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Hedgehog signalling pathway

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https://www.readbyqxmd.com/read/30114639/honokiol-an-anticancer-lignan
#1
REVIEW
Abdur Rauf, Seema Patel, Muhammad Imran, AneelaMaalik, Muhammad Umair Arshad, Farhan Saeed, Yahia N Mabkhot, Salim S Al-Showiman, Nazir Ahmad, Eman Elsharkawy
BACKGROUND: Honokiol ((3',5-di-(2-propenyl)-1,1'-biphenyl-2,2'-diol), a lignan, is a promising antitumor compound, having exerted activity against a number of human cancer cell lines. Honokiol has inhibitory role on the proliferation, invasion and survival of cancer cells in in vitro as well as in vivo studies. It interferes with signaling pathways components in order to elicit the anticancer effect. SCOPE AND APPROACH: In present review, the published data on the efficacy of honokiol against various cancer cell lines and tumor-bearing animal models has been presented and discussed...
August 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30106753/a-novel-hedgehog-inhibitor-for-the-treatment-of-hematological-malignancies
#2
Peng Lin, Yuanming He, Guodong Chen, Haikuo Ma, Jiyue Zheng, Zubin Zhang, Biyin Cao, Hongjian Zhang, Xiaohu Zhang, Xinliang Mao
The hedgehog-smoothened (HH/SMO) pathway has been proposed as a potential therapeutic target for hematological malignancies. Our previous studies designed a series of HH inhibitors with novel scaffolds distinctive from vismodegib, the first Food and Drug Administration-approved HH inhibitor for the treatment of basal-cell carcinoma and medulloblastoma. In the present study, we evaluated these HH inhibitors against blood cancers and found that HH78 displayed potent activity in suppressing the HH signaling pathway...
August 13, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/30103002/targeting-molecular-pathways-in-cancer-stem-cells-by-natural-bioactive-compounds
#3
REVIEW
Danila Cianciosi, Alfonso Varela-Lopez, Tamara Y Forbes-Hernandez, Massimiliano Gasparrini, Sadia Afrin, Patricia Reboredo-Rodriguez, JiaoJiao Zhang, José L Quiles, Seyed F Nabav, Maurizio Battino, Francesca Giampieri
Cancer Stem Cells (CSCs) or Tumor-Initiating Cells (TICs) are a small sub-population of cells within the tumor, able to give chemio- and radio-resistance and cause the onset of metastasis and the presence of relapses; for these reasons, they are recently becoming a potential target for anticancer therapy. One of the main characteristics of these cells is the self-renewal through the capability of modulating different molecular signalling pathways, including Wnt/β-Catenin, Sonic Hedgehog and Notch pathways...
August 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30102338/identification-of-genomic-alterations-in-nasopharyngeal-carcinoma-and-nasopharyngeal-carcinoma-derived-epstein-barr-virus-by-whole-genome-sequencing
#4
Chaofeng Tu, Zhaoyang Zeng, Peng Qi, Xiayu Li, Can Guo, Fang Xiong, Bo Xiang, Ming Zhou, Qianjin Liao, Jianjun Yu, Yong Li, Xiaoling Li, Guiyuan Li, Wei Xiong
Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China with marked ethnic and geographic distributions and concomitant EBV infection. However, the molecular basis of NPC remains largely unknown and the role of EBV genomic variations in the pathogenesis of NPC is unclear. Whole-genome sequencing of a collection of 12 EBV-positive paired NPC tumor/peripheral blood samples from Hunan province was performed, and the FBXO11 gene was subjected to further functional analyses. We identified 69 missense mutations in signaling pathways typically altered in cancer, including NF-κB and Wnt/Hedgehog/Notch...
August 9, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/30102120/taurine-enhances-mouse-cochlear-neural-stem-cells-proliferation-and-differentiation-to-sprial-gangli-through-activating-sonic-hedgehog-signaling-pathway
#5
Xinghua Huang, Weijing Wu, Peng Hu, Qin Wang
To investigate the molecular mechanism underlying taurine-stimulated proliferation and differentiation of cochlear neural stem cells (NSCs) and potential involvement of Sonic Hedgehog (Shh) pathway. The NSCs were characterized with immunofluorescence stained with nestin antibody. Cell viability was determined by MTT assay. The relative proliferation was measured by BrdU incorporation assay. The morphologic index was measured under light microscope. The relative protein level was determined by immunoblotting...
August 13, 2018: Organogenesis
https://www.readbyqxmd.com/read/30099257/hedgehog-pathway-inhibitors-of-the-acylthiourea-and-acylguanidine-class-show-antitumor-activity-on-colon-cancer-in-vitro-and-in-vivo
#6
Loredana Vesci, Ferdinando Maria Milazzo, Maria Antonietta Stasi, Silvia Pace, Francesco Manera, Carlo Tallarico, Elena Cini, Elena Petricci, Fabrizio Manetti, Rita De Santis, Giuseppe Giannini
Small series of acylguanidine and acylthiourea derivatives were synthesized in gram-scale and assayed for their ability to modulate the Hh signalling pathway. In vitro studies showed a low micromolar inhibitory activity toward tumor cell lines, while the oral administration revealed an excellent ADME profile in vivo. Compound 5 emerged as the most active and safe inhibitor of colon cancer cells both in vitro and in a xenograft mouse model. Based on these data, 5 could be prioritized to further development with the perspective of clinical studies...
July 27, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30098229/identification-of-novel-gli1-target-genes-and-regulatory-circuits-in-human-cancer-cells
#7
Yumei Diao, Mohammed Ferdous-Ur Rahman, Yuri Vyatkin, Ani Azatyan, Georges St Laurent, Philipp Kapranov, Peter G Zaphiropoulos
Hedgehog (HH) signaling is involved in many physiological processes, and pathway deregulation can result in a wide range of malignancies. Glioma-associated oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1 cellular targets is quite limited. In this study, we identified multiple new GLI1 target genes using a combination of different genomic surveys and then subjected them to in-depth validation in human cancer cell lines...
August 11, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/30095060/breast-cancer-stem-cells-and-sex-steroid-hormones
#8
Ivan Flores-Ramirez, Noemi Baranda-Avila, Elizabeth Langley
Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells that express stem cell-associated markers. In recent years, their properties and mechanisms of regulation have become a focus for intense research due to their intrinsic resistance to conventional cancer therapies. This review describes breast cancer stem cell origin, signaling pathways involved in self-renewal, such as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex steroid hormones on BCSC regulation...
August 10, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/30094580/altered-notch-signaling-in-developing-molar-teeth-of-pituitary-adenylate-cyclase-activating-polypeptide-pacap-deficient-mice
#9
B D Fulop, B Sandor, E Szentleleky, E Karanyicz, D Reglodi, B Gaszner, R Zakany, H Hashimoto, T Juhasz, A Tamas
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with neuroprotective and neurotrophic effects. This suggests its influence on the development of teeth, which are, similarly to the nervous system, ectoderm and neural crest derivatives. Our earlier studies have shown morphological differences between wild-type (WT) and PACAP-deficient mice, with upregulated sonic hedgehog (SHH) signaling in the lack of PACAP. Notch signaling is a key element of proper tooth development by regulating apoptosis and cell proliferation...
August 10, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/30086335/gli2-is-required-for-the-induction-and-migration-of-xenopus-laevis-neural-crest
#10
Santiago Cerrizuela, Guillermo A Vega-López, María Belén Palacio, Celeste Tríbulo, Manuel J Aybar
The neural crest (NC) is a multipotent migratory embryonic population that is formed during late gastrulation and gives rise to a wide array of derivatives, including cells from the peripheral nervous system (PNS), the craniofacial bones and cartilages, peripheral glial cells, and melanocyte cells, among others. In this work we analyzed the role of the Hedgehog signaling pathway effector gli2 in Xenopus NC. We provide evidence that the gli2 gene is expressed in the prospective, premigratory and migratory NC...
August 4, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/30081498/hedgehog-signaling-pathway-and-autophagy-in-cancer
#11
REVIEW
Xian Zeng, Dianwen Ju
Hedgehog (Hh) pathway controls complex developmental processes in vertebrates. Abnormal activation of Hh pathway is responsible for tumorigenesis and maintenance of multiple cancers, and thus addressing this represents promising therapeutic opportunities. In recent years, two Hh inhibitors have been approved for basal cell carcinoma (BCC) treatment and show extraordinary clinical outcomes. Meanwhile, a series of novel agents are being developed for the treatment of several cancers, including lung cancer, leukemia, and pancreatic cancer...
August 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30076415/the-lim1-oncogene-as-a-new-therapeutic-target-for-metastatic-human-renal-cell-carcinoma
#12
Imène Hamaidi, Catherine Coquard, Sabrina Danilin, Valérian Dormoy, Claire Béraud, Sylvie Rothhut, Mariette Barthelmebs, Nadia Benkirane-Jessel, Véronique Lindner, Hervé Lang, Thierry Massfelder
Metastatic clear cell renal cell carcinoma (CCC) remains incurable despite advances in the development of anti-angiogenic targeted therapies and the emergence of immune checkpoint inhibitors. We have previously shown that the sonic hedgehog-Gli signaling pathway is oncogenic in CCC allowing us to identify the developmental Lim1 transcription factor as a Gli target and as a new oncogene in CCC regulating cell proliferation and apoptosis, and promoting tumor growth. In this previous study, preliminary in vitro results also suggested that Lim1 may be implicated in metastatic spread...
August 3, 2018: Oncogene
https://www.readbyqxmd.com/read/30073412/the-hedgehog-pathway-and-ocular-developmental-anomalies
#13
REVIEW
Florencia Cavodeassi, Sophie Creuzet, Heather C Etchevers
Mutations in effectors of the hedgehog signaling pathway are responsible for a wide variety of ocular developmental anomalies. These range from massive malformations of the brain and ocular primordia, not always compatible with postnatal life, to subtle but damaging functional effects on specific eye components. This review will concentrate on the effects and effectors of the major vertebrate hedgehog ligand for eye and brain formation, Sonic hedgehog (SHH), in tissues that constitute the eye directly and also in those tissues that exert indirect influence on eye formation...
August 2, 2018: Human Genetics
https://www.readbyqxmd.com/read/30072823/renal-cell-carcinoma-molecular-aspects
#14
REVIEW
Aman Kumar, Niti Kumari, Vinny Gupta, Rajendra Prasad
Renal cell carcinoma is the most common form of the kidney cancer accounting for more than 85% of the cases of which clear cell renal cell carcinoma (ccRCC) is the major histological subtype. The central molecular signature for ccRCC pathogenesis is the biallelic inactivation of VHL gene due to the presence of mutations/hyper-methylation/complete gene loss, which results in the downstream HIF activation. These events lead to increased tyrosine kinase receptor signalling pathways (RAS/MEK/ERK pathway, PI3K/AKT/mTOR pathway and NF-κB pathway), which through their downstream effector proteins causes the cell to proliferate and migrate...
July 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/30066430/transcriptomic-analysis-reveals-differentially-expressed-genes-associated-with-wool-length-in-rabbit
#15
B Zhao, Y Chen, Y Hao, N Yang, M Wang, M Mei, J Wang, X Qiu, X Wu
Rabbit fur characteristics are primarily genetically determined traits. We used Illumina high-throughput sequencing technology to assess gene expression in the skin tissues of rabbits derived from a cross between Wanxi Angora rabbits and Rex rabbits, which exhibit differential characteristics of short and long wool respectively, to investigate molecular mechanisms related to wool length determination. To identify key regulatory genes involved in rabbit wool length, genes that were differentially expressed between the long- and short-wool rabbits based on a P-value < 0...
August 1, 2018: Animal Genetics
https://www.readbyqxmd.com/read/30064819/discovery-of-a-potent-hedgehog-pathway-inhibitor-capable-of-activating-caspase8-dependent-apoptosis
#16
Qin Chen, Haoran Zhang, Meng Wu, Qin Wang, Lusong Luo, Haikuo Ma, Xiaohu Zhang, Sudan He
Aberrant activation of Hedgehog (Hh) signaling is associated with the development of numerous human cancers. Vismodegib is the first Hh inhibitor approved for anti-cancer therapy by targeting Smoothened (SMO), a critical regulator of the Hh pathway. However, acquisition of drug resistance to vismodegib occurs overtime. Apoptosis is a prevalent form of programmed cell death that is executed by caspases. Induction of tumor cell apoptosis represents an attractive therapeutic strategy to eliminate tumor cells. To explore new Hh antagonists with apoptosis-inducing activity, we screened a set of ∼300 potential SMO antagonists with novel scaffold structures...
July 10, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/30064125/adipocyte-derived-exosomes-carrying-sonic-hedgehog-mediate-m1-macrophage-polarization-induced-insulin-resistance-via-ptch-and-pi3k-pathways
#17
Ming Song, Lu Han, Fang-Fang Chen, Di Wang, Feng Wang, Lei Zhang, Zhi-Hao Wang, Ming Zhong, Meng-Xiong Tang, Wei Zhang
BACKGROUND/AIMS: Adipocyte-derived exosomes (ADEs) stimulate the activation of macrophages and contribute to the development of insulin resistance. Sonic Hedgehog (Shh) is an exosome-carrying protein and stimulates macrophages to secrete inflammatory cytokines. However, the impact of ADEs carrying Shh on the pro-inflammatory activation of macrophages and consequently, adipocyte insulin resistance is unclear. METHODS: 3T3-L1 adipocytes were cultured with high glucose and insulin to imitate the pathogeny of insulin resistance...
July 31, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30063598/expression-of-signaling-molecules-involved-in-embryonic-development-of-the-insertion-site-is-inadequate-for-reformation-of-the-native-enthesis-evaluation-in-a-novel-murine-acl-reconstruction-model
#18
Xiang-Hua Deng, Amir Lebaschi, Christopher L Camp, Camila B Carballo, Nathan W Coleman, Jianchun Zong, Brian M Grawe, Scott A Rodeo
BACKGROUND: Since healing of anterior cruciate ligament (ACL) grafts occurs by formation of a fibrovascular scar-tissue interface rather than by reformation of the native fibrocartilage transition zone, the purpose of our study was to examine expression of various signaling molecules and transcription factors that are known to be involved in embryologic insertion-site development following ACL reconstruction. We also aimed to characterize a murine model of ACL reconstruction to allow future study of the molecular mechanisms of healing...
August 1, 2018: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/30061220/rbpj-and-maml3-potential-therapeutic-targets-for-small-cell-lung-cancer
#19
Hideya Onishi, Shu Ichimiya, Kosuke Yanai, Masayo Umebayashi, Katsuya Nakamura, Akio Yamasaki, Akira Imaizumi, Shuntaro Nagai, Mutsunori Murahashi, Hisanobu Ogata, Takashi Morisaki
BACKGROUND/AIM: Small cell lung cancer (SCLC) is still a deadly type of cancer for which there are few effective therapeutic strategies. Development of a new molecule targeting agent is urgently desired. Previously we showed that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) are new therapeutic targets for pancreatic cancer. In the present study, we analyzed whether RBPJ/MAML3 inhibition could also be a new therapeutic strategy for SCLC...
August 2018: Anticancer Research
https://www.readbyqxmd.com/read/30041193/loc101930370-mir-1471-axis-modulates-the-hedgehog-signaling-pathway-in-breast-cancer
#20
Xin Liu, Tong Zhao, Xue Bai, Mingqi Li, Jingli Ren, Mengxue Wang, Ranchen Xu, Shuqian Zhang, Huimin Li, Yingying Hu, Liangjun Xie, Ying Zhang, Lida Yang, Chaoqi Yan, Yong Zhang
BACKGROUND/AIMS: Non-coding RNAs (ncRNAs) play vital regulatory roles in many tumors. However, the functional roles of these transcripts responsible for their dysregulation in breast cancer (BC) are not thoroughly understood. METHODS: We examined the expression of microRNA miR-1471 in BC specimens. Online analysis tools predicted that lncRNA LOC101930370 might act as an endogenous 'sponge' by competing for miR-1471 binding targets. Luciferase assays were used to prove the interaction of LOC101930370, miR-1471 and SHH...
July 24, 2018: Cellular Physiology and Biochemistry
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