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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/29147013/integrin-alpha-11-in-the-regulation-of-the-myofibroblast-phenotype-implications-for-fibrotic-diseases
#2
Ruchi Bansal, Shigeki Nakagawa, Saleh Yazdani, Joop van Baarlen, Anu Venkatesh, Anna P Koh, Won-Min Song, Nicolas Goossens, Hideo Watanabe, Mary B Beasley, Charles A Powell, Gert Storm, Naftali Kaminski, Harry van Goor, Scott L Friedman, Yujin Hoshida, Jai Prakash
Tissue fibrosis, characterized by excessive accumulation of aberrant extracellular matrix (ECM) produced by myofibroblasts, is a growing cause of mortality worldwide. Understanding the factors that induce myofibroblastic differentiation is paramount to prevent or reverse the fibrogenic process. Integrin-mediated interaction between the ECM and cytoskeleton promotes myofibroblast differentiation. In the present study, we explored the significance of integrin alpha 11 (ITGA11), the integrin alpha subunit that selectively binds to type I collagen during tissue fibrosis in the liver, lungs and kidneys...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#3
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29143784/primary-cilium-dependent-signaling-mechanisms
#4
REVIEW
Rajasekharreddy Pala, Nedaa Alomari, Surya M Nauli
Primary cilia are hair-like organelles and play crucial roles in vertebrate development, organogenesis, health, and many genetic disorders. A primary cilium is a mechano-sensory organelle that responds to mechanical stimuli in the micro-environment. A cilium is also a chemosensor that senses chemical signals surrounding a cell. The overall function of a cilium is therefore to act as a communication hub to transfer extracellular signals into intracellular responses. Although intracellular calcium has been one of the most studied signaling messengers that transmit extracellular signals into the cells, calcium signaling by various ion channels remains a topic of interest in the field...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142600/co-activation-of-hedgehog-and-wnt-signaling-pathways-is-associated-with-poor-outcomes-in-triple-negative-breast-cancer
#5
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/29142103/an-intracellular-activation-of-smoothened-independent-of-hedgehog-stimulation-in-drosophila
#6
Kai Jiang, Yajuan Liu, Jie Zhang, Jianhang Jia
Smoothened (Smo), a GPCR family protein, plays a critical role in the reception and transduction of Hedgehog (Hh) signal. Smo is phosphorylated and activated on the cell surface, however, it is unknown whether Smo can be intracellularly activated. Here, we demonstrate that inactivation of the ESCRT-III causes dramatic accumulation of Smo, and subsequent activation of Hh signaling. In contrast, inactivation of ESCRTs 0-II induces mild Smo accumulation. We provide evidence that Kurtz (Krz), the Drosophila β-arrestin2, acts in parallel with the ESCRTs 0-II pathway to sort Smo to the multivesicular bodies and lysosome-mediated degradation...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29141533/targeting-cancer-stem-cells-and-non-stem-cancer-cells-the-potential-of-lipid-based-nanoparticles
#7
Ana Filipa Cruz, Nuno Andre Fonseca, Vera Moura, Sergio Simoes, Joao Nuno Moreira
Background Cancer stem cells (CSCs) have been described as a relevant contributor to tumorigenicity, metastasis, tumor recurrence and drug resistance, making this cell population a relevant target in solid tumors. METHODS: This has stimulated the development of different therapeutic strategies often targeting surface markers (CD44, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH) and nucleolin) and/or signaling pathways that are aberrantly activated and contribute to CSCs proliferation and survival...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29139542/temporal-and-spatial-expression-patterns-of-hedgehog-receptors-in-the-developing-inner-and-middle-ear
#8
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/29138370/-development-of-holistic-cancer-treatment-centering-cancer-patients-from-the-standpoint-of-hypoxia-and-hedgehog-signaling
#9
Hideya Onishi, Toshitatsu Ogino, Takashi Morisaki, Mitsuo Katano
Recently, hypoxia that is one of cancer microenvironments, takes much attention. Because circumstance that we usually perform experiment is 20% O2 condition, it is likely that different signaling pathways may be activated in vivo cancer. We focused Hedgehog(Hh)signaling as one of activated pathways under hypoxia. It has been shown that Hh signaling is activated under hypoxia, followed by inducing malignant phenotypes in pancreatic cancer. Therefore, Hh signaling inhibitor should elicit anti-tumor effect. However, if we consider "whole-person therapy" we should confirm how Hh signaling affects the function of immune cells...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29138054/keratinocyte-sonic-hedgehog-up-regulation-drives-the-development-of-giant-congenital-nevi-via-paracrine-endothelin-1-secretion
#10
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/29137952/neural-egfl-like-1-regulates-cartilage-maturation-through-runt-related-transcription-factor-3-mediated-indian-hedgehog-signaling
#11
Chenshuang Li, Zhong Zheng, Jie Jiang, Wenlu Jiang, Kevin Lee, Emily A Berthiaume, Eric C Chen, Cymbeline T Culiat, Yan-Heng Zhou, Xinli Zhang, Kang Ting, Chia Soo
The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)-the major regulator of chondrocyte differentiation, proliferation, and maturation. Our previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, we further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: [1] Nell-1 significantly elevated Ihh signal transduction, [2] Nell-1 deficiency markedly reduced Ihh activation in chondrocytes, and [3] Nell-1-stimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor, cyclopamine...
November 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29137400/downregulation-of-the-sonic-hedgehog-gli-pathway-transcriptional-target-neogenin-1-is-associated-with-basal-cell-carcinoma-aggressiveness
#12
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/29136303/chromosome-9-mutations-reported-absent-in-some-patients-with-basal-cell-carcinoma-nevus-syndrome
#13
S Shih, B A Urso, R Domozych, K M Updyke, A I Laughlin, J A Solomon
Basal Cell Carcinoma Nevus Syndrome (BCCNS), also known as Gorlin syndrome, is a rare autosomal dominant condition with a substantial disease burden, thought to occur secondary to chromosome 9 mutation evoking a Hedgehog (Hh) signaling aberration that leads to early development of numerous basal cell carcinomas (BCCs). Individuals with BCCNS also present with keratocystic odontogenic tumors, medulloblastomas, and palmar or plantar pits1. This condition demonstrates variable expressivity, leading to differing phenotypes, even within the same family2...
November 14, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29135268/chemoselective-one-pot-synthesis-of-functionalized-amino-azaheterocycles-enabled-by-coware
#14
Thomas A Clohessy, Alastair Roberts, Eric S Manas, Vipulkumar K Patel, Niall A Anderson, Allan J B Watson
Functionalized bicyclic amino-azaheterocycles are rapidly accessed in a one-pot cross-coupling/reduction sequence enabled by the use of COware. Incompatible reagents are physically separated in a single reaction vessel to effect two chemoselective transformations-Suzuki-Miyaura cross-coupling and heteroarene reduction. The developed method allows access to novel heterocyclic templates, including semisaturated Hedgehog and dual PI3K/mTOR inhibitors, which show enhanced physicochemical properties compared to their unsaturated counterparts...
November 14, 2017: Organic Letters
https://www.readbyqxmd.com/read/29134361/sonic-hedgehog-agonist-protects-against-complex-neonatal-cerebellar-injury
#15
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/29133390/recovery-of-taste-organs-and-sensory-function-after-severe-loss-from-hedgehog-smoothened-inhibition-with-cancer-drug-sonidegib
#16
Archana Kumari, Alexandre N Ermilov, Marina Grachtchouk, Andrzej A Dlugosz, Benjamin L Allen, Robert M Bradley, Charlotte M Mistretta
Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132729/wnt-and-hedgehog-secretion-of-lipid-modified-morphogens
#17
REVIEW
Anup Parchure, Neha Vyas, Satyajit Mayor
Morphogens are signaling molecules produced by a localized source, specifying cell fate in a graded manner. The source secretes morphogens into the extracellular milieu to activate various target genes in an autocrine or paracrine manner. Here we describe various secreted forms of two canonical morphogens, the lipid-anchored Hedgehog (Hh) and Wnts, indicating the involvement of multiple carriers in the transport of these morphogens. These different extracellular secreted forms are likely to have distinct functions...
November 10, 2017: Trends in Cell Biology
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
#18
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
#19
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
#20
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
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