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https://www.readbyqxmd.com/read/28218785/inhibition-of-shh-pathway-mechanisms-by-arsenic-trioxide-in-pediatric-medulloblastomas-a-comprehensive-literature-review
#1
P H S Klinger, A F Andrade, L E A Delsin, R G P Queiroz, C A Scrideli, L G Tone, E T Valera
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28215635/mechanical-stimulation-promote-the-osteogenic-differentiation-of-bone-marrow-stromal-cells-through-epigenetic-regulation-of-sonic-hedgehog
#2
Chuandong Wang, Shengzhou Shan, Chenglong Wang, Jing Wang, Jiao Li, Guoli Hu, Kerong Dai, Qingfeng Li, Xiaoling Zhang
Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#3
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28207535/an-investigation-of-obesity-susceptibility-genes-in-northern-han-chinese-by-targeted-resequencing
#4
Yili Wu, Weijing Wang, Wenjie Jiang, Jie Yao, Dongfeng Zhang
Our earlier genome-wide linkage study of body mass index (BMI) showed strong signals from 7q36.3 and 8q21.13. This case-control study set to investigate 2 genomic regions which may harbor variants contributed to development of obesity.We employed targeted resequencing technology to detect single nucleotide polymorphisms (SNPs) in 7q36.3 and 8q21.13 from 16 individuals with obesity. These were compared with 504 East Asians in the 1000 Genomes Project as a reference panel. Linkage disequilibrium (LD) block analysis was performed for the significant SNPs located near the same gene...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28205381/the-clinical-significance-of-equivocal-findings-on-spinal-mri-in-children-with-medulloblastoma
#5
Julie Bennett, Ramy Ashmawy, Vijay Ramaswamy, Derek Stephens, Eric Bouffet, Normand Laperriere, Michael Taylor, Manohar Shroff, Ute Bartels
BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification...
February 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28205287/upstream-regulation-for-initiation-of-restricted-shh-expression-in-the-chick-limb-bud
#6
Haruka Matsubara, Daisuke Saito, Gembu Abe, Hitoshi Yokoyama, Takayuki Suzuki, Koji Tamura
Background The organizing center, which serves as a morphogen source, has crucial functions in morphogenesis in animal development. The center is necessarily located in a certain restricted area in the morphogenetic field, and there are several ways in which an organizing center can be restricted. The organizing center for limb morphogenesis, the ZPA (zone of polarizing activity), specifically expresses the Shh gene and is restricted to the posterior region of the developing limb bud. Results The prepattern along the limb antero-posterior axis, provided by anterior Gli3 expression and posterior Hand2 expression, seems insufficient for the initiation of Shh expression restricted to a narrow, small spot in the posterior limb field...
February 16, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28202523/cancer-stem-cells-regulate-cancer-associated-fibroblasts-via-activation-of-hedgehog-signaling-in-mammary-gland-tumors
#7
Giovanni Valenti, Hazel M Quinn, Guus Jje Heynen, Linxiang Lan, Jane D Holland, Regina Vogel, Annika Wulf-Goldenberg, Walter Birchmeier
Many tumors display intracellular heterogeneity, with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here we investigated the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secreted the hedgehog ligand SHH, which regulated CAFs via paracrine activation of Hedgehog signaling...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196803/neural-tube-closure-cellular-molecular-and-biomechanical-mechanisms
#8
REVIEW
Evanthia Nikolopoulou, Gabriel L Galea, Ana Rolo, Nicholas D E Greene, Andrew J Copp
Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28195165/smoothened-is-a-poor-prognosis-factor-and-a-potential-therapeutic-target-in-glioma
#9
Yiming Tu, Mingshan Niu, Peng Xie, Chenglong Yue, Ning Liu, Zhenglei Qi, Shangfeng Gao, Hongmei Liu, Qiong Shi, Rutong Yu, Xuejiao Liu
Malignant gliomas are associated with a high mortality rate. Thus, there is an urgent need for the development of novel targeted therapeutics. Aberrant Hedgehog signaling has been directly linked to glioma. GDC-0449 is a novel small molecule inhibitor of Hedgehog signaling that blocks the activity of smoothened (Smo). In this study, we evaluated the in vitro and in vivo effects of the smoothened inhibitor GDC-0449 on cell proliferation in human gliomas. We found that high expression of smoothened in glioma is a predictor of short overall survival and poor patient outcome...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195124/pervasive-translational-regulation-of-the-cell-signalling-circuitry-underlies-mammalian-development
#10
Kotaro Fujii, Zhen Shi, Olena Zhulyn, Nicolas Denans, Maria Barna
The degree and dynamics of translational control during mammalian development remain poorly understood. Here we monitored translation of the mammalian genome as cells become specified and organize into tissues in vivo. This identified unexpected and pervasive translational regulation of most of the core signalling circuitry including Shh, Wnt, Hippo, PI3K and MAPK pathways. We further identify and functionally characterize a complex landscape of upstream open reading frames (uORFs) across 5'-untranslated regions (UTRs) of key signalling components...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194541/undermining-plastic-surgery-as-a%C3%A2-possible-option-for-treating-basal-cell-carcinoma-of-the-forehead
#11
Georgi Tchernev, Ivan Pidakev, Ilia Lozev, Torello Lotti, Jose Carlos Cardoso, James W Patterson
Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib...
February 13, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28188758/a-role-for-the-hedgehog-effector-gli1-in-mediating-stent-induced-ureteral-smooth-muscle-dysfunction-and-aperistalsis
#12
Claudia Janssen, Ralph Buttyan, Chun Y Seow, Wolfgang Jäger, Dennis Solomon, Ladan Fazli, Ben H Chew, Dirk Lange
OBJECTIVES: To better understand the effects of Double J (JJ) stenting on ureteral physiology and function. MATERIALS AND METHODS: In total, twenty-four pigs (24) were stented cystoscopically unilaterally for 48h, 1, 2, 4 and 7 wks. Controls consisted of un-stented animals (n=4) or the contralateral un-stented ureter in pigs. Ureters were harvested and tested in tissue baths to evaluate their contractility. Ureteral inflammation and expression of Sonic Hedgehog (Shh) and the transcriptional activator Gli1 (the downstream target of active HH signaling) were assessed histologically and by immunohistochemistry, respectively...
February 8, 2017: Urology
https://www.readbyqxmd.com/read/28187190/widespread-gli-expression-but-limited-canonical-hedgehog-signaling-restricted-to-the-ductular-reaction-in-human-chronic-liver-disease
#13
Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng, Nicholas Adam Shackel, Devanshi Seth, David Geoffrey Bowen, Luciano Gastón Martelotto, D Neil Watkins, Geoffrey William McCaughan
Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations...
2017: PloS One
https://www.readbyqxmd.com/read/28185928/biologically-active-and-biomimetic-dual-gelatin-scaffolds-for-tissue-engineering
#14
P Sánchez, J L Pedraz, G Orive
We have designed, developed and optimized Genipin cross-linked 3D gelatin scaffolds that were biologically active and biomimetic, show a dual activity both for growth factor and cell delivery. Type B gelatin powder was dissolved in DI water. 100mg of genipin was dissolved in 10ml of DI water. Three genipin concentrations were prepared: 0.1%, 0.2% and 0.3% (w/v). Solutions were mixed at 40°C and under stirring and then left crosslinking for 72h. Scaffolds were obtained by punching 8 mm-cylinders into ethanol 70% solution for 10min and then freeze-drying...
February 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28170441/cerebrospinal-fluid-from-patients-with-amyotrophic-lateral-sclerosis-inhibits-sonic-hedgehog-function
#15
Anna Drannik, Joan Martin, Randy Peterson, Xiaoxing Ma, Fan Jiang, John Turnbull
Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterized by selective loss of motor neurons due to poorly understood mechanisms. Evidence indicates that Shh might play an important role in ALS, and that Shh signaling might be also adversely affected in ALS...
2017: PloS One
https://www.readbyqxmd.com/read/28169282/anti-apoptotic-effects-of-sonic-hedgehog-signalling-through-oxidative-stress-reduction-in-astrocytes-co-cultured-with-excretory-secretory-products-of-larval-angiostrongylus-cantonensis
#16
Kuang-Yao Chen, Cheng-Hsun Chiu, Lian-Chen Wang
Angiostrongylus cantonensis, the rat lungworm, is an important aetiologic agent of eosinophilic meningitis and meningoencephalitis in humans. Co-culturing astrocytes with soluble antigens of A. cantonensis activated the Sonic hedgehog (Shh) signalling pathway and inhibited the apoptosis of astrocytes via the activation of Bcl-2. This study was conducted to determine the roles of the Shh signalling pathway, apoptosis, and oxidative stress in astrocytes after treatment with excretory-secretory products (ESP) from A...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161524/john-saunders-zpa-sonic-hedgehog-and-digit-identity-how-does-it-really-all-work
#17
REVIEW
Jianjian Zhu, Susan Mackem
Among John Saunders' many seminal contributions to developmental biology, his discovery of the limb 'zone of polarizing activity' (ZPA) is arguably one of the most memorable and ground-breaking. This discovery introduced the limb as a premier model for understanding developmental patterning and promoted the concept of patterning by a morphogen gradient. In the 50 years since the discovery of the ZPA, Sonic hedgehog (Shh) has been identified as the ZPA factor and the basic components of the signaling pathway and many aspects of its regulation have been elucidated...
February 2, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28159923/the-anti-neoplastic-activity-of-vandetanib-against-high-risk-medulloblastoma-variants-is-profoundly-enhanced-by-additional-pi3k-inhibition
#18
Rogerio B Craveiro, Michael Ehrhardt, Julia Velz, Martin Olschewski, Barbara Goetz, Torsten Pietsch, Dagmar Dilloo
Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28159470/hedgehog-pathway-plays-a-vital-role-in-hiv-induced-epithelial-mesenchymal-transition-of-podocyte
#19
Xiqian Lan, Hongxiu Wen, Kang Cheng, Andrei Plagov, Seyedeh Shadafarin Marashi Shoshtari, Ashwani Malhotra, Pravin C Singhal
HIV-associated nephropathy (HIVAN) is characterized by heavy proteinuria, rapidly progressive renal failure, and distinct morphological features in the kidney. HIV-induced epithelial-mesenchymal transition (EMT) is critically important for the progression of kidney injury. In this study, we tested the role of hedgehog pathway in the HIV-induced EMT and fibrosis of kidney. We used the Tg26 mice, the abundantly used HIVAN mouse model, to investigate the activation of hedgehog pathway by HIV. Western blotting and real time PCR results showed that renal tissue expression of hedgehog pathway related molecules, including hedgehog homologous (Shh, Ihh, Dhh), PTCH, and Gli1, were increased in HIVAN (Tg26) mice; while immunofluorescent staining displayed localization PTCH expression in podocytes...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28155855/evolution-of-shh-endoderm-enhancers-during-morphological-transition-from-ventral-lungs-to-dorsal-gas-bladder
#20
Tomoko Sagai, Takanori Amano, Akiteru Maeno, Tetsuaki Kimura, Masatoshi Nakamoto, Yusuke Takehana, Kiyoshi Naruse, Norihiro Okada, Hiroshi Kiyonari, Toshihiko Shiroishi
Shh signalling plays a crucial role for endoderm development. A Shh endoderm enhancer, MACS1, is well conserved across terrestrial animals with lungs. Here, we first show that eliminating mouse MACS1 causes severe defects in laryngeal development, indicating that MACS1-directed Shh signalling is indispensable for respiratory organogenesis. Extensive phylogenetic analyses revealed that MACS1 emerged prior to the divergence of cartilaginous and bony fishes, and even euteleost fishes have a MACS1 orthologue. Meanwhile, ray-finned fishes evolved a novel conserved non-coding sequence in the neighbouring region...
February 3, 2017: Nature Communications
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