging could be used to examine changes in tau burden over time.
Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC. Based on available data in The Cancer Genome Atlas, divergent expression profiles of ferroptosis regulators were noted in ccRCC and normal tissues, and we also found that the ferroptosis regulators correlated with the PD-L1 expression. Two independent subtypes were determined by consensus clustering analysis according to the expression level of ferroptosis regulators in ccRCC. Cluster 1 showed lower histological tumor stage and grade, more favorable prognosis, and higher PD-L1 expression compared to cluster 2. CIBERSORT analysis revealed that cluster 2 harbored higher infiltrated levels of CD8+ T cell, Tregs, and T follicular helper cell, while cluster 1 more correlated with the monocyte, M1 macrophage, and M2 macrophage. Gene set enrichment analysis indicated that the ERBB signaling and JAK_STAT signaling pathways were significantly enriched in cluster 1. We subsequently identified CARS as the potentially key immune infiltration-related ferroptosis regulator, whose high expression showed dismal prognosis and was positively correlated with PD-L1 expression in ccRCC. We also verified the upregulation of CARS in ccRCC tissues and cell lines via qRT-PCR method. Additionally, a pan-cancer analysis demonstrated that CARS closely related to the expression of immune checkpoint-related genes (especially PD-L1) and an unfavorable prognosis in diverse cancer types. In summary, our study suggested the crucial role of ferroptosis in immune infiltration of ccRCC, and CARS is a potentially novel prognostic biomarker and potential target for cancer immunotherapy.
BackgroundTumor-associated macrophages (TAMs) are the major immune cells in tumor microenvironment. The prognostic significance of TAMs has been confirmed in various tumors. However, whether TAMs can be prognostic factors in clear cell renal cell carcinoma (ccRCC) is unclear. In this study, we aimed to clarify the prognostic value of TAMs in ccRCC.MethodsWe searched PubMed, Embase, and the Web of Science for relevant published studies before December 19, 2020. Evidence from enrolled studies were pooled and analyzed by a meta-analysis. Hazard ratios (HRs) and odd ratios (ORs) with 95% confidence intervals (CIs) were computed to evaluate the pooled results.ResultsBoth of high CD68+ TAMs and M2-TAMs were risk factors for poor prognosis in ccRCC patients. The pooled HRs indicated that elevated CD68+ TAMs correlated with poor OS and PFS (HR: 3.97, 95% CI 1.39–11.39; HR: 5.73, 95% CI 2.36–13.90, respectively). For M2-TAMs, the pooled results showed ccRCC patients with high M2-TAMs suffered a worse OS and shorter PFS, with HR 1.32 (95% CI 1.16–1.50) and 1.40 (95% CI 1.14–1.72), respectively. Also, high density of TAMs was associated with advanced clinicopathological features in ccRCC.ConclusionsTAMs could be potential biomarkers for prognosis and novel targets for immunotherapy in ccRCC. Further researches are warranted to validate our results.
Background: Emerging evidence suggests that miR-501-3p plays an important role in the pathogenesis and progression of various carcinomas. However, its role and underlying mechanisms in renal cell carcinoma (RCC) remain to be elucidated. Methods:Quantitative RT-PCR, western blot, and bioinformatics methods were used to evaluate the expression of miR-501-3p and Wilms' tumor 1-associating protein (WTAP) in RCC cell lines and clinical tissues. The effects of miR-501-3p on the proliferation of RCC cells were investigated using flow cytometric, colony formation, and CCK8 assays. The target gene of miR-501-3p was confirmed by western blotting, qRT-PCR, and dual-luciferase reporter assays. The levels of RNA methylation with N6-methyladenosine (m 6 A) following miR-501-3p overexpression or knockdown of its target gene were quantified using a dot-blot assay.Results: miR-501-3p expression was significantly downregulated in human RCC cell lines and tissues. In contrast, its overexpression markedly inhibited cancer cell proliferation in vitro by inducing G1 phase arrest. Moreover, WTAP was verified as a direct target gene of miR-501-3p. WTAP gene knockdown alone efficiently produced the same cancer-inhibiting effects as miR-501-3p overexpression, with the level of m 6 A in RCC cells being decreased under both scenarios.The intermolecular interaction between miR-501-3p and WTAP was further substantiated by rescue experiments. Conclusion:RCC progression is regulated via the miR-501-3p/WTAP/CDK2 axis and is inhibited by the overexpression of miR-501-3p.
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