keyword
MENU ▼
Read by QxMD icon Read
search

SMO

keyword
https://www.readbyqxmd.com/read/28417299/negative-prognostic-effect-of-low-nuclear-gli1-expression-in-glioblastomas
#1
Yuil Kim, In-Gu Do, Mineui Hong, Yeon-Lim Suh
The hedgehog signaling plays supportive roles in various aspects of tumorigenesis. Increased expression of the key component, GLI1, has been shown to correlate with poor prognosis in many types of cancers. We aimed to investigate the effect of GLI1 expression in glioblastoma focusing on the nuclear localization. Immunohistochemistry for GLI1, GLI2, PTCH1, SMO, and SHH were done in 140 glioblastoma tissues, and the staining was graded. For GLI1, nuclear and cytoplasmic expression was separately assessed. No significant correlation was found between clinicopathologic parameters and expression grades of the five proteins...
April 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28416737/efficacy-of-continuous-egfr-inhibition-and-role-of-hedgehog-in-egfr-acquired-resistance-in-human-lung-cancer-cells-with-activating-mutation-of-egfr
#2
Carminia Maria Della Corte, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Vincenza Ciaramella, Teresa Troiani, Erika Martinelli, Valentina Belli, Fortunato Ciardiello, Floriana Morgillo
PURPOSE: The aim of this work was to investigate the efficacy of sequential treatment with first-, second- and third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer (NSCLC) cell line harboring EGFR activating mutation, with a sequence of first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412740/combination-epidermal-growth-factor-receptor-variant-iii-peptide-pulsed-dendritic-cell-vaccine-with-mir-326-results-in-enhanced-killing-on-egfrviii-positive-cells
#3
Jianlong Li, Feng Wang, Guangzhi Wang, Ying Sun, Jinquan Cai, Xing Liu, Junhe Zhang, Xiaoyan Lu, Yongli Li, Meng Chen, Lingchao Chen, Chuanlu Jiang
The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398255/robust-in-flight-sensor-fault-diagnostics-for-aircraft-engine-based-on-sliding-mode-observers
#4
Xiaodong Chang, Jinquan Huang, Feng Lu
For a sensor fault diagnostic system of aircraft engines, the health performance degradation is an inevitable interference that cannot be neglected. To address this issue, this paper investigates an integrated on-line sensor fault diagnostic scheme for a commercial aircraft engine based on a sliding mode observer (SMO). In this approach, one sliding mode observer is designed for engine health performance tracking, and another for sensor fault reconstruction. Both observers are employed in in-flight applications...
April 11, 2017: Sensors
https://www.readbyqxmd.com/read/28391317/smo-mutant-olfactory-groove-meningiomas-the-next-in-line-for-targeted-therapy
#5
Christopher Alvarez-Breckenridge, Priscilla K Brastianos
No abstract text is available yet for this article.
March 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28390897/identification-and-characterization-of-two-novel-ptch1-splice-variants
#6
Pei Yu, Jinqing Yang, Yan Zhang
Patched-1 (PTCH1), one of the key molecules involved in the Hedgehog (HH) signaling pathway, acts as the receptor of the HH ligand. PTCH1 also inhibits the positive signal transducer Smoothened (SMO). Several PTCH1 splice variants have been identified and confirmed to play critical roles in HH pathway regulation. In the present study, two novel alternatively spliced variants of PTCH1 transcripts, designated PTCH1-Δ10 and PTCH1-Δ15, were found in humans, mice and zebrafish using RT-PCR, direct sequencing and ribonuclease protection assays...
April 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28386950/gastrointestinal-disorders-in-curry-jones-syndrome-clinical-and-molecular-insights-from-an-affected-newborn
#7
Kristen Wigby, Stephen R F Twigg, Ryan Broderick, Katherine P Davenport, Andrew O M Wilkie, Stephen W Bickler, Marilyn C Jones
Curry-Jones syndrome (CJS) is a pattern of malformation that includes craniosynostosis, pre-axial polysyndactyly, agenesis of the corpus callosum, cutaneous and gastrointestinal abnormalities. A recurrent, mosaic mutation of SMO (c.1234 C>T; p.Leu412Phe) causes CJS. This report describes the gastrointestinal and surgical findings in a baby with CJS who presented with abdominal obstruction and reviews the spectrum of gastrointestinal malformations in this rare disorder. A 41-week, 4,165 g, female presented with craniosynostosis, pre-axial polysyndactyly, and cutaneous findings consistent with a clinical diagnosis of CJS...
April 6, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28384344/the-influence-of-the-negative-positive-ratio-and-screening-database-size-on-the-performance-of-machine-learning-based-virtual-screening
#8
Rafał Kurczab, Andrzej J Bojarski
The machine learning-based virtual screening of molecular databases is a commonly used approach to identify hits. However, many aspects associated with training predictive models can influence the final performance and, consequently, the number of hits found. Thus, we performed a systematic study of the simultaneous influence of the proportion of negatives to positives in the testing set, the size of screening databases and the type of molecular representations on the effectiveness of classification. The results obtained for eight protein targets, five machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest), two types of molecular fingerprints (MACCS and CDK FP) and eight screening databases with different numbers of molecules confirmed our previous findings that increases in the ratio of negative to positive training instances greatly influenced most of the investigated parameters of the ML methods in simulated virtual screening experiments...
2017: PloS One
https://www.readbyqxmd.com/read/28379358/loss-of-dynein-2-intermediate-chain-wdr34-results-in-defects-in-retrograde-ciliary-protein-trafficking-and-hedgehog-signaling-in-the-mouse
#9
Chuanqing Wu, Jia Li, Andrew Peterson, Kaixiong Tao, Baolin Wang
The Wdr34 gene encodes an intermediate chain of cytoplasmic dynein 2, the motor for retrograde intraflagellar transport (IFT) in primary cilia. Although mutations in human WDR34 have recently been reported, the association of WDR34 function with Hedgehog (Hh) signaling has not been established, and actual cilia defects in the WDR34 mutant cells have also not been completely characterized. In the present study, we show that Wdr34 mutant mice die in midgestation and exhibit open brain and polydactyly phenotypes...
March 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28363830/hedgehog-signaling-contributes-to-basic-fibroblast-growth-factor-regulated-fibroblast-migration
#10
Zhong Xin Zhu, Cong Cong Sun, Yu Ting Zhu, Ying Wang, Tao Wang, Li Sha Chi, Wan Hui Cai, Jia Yong Zheng, Xuan Zhou, Wei Tao Cong, Xiao Kun Li, Li Tai Jin
Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2...
March 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28360132/dose-dependent-transduction-of-hedgehog-relies-on-phosphorylation-based-feedback-between-the-gpcr-smoothened-and-the-kinase-fused
#11
Matthieu Sanial, Isabelle Bécam, Line Hofmann, Julien Behague, Camilla Argüelles, Vanessa Gourhand, Lucia Bruzzone, Robert A Holmgren, Anne Plessis
Smoothened (SMO) is a GPCR-related protein required for the transduction of Hedgehog (HH). The HH gradient leads to graded phosphorylation of SMO, mainly by the PKA and CKI kinases. How thresholds in HH morphogen regulate SMO to promote switch-like transcriptional responses is a central unsolved issue. Using the wing imaginal disc model in Drosophila, we identified novel SMO phosphosites that enhance the effects of the PKA/CKI kinases on SMO accumulation, its localization at the plasma membrane and its activity...
March 30, 2017: Development
https://www.readbyqxmd.com/read/28359267/aberrant-expression-of-alk-and-ezh2-in-merkel-cell-carcinoma
#12
Tuukka Veija, Virve Koljonen, Tom Bohling, Mia Kero, Sakari Knuutila, Virinder Kaur Sarhadi
BACKGROUND: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC...
March 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28352196/sonidegib-mechanism-of-action-pharmacology-and-clinical-utility-for-advanced-basal-cell-carcinomas
#13
REVIEW
Sachin Jain, Ruolan Song, Jingwu Xie
The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28351866/shh-promotes-direct-interactions-between-epidermal-cells-and-osteoblast-progenitors-to-shape-regenerated-zebrafish-bone
#14
Benjamin E Armstrong, Astra Henner, Scott Stewart, Kryn Stankunas
Zebrafish innately regenerate amputated fins by mechanisms that expand and precisely position injury-induced progenitor cells to re-form tissue of the original size and pattern. For example, cell signaling networks direct osteoblast progenitors (pObs) to rebuild thin cylindrical bony rays with a stereotypical branched morphology. Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed to stimulate overall fin regenerative outgrowth or promote ray branching. Using a photoconvertible patched2 reporter, we resolve active Hh/Smo output to a narrow distal regenerate zone comprising pObs and adjacent motile basal epidermal cells...
April 1, 2017: Development
https://www.readbyqxmd.com/read/28350784/targeting-smoothened-sensitizes-gastric-cancer-to-chemotherapy-in-experimental-models
#15
Huifa Ma, Yongsheng Tian, Xiangyang Yu
BACKGROUND The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. MATERIAL AND METHODS We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous syngeneic mouse models. RESULTS We found high SMO expression in paclitaxel-resistant gastric cancer clinical samples...
March 28, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28344083/cholesterol-modification-of-smoothened-is-required-for-hedgehog-signaling
#16
Xu Xiao, Jing-Jie Tang, Chao Peng, Yan Wang, Lin Fu, Zhi-Ping Qiu, Yue Xiong, Lian-Fang Yang, Hai-Wei Cui, Xiao-Long He, Lei Yin, Wei Qi, Catherine C L Wong, Yun Zhao, Bo-Liang Li, Wen-Wei Qiu, Bao-Liang Song
Hedgehog (Hh) has been known as the only cholesterol-modified morphogen playing pivotal roles in development and tumorigenesis. A major unsolved question is how Hh signaling regulates the activity of Smoothened (SMO). Here, we performed an unbiased biochemical screen and identified that SMO was covalently modified by cholesterol on the Asp95 (D95) residue through an ester bond. This modification was inhibited by Patched-1 (Ptch1) but enhanced by Hh. The SMO(D95N) mutation, which could not be cholesterol modified, was refractory to Hh-stimulated ciliary localization and failed to activate downstream signaling...
April 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28330163/probing-an-optimal-class-distribution-for-enhancing-prediction-and-feature-characterization-of-plant-virus-encoded-rna-silencing-suppressors
#17
Abhigyan Nath, Karthikeyan Subbiah
To counter the host RNA silencing defense mechanism, many plant viruses encode RNA silencing suppressor proteins. These groups of proteins share very low sequence and structural similarities among them, which consequently hamper their annotation using sequence similarity-based search methods. Alternatively the machine learning-based methods can become a suitable choice, but the optimal performance through machine learning-based methods is being affected by various factors such as class imbalance, incomplete learning, selection of inappropriate features, etc...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28318003/small-molecule-hedgehog-pathway-antagonists
#18
Trieu N Trinh, Eileen A McLaughlin, Christopher P Gordon, Ilana R Bernstein, Victoria J Pye, Kate A Redgrove, Adam McCluskey
Leveraging our quinolone-1-(2H)-one based Hedgehog signalling pathway (HSP) inhibitors we have developed two new classes of HSP inhibitors based on: l-tryptophan and benzo[1,3]dioxol-5-ylmethyl-[2-(1H-indol-3-yl)-ethyl]-amine. Synthesis of focused compound libraries identified six l-tryptophan based inhibitors, and two stimulators, of Gli at 10 μM compound concentration. 2,4-Dichloro-13 and indole 16 suppressed mRNA expression of Ptch1 in Shh LIGHT2 cells, with 13 suppressing and 16 stimulating Gli2 mRNA expression...
March 20, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#19
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#20
Harleen Khatra, Chandra Bose, Surajit Sinha
BACKGROUND: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly...
March 16, 2017: Current Medicinal Chemistry
keyword
keyword
90922
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"