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https://www.readbyqxmd.com/read/28716052/%C3%AE-arrestin1-mediated-acetylation-of-gli1-regulates-hedgehog-gli-signaling-and-modulates-self-renewal-of-shh-medulloblastoma-cancer-stem-cells
#1
Evelina Miele, Agnese Po, Federica Begalli, Laura Antonucci, Angela Mastronuzzi, Carlo Efisio Marras, Andrea Carai, Danilo Cucchi, Luana Abballe, Zein Mersini Besharat, Giuseppina Catanzaro, Paola Infante, Lucia Di Marcotullio, Gianluca Canettieri, Enrico De Smaele, Isabella Screpanti, Franco Locatelli, Elisabetta Ferretti
BACKGROUND: Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326...
July 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28704552/ptch1-is-a-reliable-marker-for-predicting-imatinib-response-in-chronic-myeloid-leukemia-patients-in-chronic-phase
#2
Juan M Alonso-Dominguez, Luis Felipe Casado, Eduardo Anguita, Maria Teresa Gomez-Casares, Ismael Buño, Francisca Ferrer-Marín, Alicia Arenas, Rafael Del Orbe, Rosa Ayala, Pilar Llamas, Rocio N Salgado, Santiago Osorio, Pedro Sanchez-Godoy, Carmen Burgaleta, Ignacio Mahíllo-Fernández, Valentin Garcia-Gutierrez, Juan Luis Steegmann, Joaquín Martinez-Lopez
Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened (SMO) expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML) patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP) using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0...
2017: PloS One
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#3
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28675107/inhibition-of-hedgehog-pathway-reveals-the-regulatory-role-of-smo-in-gastric-cancer-cells
#4
Zixin Yang, Yingqian Lv, Long Wang, Yong Chen, Jinzhu Han, Shan Zhao, Wei Liu
Previous studies report aberrant activation of the hedgehog signaling pathway in the progression of various cancers. This study aimed to investigate the expressions of smoothened and downstream glioma-associated oncogene homology-1 in gastric cancer and the underlying molecular mechanisms. Here, we first detected the expression in 58 cases of primary gastric cancer tissue and matched normal tissue specimens by western blot analysis and quantitative reverse transcription polymerase chain reaction. Cell proliferation and cycle were assayed in gastric cancer cells after blocking the hedgehog pathway by lentiviral-short hairpin RNA knockdown...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28667508/laser-irradiation-promotes-the-proliferation-of-mouse-pre-osteoblast-cell-line-mc3t3-e1-through-hedgehog-signaling-pathway
#5
Qiushi Li, Yingxin Chen, Shujun Dong, Shujie Liu, Xiaodan Zhang, Xi Si, Yanmin Zhou
Low-level laser could promote osteoblast proliferation, and it has been applied in clinical practice to promote wound healing and tissue regeneration. However, the mechanism related to laser irradiation remains unclear. This study aimed to investigate the effects of low-level laser irradiation on the cell proliferation and the expressions of hedgehog signaling molecules Indian hedgehog (Ihh), Ptch, and Gli in vitro. In our present study, the MTT method was used to evaluate the effect on cell proliferation of laser irradiation on MC3T3-E1 cells...
July 1, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28664688/socio-demographic-factors-related-to-under-diagnosis-of-childhood-asthma-in-upper-silesia-poland
#6
Jan E Zejda, Małgorzata Farnik, Irena Smółka, Joshua Lawson, Grzegorz M Brożek
<b>Introduction.</b> The presented study of 4,535 children aged 7-17 years in the Upper Silesian region of Poland yielded 186 cases of previously known asthma, and 44 children with newly diagnosed asthma. The aim of the presented study was to identify non-medical factors that could explain why children with a newly established diagnosis ('undiagnosed asthma') had not been diagnosed in the past. <b>Materials and method.</b> The study was performed according to a case-control design. Parents of the children answered questionnaires on socio-economic status and family-related factors...
June 7, 2017: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/28652248/gli1-blockade-potentiates-the-antitumor-activity-of-pi3k-antagonists-in-lung-squamous-cell-carcinoma
#7
Sahba Kasiri, Chunli Shao, Baozhi Chen, Alexandra N Wilson, Paul Yenerall, Brenda C Timmons, Luc Girard, Hui Tian, Carmen Behrens, Ignacio I Wistuba, Adi F Gazdar, James Kim
Lung squamous cell carcinoma (SCC), strongly associated with smoking, is treated primarily with traditional cytotoxic chemotherapy due to a lack of FDA-approved targeted agents available. Here we identify the Hedgehog pathway transcription factor GLI1 as a critical driver of lung SCC. Analysis of human lung cancer datasets showed that GLI1 mRNA was highly expressed in human lung SCC and portended a poor prognosis. Inhibition of GLI1 in human lung SCC cell lines suppressed tumor cell clonogenicity and proliferation in culture and in vivo...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28631844/sonic-hedgehog-wnt-and-brain-derived-neurotrophic-factor-cell-signaling-pathway-crosstalk-potential-therapy-for-depression
#8
REVIEW
Mohd Tayyab, Mehdi H Shahi, Shirin Farheen, Mubeena P M Mariyath, Nabeela Khanam, Javier S Castresana, M Mobarak Hossain
There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28630165/the-cell-adhesion-molecule-chl1-interacts-with-patched-1-to-regulate-apoptosis-during-postnatal-cerebellar-development
#9
Jelena Katic, Gabriele Loers, Jelena Tosic, Melitta Schachner, Ralf Kleene
The immunoglobulin superfamily adhesion molecule close homolog of L1 (CHL1) plays important roles during nervous system development. Here, we identified the hedgehog receptor patched-1 (PTCH1) as novel CHL1 binding partner and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Co-localization and -immunoprecipitation of CHL1 with PTCH1 suggest an association of CHL1 with this major component of the hedgehog signaling pathway. The trans-interaction of CHL1 with PTCH1 promotes neuronal survival in cultures of dissociated cerebellar granule cells and of organotypic cerebellar slices...
June 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28629394/validating-the-who-maternal-near-miss-tool-comparing-high-and-low-resource-settings
#10
Tom Witteveen, Hans Bezstarosti, Ilona de Koning, Ellen Nelissen, Kitty W Bloemenkamp, Jos van Roosmalen, Thomas van den Akker
BACKGROUND: WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. METHODS: Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria)...
June 19, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28626616/discrimination-of-picea-chihuahuana-martinez-populations-on-the-basis-of-climatic-edaphic-dendrometric-genetic-and-population-traits
#11
Iliana Karina Dominguez-Guerrero, Samantha Del Rocío Mariscal-Lucero, José Ciro Hernández-Díaz, Berthold Heinze, José Ángel Prieto-Ruiz, Christian Wehenkel
BACKGROUND: Picea chihuahuana, which is endemic to Mexico, is currently listed as "Endangered" on the Red List. Chihuahua spruce is only found in the Sierra Madre Occidental (SMO), Mexico. About 42,600 individuals are distributed in forty populations. These populations are fragmented and can be classified into three geographically distinct clusters in the SMO. The total area covered by P. chihuahuana populations is less than 300 ha. A recent study suggested assisted migration as an alternative to the ex situ conservation of P...
2017: PeerJ
https://www.readbyqxmd.com/read/28624712/classification-of-ecg-heartbeats-using-nonlinear-decomposition-methods-and-support-vector-machine
#12
Kandala N V P S Rajesh, Ravindra Dhuli
Classifying electrocardiogram (ECG) heartbeats for arrhythmic risk prediction is a challenging task due to minute variations in the amplitude, duration and morphology of the ECG signal. In this paper, we propose two feature extraction approaches to classify five types of heartbeats: normal, premature ventricular contraction, atrial premature contraction, left bundle branch block and right bundle branch block. In the first approach, ECG beats are decomposed into intrinsic mode functions (IMFs) using ensemble empirical mode decomposition (EEMD)...
June 15, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28618514/dynamics-of-a-bistable-miura-origami-structure
#13
Hongbin Fang, Suyi Li, Huimin Ji, K W Wang
Origami-inspired structures and materials have shown extraordinary properties and performances originating from the intricate geometries of folding. However, current state of the art studies have mostly focused on static and quasistatic characteristics. This research performs a comprehensive experimental and analytical study on the dynamics of origami folding through investigating a stacked Miura-Ori (SMO) structure with intrinsic bistability. We fabricate and experimentally investigated a bistable SMO prototype with rigid facets and flexible crease lines...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28618224/design-synthesis-and-structure-activity-relationship-of-tetrahydropyrido-4-3-d-pyrimidine-derivatives-as-potent-smoothened-antagonists-with-in-vivo-activity
#14
Wenfeng Lu, Yongqiang Liu, Haikuo Ma, Jiyue Zheng, Sheng Tian, Zhijian Sun, Lusong Luo, Jiajun Li, Hongjian Zhang, Zeng-Jie Yang, Xiaohu Zhang
Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its nonlinear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility...
June 30, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28611043/arl13b-promotes-gastric-tumorigenesis-by-regulating-smo-trafficking-and-activation-of-the-hedgehog-signaling-pathway
#15
Jia Shao, Linlin Xu, Limin Chen, Quqin Lu, Xinsheng Xie, Wei Shi, Huanting Xiong, Chao Shi, Xuan Huang, Jinhong Mei, Hai Rao, Hua Lu, Nonghua Lu, Shiwen Luo
Inhibitors of the Hedgehog (Hh) pathway transducer Smoothened (Smo) have been approved for cancer treatment, but Smo mutations often lead to tumor resistance and it remains unclear how Smo is regulated. In this study, we identified the small GTPase Arl13b as a novel partner and regulator of Smo. Arl13b regulated Smo stability, trafficking and localization which are each crucial for Hh signaling. In gastric cancer cells, Arl13b stimulated proliferation, migration and invasion in vitro and in vivo. In clinical specimens of gastric cancer, Arl13b expression correlated strongly with tumor size and depth of invasion; patients with high levels of Arl13b had a poor prognosis...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28599282/optimizing-a-machine-learning-based-glioma-grading-system-using-multi-parametric-mri-histogram-and-texture-features
#16
Xin Zhang, Lin-Feng Yan, Yu-Chuan Hu, Gang Li, Yang Yang, Yu Han, Ying-Zhi Sun, Zhi-Cheng Liu, Qiang Tian, Zi-Yang Han, Le-De Liu, Bin-Quan Hu, Zi-Yu Qiu, Wen Wang, Guang-Bin Cui
Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591947/-inhibition-of-cigarettes-smoke-induced-epithelial-to-mesenchymal-transition-by-the-smo-inhibitor-pf-5274857-in-beas-2b-epithelial-cells
#17
Wen-Jie Zhou, Jiao Chen, Yun Feng, Ya-Ping Fan, Qian Li, Jian Fu, Ping Zhang
OBJECTIVES: To explore the effects of the Smoothened (Smo) inhibitor PF-5274857 on cigarette smoke (CS)-induced epithelial-mesenchymal transition (EMT) and apply a new idea fororal squamous cell carcinoma (OSCC) treatment. METHODS: Beas-2b cells were used to investigate the CS-induced EMT. Both pretreat and post-treat were performed in the study. In pretreat group, after being pretreated with 3 μmol/L PF-5274857 for 2 h, cells were cultured with CS for 8 d; In post-treat group, cells were treated by 3 μmol/L PF-5274857 for 4 d after CS cultrue...
July 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28591579/sonic-hedgehog-activates-phospholipase-a2-to-enhance-smoothened-ciliary-translocation
#18
Angela M Arensdorf, Miriam E Dillard, Jacob M Menke, Matthew W Frank, Charles O Rock, Stacey K Ogden
The G protein-coupled receptor Smoothened (Smo) is the signal transducer of the Sonic Hedgehog (Shh) pathway. Smo signals through G protein-dependent and -independent routes, with G protein-independent canonical signaling to Gli effectors requiring Smo accumulation in the primary cilium. The mechanisms controlling Smo activation and trafficking are not yet clear but likely entail small-molecule binding to pockets in its extracellular cysteine-rich domain (CRD) and/or transmembrane bundle. Here, we demonstrate that the cytosolic phospholipase cPLA2α is activated through Gβγ downstream of Smo to release arachidonic acid...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588207/capping-enzyme-mrna-cap-rngtt-regulates-hedgehog-pathway-activity-by-antagonizing-protein-kinase-a
#19
Ping Chen, Zizhang Zhou, Xia Yao, Shu Pang, Meijing Liu, Weirong Jiang, Jin Jiang, Qing Zhang
Hedgehog (Hh) signaling plays a pivotal role in animal development and its deregulation in humans causes birth defects and several types of cancer. Protein Kinase A (PKA) modulates Hh signaling activity through phosphorylating the transcription factor Cubitus interruptus (Ci) and G protein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is regulated remains elusive. Here, we identify a novel regulator of the Hh pathway, the capping-enzyme mRNA-cap, which positively regulates Hh signaling activity through modulating PKA activity...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28581526/the-role-of-canonical-and-non-canonical-hedgehog-signaling-in-tumor-progression-in-a-mouse-model-of-small-cell-lung-cancer
#20
A Szczepny, S Rogers, W S N Jayasekara, K Park, R A McCloy, C R Cochrane, V Ganju, W A Cooper, J Sage, C D Peacock, J E Cain, A Burgess, D N Watkins
Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations...
June 5, 2017: Oncogene
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