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https://www.readbyqxmd.com/read/27905054/crosstalk-between-shh-and-stemness-state-signaling-pathways-in-esophageal-squamous-cell-carcinoma
#1
Maryam Najafi, Mohammad Reza Abbaszadegan, Abolfazl Rad, Mahtab Dastpak, Samaneh Boroumand-Noughabi, Mohammad Mahdi Forghanifard
The expression of GLI1 as a downstream gene of sonic hedgehog (Hh) pathway, studied in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, the interaction of Hh with other developmental pathways needs to be elucidated. In this study, we aimed to investigate the correlation of GLI1 expression with transcription factors (TFs) of stem cell signaling pathways, and their association with clinico-pathological data of ESCC. Using real-time PCR, we assessed the expression of GLI1 mRNA in 49 ESCC patients, and analyzed the correlation between GLI1 and selected TFs...
November 30, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27903126/potential-evolution-of-neurosurgical-treatment-paradigms-for-craniopharyngioma-based-on-genomic-and-transcriptomic-characteristics
#2
Leslie C Robinson, Sandro Santagata, Todd C Hankinson
The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27899509/sensory-evolution-in-blind-cavefish-is-driven-by-early-embryonic-events-during-gastrulation-and-neurulation
#3
Hélène Hinaux, Lucie Devos, Maryline Blin, Yannick Elipot, Jonathan Bibliowicz, Alexandre Alié, Sylvie Rétaux
Natural variations in sensory systems constitute adaptive responses to the environment. Here, we compared sensory placode development in the blind cave-adapted morph and the eyed river-dwelling morph of Astyanax mexicanus Focusing on the lens and olfactory placodes, we found a trade-off between these two sensory components in the two morphs: from neural plate stage onwards, cavefish have larger olfactory placodes and smaller lens placodes. In a search for developmental mechanisms underlying cavefish sensory evolution, we analyzed the roles of Shh, Fgf8 and Bmp4 signaling, which are known to be fundamental in patterning the vertebrate head and are subtly modulated in space and time during cavefish embryogenesis...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#4
Jung Hwi Lee, Young Cheul Chung, Eugene Bok, Hankyu Lee, Sue Hee Huh, Ji Eun Lee, Byung Kwan Jin, Hyuk Wan Ko
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27875522/hedgehog-inhibition-enhances-efficacy-of-radiation-and-cisplatin-in-orthotopic-cervical-cancer-xenografts
#5
Naz Chaudary, Melania Pintilie, David Hedley, Richard P Hill, Michael Milosevic, Helen Mackay
BACKGROUND: The Hedgehog (Hh) pathway is upregulated in cervical cancer and associated with poor outcome. We explored the effects of Hh pathway inhibition in combination with RTCT in a patient derived orthotopic cervical cancer xenograft model (OCICx). METHODS: 5E1, a monoclonal antibody for SHH, or Sonidegib (LDE225), a clinical SMO inhibitor (Novartis) were added to RTCT. We investigated tumour growth delay, metastasis and GI toxicity using orthotopic cervical cancer xenografts models...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27871935/a-sonic-hedgehog-coreceptor-boc-regulates-neuronal-differentiation-and-neurite-outgrowth-via-interaction-with-abl-and-jnk-activation
#6
Tuan Anh Vuong, Young-Eun Leem, Bok-Geon Kim, Hana Cho, Sang-Jin Lee, Gyu-Un Bae, Jong-Sun Kang
Neurite outgrowth is a critical step for neurogenesis and remodeling synaptic circuitry during neuronal development and regeneration. An immunoglobulin superfamily member, BOC functions as Sonic hedgehog (Shh) coreceptor in canonical and noncanonical Shh signaling in neuronal development and axon outgrowth/guidance. However signaling mechanisms responsible for BOC action during these processes remain unknown. In our previous studies, a multiprotein complex containing BOC and a closely related protein CDO promotes myogenic differentiation through activation of multiple signaling pathways, including non-receptor tyrosine kinase ABL...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27871848/sonic-hedgehog-promotes-neurite-outgrowth-of-cortical-neurons-under-oxidative-stress-involving-of-mitochondria-and-energy-metabolism
#7
Weiliang He, Lili Cui, Cong Zhang, Xiangjian Zhang, Junna He, Yanzhao Xie, Yanxia Chen
Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H2O2)...
November 18, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27869174/developmental-reprogramming-in-mesenchymal-stromal-cells-of-human-subjects-with-idiopathic-pulmonary-fibrosis
#8
Diptiman Chanda, Ashish Kurundkar, Sunad Rangarajan, Morgan Locy, Karen Bernard, Nirmal S Sharma, Naomi J Logsdon, Hui Liu, David K Crossman, Jeffrey C Horowitz, Stijn De Langhe, Victor J Thannickal
Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted capacity for regeneration, humans with age-related chronic diseases, such as cancer and fibrosis, show evidence of a recapitulation of developmental gene programs. We have previously identified a resident population of mesenchymal stromal cells (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human adult lungs. In this study, we characterized MSCs from BAL of patients with stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and ≥10% decline, respectively, in forced vital capacity over the preceding 6-month period...
November 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27867070/the-shh-topological-domain-facilitates-the-action-of-remote-enhancers-by-reducing-the-effects-of-genomic-distances
#9
Orsolya Symmons, Leslie Pan, Silvia Remeseiro, Tugce Aktas, Felix Klein, Wolfgang Huber, François Spitz
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression...
November 16, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27865563/sonic-hedgehog-signaling-and-hippocampal-neuroplasticity
#10
REVIEW
Pamela J Yao, Ronald S Petralia, Mark P Mattson
Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural progenitor cells, and their neuronal and glial progeny, during development. Emerging findings suggest that Shh also has important roles in the formation and plasticity of neuronal circuits in the hippocampus, a brain region of fundamental importance in learning and memory. Shh mediates activity-dependent and injury-induced hippocampal neurogenesis. Activation of Shh receptors in the dendrites of hippocampal neurons engages a trans-neuronal signaling pathway that accelerates axon outgrowth and enhances glutamate release from presynaptic terminals...
November 16, 2016: Trends in Neurosciences
https://www.readbyqxmd.com/read/27863192/treatment-of-children-and-adolescents-with-metastatic-medulloblastoma-and-prognostic-relevance-of-clinical-and-biologic-parameters
#11
André O von Bueren, Rolf-Dieter Kortmann, Katja von Hoff, Carsten Friedrich, Martin Mynarek, Klaus Müller, Tobias Goschzik, Anja Zur Mühlen, Nicolas Gerber, Monika Warmuth-Metz, Niels Soerensen, Frank Deinlein, Martin Benesch, Isabella Zwiener, Robert Kwiecien, Andreas Faldum, Udo Bode, Gudrun Fleischhack, Volker Hovestadt, Marcel Kool, David Jones, Paul Northcott, Joachim Kuehl, Stefan Pfister, Torsten Pietsch, Stefan Rutkowski
Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed. Results In 123 eligible patients (median age, 8.2 years old; median follow-up, 5.38 years), 5-year event-free survival (EFS) and overall survival (OS) were 62% (95% CI, 52 to 72) and 74% (95% CI, 66 to 82), respectively...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27862128/regulation-of-crucial-lncrnas-in-differentiation-of-chicken-embryonic-stem-cells-to-spermatogonia-stem-cells
#12
D Li, Y Ji, F Wang, Y Wang, M Wang, C Zhang, W Zhang, Z Lu, C Sun, M F Ahmed, N He, K Jin, S Cheng, Y Wang, Y He, J Song, Y Zhang, B Li
Regulation of crucial lncRNAs involved in differentiation of chicken embryonic stem cells (ESCs) to spermatogonia stem cells (SSCs) was explored by sequencing the transcriptome of ESCs, primordial germ cells (PGCs) and SSCs with RNA-Seq; analytical bioinformatic methods were used to excavate candidate lncRNAs. We detected expression of candidate lncRNAs in ESCs, PGCs and SSCs and forecasted related target genes. Utilizing wego, david and string, function and protein-protein interactions of target genes were analyzed...
November 14, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27857128/adipose-tissue-shh-and-dermal-adipogenesis
#13
Tim Geach
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27853247/six2crefrs2%C3%AE-knockout-mice-are-a-novel-model-of-renal-cystogenesis
#14
Pawan Puri, Daniel Bushnell, Caitlin M Schaefer, Carlton M Bates
Six2cre-mediated deletion of Frs2α (Six2creFrs2αKO), a major fibroblast growth factor receptor (Fgfr) docking protein in mouse nephron progenitors results in perinatal renal hypoplasia; however, postnatal Six2creFrs2αKO kidneys develop cysts. We sought to determine the pathogenesis of Six2creFrs2αKO cyst formation. We performed histological assays, Western blots, and quantitative PCR (qPCR). While embryonic day (E) 18.5 Six2Frs2αKO kidneys were hypoplastic and not cystic, postnatal day (P) 7 mutants had proximal tubular-derived cysts that nearly replaced the renal parenchyma by P21...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852806/sbe6-a-novel-long-range-enhancer-involved-in-driving-sonic-hedgehog-expression-in-neural-progenitor-cells
#15
Nezha S Benabdallah, Philippe Gautier, Betul Hekimoglu-Balkan, Laura A Lettice, Shipra Bhatia, Wendy A Bickmore
The expression of genes with key roles in development is under very tight spatial and temporal control, mediated by enhancers. A classic example of this is the sonic hedgehog gene (Shh), which plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both in vivo and in vitro. Shh expression in the brain is tightly controlled by several known enhancers that have been identified through genetic, genomic and functional assays. Using chromatin profiling during the differentiation of embryonic stem cells to neural progenitor cells, here we report the identification of a novel long-range enhancer for Shh-Shh-brain-enhancer-6 (SBE6)-that is located 100 kb upstream of Shh and that is required for the proper induction of Shh expression during this differentiation programme...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27849569/suppressor-of-fused-chaperones-gli-proteins-to-generate-transcriptional-responses-to-sonic-hedgehog-signaling
#16
Ziyu Zhang, Longyan Shen, Kelvin Law, Zengdi Zhang, Xiaotong Liu, Hu Hua, Sanen Li, Huijie Huang, Shen Yue, Chi-Chung Hui, Steven Y Cheng
Cellular responses to the graded Sonic hedgehog (Shh) morphogenic signal are orchestrated by three Gli genes that give rise to both transcription activators and repressors. An essential downstream regulator of the pathway, encoded by the tumor suppressor gene Suppressor of fused (Sufu), plays critical roles in the production, trafficking and function of Gli proteins, but the mechanism remains controversial. Here, we show that Sufu is up-regulated in active Shh responding tissues and accompanies Gli activators translocating into and Gli repressors out of the nucleus...
November 14, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27845689/expression-patterns-of-fgf8-and-shh-in-the-developing-external-genitalia-of-suncus-murinus
#17
Mami Miyado, Kenji Miyado, Akihiro Nakamura, Maki Fukami, Gen Yamada, Sen-Ichi Oda
Reciprocal epithelial-mesenchymal interactions and several signalling pathways regulate the development of the genital tubercle (GT), an embryonic primordium of external genitalia. The morphology of the adult male external genitalia of the Asian house musk shrew Suncus murinus (hereafter, laboratory name: suncus) belonging to the order Eulipotyphla (the former order Insectivora or Soricomorpha), differs from those of mice and humans. However, the developmental process of the suncus GT and its regulatory genes are unknown...
November 14, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27825128/activation-of-the-basal-cell-carcinoma-pathway-in-a-patient-with-cns-hgnet-bcor-diagnosis-consequences-for-personalized-targeted-therapy
#18
Claudia Paret, Johanna Theruvath, Alexandra Russo, Bettina Kron, Khalifa El Malki, Nadine Lehmann, Arthur Wingerter, Marie A Neu, Aslihan Gerhold-Ay, Wolfgang Wagner, Clemens Sommer, Torsten Pietsch, Larissa Seidmann, Jörg Faber
High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity with a dismal prognosis. The objective of this study was to identify and validate pathways deregulated in CNS HGNET-BCOR as basis for targeted therapy approaches.We characterized the BCOR alteration in a pediatric patient with CNS HGNET-BCOR diagnosis by Sanger sequencing and demonstrated an elevated BCOR expression by qRT-PCR and western blot. By whole transcriptome sequencing and Ingenuity Pathway Analysis, we identified the activation of the Sonic Hedgehog (SHH) and of the WNT signaling pathway in two different regions of the primary tumor and of one inoculation metastasis compared to normal brain...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27821486/heterogeneous-stromal-signaling-within-the-tumor-microenvironment-controls-the-metastasis-of-pancreatic-cancer
#19
Agnieszka A Rucki, Kelly Foley, Pingbo Zhang, Qian Xiao, Jennifer Kleponis, Annie Wu, Rajni Sharma, Guanglan Mo, Angen Liu, Jennifer Van Eyk, Elizabeth M Jaffee, Lei Zheng
Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the pro-metastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth and metastasis...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27819521/microrna-326-sensitizes-human-glioblastoma-cells-to-curcumin-via-the-shh-gli1-signaling-pathway
#20
Shi Yin, Wenzhong Du, Feng Wang, Bo Han, Yuqiong Cui, Dongbo Yang, Hui Chen, Daming Liu, Xing Liu, Chuanlu Jiang
Glioblastoma multiforme is the most malignant and common brain tumor in adults and is characterized by poor survival and high resistance to chemotherapy and radiotherapy. Among the new chemotherapy drugs, curcumin, a popular dietary supplement, has proven to have a potent anticancer effect on a variety of cancer cell types; however, it remains difficult to achieve a satisfactory therapeutic effect with curcumin using the traditional single-drug treatment. In this study, we found that expression of miR-326, a tumor suppressor microRNA in various tumor types, resulted in a marked increase of curcumin-induced cytotoxicity and apoptosis and a decrease of proliferation and migration in glioma cells...
November 7, 2016: Cancer Biology & Therapy
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