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https://www.readbyqxmd.com/read/29147840/medulloblastoma-in-adults-a%C3%A2-retrospective-single-institution-analysis
#1
Indrawati Hadi, Olarn Roengvoraphoj, Maximilian Niyazi, Falk Roeder, Ulrich Schüller, Claus Belka, Silke Birgit Nachbichler
PURPOSE: Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution. METHODS: Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed...
November 16, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29142600/co-activation-of-hedgehog-and-wnt-signaling-pathways-is-associated-with-poor-outcomes-in-triple-negative-breast-cancer
#2
Kimberly M Arnold, Ryan T Pohlig, Jennifer Sims-Mourtada
Hedgehog (HH) and Wnt pathway activation have been implicated in poor prognosis of breast cancer. Crosstalk between these two pathways has been demonstrated to be important in breast cancer progression, however the association between these two pathways and breast cancer survival rate is unknown. The present study comprised a cohort of 36 patients with triple negative breast cancer (TNBC) to investigate co-activation of HH and canonical Wnt pathway in association to patient outcome. All patients had varying degrees of cytoplasmic sonic HH and glioma-associated oncogene homolog (Gli)-1 staining, which positively correlated with tumor stage...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29139542/temporal-and-spatial-expression-patterns-of-hedgehog-receptors-in-the-developing-inner-and-middle-ear
#3
Jeong-Oh Shin, Harinarayana Ankamreddy, Naga Mahesh Jakka, Seokwon Lee, Un-Kyung Kim, Jinwoong Bok
The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc)...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29138054/keratinocyte-sonic-hedgehog-up-regulation-drives-the-development-of-giant-congenital-nevi-via-paracrine-endothelin-1-secretion
#4
Arash Chitsazan, Blake Ferguson, Rehan Villani, Herlina Y Handoko, Pamela Mukhopadhyay, Brian Gabrielli, Wolter J Mooi, H Peter Soyer, Duncan Lambie, Kiarash Khosrotehrani, Grant Morahan, Graeme J Walker
Giant congenital nevi are associated with clinical complications such as neurocutaneous melanosis and melanoma. Virtually nothing is known about why some individuals develop these lesions. We previously identified the sonic hedgehog (Shh) pathway regulator Cdon as a candidate nevus modifier gene. Here we validate this by studying Cdon knockout mice, and go on to establishment the mechanism by which Shh exacerbates nevogenesis. Cdon knockout mice develop blue nevi without the need for somatic melanocyte oncogenic mutation...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29137400/downregulation-of-the-sonic-hedgehog-gli-pathway-transcriptional-target-neogenin-1-is-associated-with-basal-cell-carcinoma-aggressiveness
#5
Bárbara S Casas, Christelle Adolphe, Pablo Lois, Nelson Navarrete, Natalia Solís, Eva Bustamante, Patricio Gac, Patricio Cabané, Ivan Gallegos, Brandon J Wainwright, Verónica Palma
Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134361/sonic-hedgehog-agonist-protects-against-complex-neonatal-cerebellar-injury
#6
Vien Nguyen, Khalida Sabeur, Emin Maltepe, Kurosh Ameri, Omer Bayraktar, David H Rowitch
The cerebellum undergoes rapid growth during the third trimester and is vulnerable to injury and deficient growth in infants born prematurely. Factors associated with preterm cerebellar hypoplasia include chronic lung disease and postnatal glucocorticoid administration. We modeled chronic hypoxemia and glucocorticoid administration in neonatal mice to study whole cerebellar and cell type-specific effects of dual exposure. Chronic neonatal hypoxia resulted in permanent cerebellar hypoplasia. This was compounded by administration of prednisolone as shown by greater volume loss and Purkinje cell death...
November 13, 2017: Cerebellum
https://www.readbyqxmd.com/read/29132010/inhibition-of-sonic-hedgehog-signaling-blocks-cell-migration-and-growth-but-induces-apoptosis-via-suppression-of-foxq1-in-natural-killer-t-cell-lymphoma
#7
Pingyi Liu, Lingling Chen
The present study explored the effects of Forkhead box Q1 (FOXQ1) on cell proliferation, cell cycle and apoptosis via the Sonic hedgehog (Shh) pathway in Natural killer/T-cell lymphoma (NKTCL). Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect FOXQ1 expression in 117 NKTCL patients and 120 healthy controls. Additionally, FOXQ1 expression in NKTCL cell lines (HANK-1, NK-92, SNK-6, SNT-8 and YT) was determined by western blotting and qRT-PCR. SNK-6 cells were transfected with FOXQ1-shRNA or Shh pathway inhibitor Cyclopamine/recombinant protein Shh...
November 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29129749/quantitative-proteomic-analysis-of-deciduous-molars-during-cap-to-bell-transition-in-miniature-pig
#8
Yang Li, Yiyi Gong, Xiaoshan Wu, Fu Wang, Yilin Xie, Zhao Zhu, Yingying Su, Jinsong Wang, Chunmei Zhang, Junqi He, Haiteng Deng, Songlin Wang
Taking advantage of genetic manipulation tools and accessibility, almost all molecular knowledge on vertebrate tooth development was obtained from rodent models that only have one dentition in their entire lives. Whether the tooth development in other vertebrates such as swine or human follows the same rules remains elusive. Rodent dentitions differ considerably from human dentitions, therefore limiting the application of knowledge from rodent tooth to human tooth. Signal-mediated communication between cells and complex gene and protein regulatory networks are key components of tooth development...
November 9, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29128669/wip1-regulates-blood-brain-barrier-function-and-neuro-inflammation-induced-by-lipopolysaccharide-via-the-sonic-hedgehog-signaling-signaling-pathway
#9
Hong Zhen, Lize Zhao, Zhangjun Ling, Li Kuo, Xiarui Xue, Jiaxiu Feng
The blood brain barrier (BBB) is a diffusion barrier that maintains the brain environment. Wip1 is a nuclear phosphatase induced by many factors and involved in various stresses, tumorigenesis, organismal aging, and neurogenesis. Wip1's role in BBB integrity has not been thoroughly investigated. The purpose of the present study was to investigate the effect and mechanism of Wip1 on lipopolysaccharide (LPS)-induced BBB dysfunction and inflammation in an in vitro BBB model. The in vitro BBB model was established by co-culturing human brain-microvascular endothelial cells and human astrocytes and then exposing them to 1μg/ml LPS for 6, 12, 18, 24, and 48h...
November 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29127258/homozygous-mutation-in-cep19-a-gene-mutated-in-morbid-obesity-in-bardet-biedl-syndrome-with-predominant-postaxial-polydactyly
#10
Esra Yıldız Bölükbaşı, Sara Mumtaz, Muhammad Afzal, Ute Woehlbier, Sajid Malik, Aslıhan Tolun
BACKGROUND: Bardet-Biedl syndrome (BBS) is a ciliopathy with extensive phenotypic variability and genetic heterogeneity. We aimed to discover the gene mutated in a consanguineous kindred with multiple cases of a BBS phenotype. METHODS: SNP genotype data were used for linkage analysis and exome sequencing to identify mutations. Modelling and in silico analysis were performed to predict mutation severity. RESULTS: Patients had postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver...
November 10, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29122585/strong-sonic-hedgehog-signaling-in-the-mouse-ventral-spinal-cord-is-not-required-for-oligodendrocyte-precursor-cell-opc-generation-but-is-necessary-for-correct-timing-of-its-generation
#11
Hirokazu Hashimoto, Wen Jiang, Takeshi Yoshimura, Kyeong-Hye Moon, Jinwoong Bok, Kazuhiro Ikenaka
In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear...
November 6, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29118110/cellular-functions-of-the-autism-risk-factor-ptchd1-in-mice
#12
David Tora, Andrea M Gomez, Jean-Francois Michaud, Patricia T Yam, Frédéric Charron, Peter Scheiffele
The gene PTCHD1 is mutated in patients with autism spectrum disorders (ASD) and intellectual disabilities (ID) and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1 interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out male mice exhibit cognitive alterations, including defects in a novel object recognition task...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29115573/fibroblast-activation-protein-%C3%AE-promotes-the-growth-and-migration-of-lung-cancer-cells-via-the-pi3k-and-sonic-hedgehog-pathways
#13
Jun Jia, Tracey A Martin, Lin Ye, Lin Meng, Nan Xia, Wen G Jiang, Xiaodong Zhang
A characteristic of the epithelial-to-mesenchymal transition in cancer cells is the upregulation of mesenchymal markers. Fibroblast activation protein α (FAPα) is predominantly expressed by stromal fibroblasts. Previous studies have demonstrated that FAPα is also expressed by certain epithelium-derived cancer cells and is involved in the regulation of certain signaling pathways. One of our previous studies showed that FAPα promoted the proliferation of breast cancer cells via the phosphatidylinositol-3-kinase (PI3K) signaling pathway...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113369/prognostic-role-of-gli1-expression-in-breast-cancer-a-meta-analysis
#14
Bilan Wang, Ting Yu, Yuzhu Hu, Mengmeng Xiang, Haoning Peng, Yunzhu Lin, Lu Han, Lingli Zhang
Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtypes and prognosis in breast cancer. According to included criteria, 13 eligible studies containing 2816 patients all around the world were selected in this study...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109946/the-binding-mode-of-the-sonic-hedgehog-inhibitor-robotnikinin-a-combined-docking-and-qm-mm-md-study
#15
Manuel Hitzenberger, Daniela Schuster, Thomas S Hofer
Erroneous activation of the Hedgehog pathway has been linked to a great amount of cancerous diseases and therefore a large number of studies aiming at its inhibition have been carried out. One leverage point for novel therapeutic strategies targeting the proteins involved, is the prevention of complex formation between the extracellular signaling protein Sonic Hedgehog and the transmembrane protein Patched 1. In 2009 robotnikinin, a small molecule capable of binding to and inhibiting the activity of Sonic Hedgehog has been identified, however in the absence of X-ray structures of the Sonic Hedgehog-robotnikinin complex, the binding mode of this inhibitor remains unknown...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29107893/lung-regeneration-after-toxic-injury-is-improved-in-absence-of-dioxin-receptor
#16
Antonio Morales-Hernández, Ana Nacarino-Palma, Nuria Moreno-Marín, Eva Barrasa, Beroé Paniagua-Quiñones, Inmaculada Catalina-Fernández, Alberto Alvarez-Barrientos, Xosé R Bustelo, Jaime M Merino, Pedro M Fernández-Salguero
Recent experimental evidences from cellular systems and from mammalian and non-mammalian animal models highlight novel functions for the aryl hydrocarbon/dioxin receptor (AhR) in maintaining cell differentiation and tissue homeostasis. Notably, AhR depletion stimulates an undifferentiated and pluripotent phenotype likely associated to a mesenchymal transition in epithelial cells and to increased primary tumorigenesis and metastasis in melanoma. In this work, we have used a lung model of epithelial regeneration to investigate whether AhR regulates proper tissue repair by adjusting the expansion of undifferentiated stem-like cells...
October 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29107475/development-and-connectivity-of-the-habenular-nuclei
#17
REVIEW
Sara Roberson, Marnie E Halpern
Accumulating evidence has reinforced that the habenular region of the vertebrate dorsal forebrain is an essential integrating center, and a region strongly implicated in neurological disorders and addiction. Despite the important and diverse neuromodulatory roles the habenular nuclei play, their development has been understudied. The emphasis of this review is on the dorsal habenular nuclei of zebrafish, homologous to the medial nuclei of mammals, as recent work has revealed new information about the signaling pathways that regulate their formation...
October 26, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29095557/developmental-genetic-and-genomic-insights-into-the-evolutionary-loss-of-limbs-in-snakes
#18
REVIEW
Francisca Leal, Martin J Cohn
The evolution of snakes involved dramatic modifications to the ancestral lizard body plan. Limb loss and elongation of the trunk are hallmarks of snakes, although convergent evolution of limb-reduced and trunk-elongated forms occurred multiple times in snake-like lizards. Advanced snakes are completely limbless, but intermediate and basal snakes have retained rudiments of hindlimbs and pelvic girdles. Moreover, the snake fossil record indicates that complete legs were re-acquired at least once, suggesting that the potential for limb development was retained in some limb-reduced taxa...
November 2, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29094201/a-review-of-genetic-factors-contributing-to-the-etiopathogenesis-of-anorectal-malformations
#19
REVIEW
Kashish Khanna, Shilpa Sharma, Noel Pabalan, Neetu Singh, D K Gupta
BACKGROUND: Anorectal malformation (ARM) is a common congenital anomaly with a wide clinical spectrum. Recently, many genetic and molecular studies have been conducted worldwide highlighting the contribution of genetic factors in its etiology. We summarize the current literature on such genetic factors. MATERIALS AND METHODS: Literature search was done using different combinations of terms related to genetics in anorectal malformations. From 2012 to June 2017, articles published in the English literature and studies conducted on human population were included...
November 1, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/29081811/transplanted-adult-neural-stem-cells-express-sonic-hedgehog-in-vivo-and-suppress-white-matter-neuroinflammation-after-experimental-traumatic-brain-injury
#20
Genevieve M Sullivan, Regina C Armstrong
Neural stem cells (NSCs) delivered intraventricularly may be therapeutic for diffuse white matter pathology after traumatic brain injury (TBI). To test this concept, NSCs isolated from adult mouse subventricular zone (SVZ) were transplanted into the lateral ventricle of adult mice at two weeks post-TBI followed by analysis at four weeks post-TBI. We examined sonic hedgehog (Shh) signaling as a candidate mechanism by which transplanted NSCs may regulate neuroregeneration and/or neuroinflammation responses of endogenous cells...
2017: Stem Cells International
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