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Sökning: WFRF:(Feng Shuang)

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  • Sjöström, Martin, et al. (författare)
  • Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer.
  • 2019
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - : American Society of Clinical Oncology. - 1527-7755. ; 37:35, s. 3340-3349
  • Tidskriftsartikel (refereegranskat)abstract
    • Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit (Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
  • Feng, Zhenhua, et al. (författare)
  • Multicore-Fiber-Enabled WSDM Optical Access Network With Centralized Carrier Delivery and RSOA-Based Adaptive Modulation
  • 2015
  • Ingår i: IEEE PHOTONICS JOURNAL. - [Feng, Zhenhua; Li, Borui; Tang, Ming; Gan, Lin; Wang, Ruoxu; Lin, Rui; Xu, Zhilin; Fu, Songnian; Deng, Lei; Liu, Shuang] Huazhong Univ Sci & Technol, Next Generat Internet Access Natl Engn Lab NGIA, Sch Opt & Elect Informat, Wuhan 430030, Peoples R China. [Lin, Rui] Royal Inst Technol KTH, Sch Informat & Commun Technol ICT, S-16440 Kista, Sweden. [Tong, Weijun; Long, Shengya; Zhang, Lei; Zhou, Hongyan; Zhang, Rui] Yangtze Opt Fibre & Cable Co Ltd YOFC, State Key Lab Opt Fiber & Cable Mfg Technol, Chengdu 610072, Peoples R China. [Shum, Perry Ping] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore.. - 1943-0655. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We proposed and experimentally demonstrated a wavelength-space division multiplexing (WSDM) optical access network architecture with centralized optical carrier delivery utilizing multicore fibers (MCFs) and adaptive modulation based on reflective semiconductor amplifier (RSOA). In our experiment, five of the outer cores are used for undirectional downstream (DS) transmission only, whereas the remaining outer core is utilized as a dedicated channel to transmit upstream (US) signals. Optical carriers for US are delivered from the optical line terminal (OLT) to the optical network unit (ONU) via the inner core and then transmitted back to the OLT after amplification and modulation by the RSOA in the colorless ONU side. The mobile backhaul (MB) service is also supported by the inner core. Wavelengths used in US transmission should be different from that of the MB in order to avoid the Rayleigh backscattering effect in bidirectional transmission. With quadrature phase-shift keying-orthogonal frequency-division multiplexing (QPSK-OFDM) modulation format, the aggregation DS capacity reaches 250 Gb/s using five outer cores and ten wavelengths, and it can be further scaled to 1 Tb/s using 20 wavelengths modulated with 16 QAM-OFDM. For US transmission, 2.5 Gb/s QPSK-OFDM transmission can be achieved just using a low-bandwidth RSOA, and adaptive modulation is applied to the RSOA to further enhance the US data rate to 3.12 Gb/s. As an emulation of high-speed MB transmission, 48 Gb/s inphase and quadrature (IQ) modulated popularization division multiplexing (PDM)-QPSK signal is transmitted in the inner core of MCF and coherently detected in the OLT side. Both DS and US optical signals exhibit acceptable performance with sufficient power budget.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
  • Liu, Dajiang J, et al. (författare)
  • Meta-analysis of gene-level tests for rare variant association.
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718. ; 46:2, s. 200-200
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
  • Xu, Shuang Feng, et al. (författare)
  • Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
  • Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifunctional iron-binding globular glycoprotein, was screened to identify novel neuroprotective pathways against dopaminergic neuronal impairment. We found that Lf substantially ameliorated PD-like motor dysfunction in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We further showed that Lf could alleviate MPTP-triggered apoptosis of DA neurons, neuroinflammation, and histological alterations. As expected, we also found that Lf suppressed MPTP-induced excessive iron accumulation and the upregulation of divalent metal transporter (DMT1) and transferrin receptor (TFR), which is the main intracellular iron regulation protein, and subsequently improved the activity of several antioxidant enzymes. We probed further and determined that the neuroprotection provided by Lf was involved in the upregulated levels of brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor 1α (HIF-1α) and its downstream protein, accompanied by the activation of extracellular regulated protein kinases (ERK) and cAMP response element binding protein (CREB), as well as decreased phosphorylation of c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. Our findings suggest that Lf may be an alternative safe drug in ameliorating MPTP-induced brain abnormalities and movement disorder.
  • Yu, Miao mei, et al. (författare)
  • Apolipoprotein M increases the expression of Vitamin D receptor mRNA in colorectal cancer cells detected with duplex fluorescence reverse transcription-quantitative polymerase chain reaction
  • Ingår i: Molecular Medicine Reports. - : Spandidos Publications Ltd. - 1791-2997. ; 16:2, s. 1167-1172
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein M (ApoM) and the Vitamin D receptor (VDR) are apolipoproteins predominantly presenting in high-density lipoprotein (HDL) and a karyophilic protein belonging to the steroid-thyroid receptor superfamily, respectively. Previous studies have demonstrated that ApoM and VDR are associated with cholesterol metabolism, immune and colorectal cancer regulation. In order to investigate whether ApoM affected the expression of VDR in colorectal cancer cells, a single-tube duplex fluorescence reverse transcription-quantitative polymerase chain reaction (RT-qPCR) system was developed to simultaneously detect the mRNA levels of VDR and GAPDH in HT-29 cells overexpressing ApoM. The results demonstrated that the amplification products were confirmed as the specific fragment of VDR/GAPDH using the DNA sequencing instrument. The sensitivity, linear range, correlation coefficient, amplification efficiency, intra-assay and inter-assay coefficients of variation were 40 copies/μl, 4.00×101-4.00×105 copies/μl, 0.999, 92.42%, 0.09-0.34% and 0.32-0.65% for VDR, and 40 copies/μl, 400×101-4.00×105 copies/μl, 0.999, 98.07%, 0.19-0.43% and 0.40-0.75% for GAPDH, respectively. The results indicated that the expression of VDR mRNA was significantly higher in HT-29 cells overexpressing ApoM, compared with the negative control group (P<0.05). In conclusion, the current study successfully developed the single-tube duplex RT-qPCR to simultaneously detect VDR and GAPDH expression in colorectal cancer cells. The methodology results demonstrated that the duplex RT-qPCR system with high sensitivity and specificity could ensure the objectivity and credibility of the detection. The present study confirmed that ApoM significantly increased the expression of VDR in HT-29 cells. In addition, it was hypothesized that ApoM may be involved in antineoplastic activity via the upregulation of VDR expression, which may provide novel directions for the investigation of ApoM in cancer.
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