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https://www.readbyqxmd.com/read/28212537/itraconazole-exerts-its-anti-melanoma-effect-by-suppressing-hedgehog-wnt-and-pi3k-mtor-signaling-pathways
#1
Guanzhao Liang, Musang Liu, Qiong Wang, Yongnian Shen, Huan Mei, Dongmei Li, Weida Liu
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211214/anti-cancer-stem-cell-activity-of-a-hedgehog-inhibitor-gant61-in-estrogen-receptor-positive-breast-cancer-cells
#2
Junichi Kurebayashi, Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya
Estradiol (E2) increases not only the cell growth but also cancer stem cell (CSC) proportion in estrogen receptor (ER)-positive breast cancer cells. It was suggested that the non-canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER-positive breast cancer cells. We studied anti-CSC activity of a non-canonical Hh inhibitor GANT61 in ER-positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER-positive breast cancer cell lines...
February 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28210556/are-breast-cancer-stem-cells-the-key-to-resolving-clinical-issues-in-breast-cancer-therapy
#3
REVIEW
Hidetaka Shima, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo
Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#4
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#5
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208466/motion-of-a-colloidal-particle-in-a-nonuniform-director-field-of-a-nematic-liquid-crystal
#6
Beom-Kyu Lee, Sung-Jo Kim, Bohdan Lev, Jong-Hyun Kim
We investigate the dynamics of a single spherical particle immersed in a nematic liquid crystal. A nonuniform director field is imposed on the substrate by a stripe alignment pattern with splay deformation. The particle of homeotropic anchoring at the surface is accompanied by hyperbolic hedgehog or Saturn-ring defects. The particle motion is dependent on the defect structure. We study the two types of motions theoretically and confirm the obtained results experimentally. The particle accompanied by a hyperbolic hedgehog defect is pulled to a deformed region to relax the elastic deformation energy...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28205381/the-clinical-significance-of-equivocal-findings-on-spinal-mri-in-children-with-medulloblastoma
#7
Julie Bennett, Ramy Ashmawy, Vijay Ramaswamy, Derek Stephens, Eric Bouffet, Normand Laperriere, Michael Taylor, Manohar Shroff, Ute Bartels
BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification...
February 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28205343/association-of-chloride-intracellular-channel-4-and-indian-hedgehog-proteins-with-survival-of-patients-with-pancreatic-ductal-adenocarcinoma
#8
Qiong Zou, Zhulin Yang, Daiqiang Li, Ziru Liu, Yuan Yuan
Pancreatic cancer is the fourth most common cause of cancer-related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question...
February 16, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28202523/cancer-stem-cells-regulate-cancer-associated-fibroblasts-via-activation-of-hedgehog-signaling-in-mammary-gland-tumors
#9
Giovanni Valenti, Hazel M Quinn, Guus Jje Heynen, Linxiang Lan, Jane D Holland, Regina Vogel, Annika Wulf-Goldenberg, Walter Birchmeier
Many tumors display intracellular heterogeneity, with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here we investigated the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secreted the hedgehog ligand SHH, which regulated CAFs via paracrine activation of Hedgehog signaling...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198775/combining-smoothened-agonist-sag-and-nel-like-protein-1-nell-1-enhances-bone-healing
#10
Soonchul Lee, Chenchao Wang, Hsin Chuan Pan, Swati Shrestha, Carolyn Meyers, Catherine Ding, Jia Shen, Eric Chen, Min Lee, Chia Soo, Kang Ting, Aaron W James
BACKGROUND: Non-healing bone defects represent an immense biomedical burden. Despite recent advances in protein based bone regeneration, safety concerns over bone morphogenetic protein-2 have prompted the search for alternative factors. Previously, we examined the additive / synergistic effects of Hedgehog (Hh) and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. Here, we sought to leverage our previous findings by applying the combination of Smoothened agonist (SAG), Hh signal activator, and NELL-1 to an in vivo critical size bone defect model...
February 13, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28198504/complete-mitochondrial-genome-of-the-amur-hedgehog-erinaceus-amurensis-erinaceidae-and-higher-phylogeny-of-the-family-erinaceidae
#11
N H Kim, S J Lim, H M Chae, Y C Park
We sequenced and characterized the complete mitogenome (KX964606) of the Amur hedgehog Erinaceus amurensis to provide more data for comparative mitogenomics of the genus Erinaceus (Erinaceidae). The mitogenome of E. amurensis is a circular molecule 16,941 bp long, consisting of a control region and a conserved set of 37 genes containing 13 protein-coding genes, 22 tRNA genes, and two rRNA genes (12S rRNA and 16S rRNA). The mitogenome of E. amurensis is AT-biased, with a nucleotide composition of 33.9% A, 21...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28198062/curcumin-suppresses-lung-cancer-stem-cells-via-inhibiting-wnt-%C3%AE-catenin-and-sonic-hedgehog-pathways
#12
Jian-Yun Zhu, Xue Yang, Yue Chen, Ye Jiang, Shi-Jia Wang, Yuan Li, Xiao-Qian Wang, Yu Meng, Ming-Ming Zhu, Xiao Ma, Cong Huang, Rui Wu, Chun-Feng Xie, Xiao-Ting Li, Shan-Shan Geng, Jie-Shu Wu, Cai-Yun Zhong, Hong-Yu Han
Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells...
February 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28195188/sumo-regulates-the-activity-of-smoothened-and-costal-2-in-drosophila-hedgehog-signaling
#13
Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia
In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195165/smoothened-is-a-poor-prognosis-factor-and-a-potential-therapeutic-target-in-glioma
#14
Yiming Tu, Mingshan Niu, Peng Xie, Chenglong Yue, Ning Liu, Zhenglei Qi, Shangfeng Gao, Hongmei Liu, Qiong Shi, Rutong Yu, Xuejiao Liu
Malignant gliomas are associated with a high mortality rate. Thus, there is an urgent need for the development of novel targeted therapeutics. Aberrant Hedgehog signaling has been directly linked to glioma. GDC-0449 is a novel small molecule inhibitor of Hedgehog signaling that blocks the activity of smoothened (Smo). In this study, we evaluated the in vitro and in vivo effects of the smoothened inhibitor GDC-0449 on cell proliferation in human gliomas. We found that high expression of smoothened in glioma is a predictor of short overall survival and poor patient outcome...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195128/a-ligand-directed-divergent-catalytic-approach-to-establish-structural-and-functional-scaffold-diversity
#15
Yen-Chun Lee, Sumersing Patil, Christopher Golz, Carsten Strohmann, Slava Ziegler, Kamal Kumar, Herbert Waldmann
The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194541/undermining-plastic-surgery-as-a%C3%A2-possible-option-for-treating-basal-cell-carcinoma-of-the-forehead
#16
Georgi Tchernev, Ivan Pidakev, Ilia Lozev, Torello Lotti, Jose Carlos Cardoso, James W Patterson
Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib...
February 13, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28192800/molecular-profiling-of-the-developing-lacrimal-gland-reveals-putative-role-of-notch-signaling-in-branching-morphogenesis
#17
Galina Dvoriantchikova, Wensi Tao, Steve Pappas, Gabriel Gaidosh, David T Tse, Dmitry Ivanov, Daniel Pelaez
Purpose: Although normal function of the lacrimal gland is essential for vision (and thus for human well-being), the lacrimal gland remains rather poorly understood at a molecular level. The purpose of this study was to identify new genes and signaling cascades involved in lacrimal gland development. Methods: To identify these genes, we used microarray analysis to compare the gene expression profiles of developing (embryonic) and adult lacrimal glands. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by immunohistochemistry and Western blot analysis...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28192166/detailed-expression-profile-of-the-six-glypicans-and-their-modifying-enzyme-notum-during-chick-limb-and-feather-development
#18
Kawakeb Saad, Susanne Theis, Anthony Otto, Graham Luke, Ketan Patel
The development of vertebrate appendages, especially the limb and feather buds are orchestrated by numerous secreted signalling molecules including Sonic Hedgehog, Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnts. These proteins coordinate the growth and patterning of ectodermal and mesenchymal cells. The influence of signalling molecules is affected over large distances by their concentration (morphogen activity) but also at local levels by the presence of proteins that either attenuate or promote their activity...
February 10, 2017: Gene
https://www.readbyqxmd.com/read/28192057/tongue-and-taste-organ-biology-and-function-homeostasis-maintained-by-hedgehog-signaling
#19
Charlotte M Mistretta, Archana Kumari
The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28188758/a-role-for-the-hedgehog-effector-gli1-in-mediating-stent-induced-ureteral-smooth-muscle-dysfunction-and-aperistalsis
#20
Claudia Janssen, Ralph Buttyan, Chun Y Seow, Wolfgang Jäger, Dennis Solomon, Ladan Fazli, Ben H Chew, Dirk Lange
OBJECTIVES: To better understand the effects of Double J (JJ) stenting on ureteral physiology and function. MATERIALS AND METHODS: In total, twenty-four pigs (24) were stented cystoscopically unilaterally for 48h, 1, 2, 4 and 7 wks. Controls consisted of un-stented animals (n=4) or the contralateral un-stented ureter in pigs. Ureters were harvested and tested in tissue baths to evaluate their contractility. Ureteral inflammation and expression of Sonic Hedgehog (Shh) and the transcriptional activator Gli1 (the downstream target of active HH signaling) were assessed histologically and by immunohistochemistry, respectively...
February 8, 2017: Urology
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