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https://www.readbyqxmd.com/read/29045680/report-of-a-novel-case-of-anaplastic-olfactory-groove-meningioma-and-its-methylation-subtype
#1
Aaron Song Chuan Foo, Dominic Ti Ming Tan, Char Loo Tan, Felix Sahm, Andreas von Deimling, Tseng Tsai Yeo
We report a novel case of a World Health Organization grade 3 anaplastic meningioma arising from the olfactory groove in an 83-year-old woman. Molecular and methylation profiling confirm this lesion to be an NF2 subtype, methylation class intermediate type B meningioma. As most meningiomas in this location are indolent SMO subtype lesions, our report suggests that even though rare, aggressive NF2 subtype meningiomas can also occur along the midline anterior skull base.
October 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29045470/structural-and-functional-analysis-of-smo-1-the-sumo-homolog-in-caenorhabditis-elegans
#2
Parag Surana, Chandrakala M Gowda, Vasvi Tripathi, Limor Broday, Ranabir Das
SUMO proteins are important post-translational modifiers involved in multiple cellular pathways in eukaryotes, especially during the different developmental stages in multicellular organisms. The nematode C. elegans is a well known model system for studying metazoan development and has a single SUMO homolog, SMO-1. Interestingly, SMO-1 modification is linked to embryogenesis and development in the nematode. However, high-resolution information about SMO-1 and the mechanism of its conjugation is lacking. In this work, we report the high-resolution three dimensional structure of SMO-1 solved by NMR spectroscopy...
2017: PloS One
https://www.readbyqxmd.com/read/29042665/gdc-0449-improves-the-antitumor-activity-of-nano-doxorubicin-in-pancreatic-cancer-in-a-fibroblast-enriched-microenvironment
#3
Quan Zhou, Yongcun Zhou, Xiangrui Liu, Youqing Shen
Pancreatic cancer is one of the most lethal human cancers that currently does not have effective therapies. Novel treatments including nanomedicines and combination therapies are thus urgently needed for these types of deadly diseases. A key feature of pancreatic cancer is its tumor protective dense stroma, which is generated by cancer-associated fibroblasts (CAFs). The interaction between CAFs and pancreatic cancer cells abnormally activates sonic hedgehog (SHH) signaling and facilitates tumor growth, metastasis, and drug resistance...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29039491/non-canonical-hedgehog-signaling-activation-in-ovarian-borderline-tumors-and-ovarian-carcinomas
#4
Petar Ozretić, Diana Trnski, Vesna Musani, Ivana Maurac, Držislav Kalafatić, Slavko Orešković, Sonja Levanat, Maja Sabol
Hedgehog signaling pathway has been implicated in the pathology of ovarian cancer, and Survivin (BIRC5) has been suggested as a novel target of this pathway. Herein we investigated the role of Hedgehog signaling pathway and Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine possible ways of pathway modulation on primary ovarian cancer cells and an established cell line. RNA was extracted from fresh tumors and control tissues and gene expression was examined using qRT-PCR. Pathway activity in cell lines was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium chloride using qRT-PCR, western blot and confocal microscopy...
October 12, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29034935/hedgehog-mesenchyme-gene-signature-identifies-bi-modal-prognosis-in-luminal-and-basal-breast-cancer-sub-types
#5
Wandaliz Torres-García, Maribella Domenech
Hedgehog signaling (Hh) has been shown to be hyper-activated in several cancers. However, active Hh signaling can promote or inhibit tumor growth; thus identification of markers beyond main canonical Hh target genes is needed to improve patient selection and clinical outcome in response to Hh inhibitors. Cancer-associated fibroblasts (CAFs) have been linked with tumor progression and beneficial response to Hh inhibitors. Thus, we hypothesized that genes associated with Hh-activated CAFs can be used for stratification of tumors that will benefit from Hh inhibitors...
October 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28993237/sonic-hedgehog-induces-glt-1-degradation-via-pkc-delta-to-suppress-its-transporter-activities
#6
Yuqing Wang, Shanshan Lu, Zhongwei Qu, Lin Wu, Yizheng Wang
GLT-1 is mainly expressed in astrocytes and has a crucial role in glutamate uptake. Sonic hedgehog (SHH) can inhibit glutamate uptake and its pathway is activated in many brain diseases related with glutamate excitotoxicity. However, whether SHH regulates GLT-1 to affect glutamate uptake is not clear. Here, we use pharmacological and genetic methods to show that SHH induces GLT-1 degradation in astrocytes in a manner that is dependent on PKC delta (PKCδ) to regulate GLT-1 activities. GLT-1 protein levels are reduced as early as 2 hs in astrocytes after incubation with SHH, whereas its mRNA levels are not changed...
October 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28992318/the-deubiquitinase-uchl5-uch37-positively-regulates-hedgehog-signaling-by-deubiquitinating-smoothened
#7
Zizhang Zhou, Xia Yao, Shu Pang, Ping Chen, Weirong Jiang, Zhaoliang Shan, Qing Zhang
The Hedgehog (Hh) signaling pathway plays important roles in developmental processes including pattern formation and tissue homeostasis. The seven-pass transmembrane receptor Smoothened (Smo) is the pivotal transducer in the pathway; it, and thus the pathway overall, is regulated by ubiquitin-mediated degradation, which occurs in the absence of Hh. In the presence of Hh, the ubiquitination levels of Smo are decreased, but the molecular basis for this outcome is not well understood. Here, we identify the deubiquitinase UCHL5 as a positive regulator of the Hh pathway...
August 23, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28969581/molecular-modelling-of-berberine-derivatives-as-inhibitors-of-human-smoothened-receptor-and-hedgehog-signalling-pathway-using-a-newly-developed-algorithm-on-anti-cancer-drugs
#8
Parham Jabbarzadeh Kaboli, Mohammad Bazrafkan, Patimah Ismail, King-Hwa Ling
BACKGROUND: Protoberberine isoquinoline alkaloids are found in many plant species. They consist of a diverse class of secondary metabolites with many pharmacologically active members, such as different derivatives of berberine already patented. In the development of approximately 20-25% of all cancers, altered hedgehog (Hh) signalling is involved where the smoothened (Smo) transmembrane receptor triggers Hh signalling pathway towards Gli1 gene expression. OBJECTIVE: The current study aimed to model and verify the anti-Smo activity of berberine and its derivatives using a novel automated script...
September 29, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28957797/resveratrol-enhances-neurite-outgrowth-and-synaptogenesis-via-sonic-hedgehog-signaling-following-oxygen-glucose-deprivation-reoxygenation-injury
#9
Fanren Tang, Shuang Guo, Hongyan Liao, Pingping Yu, Li Wang, Xiaosong Song, Jixiang Chen, Qin Yang
BACKGROUND/AIMS: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh) signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt)1, the present study examined whether this is mediated by Shh signaling. METHODS: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R)...
September 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28950910/stimulation-of-il-1%C3%AE-and-il-6-through-nf-%C3%AE%C2%BAb-and-sonic-hedgehog-dependent-pathways-in-mouse-astrocytes-by-excretory-secretory-products-of-fifth-stage-larval-angiostrongylus-cantonensis
#10
Kuang-Yao Chen, Lian-Chen Wang
BACKGROUND: Angiostrongylus cantonensis is an important causative agent of eosinophilic meningitis and eosinophilic meningoencephalitis in humans. Previous studies have shown that the Sonic hedgehog (Shh) signaling pathway may reduce cell apoptosis by inhibiting oxidative stress in A. cantonensis infection. In this study, we investigated the relationship between cytokine secretion and Shh pathway activation after treatment with excretory/secretory products (ESP) of fifth-stage larval A...
September 26, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28941984/neural-crest-cells-utilize-primary-cilia-to-regulate-ventral-forebrain-morphogenesis-via-hedgehog-dependent-regulation-of-oriented-cell-division
#11
Elizabeth N Schock, Samantha A Brugmann
Development of the brain directly influences the development of the face via both physical growth and Sonic hedgehog (SHH) activity; however, little is known about how neural crest cells (NCCs), the mesenchymal population that comprise the developing facial prominences, influence the development of the brain. We utilized the conditional ciliary mutant Wnt1-Cre;Kif3a(fl/fl) to demonstrate that loss of primary cilia on NCCs resulted in a widened ventral forebrain. We found that neuroectodermal Shh expression, dorsal/ventral patterning, and amount of proliferation in the ventral neuroectoderm was not changed in Wnt1-Cre;Kif3a(fl/fl) mutants; however, tissue polarity and directional cell division were disrupted...
September 21, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28934490/number-of-inadvertent-rna-targets-for-morpholino-knockdown-in-danio-rerio-is-largely-underestimated-evidence-from-the-study-of-ser-arg-rich-splicing-factors
#12
Marine Joris, Marie Schloesser, Denis Baurain, Marc Hanikenne, Marc Muller, Patrick Motte
Although the involvement of Ser/Arg-rich (SR) proteins in RNA metabolism is well documented, their role in vertebrate development remains elusive. We, therefore, elected to take advantage of the zebrafish model organism to study the SR genes' functions using the splicing morpholino (sMO) microinjection and the programmable site-specific nucleases. Consistent with previous research, we revealed discrepancies between the mutant and morphant phenotypes and we show that these inconsistencies may result from a large number of unsuspected inadvertent morpholino RNA targets...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28923910/a-transposon-screen-identifies-loss-of-primary-cilia-as-a-mechanism-of-resistance-to-smo-inhibitors
#13
Xuesong Zhao, Ekaterina Pak, Kimberly J Ornell, Maria F Pazyra-Murphy, Ethan L MacKenzie, Emily J Chadwick, Tatyana Ponomaryov, Joseph F Kelleher, Rosalind A Segal
Drug resistance poses a great challenge to targeted cancer therapies. In Hedgehog pathway-dependent cancers, the scope of mechanisms enabling resistance to Smo-inhibitors is not known. Here, we performed a transposon mutagenesis screen in medulloblastoma and identified multiple modes of resistance. Surprisingly, mutations in ciliogenesis genes represent a frequent cause of resistance, and patient datasets indicate that cilia loss constitutes a clinically relevant category of resistance. Conventionally, primary cilia are thought to enable oncogenic Hedgehog signaling...
September 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28923733/demulsification-to-control-solute-release-from-pickering-crystal-stabilized-water-in-oil-emulsions
#14
Xin Zhao, Biyun Huang, Malek El-Aooiti, Dérick Rousseau
Controlled demulsification was used to tailor the release of NaCl as a solute from water-in-oil (W/O) emulsion droplets encased in glycerol monostearate (GMS) crystalline shells. Under quiescent conditions at room temperature, the GMS shells behaved as an effective barrier against salt diffusion. A second surfactant, sorbitan monooleate (SMO), added to the emulsion post-preparation to controllably demulsify, resulted in concentration-dependent removal of the interfacially-bound GMS crystals resulting in aqueous droplet coalescence...
August 31, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28917838/human-smoothened-inhibits-human-immunodeficiency-virus-type-1-infection
#15
Takeshi Yoshida, Akiko Hamano, Asuka Ueda, Hiroaki Takeuchi, Shoji Yamaoka
Human SMOOTHENED (SMO) was identified by expression cloning as a new host factor that inhibits HIV-1 infection. Forced expression of SMO inhibited HIV-1 replication and infection with a single-round lentiviral vector, but not infection with a murine leukemia virus-based retroviral vector in human MT-4 T cells. Quantitative PCR analyses revealed that stable expression of SMO impaired formation of the integrated form of lentiviral DNA, but did not interrupt reverse transcription. This inhibition was evident in MT-4 and HUT102 human T cell lines expressing low levels of SMO mRNA, but not in SupT1 or Jurkat T cell lines expressing higher levels of SMO mRNA...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28914635/clinical-genetics-of-craniosynostosis
#16
Andrew O M Wilkie, David Johnson, Steven A Wall
PURPOSE OF REVIEW: When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis. RECENT FINDINGS: Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases...
September 14, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28905994/microrna-324-5p-regulates-stemness-pathogenesis-and-sensitivity-to-bortezomib-in-multiple-myeloma-cells-by-targeting-hedgehog-signaling
#17
Bo Tang, Aoshuang Xu, Jian Xu, Haifan Huang, Lei Chen, Yan Su, Lannan Zhang, Junying Li, Fengjuan Fan, Jun Deng, Liang Tang, Chunyan Sun, Yu Hu
Chromosome 17p deletions are present in 10% of patients with newly diagnosed multiple myeloma (MM), and are associated with inferior prognosis. miR-324-5p is located on chromosome 17p, and shows diverse functions in different types of cancers. However, its role in MM is largely unknown. Here we found the expression of miR-324-5p was decreased in MM, especially in del(17p) MM. In contrast, the expression of Hedgehog (Hh) signaling components was elevated, indicating a correlation between miR-324-5p and Hh signaling in MM...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28901666/clinicopathological-and-molecular-characteristics-of-pediatric-meningiomas
#18
Sudha Battu, Anupam Kumar, Pankaj Pathak, Suvendu Purkait, Linchi Dhawan, Mehar C Sharma, Ashish Suri, Manmohan Singh, Chitra Sarkar, Vaishali Suri
Molecular and clinical characteristics of pediatric meningiomas are poorly defined. Therefore, we analyzed clinical, morphological and molecular profiles of pediatric meningiomas. Forty pediatric meningiomas from January 2002 to June 2015 were studied. 1p36, 14q32 and 22q-deletion were assessed by fluorescent in situ hybridization and mutations of most relevant exons of AKT, SMO, KLF4, TRAF and pTERT using sequencing. Expression of GAB1, stathmin, progesterone receptor (PR), p53 along with MIB-1 LI was examined using immunohistochemistry...
September 13, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28888693/n-terminus-determines-activity-and-specificity-of-styrene-monooxygenase-reductases
#19
Thomas Heine, Anika Scholtissek, Adrie H Westphal, Willem J H van Berkel, Dirk Tischler
Styrene monooxygenases (SMOs) are two-enzyme systems that catalyze the enantioselective epoxidation of styrene to (S)-styrene oxide. The FADH2 co-substrate of the epoxidase component (StyA) is supplied by an NADH-dependent flavin reductase (StyB). The genome of Rhodococcus opacus 1CP encodes two SMO systems. One system, which we define as E1-type, displays homology to the SMO from Pseudomonas taiwanensis VLB120. The other system, originally reported as a fused system (RoStyA2B), is defined as E2-type. Here we found that E1-type RoStyB is inhibited by FMN, while RoStyA2B is known to be active with FMN...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28888229/changes-in-ankle-joint-motion-after-supramalleolar-osteotomy-a-cadaveric-model
#20
Hak Jun Kim, Eui Dong Yeo, Im Joo Rhyu, Soon-Hyuck Lee, Yeon Soo Lee, Young Koo Lee
BACKGROUND: Malalignment of the ankle joint has been found after trauma, by neurological disorders, genetic predisposition and other unidentified factors, and results in asymmetrical joint loading. For a medial open wedge supramalleolar osteotomy(SMO), there are some debates as to whether concurrent fibular osteotomy should be performed. We assessed the changes in motion of ankle joint and plantar pressure after supramalleolar osteotomy without fibular osteotomy. METHODS: Ten lower leg specimens below the knee were prepared from fresh-frozen human cadavers...
September 9, 2017: BMC Musculoskeletal Disorders
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