Bone scintigraphy plays an important role in the early detection of bone metastases in patients with nasopharyngeal carcinoma and serial scans may aid the clinician to assess the therapeutic ...response. A superscan is a pattern described as abnormal bone scan, indicating extensive bony metastases associated with various neoplastic diseases. Bone scans from 407 patients with nasopharyngeal carcinoma were reviewed retrospectively. Only six superscans (1.5%) were found. The appearance of a superscan is frequently accompanied by an abnormal titer of serological markers IgG-VCA and IgA-VCA, liver metastases, and poor survival. Although a superscan rarely occurs in nasopharyngeal carcinoma, its appearance may represent a poor prognosis in these patients.
This study was designed to examine the effects of feeding diets containing different levels of isoflavone on plasma glucose, insulin concentrations, and lipid profiles as well as tissue antioxidant ...enzyme activities in diabetic rats. Diabetes was induced in the rats with streptozotocin. Diabetic rats were further assigned to 1 control group and 3 experimental groups (ISO-1, ISO-2, and ISO-8). The control group received a casein-based diet without isoflavone, whereas the ISO-1, ISO-2, and ISO-8 groups received a similar diet but supplemented with 1, 2 and 8 times of isoflavone equivalent of normal human consumption as suggested by the manufacturer. All diets were adjusted to contain identical nutrients and were maintained for 24 days. Fasted and non-fasted blood was drawn after feeding for 21 and 24 days, respectively, and blood chemistry was analyzed. The liver, lung, and kidney were excised after sacrifice, and antioxdiant enzyme activities and lipid peroxidation products were measured. The results demonstrate that there were no differences in plasma glucose or insulin levels among groups, irregardless of whether rats had fasted or not. However, hemoglobin A
1c tended to be lower in the ISO-2 group than in the control and the ISO-1 groups. Plasma total cholesterol and low-density lipoprotein-cholesterol were significantly lower in the ISO-8 group than in the other groups. No differences in plasma triglyceride or high-density lipoprotein-cholesterol were observed among groups in the non-fasting state. There were no significant differences in superoxide dismutase, glutathione peroxidase activities, and malondialdehyde concentrations in liver, lung, and kidney homogenates among groups. These results suggest that 3 doses of isoflavone supplementation had no favorable effect on plasma glucose or insulin concentrations, nor had any influence on attenuating oxidative stress in diabetic rats. However, the ISO-2 group tended to have better chronic glycemic control than did the control and the ISO-1 group. In addition, a larger amount of isoflavone supplementation had beneficial effects on reducing plasma total cholesterol and low-density lipoprotein-cholesterol levels.
Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer’s disease (AD). Starting from an unbiased protein microarray screen, we identified ...a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity. Trem2 knockout microglia showed reduced internalization of LDL and CLU. β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion. Uptake of Aβ-lipoprotein complexes was reduced in macrophages from human subjects carrying a TREM2 AD variant. These data link three genetic risk factors for AD and reveal a possible mechanism by which mutant TREM2 increases risk of AD.
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•TREM2 binds to lipoproteins and apolipoproteins including APOE and CLU•Disease-linked mutations in TREM2 impair lipoprotein binding and uptake into cells•Aβ-lipoprotein complexes are efficiently taken up by microglia, dependent on TREM2•Human carriers of a TREM2 AD variant show reduced uptake of Aβ-lipoprotein complexes
Yeh et al. show that TREM2 is a receptor for lipoproteins, including APOE and CLU, and thereby mediates uptake of lipoprotein-Aβ complexes by microglia. The study links together three genetic risk factors of Alzheimer’s disease and offers new insight into the mechanisms of Aβ clearance.
Aberrant activation of signaling by the Wnt pathway is strongly implicated in the onset and progression of numerous types of cancer. Owing to the persistent dependence of these tumors on Wnt ...signaling for growth and survival, inhibition of this pathway is considered an attractive mechanism-based therapeutic approach. Oncogenic activation of Wnt signaling can ensue from a variety of distinct aberrations in the signaling pathway, but most share the common feature of causing increased cellular levels of β-catenin by interfering with its constitutive degradation. β-Catenin serves as a central hub in Wnt signaling by engaging in crucial protein-protein interactions with both negative and positive effectors of the pathway. Direct interference with these protein-protein interactions is a biologically compelling approach toward suppression of β-catenin hyperactivity, but such interactions have proven intransigent with respect to small-molecule targeting. Hence β-catenin remains an elusive target for translational cancer therapy. Here we report the discovery of a hydrocarbon-stapled peptide that directly targets β-catenin and interferes with its ability to serve as a transcriptional coactivator for T-cell factor (TCF) proteins, the downstream transcriptional regulators of the Wnt pathway.
Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue ...origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.
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