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Dickkopf

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https://www.readbyqxmd.com/read/29779087/down-regulation-of-mdr1-by-ad-dkk3-via-akt-nf%C3%AE%C2%BAb-pathways-augments-the-anti-tumor-effect-of-temozolomide-in-glioblastoma-cells-and-a-murine-xenograft-model
#1
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, Keiko T Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro, Yasushi Takagi
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29774401/high-levels-of-serum-sclerostin-and-dkk1-in-a-case-of-klippel-tr%C3%A3-naunay-syndrome
#2
P Muto, A Lo Gullo, G Mandraffino, S Loddo, M Atteritano
Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH)...
May 17, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29772510/dkk1-and-kremen-expression-predicts-the-osteoblastic-response-to-bone-metastasis
#3
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#4
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29753515/long-term-prognostic-impact-of-osteopontin-and-dickkopf-related-protein-1-in-patients-with-hepatocellular-carcinoma-after-hepatectomy
#5
Hyerim Byeon, Seung Duk Lee, Eun-Kyung Hong, Dong Eun Lee, Bo Hyun Kim, Yunsung Seo, Jungnam Joo, Sung-Sik Han, Seong Hoon Kim, Sang-Jae Park
BACKGROUND: New biomarkers are essential for improving the prediction of the survival and prognosis of patients with hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the most widely used biomarker, but the low sensitivity and specificity limit its clinical applications. The diagnostic and prognostic capabilities of osteopontin (OPN), dickkopf-related protein 1 (DKK1), and a combination of these biomarkers are being studied. METHODS: From January 2006 to December 2008, patients undergoing hepatectomy for HCC were screened and their serum stored in tumor banks was analyzed...
May 6, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29749516/downregulation-of-n%C3%A2-myc-inhibits-neuroblastoma-cell-growth-via-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway
#6
Yingge Wang, Shan Gao, Weiguang Wang, Yuting Xia, Jingyan Liang
Neuroblastoma, one of the most common types of cancer in childhood, is commonly treated with surgery, radiation and chemotherapy. However, prognosis and survival remain poor for children with high‑risk neuroblastoma. Therefore, the identification of novel, effective therapeutic targets is necessary. N‑Myc, a proto‑oncogene protein encoded by the v‑myc avial myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) gene, is associated with tumorigenesis. In the present study, the effect of N‑Myc silencing on MYCN‑amplified CHP134 and BE‑2C neuroblastoma cells was evaluated, and the underlying molecular mechanism was investigated...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29734465/postnatal-skeletal-deletion-of-dickkopf-1-increases-bone-formation-and-bone-volume-in-male-and-female-mice-despite-increased-sclerostin-expression
#7
Juliane Colditz, Sylvia Thiele, Ulrike Baschant, Christof Niehrs, Lynda F Bonewald, Lorenz C Hofbauer, Martina Rauner
The Wnt antagonist Dickkopf-1 (Dkk1) is a negative regulator of osteoblast function and bone mass. However, due to the lack of appropriate models, many aspects of its role in the regulation of postnatal bone turnover and its cellular source have remained unknown. In this study, we deleted Dkk1 postnatally and in different cell types using various Cre-drivers (Rosa26-ERT2-Cre, Osx-cre,Dmp1-Cre) and assessed to which extent cells of the osteoblastic lineage contribute to the effects of Dkk1 on bone turnover and homeostasis...
May 7, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29731902/identification-of-candidate-genes-associated-with-tubal-origin-of-high-grade-serous-ovarian-cancer
#8
Li Xiang, Guohua Rong, Jing Zhao, Zhenyan Wang, Fengfeng Shi
Evidence indicates that high-grade serous ovarian carcinoma arises from the fallopian tube, rather than ovarian surface epithelium. This is termed the 'tubal origin' theory. The aim of the present study was to compare the immunophenotype and gene expression profiling among high-grade serous ovarian carcinoma (HGSOC), fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) based on tubal origin theory, and identify the differential genes associated with ovarian carcinogenesis. A total of 61 cases of fresh tissue samples including 21 cases of HGSOC, 20 cases of OSE, and 20 cases of FTE were obtained following surgical resection...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29726981/dickkopf-3-in-aberrant-endothelial-secretome-triggers-renal-fibroblast-activation-and-endothelial-mesenchymal-transition
#9
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29725706/abaloparatide-exerts-bone-anabolic-effects-with-less-stimulation-of-bone-resorption-related-factors-a-comparison-with-teriparatide
#10
Akito Makino, Hideko Takagi, Yoshimasa Takahashi, Naoki Hase, Hiroyuki Sugiyama, Kei Yamana, Tsunefumi Kobayashi
Abaloparatide (ABL) is a novel synthetic peptide analog of parathyroid hormone-related protein. In previous reports, intermittent ABL administration showed robust bone mineral density (BMD) increase and reduced the incidence of fractures in patients with osteoporosis, while its calcemic effect was reduced, as compared with teriparatide (TPTD), a parathyroid hormone N-terminal fragment. The present study aimed to elucidate the effects of ABL on bone anabolism and bone turnover as compared with TPTD. In ovariectomized (OVX) rats, ABL increased the bone strength and BMD of lumbar spine by intermittent administration similar to TPTD...
May 3, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29720122/prognostic-value-of-dickkopf-1-and-%C3%A3-catenin-expression-in-advanced-gastric-cancer
#11
Soon Auck Hong, Su Hyun Yoo, Han Hong Lee, Der Sheng Sun, Hye Sung Won, Okran Kim, Yoon Ho Ko
BACKGROUND: Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. METHODS: In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. RESULTS: DKK1 expression was high in 73 (46...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29717119/dkk3-dependent-transcriptional-regulation-controls-age-related-skeletal-muscle-atrophy
#12
Jie Yin, Lele Yang, Yangli Xie, Yan Liu, Sheng Li, Wenjun Yang, Bo Xu, Hongbin Ji, Lianghua Ding, Kun Wang, Gang Li, Lin Chen, Ping Hu
Age-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63, driving muscle atrophy...
May 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29715368/cross-inhibition-of-norrin-and-tgf-%C3%AE-signaling-modulates-development-of-retinal-and-choroidal-vasculature
#13
Roswitha Seitz, Gregor Weber, Sebastian Albrecht, Rudolf Fuchshofer, Ernst R Tamm, Andreas Ohlmann
Purpose: Norrin is essential for the formation of the retinal vasculature during development and promotes its repair after damage via activation of Wnt/β-catenin signaling. Since retinal TGF-β signaling has essentially opposite effects on the retinal vasculature we investigated if and how Norrin inhibits TGF-β signaling, and vice versa. Methods: Eyes from transgenic mice with an overexpression of Norrin (βB1-Norrin) and/or active TGF-β (βB1-TGF-β1) in the lens were generated and analyzed by light microscopy, immunohistochemistry, and TUNEL...
May 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29704238/microrna-3064-3p-regulates-the-differentiation-of-cementoblasts-through-targeting-dkk1
#14
C Wang, H Liao, H Sun, Y Zhang, Z Cao
BACKGROUND AND OBJECTIVE: MicroRNAs (miRNAs) are short, noncoding RNAs that interfere with translation of target mRNAs and thereby play a pivotal role in a variety of biological processes. Cementoblasts are the cells that build up cementum. They share a similar gene expression pattern with osteoblasts. Recent studies have suggested that miRNAs are able to control osteoblast-mediated bone formation. However, the effects of miRNA on cementoblast differentiation still remain unsolved. Herein, we wanted to elucidate the role of miR-3064-3p in cementoblast differentiation...
April 27, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29695980/cardiac-remodeling-endothelial-cells-have-more-to-say-than-just-no
#15
REVIEW
Vincent F M Segers, Dirk L Brutsaert, Gilles W De Keulenaer
The heart is a highly structured organ consisting of different cell types, including myocytes, endothelial cells, fibroblasts, stem cells, and inflammatory cells. This pluricellularity provides the opportunity of intercellular communication within the organ, with subsequent optimization of its function. Intercellular cross-talk is indispensable during cardiac development, but also plays a substantial modulatory role in the normal and failing heart of adults. More specifically, factors secreted by cardiac microvascular endothelial cells modulate cardiac performance and either positively or negatively affect cardiac remodeling...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29694926/gh-prevents-adipogenic-differentiation-of-mesenchymal-stromal-stem-cells-derived-from-human-trabecular-bone-via-canonical-wnt-signaling
#16
Simona Bolamperti, Michela Signo, Alice Spinello, GianLuigi Moro, Gianfranco Fraschini, Francesca Guidobono, Alessandro Rubinacci, Isabella Villa
The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA)...
April 22, 2018: Bone
https://www.readbyqxmd.com/read/29693006/baicalein-accelerates-tendon-bone-healing-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway-in-rats
#17
Xinggui Tian, Huaji Jiang, Yuhui Chen, Xiang Ao, Chuan Chen, Wentao Zhang, Feilin He, Xiaoqing Liao, Xiaocheng Jiang, Tao Li, Zhongmin Zhang, Xintao Zhang
Background: Tendon-bone healing is a reconstructive procedure which requires a tendon graft healing to a bone tunnel or to the surface of bone after the junction injury between tendon, ligament, and bone. The surgical reattachment of tendon to bone often fails due to regeneration failure of the specialized tendon-bone junction. Materials and Methods: An extra-articular tendon-bone healing rat model was established to discuss the effect of the baicalein 10 mg/(kg·d) in accelerating tendon-bone healing progress...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29690705/-comparison-of-bone-destruction-markers-in-patients-with-gouty-arthritis-under-different-musculoskeletal-ultrasonic-manifestations
#18
Y N Fei, S M Tang, G Zhang, Y H Li, M Shao, L F Xie, Y C Zhong, X W Zhang
Objectives: To observe the correlation between the different ultrasonic manifestations of gouty arthritis and the indexes of bone destruction (Dickkopf-1, RANKL), in order to further explore the role of musculoskeletal ultrasonography in the diagnosis and monitoring of gouty arthritis. Methods: 160 cases of gouty arthritis from clinic of the Department of Rheumatology of Peking University People's Hospital between July 2016 and June 2017 were recruited in this study. These patients were examined by musculoskeletal ultrasonography (bilateral first metatarsophalangeal joints, bilateral ankle joints and bilateral knee joints)...
April 3, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29683771/wnt-signaling-related-osteokines-at-rest-and-following-plyometric-exercise-in-prepubertal-and-early-pubertal-boys-and-girls
#19
Panagiota Klentrou, Kirina Angrish, Nafisa Awadia, Nigel Kurgan, Rozalia Kouvelioti, Bareket Falk
PURPOSE: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. METHODS: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-β ligand (RANKL). RESULTS: Girls had higher resting sclerostin than boys [187...
April 23, 2018: Pediatric Exercise Science
https://www.readbyqxmd.com/read/29674765/clinical-and-functional-significance-of-intracellular-and-extracellular-microrna-25-3p-in-osteosarcoma
#20
Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki
Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients' serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis...
April 2018: Acta Medica Okayama
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