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Zhe Huang, Yong Feng
Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remains unknown. Here, we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal induced proliferation and migration of endothelial cells...
October 5, 2016: Oncology Research
Anne Tr Noll, Thorsten Cramer, Steven Wm Olde Damink, Frank G Schaap
Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells...
September 18, 2016: World Journal of Hepatology
Tim Koopmans, Stijn Crutzen, Mark H Menzen, Andrew J Halayko, Tillie-Louise Hackett, Darryl A Knight, Reinoud Gosens
BACKGROUND AND PURPOSE: Asthma is a heterogeneous chronic inflammatory disease, characterized by the development of structural changes (airway remodelling). β-catenin, a transcriptional co-activator is fundamentally involved in airway smooth muscle growth, and may be a potential target in the treatment of airway smooth muscle remodelling. EXPERIMENTAL APPROACH: Using small-molecule compounds that selectively target β-catenin breakdown or its interactions with transcriptional co-activators, we assessed their ability to inhibit airway smooth muscle remodelling in vitro and in vivo...
September 15, 2016: British Journal of Pharmacology
Lihong Yao, Haijin Zhao, Haixiong Tang, Jing Xiong, Wenqu Zhao, Laiyu Liu, Hangming Dong, Fei Zou, Shaoxi Cai
Aberrant activation of β-catenin signaling by both WNT-dependent and -independent pathways has been demonstrated in asthmatic airways, which is thought to contribute critically in remodeling of the airways. Yet the exact role of β-catenin in asthma is very poorly defined. As we've previously reported abnormal expression of β-catenin in a toluene diisocyanate (TDI)-induced asthma model, in this study we evaluated the therapeutic efficacy of two small molecules XAV-939 and ICG-001 in TDI-asthmatic male BALB/c mice, which selectively block β-catenin mediated transcription...
September 14, 2016: Allergy
Kyung-Il Kim, Do-Sun Jeong, Eui Chang Jung, Jeung-Hoon Lee, Chang Deok Kim, Tae-Jin Yoon
BACKGROUND: Wnt/β-catenin signaling is important in development and differentiation of melanocytes. OBJECTIVE: The object of this study was to evaluate the effects of several Wnt/β-catenin signaling inhibitors on pigmentation using melanoma cells. METHODS: Melanoma cells were treated with Wnt/β-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked. RESULTS: Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells...
August 20, 2016: Journal of Dermatological Science
Hsiao-Hui Lin, Wen-Chi Feng, Li-Chun Lu, Yu-Yun Shao, Chih-Hung Hsu, Ann-Lii Cheng
Sorafenib, a multikinase inhibitor, is currently the only approved drug for advanced hepatocellular carcinoma (HCC). The current study tested the hypothesis whether inhibition of the Wnt/β-catenin signaling pathway could improve the anti-tumor effects of sorafenib in HCC. ICG-001, a small molecule which blocks the interaction of β-catenin with its transcriptional coactivator CBP, dose-dependently enhanced the growth-suppressive and apoptosis-induction effects of sorafenib in multiple HCC cell lines. Downregulation of β-catenin by RNA interference increased sorafenib sensitivity, whereas overexpression of β-catenin reduced sorafenib sensitivity in Huh7 cells...
October 10, 2016: Cancer Letters
Hye Sung Won, Kyung Mee Lee, Ju Eon Oh, Eun Mi Nam, Kyoung Eun Lee
BACKGROUND: The β-catenin signaling is important in cell growth and differentiation and is frequently dysregulated in various cancers. The most well-known mechanism of endocrine resistance is cross-talk between the estrogen receptor (ER) and other growth factor signaling, such as phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathway. In the present study, we investigated whether β-catenin could be a potential target to overcome endocrine resistance in breast cancer...
2016: PloS One
Michael Bordonaro, Darina Lazarova Lazarova
BACKGROUND: The Wnt signaling pathway, mediated through active beta-catenin, is responsible for initiating the majority of cases of human colorectal cancer (CRC), and we have previously shown that hyperactivation of this pathway by histone deacetylase inhibitors (HDACis), such as butyrate, can induce the death of CRC cells. An important cellular switch that mediates the effects of Wnt-signaling activation is variation in the association between beta-catenin and the transcriptional coactivators cAMP response element binding (CREB) binding protein (CBP) and p300...
2016: JMIR Research Protocols
Przemyslaw Blyszczuk, Björn Müller-Edenborn, Tomas Valenta, Elena Osto, Mara Stellato, Silvia Behnke, Katharina Glatz, Konrad Basler, Thomas F Lüscher, Oliver Distler, Urs Eriksson, Gabriela Kania
AIMS: Myocardial fibrosis critically contributes to cardiac dysfunction in inflammatory dilated cardiomyopathy (iDCM). Activation of transforming growth factor-β (TGF-β) signalling is a key-step in promoting tissue remodelling and fibrosis in iDCM. Downstream mechanisms controlling these processes, remain elusive. METHODS AND RESULTS: Experimental autoimmune myocarditis (EAM) was induced in BALB/c mice with heart-specific antigen and adjuvant. Using heart-inflammatory precursors, as well as mouse and human cardiac fibroblasts, we demonstrated rapid secretion of Wnt proteins and activation of Wnt/β-catenin pathway in response to TGF-β signalling...
April 20, 2016: European Heart Journal
Jian Wang, Zhi-Hong Yang, Hua Chen, Hua-Hui Li, Li-Yong Chen, Zhu Zhu, Ying Zou, Cong-Cong Ding, Jing Yang, Zhi-Wei He
BACKGROUND: Nurr1, a member of the orphan receptor family, plays an important role in several types of cancer. Our previous work demonstrated that increased expression of Nurr1 plays a significant role in the initiation and progression of prostate cancer (PCa), though the mechanisms for regulation of Nurr1 expression remain unknown. In this study, we investigated the hypothesis that Nemo-like kinase (NLK) is a key regulator of Nurr1 expression in PCa. METHODS: Immunohistochemistry and Western blot analysis were used to evaluate levels of NLK and Nurr1 in prostatic tissues and cell lines...
2016: BMC Cancer
Junhua Wang, Yunxia Tao, Zichuan Ping, Wen Zhang, Xuanyang Hu, Yijun Wang, Liangliang Wang, Jiawei Shi, Xiexing Wu, Huilin Yang, Yaozeng Xu, Dechun Geng
Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs)...
2016: Scientific Reports
Xiaomu Guan, Mingang Xu, Sarah E Millar, John D Bartlett
Beta-catenin is a multifunctional protein that plays key roles in cadherin-based cell adherens junctions and in the Wnt signaling pathway. The canonical Wnt/β-catenin pathway can regulate transcription factors that control cell movement/invasion. We investigated whether β-catenin regulates ameloblast movement through canonical Wnt signaling. The morphological and physical properties of enamel were assessed in enamel from control and β-catenin conditional knockout (cKO) mice. Ameloblast-lineage cells (ALC) were used to investigate the potential roles of β-catenin in cell migration and in E-cadherin expression...
June 2016: European Journal of Oral Sciences
Lili Zhou, Youhua Liu
PURPOSE OF REVIEW: Intrarenal activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of hypertension and chronic kidney diseases (CKD). However, how RAS genes are regulated in vivo was poorly understood until recently. This review focuses on recent findings of the transcriptional regulation of RAS components, as well as their implication in developing novel strategies to treat the patients with CKD. RECENT FINDINGS: Bioinformatics analyses have uncovered the presence of putative binding sites for T-cell factor/β-catenin in the promoter region of all RAS genes...
March 2016: Current Opinion in Nephrology and Hypertension
Y Zhao, D Masiello, M McMillian, C Nguyen, Y Wu, E Melendez, G Smbatyan, A Kida, Y He, J-L Teo, M Kahn
CREB-binding protein (CBP) and p300 are highly homologous transcriptional coactivators with unique, non-redundant roles that bind a wide array of proteins, including catenins-β and γ. ICG-001 is a small-molecule inhibitor that specifically inhibits the CBP/catenin interaction. Importantly, ICG-001 does not inhibit the p300/catenin interaction. We demonstrate that specifically inhibiting the interaction between CBP and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells (CML LICs), thereby sensitizing them to BCR-ABL tyrosine kinase inhibitors, for example, Imatinib...
July 14, 2016: Oncogene
Kaile Zhang, Xuran Guo, Weixin Zhao, Guoguang Niu, Xiumei Mo, Qiang Fu
OBJECTIVE: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(L-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo. METHODS: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC)...
2015: International Journal of Molecular Sciences
Liangxiang Xiao, Dong Zhou, Roderick J Tan, Haiyan Fu, Lili Zhou, Fan Fan Hou, Youhua Liu
AKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing AKI to CKD progression are poorly understood. In this study, we investigated this issue using moderate (20 minutes) and severe (30 minutes) ischemia/reperfusion injury (IRI) in mice. Moderate IRI led to acute kidney failure and transient Wnt/β-catenin activation, which was followed by the restoration of kidney morphology and function. However, severe IRI resulted in sustained and exaggerated Wnt/β-catenin activation, which was accompanied by development of renal fibrotic lesions characterized by interstitial myofibroblast activation and excessive extracellular matrix deposition...
June 2016: Journal of the American Society of Nephrology: JASN
Xuejun Kuang, Jiye Zhu, Zhao Peng, Jianjun Wang, Zhigang Chen
BACKGROUND: Recent studies have demonstrated that transducin (beta)-like 1 X-linked receptor 1 (TBLR1) is involved in tumor progression. However, the exact role and clinical significance of TBLR1 in hepatocellular carcinoma (HCC) are poorly understood. AIM: In this study, we aimed to investigate the expression and clinical significance of TBLR1 in HCC. METHODS: Quantitative polymerase chain reaction and immunohistochemical staining were performed to detect the expression levels of TBLR1 in HCC tissue and adjacent noncancerous tissue (ANT)...
February 2016: Digestive Diseases and Sciences
Hiroaki Nomori, Yue Cong, Hiroshi Sugimura
PURPOSES: Sentinel node identification using indocyanine green (ICG) is not only simpler, but also more cost-effective, than using radioisotope tracers. We herein examined the utility and pitfalls of sentinel node (SN) identification using ICG during segmentectomy in patients with cT1N0M0 non-small cell lung cancer (NSCLC). METHODS: ICG was injected around the tumor after thoracotomy, followed by segmentectomy and lymph node dissection, in 135 patients with cT1N0M0 NSCLC...
August 2016: Surgery Today
Monica Parry, Chantelle A Nielson, Fiona Muckle, Sheila O'Keefe-McCarthy, Rene van Lien, Jan H Meijer
BACKGROUND: Heart failure is a complex syndrome associated with sympathetic nervous system and renin-angiotensin-aldosterone system hyperactivity. Sympathoinhibition and downregulation of sympathetic activity using medications and exercise training improve outcomes in patients with heart failure. Impedance cardiography provides data on hemodynamic and autonomic function that may assist with safe medication, exercise monitoring, and titration. PURPOSE: The purpose of this pilot study was to evaluate the sensitivity of the Vrije Universiteit Ambulatory Monitoring System (VU-AMS) version 5fs to detect hemodynamic and sympathetic nervous system changes associated with postural shift in persons with heart failure with reduced ejection fraction...
September 2015: Nursing Research
Fatemeh Moheimani, Hollis M Roth, Jennifer Cross, Andrew T Reid, Furquan Shaheen, Stephanie M Warner, Jeremy A Hirota, Anthony Kicic, Teal S Hallstrand, Michael Kahn, Stephen M Stick, Philip M Hansbro, Tillie-Louise Hackett, Darryl A Knight
The epithelium of asthmatics is characterized by reduced expression of E-cadherin and increased expression of the basal cell markers ck-5 and p63 that is indicative of a relatively undifferentiated repairing epithelium. This phenotype correlates with increased proliferation, compromised wound healing and an enhanced capacity to undergo epithelial-mesenchymal transition (EMT). The transcription factor β-catenin plays a vital role in epithelial cell differentiation and regeneration, depending on the co-factor recruited...
November 2015: International Journal of Biochemistry & Cell Biology
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