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https://www.readbyqxmd.com/read/28323557/seroprevalence-of-severe-fever-with-thrombocytopenia-syndrome-virus-in-hedgehog-from-china
#1
Yue Sun, Miao-Miao Liu, Li-Mei Luo, Li Zhao, Hong-Ling Wen, Zhen-Tang Zhang, Jian-Wei Liu, Zai-Feng Xue, Dong-Qiang Ma, Shu-Jun Ding, Xiao-Ying Lei, Xue-Jie Yu
Severe fever with thrombocytopenia syndrome, an emerging hemorrhagic fever, is caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne bunyavirus. Information regarding SFTSV animal hosts is very limited. In this study, we showed that 64% (9/14) of hedgehogs in Shandong Province, China were seropositive to SFTSV antibody, suggesting that hedgehog could be a vertebrate parasitifer for SFTSV.
March 21, 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28318003/small-molecule-hedgehog-pathway-antagonists
#2
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/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#3
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
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
#4
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/28314894/development-of-anticancer-agents-targeting-the-hedgehog-signaling
#5
REVIEW
Xiangqian Zhang, Ye Tian, Yanling Yang, Jijun Hao
Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment. Here, we review the therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#6
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
https://www.readbyqxmd.com/read/28300473/cells-on-the-move-modulation-of-guidance-cues-during-germ-cell-migration
#7
Girish Deshpande, Justinn Barr, Offer Gerlitz, Lyubov Lebedeva, Yulii Shidlovskii, Paul Schedl
In Drosophila melanogaster the progenitors of the germ-line stem cells, the primordial germ cells (PGCs) are formed on the outside surface of the early embryo, while the somatic gonadal precursor cells (SGPs) are specified during mid-embryogenesis. To form the primitive embryonic gonad, the PGCs travel from outside of the embryo, across the mid-gut and then migrate through the mesoderm to the SGPs. The migratory path of PGCs is dictated by a series of attractive and repulsive cues. Studies in our lab have shown that one of the key chemoattractants is the Hedgehog (Hh) ligand...
March 16, 2017: Fly
https://www.readbyqxmd.com/read/28298319/analysis-of-axonal-trafficking-via-a-novel-live-imaging-technique-reveals-distinct-hedgehog-transport-kinetics
#8
Joseph R Daniele, Rehan M Baqri, Samuel Kunes
The Drosophila melanogaster (Dmel) eye is an ideal model to study development, intracellular signaling, behavior, and neurodegenerative disease. Interestingly, dynamic data is not commonly employed to investigate eye-specific disease models. Using axonal transport of the morphogen Hedgehog (Hh), which is integral to Dmel eye-brain development and implicated in stem cell maintenance and neoplastic disease, we demonstrate the ability to comprehensively quantify and characterize its trafficking in various neuron types and a neurodegeneration model in live early 3(rd) instar larval Drosophila We find that neuronal Hh, whose kinetics have not been reported previously, favors fast anterograde transport and varies in speed and flux with respect to axonal position...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28298318/a-novel-proteolytic-event-controls-hedgehog-intracellular-sorting-and-distribution-to-receptive-fields
#9
Joseph R Daniele, Tehyen Chu, Sam Kunes
The patterning activity of a morphogen depends on secretion and dispersal mechanisms that shape its distribution to the cells of a receptive field. In the case of the protein Hedgehog (Hh), these mechanisms of secretion and transmission remain unclear. In the developing Drosophila visual system, Hedgehog is partitioned for release at opposite poles of photoreceptor neurons. Release into the retina regulates the progression of eye development; axon transport and release at axon termini trigger the development of postsynaptic neurons in the brain...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28297142/vismodegib-therapy-for-basal-cell-carcinoma-in-an-8-year-old-chinese-boy-with-xeroderma-pigmentosum
#10
Douglas Fife, Marko A Laitinen, David J Myers, Pamela B Landsteiner
Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance...
March 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28296537/microfluidic-mobility-shift-assay-for-real-time-analysis-of-peptide-n-palmitoylation
#11
Thomas Lanyon-Hogg, Neki V Patel, Markus Ritzefeld, Katherine J Boxall, Rosemary Burke, Julian Blagg, Anthony I Magee, Edward W Tate
The Hedgehog pathway is a key developmental signaling pathway but is also implicated in many types of cancer. The extracellular signaling protein Sonic hedgehog (Shh) requires dual lipidation for functional signaling, whereby N-terminal palmitoylation is performed by the enzyme Hedgehog acyltransferase (Hhat). Hhat is an attractive target for small-molecule inhibition to arrest Hedgehog signaling, and methods for assaying Hhat activity are central to understanding its function. However, all existing assays to quantify lipidation of peptides suffer limitations, such as safety hazards, high costs, extensive manual handling, restriction to stopped-assay measurements, or indirect assessment of lipidation...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28293554/sonic-hedgehog-signaling-in-limb-development
#12
REVIEW
Cheryll Tickle, Matthew Towers
The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28291807/the-meckel-syndrome-associated-protein-mks1-functionally-interacts-with-components-of-the-bbsome-and-ift-complexes-to-mediate-ciliary-trafficking-and-hedgehog-signaling
#13
Sarah C Goetz, Fiona Bangs, Chloe L Barrington, Nicholas Katsanis, Kathryn V Anderson
The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28286175/cilia-dependent-gli-processing-in-neural-crest-cells-is-required-for-tongue-development
#14
Grethel Millington, Kelsey Elliott, Ya-Ting Chang, Ching-Fang Chang, Andrzej Dlugosz, Samantha A Brugmann
Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3a(f/f);Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3a(f/f);Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage...
March 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28286127/hedgehog-signaling-from-basic-biology-to-cancer-therapy
#15
REVIEW
Fujia Wu, Yu Zhang, Bo Sun, Andrew P McMahon, Yu Wang
The Hedgehog (HH) signaling pathway was discovered originally as a key pathway in embryonic patterning and development. Since its discovery, it has become increasingly clear that the HH pathway also plays important roles in a multitude of cancers. Therefore, HH signaling has emerged as a therapeutic target of interest for cancer therapy. In this review, we provide a brief overview of HH signaling and the key molecular players involved and offer an up-to-date summary of our current knowledge of endogenous and exogenous small molecules that modulate HH signaling...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28282054/hedgehogs-and-foxes-and-a-bear
#16
Bruce Gibb
No abstract text is available yet for this article.
January 24, 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28281543/egfr-arf6-regulation-of-hh-signalling-stimulates-oncogenic-ras-tumour-overgrowth
#17
Chiswili Chabu, Da-Ming Li, Tian Xu
Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling...
March 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28280721/tissue-biomarkers-in-hepatocellular-tumors-which-when-and-how
#18
REVIEW
Luca Di Tommaso, Massimo Roncalli
Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28277836/approaches-for-targeting-self-renewal-pathways-in-cancer-stem-cells-implications-for-haematological-treatments
#19
Gillian A Horne, Mhairi Copland
Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas Covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP...
March 6, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28276480/selective-targeting-of-hdac1-2-elicits-anticancer-effects-through-gli1-acetylation-in-preclinical-models-of-shh-medulloblastoma
#20
Sonia Coni, Anna Barbara Mancuso, Laura Di Magno, Giulia Sdruscia, Simona Manni, Silvia Maria Serrao, Dante Rotili, Eleonora Spiombi, Francesca Bufalieri, Marialaura Petroni, Monika Kusio-Kobialka, Enrico De Smaele, Elisabetta Ferretti, Carlo Capalbo, Antonello Mai, Pawel Niewiadomski, Isabella Screpanti, Lucia Di Marcotullio, Gianluca Canettieri
SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach...
March 9, 2017: Scientific Reports
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