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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/28423208/combined-activity-of-temozolomide-and-the-mtor-inhibitor-temsirolimus-in-metastatic-melanoma-involves-dkk1
#1
Heike Niessner, Corinna Kosnopfel, Tobias Sinnberg, Daniela Beck, Kathrin Krieg, Ines Wanke, Konstantinos Lasithiotakis, Michael Bonin, Claus Garbe, Friedegund Meier
The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in patients with BRAF-mutant melanoma, but its effects are limited by the onset of drug resistance. In the case of resistance, chemotherapy can still be applied as second line therapy. However, it yields low response rates and strategies are urgently needed to potentiate its effects. In a previous study, we showed that the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity of melanoma cells to chemotherapeutic drugs (1)...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28396299/plasma-cytokine-profiling-to-predict-susceptibility-to-acute-mountain-sickness
#2
Hui Lu, Rong Wang, Wenbin Li, Hua Xie, Chang Wang, Ying Hao, Yuhuan Sun, Zhengping Jia
Extensive studies have been performed on acute mountain sickness (AMS), but biomarkers predicting AMS are lacking. Presently, the mainstay methods to identify AMS biomarkers include proteomic and genetic methods at high altitudes or in hypoxic simulated chambers. In the present study, we compared plasma cytokine profiles between AMS-susceptible individuals and AMS-resistant individuals at low altitude by cytokine array analysis. In total, 75 differentially expressed cytokines were identified between AMS-susceptible individuals and AMS-resistant individuals, most involved in inflammation...
November 1, 2016: European Cytokine Network
https://www.readbyqxmd.com/read/28388723/high-sclerostin-and-dickkopf-1-dkk-1-serum-levels-in-children-and-adolescents-with-type-1-diabetes-mellitus
#3
Maria Felicia Faienza, Annamaria Ventura, Maurizio Delvecchio, Anna Fusillo, Laura Piacente, Gabriella Aceto, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, Giacomina Brunetti
Context: Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors that regulate bone formation. Objective: To evaluate sclerostin and DKK-1 levels in T1DM children and to analyze the influence of glycemic control on bone health. Design and setting: Cross-sectional study conducted at a clinical research center. Participants: One hundred and six T1DM subjects (12...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28384913/study-of-dickkopf-1-dkk-1-gene-expression-in-hepatocellular-carcinoma-patients
#4
Mona Watany, Rehab Badawi, Walaa Elkhalawany, Sherief Abd-Elsalam
INTRODUCTION: Hepatocellular Carcinoma (HCC) is the sixth most common cancer in the world. Dickkopf -1 (DKK-1) protein is a new biomarker used in conjunction with Alpha Fetoprotein (AFP) to differentiate HCC from "non-malignant" liver disease. DKK-1 is an inhibitor of Wnt/β-catenin signaling pathway which is involved in embryogenesis and has been implicated in tumorigenesis in many tissues. AIM: To investigate the level of DKK-1 gene expression in the peripheral blood of patients with HCC who had a history of Hepatitis C Virus (HCV) and schistosomal infections...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28373995/dickkopf-1-is-a-biomarker-for-systemic-lupus-erythematosus-and-active-lupus-nephritis
#5
Jing Xue, Jiali Yang, Lijuan Yang, Shaolan Zhou, Chen Ji, Xuemei Wang, Nan Yu, Xiaoming Liu, Shuhong Chi
An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28365691/dickkopf-related-protein-2-is-epigenetically-inactivated-and-suppresses-colorectal-cancer-growth-and-tumor-metastasis-by-antagonizing-wnt-%C3%AE-catenin-signaling
#6
Can Wang, Yujuan Yue, Bianfei Shao, Zhu Qiu, Junhao Mu, Jun Tang, Xiaofan Han, Tingxiu Xiang, Guosheng Ren
BACKGROUND/AIMS: Aberrant activation of the Wnt/β-catenin signaling pathway plays a key role in the pathogenesis of multiple tumors including digestive cancers. Recent studies have reported that Dickkopf-related protein 2 (DKK2) is epigenetically inactivated in numerous types of cancers and that its gene products exhibit tumor-suppressive properties. However, the biological functions and underlying molecular mechanisms of DKK2 in colon carcinoma remains obscure. METHODS: We examined the expression of DKK2 in colon tumor cell lines by RT-PCR and its promoter methylation status in colon tumor cell lines and primary tumors by methylation-specific PCR (MSP)...
March 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28358733/plasma-dickkopf-related-protein-1-an-antagonist-of-the-wnt-pathway-is-associated-with-hiv-associated-neurocognitive-impairment
#7
Chunjiang Yu, Melanie Seaton, Scott Letendre, Robert Heaton, Lena Al-Harthi
OBJECTIVE: DKK1 is a soluble antagonist of the Wnt pathway. It binds to and sequesters LRP5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV+ individuals. We evaluated here the relationship between plasma DKK1 and global NCI. METHODS: Plasma samples and data from 41 HIV+ and 42 HIV- adults were obtained from the University of California, San Diego...
March 29, 2017: AIDS
https://www.readbyqxmd.com/read/28356931/microrna-320a-downregulation-mediates-human-liver-cancer-cell-proliferation-through-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Caicheng Lu, Zengwei Liao, Minxian Cai, Guirong Zhang
MicroRNAs (miRs) have emerged as key epigenetic regulators involved in cancer progression. miR-320a has been demonstrated to be a novel tumor suppressive microRNA in several types of cancers. In the present study, the role of miR-320a in human hepatocellular carcinoma (HCC) was investigated. The expression levels of miR-320a and messenger RNA were determined by reverse transcription-quantitative polymerase chain reaction, while cell cycle and cell apoptosis were analyzed by flow cytometry. The cell proliferative ability was determined by Cell Counting Kit-8 assay and colony formation assay...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28352232/dickkopf-3-upregulates-vegf-in-cultured-human-endothelial-cells-by-activating-activin-receptor-like-kinase-1-alk1-pathway
#9
Carla L Busceti, Simona Marchitti, Franca Bianchi, Paola Di Pietro, Barbara Riozzi, Rosita Stanzione, Milena Cannella, Giuseppe Battaglia, Valeria Bruno, Massimo Volpe, Francesco Fornai, Ferdinando Nicoletti, Speranza Rubattu
Dkk-3 is a member of the dickkopf protein family of secreted inhibitors of the Wnt pathway, which has been shown to enhance angiogenesis. The mechanism underlying this effect is currently unknown. Here, we used cultured HUVECs to study the involvement of the TGF-β and VEGF on the angiogenic effect of Dkk-3. Addition of hrDkk-3 peptide (1 or 10 ng/ml) to HUVECs for 6 or 12 h enhanced the intracellular and extracellular VEGF protein levels, as assessed by RTPCR, immunoblotting, immunocytochemistry and ELISA...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28346008/wnt-%C3%AE-catenin-signaling-is-required-for-distraction-osteogenesis-in-rats
#10
Xuemei Wang, En Luo, Ruiye Bi, Bin Ye, Jing Hu, Shujuan Zou
OVERVIEW: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized. MATERIALS AND METHODS: We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process...
March 1, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28337453/mir-373-3p-targets-dkk1-to-promote-emt-induced-metastasis-via-the-wnt-%C3%AE-catenin-pathway-in-tongue-squamous-cell-carcinoma
#11
Junquan Weng, Hui Zhang, Cheng Wang, Jianfeng Liang, Guanhui Chen, Wenqing Li, Haikuo Tang, Jinsong Hou
MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28332354/cyclized-oligopeptide-targeting-lrp5-6-dkk1-interaction-reduces-the-growth-of-tumor-burden-in-a-multiple-myeloma-mouse-model
#12
Bo Mi Park, Eun Jin Kim, Hee Jin Nam, Dongdong Zhang, Chu Hyun Bae, Myeongmo Kang, Heeyoun Kim, Weontae Lee, Bjarne Bogen, Sung Kil Lim
PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28259940/dickkopf-related-protein-3-negatively-regulates-the-osteogenic-differentiation-of-rat-dental-follicle-cells
#13
Xinchun Zhang, Yu Du, Junqi Ling, Weiqiang Li, Yan Liao, Xi Wei
The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DFCs). A PCR array analysis of Wnt pathway activation in DFCs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DFC osteogenesis. By comparing DFCs grown in normal growth and mineral‑induction media for 4 weeks, the present study confirmed that DKK3 was a potential target gene of osteogenesis through reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and western blotting (WB)...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259755/chordin-and-dickkopf-1b-are-essential-for-the-formation-of-head-structures-through-activation-of-the-fgf-signaling-pathway-in-zebrafish
#14
Shingo Tanaka, Hiroshi Hosokawa, Eric S Weinberg, Shingo Maegawa
The ability of the Spemann organizer to induce dorsal axis formation is dependent on downstream factors of the maternal Wnt/β-catenin signaling pathway. The fibroblast growth factor (FGF) signaling pathway has been identified as one of the downstream components of the maternal Wnt/β-catenin signaling pathway. The ability of the FGF signaling pathway to induce the formation of a dorsal axis with a complete head structure requires chordin (chd) expression; however, the molecular mechanisms involved in this developmental process, due to activation of FGF signaling, remain unclear...
March 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28249601/a-novel-foxo1-mediated-dedifferentiation-blocking-role-for-dkk3-in-adrenocortical-carcinogenesis
#15
Joyce Y Cheng, Taylor C Brown, Timothy D Murtha, Adam Stenman, C Christofer Juhlin, Catharina Larsson, James M Healy, Manju L Prasad, Wolfram T Knoefel, Andreas Krieg, Ute I Scholl, Reju Korah, Tobias Carling
BACKGROUND: Dysregulated WNT signaling dominates adrenocortical malignancies. This study investigates whether silencing of the WNT negative regulator DKK3 (Dickkopf-related protein 3), an implicated adrenocortical differentiation marker and an established tumor suppressor in multiple cancers, allows dedifferentiation of the adrenal cortex. METHODS: We analyzed the expression and regulation of DKK3 in human adrenocortical carcinoma (ACC) by qRT-PCR, immunofluorescence, promoter methylation assay, and copy number analysis...
March 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28248066/serum-dickkopf-1-act-as-a-new-biomarker-in-human-breast-cancer
#16
Jin-Tao Liu, Wen-Bin Guo, Jia-Yi Sun
BACKGROUND: The serum levels of Dickkopf-1 (Dkk1), a secreted Wnt family protein is changed in patients suffering various types of cancers. In the present study, we aim to explore the diagnostic value of Dkk1 as a new biomarker in breast cancer. METHODS: Serum was collected from 38 patients with breast cancer and 23 healthy controls. Serological levels of DKK1 were examined by enzyme-linked immunosorbent assay (ELISA). Significance and diagnostic performance including receiver operator characteristic (ROC) and areas under the curve (AUC) were determined by SPSS software...
March 1, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28235973/endothelin-signaling-regulates-mineralization-and-posttranscriptionally-regulates-sost-in-tmob-cells-via-mir-126-3p
#17
Michael G Johnson, Kathryn Konicke, Jasmin Kristianto, Anne Gustavson, Rachel Garbo, Xiaohu Wang, Baozhi Yuan, Robert D Blank
Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST)...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28222387/baicalein-enhances-the-osteogenic-differentiation-of-human-periodontal-ligament-cells-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#18
Li-Jiao Chen, Bi-Bo Hu, Xin-Lian Shi, Man-Man Ren, Wen-Bin Yu, Sheng-Dan Cen, Rong-Dang Hu, Hui Deng
OBJECTIVE: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCs osteogenic differentiation by baicalein. DESIGN: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1...
February 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28219919/dickkopf-3-ablation-attenuates-the-development-of-atherosclerosis-in-apoe-deficient-mice
#19
Wen-Lin Cheng, Yang Yang, Xiao-Jing Zhang, Junhong Guo, Jun Gong, Fu-Han Gong, Zhi-Gang She, Zan Huang, Hao Xia, Hongliang Li
BACKGROUND: Dickkopf-3 (DKK3) is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis. METHODS AND RESULTS: Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice...
February 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28185033/stimulation-of-osteogenic-differentiation-by-saikosaponin-a-in-bone-marrow-stromal-cells-via-wnt-%C3%AE-catenin-pathway
#20
Weiqi Huang, Xiaoling Zheng, Xiaodong Yang, Shicai Fan
Saikosaponin-A (SA), a class of native compound with numerous biological activities, may exert protective effect against postmenopausal bone loss. However, it remains unknown whether SA regulates the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the treatment and prevention of osteoporosis. In this study, BMSCs were treated with various concentrations of SA to stimulate osteogenic differentiation over a 14-day period. Additionally, a canonical ovariectomized (OVX) mouse model was used to evaluate the effect of 3-month SA treatment in preventing postmenopausal osteoporosis...
February 9, 2017: Calcified Tissue International
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