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https://www.readbyqxmd.com/read/27913313/the-role-of-vitamin-d-and-vdr-in-carcinogenesis-through-epidemiology-and-basic-sciences
#1
REVIEW
Borja Bandera Merchan, Sonsoles Morcillo, Gracias Martin-Nuñez, Francisco José Tinahones, Manuel Macías-González
In the last two decades vitamin D (VD) research has demonstrated new extraskeletal actions of this pre-hormone, suggesting a protective role of this secosteroid in the onset, progression and prognosis of several chronic noncommunicable diseases, such as cardiovascular disease, diabetes mellitus or cancer. Regarding carcinogenesis, both preclinical and epidemiological evidence available show oncoprotective actions of VD and its receptor, the VDR. However, in late neoplastic stages the VD system (VDS) seems to be less functional, which appears to be due to an epigenetic silencing of the system...
November 29, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27911708/regulation-of-primary-cilia-formation-by-the-ubiquitin-proteasome-system
#2
REVIEW
Robert F Shearer, Darren N Saunders
Primary cilia form at the surface of most vertebrate cell types, where they are essential signalling antennae for signal transduction pathways important for development and cancer, including Hedgehog. The importance of primary cilia in development is clearly demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin-proteasome system (UPS) as a key regulator of ciliogenesis...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909729/self-renewal-molecular-mechanisms-of-colorectal-cancer-stem-cells
#3
Tianhui Pan, Jinghong Xu, Yongliang Zhu
Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal...
November 30, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27905158/metastatic-spinal-cord-compression-from-basal-cell-carcinoma-of-the-skin-treated-with-surgical-decompression-and-vismodegib-case-report-and-review-of-hedgehog-signalling-pathway-inhibition-in-advanced-basal-cell-carcinoma
#4
J McGrane, S Carswell, T Talbot
We report a case of a 66-year-old man with locally advanced and metastatic basal cell carcinoma (BCC) causing spinal cord compression, which was treated with spinal surgery and subsequent vismodegib. The patient presented with a large fungating chest wall lesion and a metastasis in T8 that was causing cord compression. He had neurosurgical decompression of the T8 lesion and fixation of the spine. Punch biopsy from the fungating chest wall lesion showed a BCC with some malignant squamous differentiation (basosquamous)...
November 30, 2016: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27905054/crosstalk-between-shh-and-stemness-state-signaling-pathways-in-esophageal-squamous-cell-carcinoma
#5
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/27904711/naringin-promotes-osteogenic-differentiation-of-bone-marrow-stromal-cells-by-up-regulating-foxc2-expression-via-the-ihh-signaling-pathway
#6
Fei-Xiang Lin, Shi-Xin Du, De-Zhong Liu, Qin-Xiao Hu, Guo-Yong Yu, Chu-Cheng Wu, Gui-Zhou Zheng, Da Xie, Xue-Dong Li, Bo Chang
Naringin is an active compound extracted from Rhizoma Drynariae, and studies have revealed that naringin can promote proliferation and osteogenic differentiation of bone marrow stromal cells (BMSCs). In this study, we explored whether naringin could promote osteogenic differentiation of BMSCs by upregulating Foxc2 expression via the Indian hedgehog (IHH) signaling pathway. BMSCs were cultured in basal medium, basal medium with naringin, osteogenic induction medium, osteogenic induction medium with naringin and osteogenic induction medium with naringin in the presence of the IHH inhibitor cyclopamine (CPE)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903983/dyrk1b-blocks-canonical-and-promotes-non-canonical-hedgehog-signaling-through-activation-of-the-mtor-akt-pathway
#7
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/27903126/potential-evolution-of-neurosurgical-treatment-paradigms-for-craniopharyngioma-based-on-genomic-and-transcriptomic-characteristics
#8
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/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#9
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899820/inhibition-of-hedgehog-dependent-tumors-and-cancer-stem-cells-by-a-newly-identified-naturally-occurring-chemotype
#10
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/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#11
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/27895972/genetic-basis-of-nonsyndromic-and-syndromic-tooth-agenesis
#12
REVIEW
Xiaoqian Ye, Ali B Attaie
Human dentition development is a long and complex process which involves a series of reciprocal and sequential interactions between the embryonic stomodeal epithelium and the underlying neural crest-derived mesenchyme. Despite environment disturbances, tooth development is predominantly genetically controlled. To date, more than 200 genes have been identified in tooth development. These genes implied in various signaling pathways such as the bone morphogenetic protein, fibroblast growth factor, sonic hedgehog homolog, ectodysplasin A, wingless-type MMTV integration site family (Wnt), and transform growth factor pathways...
December 2016: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#13
Jianlong Li, Jinquan Cai, Shihong Zhao, Kun Yao, Ying Sun, Yongli Li, Lingchao Chen, Ruiyan Li, Xiuwei Zhai, Junhe Zhang, Chuanlu Jiang
BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27894099/peroxiredoxin-2-is-essential-for-maintaining-cancer-stem-cell-like-phenotype-through-activation-of-hedgehog-signaling-pathway-in-colon-cancer
#14
Rong Wang, Jinlai Wei, Shouru Zhang, Xingye Wu, Jinbao Guo, Maoxi Liu, Kunli Du, Jun Xu, Linglong Peng, Zhenbing Lv, Wenxian You, Yongfu Xiong, Zhongxue Fu
Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893742/maintenance-of-taste-organs-is-strictly-dependent-on-epithelial-hedgehog-gli-signaling
#15
Alexandre N Ermilov, Archana Kumari, Libo Li, Ariell M Joiner, Marina A Grachtchouk, Benjamin L Allen, Andrzej A Dlugosz, Charlotte M Mistretta
For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27892540/pancreatic-mesenchyme-regulates-islet-cellular-composition-in-a-patched-hedgehog-dependent-manner
#16
Daniel Hibsher, Alona Epshtein, Nufar Oren, Limor Landsman
Pancreas development requires restrained Hedgehog (Hh) signaling activation. While deregulated Hh signaling in the pancreatic mesenchyme has been long suggested to be detrimental for proper organogenesis, this association was not directly shown. Here, we analyzed the contribution of mesenchymal Hh signaling to pancreas development. To increase Hh signaling in the pancreatic mesenchyme of mouse embryos, we deleted Patched1 (Ptch1) in these cells. Our findings indicate that deregulated Hh signaling in mesenchymal cells was sufficient to impair pancreas development, affecting both endocrine and exocrine cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889934/vascular-cell-transcriptomic-changes-to-exercise-training-differ-directionally-along-and-between-skeletal-muscle-arteriolar-trees
#17
M Harold Laughlin, Hsiao T Yang, Darla L Tharp, R Scott Rector, Jaume Padilla, Douglas K Bowles
EXT-induced arteriolar adaptations in skeletal muscle are heterogeneous because of spatial variations in muscle fiber type composition and fiber recruitment patterns during exercise. The purpose of this report is to summarize a series of experiments conducted to test the hypothesis that changes in vascular gene expression are signaled by alterations in shear stress resulting from increases in blood flow, muscle fiber type composition and fiber recruitment patterns. We also report results from a follow-up study of Ankrd23, one gene whose expression was changed by EXT...
November 27, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/27888216/drosophila-sulf1-is-required-for-the-termination-of-intestinal-stem-cell-division-during-regeneration
#18
Masahiko Takemura, Hiroshi Nakato
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here we show that a specific modification of heparan sulfate (HS) is critical in regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular HS endosulfatase Sulf1 results in increased ISC division during normal homeostasis, which is caused by upregulation of mitogenic signaling including the JAK/STAT, EGFR, and Hedgehog pathways...
November 25, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27887870/involvement-of-indian-hedgehog-signaling-in-mesenchymal-stem-cell-augmented-rotator-cuff-tendon-repair-in-an-athymic-rat-model
#19
Jian-Chun Zong, Michael J Mosca, Ryan M Degen, Amir Lebaschi, Camila Carballo, Andrew Carbone, Guang-Ting Cong, Liang Ying, Xiang-Hua Deng, Scott A Rodeo
BACKGROUND: Bone marrow aspirate has been used in recent years to augment tendon-to-bone healing, including in rotator cuff repair. However, the healing mechanism in cell-based therapy has not been elucidated in detail. METHODS: Sixteen athymic nude rats were randomly allocated to 2 groups: experimental (human mesenchymal stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing enthesis...
November 22, 2016: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/27885984/a-new-trick-for-an-old-lipid
#20
Hayley Sharpe
Cholesterol can regulate the Hedgehog signalling pathway by directly binding to a receptor on the cell surface.
November 25, 2016: ELife
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