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https://www.readbyqxmd.com/read/27917272/the-hedgehog-gli-1-signaling-pathways-is-involved-in-the-inhibitory-effect-of-resveratrol-on-human-colorectal-cancer-hct116-cells
#1
Zhou Du, Feng Zhou, Zengrong Jia, Beishi Zheng, Shaoliang Han, Jun Cheng, Guanbao Zhu, Ping Huang
OBJECTIVES: The study aimed to investigate the effects of resveratrol on colorectal cancer HCT116 cells, including cell viability, apoptosis, and migration, and the partial mechanisms focused on hedgehog/gli-1 signaling pathways. MATERIALS AND METHODS: We chose the appropriate time and concentration of recombinant human Sonic hedgehog (Shh) stimulation by cell viability. The proportion of cell apoptosis was detected by flow cytometry; HCT116 cell migration was measured by scratch test; the expression of Ptch, Smo, and Gli-1 was measured by Western blot analysis...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27903983/dyrk1b-blocks-canonical-and-promotes-non-canonical-hedgehog-signaling-through-activation-of-the-mtor-akt-pathway
#2
Rajeev Singh, Pavan Kumar Dhanyamraju, Matthias Lauth
Hedgehog (Hh) signaling plays important roles in embryonic development and in tumor formation. Apart from the well-established stimulation of the GLI family of transcription factors, Hh ligands promote the phosphorylation and activation of mTOR and AKT kinases, yet the molecular mechanism underlying these processes are unknown. Here, we identify the DYRK1B kinase as a mediator between Hh signaling and mTOR/AKT activation. In fibroblasts, Hh signaling induces DYRK1B protein expression, resulting in activation of the mTOR/AKT kinase signaling arm...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899820/inhibition-of-hedgehog-dependent-tumors-and-cancer-stem-cells-by-a-newly-identified-naturally-occurring-chemotype
#3
Paola Infante, Romina Alfonsi, Cinzia Ingallina, Deborah Quaglio, Francesca Ghirga, Ilaria D'Acquarica, Flavia Bernardi, Laura Di Magno, Gianluca Canettieri, Isabella Screpanti, Alberto Gulino, Bruno Botta, Mattia Mori, Lucia Di Marcotullio
Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27897284/ytterbium-erbium-ion-doped-strontium-molybdate-srmoo4-synthesis-characterization-photophysical-properties-and-application-in-solar-cells
#4
Weifu Sun, Zihan Chen, Junli Zhou, Dongyu Li, Zhen Huang, Xiao Jin, Qin Zhang, Feng Li, Qinghua Li
In this work, ytterbium-erbium co-doped strontium molybdate (SrMoO4, SMO) nanophosphors (NPs), denoted as SMO:Yb/Er, have been successfully prepared. These NPs were then incorporated into TiO2 acceptor films in hybrid solar cells to enhance light harvesting by virtue of an up-conversion process where low energy photons can be converted into high energy photons through multi-photon processes. The results showed that the SMO:Yb/Er single crystal NPs are capable of turning near infrared photons into visible ones that can be easily captured by poly(thieno[3,4-b]-thiophene/benzodithiophene) (PTB7)...
November 29, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27885953/targeted-sequencing-of-smo-and-akt1-in-anterior-skull-base-meningiomas
#5
Matthew R Strickland, Corey M Gill, Naema Nayyar, Megan R D'Andrea, Christian Thiede, Tareq A Juratli, Gabriele Schackert, Darrell R Borger, Sandro Santagata, Matthew P Frosch, Daniel P Cahill, Priscilla K Brastianos, Fred G Barker
OBJECTIVE Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove...
November 25, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27877222/hedgehog-signaling-non-canonical-activated-by-pro-inflammatory-cytokines-in-pancreatic-ductal-adenocarcinoma
#6
Yuqiong Wang, Gang Jin, Quanjiang Li, Zhiping Wang, Weimin Hu, Ping Li, Shude Li, Hongyu Wu, Xiangyu Kong, Jun Gao, Zhaoshen Li
Hedgehog(HH) pathway is found to be activated through a manner of canonical, or the non-canonical HH pathways. Distinct hyperplasia stroma around tumor cells is supposed to express pro-inflammatory cytokines abundantly, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), etc. in pancreatic ductal adenocarcinoma (PDAC) tissues. In this study we observed the effects of TNF-α and IL-1β on HH pathway activation in PDAC cells, and explored their activation manners. Our results showed that pro-inflammatory cytokines, TNF-α and IL-1β, could up-regulate the expression of GLI1 gene, increase its nuclear protein expression and promote malignant cell behaviors including migration, invasion, epithelial-mesenchymal transition (EMT) and drug resistance as well...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27875522/hedgehog-inhibition-enhances-efficacy-of-radiation-and-cisplatin-in-orthotopic-cervical-cancer-xenografts
#7
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/27835885/galectin-1-induces-invasion-and-the-epithelial-mesenchymal-transition-in-human-gastric-cancer-cells-via-non-canonical-activation-of-the-hedgehog-signaling-pathway
#8
Yang Chong, Dong Tang, Jun Gao, Xuetong Jiang, Chuanqi Xu, Qingquan Xiong, Yuqin Huang, Jie Wang, Huaicheng Zhou, Youquan Shi, Daorong Wang
Galectin-1 (Gal-1) has been reported to be an independent prognostic indicator of poor survival in gastric cancer and overexpression of Gal-1 enhances the invasiveness of gastric cancer cells. However, the downstream mechanisms by which Gal-1 promotes invasion remains unclear. Moreover, the function of Gal-1 in the epithelial-mesenchymal transition (EMT) in gastric cancer has not yet been elucidated. In this study, we observed Gal-1 expression was upregulated and positively associated with metastasis and EMT markers in 162 human gastric cancer tissue specimens...
November 8, 2016: Oncotarget
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
#9
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/27816202/bariatric-surgery-outcomes-in-black-patients-with-super-morbid-obesity-a-1-year-postoperative-review
#10
Samuel C Onyewu, Ololade O Ogundimu, Gezzer Ortega, Edward S Bauer, Chijindu C Emenari, Neh D Molyneaux, Sylvonne A Layne, Navin R Changoor, Denia Tapscott, Daniel D Tran, Terrence M Fullum
BACKGROUND: Super morbid obesity (body mass index [BMI] > 50 kg/m(2)) is associated with significant comorbidities and is disparagingly prevalent among the black population. There is paucity of data regarding bariatric surgery outcomes among super morbid obese (SMO) blacks. Our aim is to evaluate the reduction in weight and resolution of comorbidities after bariatric surgery among SMO black patients at an urban academic institution. METHODS: A retrospective review of SMO black patients who underwent bariatric surgery from August 2008 to June 2013 at Howard University Hospital...
June 16, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27814759/maternal-near-miss-and-predictive-ability-of-potentially-life-threatening-conditions-at-selected-maternity-hospitals-in-latin-america
#11
Bremen De Mucio, Edgardo Abalos, Cristina Cuesta, Guillermo Carroli, Suzanne Serruya, Daniel Giordano, Gerardo Martinez, Claudio G Sosa, João Paulo Souza
BACKGROUND: Every year millions of women around the world suffer from pregnancy, childbirth and postpartum complications. Women who survive the most serious clinical conditions are regarded as to have experienced a severe acute maternal complication called maternal near miss (MNM). Information about MNM cases may complement the data collected through the analysis of maternal death, and was proposed as a helpful tool to identify strengths and weaknesses of health systems in relation to maternal health care...
November 4, 2016: Reproductive Health
https://www.readbyqxmd.com/read/27810591/design-synthesis-and-biological-evaluation-of-structurally-modified-isoindolinone-and-quinazolinone-derivatives-as-hedgehog-pathway-inhibitors
#12
Deepak Bhattarai, Joo Hyun Jung, Seunghyeon Han, Hankyu Lee, Soo Jin Oh, Hyuk Wan Ko, Kyeong Lee
The Hedgehog (Hh) signaling pathway is associated with diverse aspects of cellular events, such as cell migration, proliferation, and differentiation throughout embryonic development and tissue patterning. An abnormal Hh signaling pathway is linked to numerous human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB), lung cancer, prostate cancer, and ovarian cancer, and it is therefore a promising target in cancer therapy. Using a structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biologically evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells...
October 19, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27807033/hair-follicles-transit-amplifying-cells-govern-concurrent-dermal-adipocyte-production-through-sonic-hedgehog
#13
Bing Zhang, Pai-Chi Tsai, Meryem Gonzalez-Celeiro, Oliver Chung, Benjamin Boumard, Carolina N Perdigoto, Elena Ezhkova, Ya-Chieh Hsu
Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH)...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27801979/preaxial-polydactyly-following-early-gestational-exposure-to-the-smoothened-agonist-sag-in-c57bl-6j-mice
#14
Eric W Fish, Scott E Parnell, Kathleen K Sulik, Lorinda K Baker, Laura B Murdaugh, David Lamson, Kevin P Williams
BACKGROUND: While pharmacological activation of the Hedgehog (HH) signaling pathway may have therapeutic benefits for developmental and adult diseases, its teratogenic potential is of concern. The membrane molecule Smoothened (SMO) transduces HH signaling and can be acutely modulated by antagonists and agonists. The objective of the current experiments was to determine how maternal treatment with the Smo agonist, SAG, affects the developing limb. METHODS: Pregnant C57BL/6J mice received a single injection of SAG (15, 17, or 20 mg/kg, i...
November 1, 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
https://www.readbyqxmd.com/read/27793816/the-transcription-factor-gli2-as-a-downstream-mediator-of-transforming-growth-factor-%C3%AE-induced-fibroblast-activation-in-ssc
#15
Ruifang Liang, Barbora Šumová, Cinzia Cordazzo, Tatjana Mallano, Yun Zhang, Thomas Wohlfahrt, Clara Dees, Andreas Ramming, Dorota Krasowska, Małgorzata Michalska-Jakubus, Oliver Distler, Georg Schett, Ladislav Šenolt, Jörg H W Distler
OBJECTIVES: Hedgehog signalling plays a critical role during the pathogenesis of fibrosis in systemic sclerosis (SSc). Besides canonical hedgehog signalling with smoothened (SMO)-dependent activation of GLI transcription factors, GLI can be activated independently of classical hedgehog ligands and receptors (so-called non-canonical pathways). Here, we aimed to evaluate the role of non-canonical hedgehog signalling in SSc and to test the efficacy of direct GLI inhibitors that target simultaneously canonical and non-canonical hedgehog pathways...
October 28, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27793670/ciliary-smoothened-mediated-noncanonical-hedgehog-signaling-promotes-tubulin-acetylation
#16
Hankyu Lee, Hyuk Wan Ko
Hedgehog (Hh) signaling plays key roles in animal development and tissue homeostasis. Binding of the secreted ligand to its Ptch1 receptor triggers Hh signaling through distinct canonical or noncanonical signaling pathways. Canonical Hh signaling leads to the activation of Gli transcription factors to induce Hh target-gene expression. In contrast, noncanonical Hh signaling regulates cytoskeleton rearrangement and apoptosis. Recently, it has been shown that primary cilia are important for canonical Hh signaling, but the ciliary role for signaling through the noncanonical pathway remains unresolved...
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27789472/a-positive-vestibular-ocular-motor-screening-voms-is-associated-with-increased-recovery-time-after-sports-related-concussion-in-youth-and-adolescent-athletes
#17
Anthony J Anzalone, Damond Blueitt, Tami Case, Tiffany McGuffin, Kalyssa Pollard, J Craig Garrison, Margaret T Jones, Robert Pavur, Stephanie Turner, Jonathan M Oliver
BACKGROUND: Vestibular and ocular motor impairments are routinely reported in patients with sports-related concussion (SRC) and may result in delayed return to play (RTP). The Vestibular/Ocular Motor Screening (VOMS) assessment has been shown to be consistent and sensitive in identifying concussion when used as part of a comprehensive examination. To what extent these impairments or symptoms are associated with length of recovery is unknown. PURPOSE: To examine whether symptom provocation or clinical abnormality in specific domains of the VOMS results in protracted recovery (time from SRC to commencement of RTP protocol)...
October 27, 2016: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/27785591/the-dna-methyltransferase-inhibitor-zebularine-exerts-antitumor-effects-and-reveals-batf2-as-a-poor-prognostic-marker-for-childhood-medulloblastoma
#18
Augusto Faria Andrade, Kleiton Silva Borges, Veridiana Kiill Suazo, Lenisa Geron, Carolina Alves Pereira Corrêa, Angel Mauricio Castro-Gamero, Elton José Rosas de Vasconcelos, Ricardo Santos de Oliveira, Luciano Neder, José Andres Yunes, Simone Dos Santos Aguiar, Carlos Alberto Scrideli, Luiz Gonzaga Tone
Medulloblastoma (MB) is the most common solid tumor among pediatric patients and corresponds to 20 % of all pediatric intracranial tumors in this age group. Its treatment currently involves significant side effects. Epigenetic changes such as DNA methylation may contribute to its development and progression. DNA methyltransferase (DNMT) inhibitors have shown promising anticancer effects. The agent Zebularine acts as an inhibitor of DNA methylation and shows low toxicity and high efficacy, being a promising adjuvant agent for anti-cancer chemotherapy...
October 26, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27784375/-synergistic-inhibitory-effect-of-arsenic-trioxide-combined-with-itraconazole-on-hedgehog-pathway-of-multiple-myeloma-nci-h929-cells
#19
Xiao-Bing Huang, Yi Shi, Chun-Sheng Wang, Xiao-Dong Wang, Jiao Cheng, Fei-Fei Che
OBJECTIVE: To investigate the antitumor effect of arsenic trioxide (ATO) combined with itraconazole (ITRA) on human multiple myeloma NCI-H929 cells by synergistically inhibiting Hedgehog (HH) signaling pathway. METHODS: The inhibitory rate of NCI-H929 cells was assayed by MTT method. Tumor weight, tumor weight inhibition rate, and tumor volume of mouse model with multiple myeloma were examined. The ELISA were appled to detect the M-protein, qPCR and Western blot were used respectively to detect the expression level of Ptch, SMO, Gli and downstream target genes, the survival rate of tumor-bearing mice was analyzed...
October 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27783689/epithelial-to-stromal-re-distribution-of-primary-cilia-during-pancreatic-carcinogenesis
#20
Simon Schimmack, Sarah Kneller, Nigora Dadabaeva, Frank Bergmann, Andrew Taylor, Thilo Hackert, Jens Werner, Oliver Strobel
BACKGROUND: The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. METHODS: PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated α-tubuline and γ-tubuline...
2016: PloS One
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