1535 Background: Inherited mutations in cancer predisposition genes typically associated with adult-onset cancers, including BRCA1/2, have been found in children with cancer. However, it is unknown whether such mutations are causative. Our objective is to determine whether there is an increased risk of pediatric malignancy in families known to carry BRCA1/2 mutations. Methods: We utilized the Cancer Risk Evaluation Program (CREP), a registry of high-risk breast and ovarian cancer families undergoing BRCA1/2 testing. We compared the proportion of pediatric malignancies (age ≤ 18 years) among families tested positive vs negative for BRCA1/2 mutations in 1) the proband’s siblings and 2) other potential at risk relatives of the proband (siblings, children, nieces and nephews). We used generalized estimating equations to account for familial clustering. We compared pediatric malignancy rates in BRCA1/2 mutation positive families from CREP to the general population from SEER (Surveillance, Epidemiology and End-Results) using an incidence rate ratio (IRR). Results: We compared 1,313 BRCA1/2 mutation negative and 1,402 BRCA1/2 mutation positive families. 3,168 siblings had 10 pediatric malignancies (0.3%) in BRCA1/2 negative families and 3,185 siblings had 9 pediatric malignancies (0.3%) in BRCA1/2 positive families. When examining at-risk family members there were 30 BRCA1/2 negative families (2.3%) with a pediatric malignancy (31 malignancies) and 24 BRCA1/2 positive families (1.7%) with a pediatric malignancy (25 malignancies). We found no evidence for an increased risk of pediatric malignancy in BRCA1/2 positive vs BRCA1/2 negative families in the sibling (OR = 0.69, 95% CI, 0.25-1.92; p = 0.482) or family based (OR = 0.76; 95% CI, 0.42-1.35; p = 0.342) multivariable adjusted analyses. The pediatric malignancy rates (per 100,000 person-years) among BRCA1/2 positive families in CREP (incidence rate [IR] = 16.1, 95% CI, 10.9-23.9) and SEER (IR = 16.1, 95% CI, 16.0-16.3) were similar (IRR = 1.00; 95% CI, 0.65-1.48). Conclusions: We find no evidence for an increased risk of pediatric malignancy in BRCA1/2 mutation positive families. Our data supports delaying BRCA1/2 testing in BRCA1/2 mutation positive families until adulthood.
Objective To investigate the hypermethylation of GSTP1 and DAPK gene and its correlation with clinicopathological features in prostate cancer.Methods Methylation of GSTP1 and DAPK gene was detected by nested methylation specific PCR(NMSP) in 57 prostate carcinoma(PCa) and 35 benign prostate hyperplasia(BPH) tissues.The association between hypermethylation and clinicopathology characters of prostate cancer was analyzed.Results Hypermethylation frequencies of GSTP1 and DAPK gene in PCa tissue were significantly higher than those in BPH tissue(GSTP1: 61.4% vs 2.9%;DAPK: 43.9% vs 8.6%;P 0.01).Hypermethylation frequencies of GSTP1 gene were different among tissues with different Gleason score(χ2 = 11.53,P = 0.001),but were not different among patients with different age,different level of prostate specific antigen(PSA),and different Jewett stage(χ2 = 0.111,1.662,and 1.975,P 0.05).There were no significant differences among patients with different age,different level of PSA,different Gleason score,and different Jewett stage about hypermethylation frequencies of DAPK gene(χ2 = 0.071,0.002,1.290,and 2.309,P 0.05).Conclusion Hypermethylation of GSTP1 and DAPK gene is correlated with tumorigenesis and progression of prostate cancer.
Abstract Recurrence is a major cause of death among BRCA1/2 mutation carriers with breast (BrCa) and ovarian cancers (OvCa). We performed multi-omic sequencing on 67 paired primary and recurrent BrCa and OvCa from 27 BRCA1/2 mutation carriers to identify potential recurrence-specific drivers. PARP1 amplifications were identified in recurrences (FDR q = 0.05), and PARP1 was significantly overexpressed across primary BrCa and recurrent BrCa and OvCa, independent of amplification status. RNA-seq analysis found two BRCA2 isoforms, BRCA2-201/Long and BRCA2-001/Short , predicted sensitive and insensitive to nonsense-mediated decay, respectively. BRCA2-001/Short was expressed more frequently in recurrences and associated with reduced overall survival in breast cancer (87 vs. 121 months; HR = 2.5 [1.18–5.5]). Loss of heterozygosity (LOH) status was discordant in 25% of patient’s primary and recurrent tumors, with switching between both LOH and lack of LOH found. Our study revealed multiple potential drivers of recurrent disease in BRCA1/2 mutation-associated cancer, improving our understanding of tumor evolution and suggesting potential biomarkers.
BACKGROUND At present, a number of long non-coding RNAs (lncRNAs) have been realized as the critical regulators of breast cancers. Current evidence indicates that dysregulation of UFC1 contributes to the tumorigenesis and progression of various types of human cancer. However, the roles of UFC1 in breast cancer are still unclear. MATERIAL AND METHODS Firstly, we measured the expression of UFC1 in breast cancer tissues and cells lines compared with corresponding controls. Then, cell functional assays were performed to determine the roles of UFC1 in breast cancer progression in vitro. Moreover, the correlation between UFC1 and miR-34a was determined by luciferase reporter assays. Further, the role of miR-34a in regulating biological function of breast cancer and its downstream target CXCL10 was applied by a series of functional assays. RESULTS In present study, we found that UFC1 was highly expressed in breast tissue and cells lines compared with normal tissues and cell lines. Silenced UFC1 suppressed multiple biological activities of breast cancer cells, which also functioned as a miR-34a sponge in breast cancer. Furthermore, over-expressing miR-34a could prominently suppress cell growth, invasion, migration and inducing apoptosis in breast cancer cells. In addition, we verified that miR-34a was a target of CXCL10 by bioinformatics analysis and luciferase reporter assay. CONCLUSIONS LncRNA UFC1 regulated biological activity of breast cancer via miR-34a/CXCL10 axis, providing a novel diagnosis biomarker and potential therapeutic target for breast cancer.
Intracranial aneurysms are local dilations of the cerebral blood vessels; people with intracranial aneurysms have a high risk to cause bleeding in the brain, which is related to high mortality and morbidity rates. Accurate detection and segmentation of intracranial aneurysms from Magnetic Resonance Angiography (MRA) images are essential in the clinical routine. Manual annotations used to assess the intracranial aneurysms on MRA images are substantial interobserver variability for both aneurysm detection and assessment of aneurysm size and growth. Many prior automated segmentation works have focused their efforts on tackling the problem, but there is still room for performance improvement due to the significant variability of lesions in the location, size, structure, and morphological appearance. To address these challenges, we propose a novel One-Two-One Fully Convolutional Networks (OTO-Net) for intracranial aneurysms automated segmentation in MRA images. The OTO-Net uses full convolution to achieve intracranial aneurysms automated segmentation through the combination of downsampling, upsampling, and skip connection. In addition, loss ensemble is used as the objective function to steadily improve the backpropagation efficiency of the network structure during the training process. We evaluated the proposed OTO-Net on one public benchmark dataset and one private dataset. Our proposed model can achieve the automated segmentation accuracy with 98.37% and 97.86%, average surface distances with 1.081 and 0.753, dice similarity coefficients with 0.9721 and 0.9813, and Hausdorff distance with 0.578 and 0.642 on these two datasets, respectively.
Abstract Background Many studies have explored the relationship between skin microcirculation and meridian activation. However, few studies have examined blood perfusion coherence along the meridians, and other studies have suggested that the skin vasodilator response relates to age. This study investigated blood perfusion coherence characteristics along the meridian of the forearm in healthy volunteers. Methods A total of 15 young subjects (25.53 ± 2.20) and 15 middle-aged subjects (50.07 ± 3.37) were recruited for this study. Before experiments, each subject was placed in a temperature-controlled room for 60 min. Skin blood perfusion from five points was recorded simultaneously using a full-field laser perfusion imager before and after inflatable occlusion. The five points comprised three points located on the pericardium meridian, and two points from different locations. Coherence analysis between these points was performed at different frequency intervals from 0.0095 to 2 Hz. Results In young subjects, the coherence value was unchanged before and after occlusion, and there was no significant difference in coherence value between meridian-meridian points (M-M) and meridian-parameridian points (M-P). In middle-aged subjects, the coherence value increased significantly in both M-M and M-P at frequency intervals of 0.14-0.4 Hz, 0.4-1.6 Hz, and 1.6-2 Hz. However, there was no significant difference in coherence values between M-M and M-P. Conclusions Inflatable occlusion can increase middle-aged subjects’ blood perfusion coherence value of the forearm. However, there is no specificity in meridian location.
Resistance to antibiotics is one the main factors constraining the treatment and control of Helicobacter pylori (H. pylori) infections. Therefore, there is an urgent need to develop new antimicrobial agents to replace antibiotics. Our previous study found that linolenic acid-metronidazole (Lla-Met) has a good antibacterial effect against H. pylori, both antibiotic-resistant and sensitive H. pylori. Also, H. pylori does not develop resistance to Lla-Met. Therefore, it could be used for preparing broad-spectrum antibacterial agents. However, since the antibacterial mechanism of Lla-Met is not well understood, we explored this phenomenon in the present study.To understand the antimicrobial effect of Lla-Met and how this could be applied in treating corresponding infections.H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified.Lla-Met treatment induced several changes in H. pylori cells, including roughening and swelling. In vivo experiments revealed that Lla-Met induced oxidation, DNA fragmentation, and phosphatidylserine ectropionation in H. pylori cells. Inhibiting Lla-Met with L-cysteine abrogated the above phenomena. Transcriptome analysis revealed that Lla-Met treatment up-regulated the expression of superoxide dismutase SodB and MdaB genes, both anti-oxidation-related genes.Lla-Met kills H. pylori mainly by inducing oxidative stress, DNA damage, phosphatidylserine ectropionation, and changes on cell morphology.
Background. The specificity of acupuncture points (acupoints) is one of the key concepts in traditional acupuncture theory, but the question of whether there is adequate scientific evidence to prove or disprove specificity has been vigorously debated in recent years. Acupoint laterality is an important aspect of acupoint specificity. Data is particularly scarce regarding the laterality of the same channel, namesake acupoint located on opposite sides of the body. Our previous study results suggest that Neiguan acupoint (PC6) has the laterality. The aim of this study was to investigate whether Hegu (LI4) also has laterality from the perspective of heart rate variability. Methods. A total of twenty-eight healthy female volunteers were recruited for this study and were randomly separated into the group I (n = 14) and the group II (n = 14) according to the register order. In the group I, left LI4 was stimulated in the first epoch and the right LI4 was stimulated in the second epoch. In the group II, right LI4 was stimulated in the first epoch and left LI4 was stimulated in the second epoch. Electrocardiogram was recorded and heart rate variability was analyzed. Results. The results show that there were no significant differences of heart rate variablity between the group I and the group II in the time domain and in the frequency domain. Conclusions. Bilateral Hegu acupoints have the same effect on the heart rate variability of the healthy subjects.
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