• Title/Summary/Keyword: SFRP

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Concurrent Hypermethylation of SFRP2 and DKK2 Activates the Wnt/β-Catenin Pathway and Is Associated with Poor Prognosis in Patients with Gastric Cancer

  • Wang, Hao;Duan, Xiang-Long;Qi, Xiao-Li;Meng, Lei;Xu, Yi-Song;Wu, Tong;Dai, Peng-Gao
    • Molecules and Cells
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    • v.40 no.1
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    • pp.45-53
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    • 2017
  • Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

In silico Identification of SFRP1 as a Hypermethylated Gene in Colorectal Cancers

  • Kim, Jongbum;Kim, Sangsoo
    • Genomics & Informatics
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    • v.12 no.4
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    • pp.171-180
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    • 2014
  • Aberrant DNA methylation, as an epigenetic marker of cancer, influences tumor development and progression. We downloaded publicly available DNA methylation and gene expression datasets of matched cancer and normal pairs from the Cancer Genome Atlas Data Portal and performed a systematic computational analysis. This study has three aims to screen genes that show hypermethylation and downregulated patterns in colorectal cancers, to identify differentially methylated regions in one of these genes, SFRP1, and to test whether the SFRP genes affect survival or not. Our results show that 31 hypermethylated genes had a negative correlation with gene expression. Among them, SFRP1 had a differentially methylated pattern at each methylation site. We also show that SFRP1 may be a potential biomarker for colorectal cancer survival.

MGMT-B Gene Promoter Hypermethylation in Patients with Inflammatory Bowel Disease - A Novel Finding

  • Mokarram, Pooneh;Kavousipour, Soudabeh;Sarabi, Mostafa Moradi;Mehrabani, Golnosh;Fahmidehkar, Mohammad Ali;Shamsdin, Seyedeh Azra;Alipour, Abbas;Naini, Mahvash Alizade
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1945-1952
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    • 2015
  • Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

Finite Element Analysis for Evaluating the Performance of RC Beams Strengthened with SFRP Coating (분사식 섬유보강 코팅으로 보강된 RC보의 성능평가를 위한 유한요소해석 연구)

  • Ha, Sung-Kug;Yang, Bum-Joo;Lee, Haeng-Ki
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.22 no.6
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    • pp.579-585
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    • 2009
  • In this paper, a series of finite element analyzes were carried out to evaluate the performance of the RC beams strengthened with sprayed fiber reinforced polymer(SFRP) coating. A damage constitutive model based on the micromechanical constitutive model(Lee, 2001) in conjunction with the damage models(Lee 등, 2000) for SFRP coating was implemented into the finite element code ABAQUS. The present prediction results were compared with experimental data(Ha, 2007; Ha 등, 2009) to assess the accuracy of the damage constitutive model. It was concluded from the comparative study that the computational model developed by implementing the damage constitutive model into ABAQUS is suitable for the prediction of the performance of RC beams strengthened with SFRP coating.

Performance-based and damage assessment of SFRP retrofitted multi-storey timber buildings

  • Vahedian, Abbas;Mahini, Seyed Saeed;Glencross-Grant, Rex
    • Structural Monitoring and Maintenance
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    • v.2 no.3
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    • pp.269-282
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    • 2015
  • Civil structures should be designed with the lowest cost and longest lifetime possible and without service failure. The efficient and sustainable use of materials in building design and construction has always been at the forefront for civil engineers and environmentalists. Timber is one of the best contenders for these purposes particularly in terms of aesthetics; fire protection; strength-to-weight ratio; acoustic properties and seismic resistance. In recent years, timber has been used in commercial and taller buildings due to these significant advantages. It should be noted that, since the launch of the modern building standards and codes, a number of different structural systems have been developed to stabilise steel or concrete multistorey buildings, however, structural analysis of high-rise and multi-storey timber frame buildings subjected to lateral loads has not yet been fully understood. Additionally, timber degradation can occur as a result of biological decay of the elements and overloading that can result in structural damage. In such structures, the deficient members and joints require strengthening in order to satisfy new code requirements; determine acceptable level of safety; and avoid brittle failure following earthquake actions. This paper investigates performance assessment and damage assessment of older multi-storey timber buildings. One approach is to retrofit the beams in order to increase the ductility of the frame. Experimental studies indicate that Sprayed Fibre Reinforced Polymer (SFRP) repairing/retrofitting not only updates the integrity of the joint, but also increases its strength; stiffness; and ductility in such a way that the joint remains elastic. Non-linear finite element analysis ('pushover') is carried out to study the behaviour of the structure subjected to simulated gravity and lateral loads. A new global index is re-assessed for damage assessment of the plain and SFRP-retrofitted frames using capacity curves obtained from pushover analysis. This study shows that the proposed method is suitable for structural damage assessment of aged timber buildings. Also SFRP retrofitting can potentially improve the performance and load carrying capacity of the structure.

Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps

  • Naini, M Alizade;Mokarram, P;Kavousipour, S;Zare, N;Atapour, A;Zarin, M Hassan;Mehrabani, G;Borji, M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.2185-2193
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    • 2016
  • Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

Methylation of SFRPs and APC Genes in Ovarian Cancer Infected with High Risk Human Papillomavirus

  • Al-Shabanah, Othman Abdulla;Hafez, Mohamed Mahmoud;Hassan, Zeinab Korany;Sayed-Ahmed, Mohamed Mohamed;Abozeed, Waleed Nabeel;Alsheikh, Abdulmalik;Al-Rejaie, Salem Saleh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2719-2725
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    • 2014
  • Background: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Materials and Methods: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

SFRP Synthesis of Acenaphthylene Oligomers and Block Copolymers. Potential Light Harvesting Structures

  • Ali, Dildar;Ahmed, Zaheer;Dust, Julian M.;Kazmaier, Peter M.;Buncel, Erwin
    • Bulletin of the Korean Chemical Society
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    • v.32 no.7
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    • pp.2377-2384
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    • 2011
  • Azo-acenaphthylene oligomers with repeating acenaphthylene units "n" up to 4, 5, 7, 17 and 19 have been prepared successfully using nitroxide mediated Stable Free Radical Polymerization (SFRP). Azo-acenaphthylene oligomers, reversibly end-capped by the stable nitroxide 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO), were further reacted via radical addition to 4-(naphthalenemethoxy)styrene monomer for diblock co-polymer formation. Characterization of the oligomers and diblock co-polymers was accomplished using MALDI-MS supported by GPC (Gel Permeation Chromatography) and $^1H$ NMR spectrometry. MALDI-MS afforded definitive results by providing an inter-peak interval of 152 (m/z), corresponding to acenaphthylene monomer, and inter-peak interval of 260 (m/z) for the naphthalenemethoxystyrene monomer unit in block copolymers. Our study opens the way to control the number of repeat units in the oligomers. Further these oligomers can be tailored with various monomers for the formation of block copolymers.

Evaluation on Strengthening Capacities and Rebound Rate of Structures with Sprayed FRP (분사식 FRP에 의한 구조물의 보강 성능 및 반발률 평가)

  • Han, Seung-Chul;Yang, Jun-Mo;Yoon, Young-Soo
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.12 no.1
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    • pp.193-202
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    • 2008
  • This paper investigates experimentally the confining effect, strengthening capacity and rebound rate of sprayed Fiber-Reinforced-Polymer (SFRP). From the method, resin and chopped fibers are sprayed separately from the nozzle with high pressure, and then they are attached to the concrete surface, so structure could be repaired. To evaluate the strengthening effect of sprayed FRP, cylindrical specimens and beam specimens were strengthening with SFRP. As main material of FRP, glass fiber and polyester resin are used. To investigate the optimum condition of sprayed FRP, the effects of fiber length, coating thickness, fiber volume ratio and concrete strength were examined. Capacities of sprayed FRP method were also compared to the FRP sheet method. In case of the sprayed FRP, rebound rate is important parameter considering economical efficiency and constructibility, so rebound rate of was discussed. From the test results, optimum conditions of sprayed FRP were determined. SFRP method showed superior strengthening capacities than FRP sheet method.

Downregulation of Foxe1 by HR suppresses Msx1 expression in the hair follicles of HrHp mice

  • Choi, Jee-Hyun;Kim, Byong-Kyu;Kim, Jeong-Ki;Lee, Hwa-Young;Park, Jong-Keun;KimYoon, Sung-Joo
    • BMB Reports
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    • v.44 no.7
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    • pp.478-483
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    • 2011
  • Hairless (HR), a transcriptional cofactor, is highly expressed in the skin and brain. To characterize the effects of HR expression in the skin, we examined its capacity for transcriptional regulation of its target genes in mouse skin and keratinocytes. We found that Foxe1 mRNA expression was suppressed in HR-overexpressing skin, as well as in HR-expressing keratinocytes. In turn, Msx1 expression was downregulated contingent on Foxe1 downregulation in skin and keratinocytes. We also found that expression of Sfrp1 was also correlated with that of Foxe1. Further investigation of the mechanisms involved in the transcriptional regulation of these genes will facilitate our understanding of the relationship among genes involved in hair follicle morphogenesis and cycling.