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https://www.readbyqxmd.com/read/28426725/dynamic-regulation-of-pin1-expression-and-function-during-zebrafish-development
#1
Maria Solange Ibarra, Carla Borini Etichetti, Carolina Di Benedetto, Germán L Rosano, Ezequiel Margarit, Giannino Del Sal, Marina Mione, Javier Girardini
The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed phosphorylation signaling by inducing local conformational changes in phosphorylated protein substrates. Extensive studies showed different roles for Pin1 in physiological processes and pathological conditions such as cancer and neurodegenerative diseases. However, there are still several unanswered questions regarding its biological role. Notably, despite evidences from cultured cells showing that Pin1 expression and activity may be regulated by different mechanisms, little is known on their relevance in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28424417/mesenchymal-stem-cells-differentially-affect-the-invasion-of-distinct-glioblastoma-cell-lines
#2
Barbara Breznik, Helena Motaln, Miloš Vittori, Ana Rotter, Tamara Lah Turnšek
Glioblastoma multiforme are an aggressive form of brain tumors that are characterized by distinct invasion of single glioblastoma cells, which infiltrate the brain parenchyma. This appears to be stimulated by the communication between cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the glioblastoma microenvironment, and their 'cross-talk' with glioblastoma cells is still poorly understood. Here, we examined the effects of bone marrow-derived MSCs on two different established glioblastoma cell lines U87 and U373...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420724/a-zebrafish-model-discovers-a-novel-mechanism-of-stromal-fibroblast-mediated-cancer-metastasis
#3
Cai Feng Liu, Yunjian Zhang, Sharon Lim, Kayoko Hosaka, Yunlong Yang, Tatiana Pavlova, Twana Alkasalias, Johan Hartman, Lasse Jensen, Xiao-Ming Xing, Xingsheng Wang, Yong-Tian Lu, Guo Hui Nie, Yihai Cao
Purpose: Cancer metastasis can occur at the early stage of tumor development when a primary tumor at the microscopic size. In particular, the interaction of malignant cells with other cell types including cancer-associated fibroblasts (CAFs) in promoting metastasis at the early stage of tumor development remains largely unknown. Here, we investigated the role of CAFs in facilitating the initial events of cancer metastasis when primary tumors were at microscopic sizes.  <p>Experimental design: Multi-color-coded cancer cells and CAFs were co-implanted into the transparent zebrafish body and metastasis at a single cell level was monitored in living animals...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28417011/chemical-biology-reveals-carf-as-a-positive-regulator-of-canonical-wnt-signaling-by-promoting-tcf-%C3%AE-catenin-transcriptional-activity
#4
Xiaoli He, Wenjuan Zhang, Chen Yan, Fen Nie, Chen Li, Xiaofen Liu, Cong Fei, Shengdi Li, Xiaomin Song, Yingying Jia, Rong Zeng, Dianqing Wu, Weijun Pan, Xiaojiang Hao, Lin Li
Wnt/β-catenin signaling regulates multiple biological processes and aberration of this pathway is frequently observed in human cancers. Previously, we uncovered NC043 as a small-molecule inhibitor of Wnt/β-catenin signaling. Here, we identified CARF as the cellular target of NC043. We found that NC043 binds directly to CARF through forming a covalent bond with the Cys-516 residue of CARF. Further study revealed that CARF interacts with Dvl, which potentiates the Dvl-c-Jun-β-catenin-TCF transcriptional complex and thus promotes Wnt signaling activation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28416275/cisplatin-analogs-confer-protection-against-cyanide-poisoning
#5
Anjali K Nath, Xu Shi, Devin L Harrison, Jordan E Morningstar, Sari Mahon, Adriano Chan, Patrick Sips, Jangwoen Lee, Calum A MacRae, Gerry R Boss, Matthew Brenner, Robert E Gerszten, Randall T Peterson
Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro...
April 7, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28411182/pegylation-rate-influences-peptide-based-nanoparticles-mediated-sirna-delivery-in-vitro-and-in-vivo
#6
Gudrun Aldrian, Anaïs Vaissière, Karidia Konate, Quentin Seisel, Eric Vivès, Frédéric Fernandez, Véronique Viguier, Coralie Genevois, Franck Couillaud, Héléne Démèné, Dina Aggad, Aurélie Covinhes, Stéphanie Barrère-Lemaire, Sébastien Deshayes, Prisca Boisguerin
Small interfering RNAs (siRNAs) present a strong therapeutic potential because of their ability to inhibit the expression of any desired protein. Recently, we developed the retro-inverso amphipathic RICK peptide as novel non-covalent siRNA carrier. This peptide is able to form nanoparticles (NPs) by self-assembling with the siRNA resulting in the fully siRNA protection based on its protease resistant peptide sequence. With regard to an in vivo application, we investigated here the influence of the polyethylene glycol (PEG) grafting to RICK NPs on their in vitro and in vivo siRNA delivery properties...
April 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28397687/a-metabolic-switch-controls-intestinal-differentiation-downstream-of-adenomatous-polyposis-coli-apc
#7
Imelda T Sandoval, Richard Glenn C Delacruz, Braden N Miller, Shauna Hill, Kristofor A Olson, Ana E Gabriel, Kevin Boyd, Christeena Satterfield, Holly Van Remmen, Jared Rutter, David A Jones
Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28394345/cripto-and-its-signaling-partner-grp78-drive-the-metastatic-phenotype-in-human-osteotropic-prostate-cancer
#8
E Zoni, L Chen, S Karkampouna, Z Granchi, E I Verhoef, F La Manna, J Kelber, R C M Pelger, M D Henry, E Snaar-Jagalska, G J L H van Leenders, L Beimers, P Kloen, P C Gray, G van der Pluijm, M Kruithof-de Julio
CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDH(high) sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDH(low). Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDH(high) sub-population...
April 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28385952/dieldrin-augments-mtor-signaling-and-inhibits-lysosomal-acidification-in-the-adult-zebrafish-heart-danio-rerio
#9
Logan Slade, Andrew Cowie, Chris J Martynuik, Petra C Kienesberger, Thomas Pulinilkunnil
Dieldrin is a legacy organochlorine pesticide that is persistent in the environment, despite being discontinued from use in North America since the 1970s. Some epidemiological studies suggest that exposure to dieldrin is associated with increased risks of neurodegenerative disease and breast cancer by inducing inflammatory responses in tissues as well as oxidative stress. However, the direct effects of organochlorine pesticides on the heart have not been adequately addressed to date given that these chemicals are detectable in human serum and are environmentally persistent, thus individuals may show latent adverse effects in the cardiovasculature system due to chronic, low dose exposure over time...
April 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28382676/natural-genomic-amplification-of-cholinesterase-genes-in-animals
#10
REVIEW
Arnaud Chatonnet, Nicolas Lenfant, Pascale Marchot, Murray E Selkirk
Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases...
April 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28379616/from-fish-bowl-to-bedside-the-power-of-zebrafish-to-unravel-melanoma-pathogenesis-and-discover-new-therapeutics
#11
REVIEW
Ellen van Rooijen, Maurizio Fazio, Leonard I Zon
Melanoma is the most aggressive and deadliest form of skin cancer. A detailed knowledge of the cellular, molecular and genetic events underlying melanoma progression is highly relevant to diagnosis, prognosis and risk stratification, and the development of new therapies. In the last decade, zebrafish have emerged as a valuable model system for the study of melanoma. Pathway conservation, coupled with the availability of robust genetic, transgenic and chemical tools, has made the zebrafish a powerful model for identifying novel disease genes, visualizing cancer initiation, interrogating tumor-microenvironment interactions and discovering new therapeutics that regulate melanocyte and melanoma development...
April 5, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28378824/chemical-inhibition-reveals-differential-requirements-of-signaling-pathways-in-kras-v12-and-myc-induced-liver-tumors-in-transgenic-zebrafish
#12
Chuan Yan, Qiqi Yang, Xiaojing Huo, Hankun Li, Li Zhou, Zhiyuan Gong
Previously we have generated inducible liver tumor models by transgenic expression of an oncogene and robust tumorigenesis can be rapidly induced by activation of the oncogene in both juvenile and adult fish. In the present study, we aimed at chemical intervention of tumorigenesis for understanding molecular pathways of tumorigenesis and for potential development of a chemical screening tool for anti-cancer drug discovery. Thus, we evaluated the roles of several major signaling pathways in kras(V12)- or Myc-induced liver tumors by using several small molecule inhibitors: SU5402 and SU6668 for VEGF/FGF signaling; IWR1 and cardionogen 1 for Wnt signaling; and cyclopamine and Gant61 for Hedgehog signaling...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371640/lipophilicity-antiproliferative-activity-relationship-study-leads-to-the-preparation-of-a-ruthenium-ii-arene-complex-with-considerable-in%C3%A2-vitro-cytotoxicity-against-cancer-cells-and-a-lower-in%C3%A2-vivo-toxicity-in-zebrafish-embryos-than-clinically-approved-cis
#13
MohammadMehdi Haghdoost, Golara Golbaghi, Myriam Létourneau, Shunmoogum A Patten, Annie Castonguay
Ru(II)-arene complexes are attracting increasing attention due to their considerable antitumoral activity. However, it is difficult to clearly establish a direct relationship between their structure and antiproliferative activity, as substantial structural changes might not only affect their anticancer activity but also tightly control their activation site(s) and/or their biological target(s). Herein, we describe the synthesis and characterization of four ruthenium(II) arene complexes bearing bidentate N,O-donor Schiff-base ligands ([Ru(η(6)-benzene)(N-O)Cl]) that display a significantly distinct antiproliferative activity against cancer cells, despite their close structural similarity...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28350298/oncogenic-braf-disrupts-thyroid-morphogenesis-and-function-via-twist-expression
#14
Viviana Anelli, Jacques A Villefranc, Sagar Chhangawala, Raul Martinez-McFaline, Eleonora Riva, Anvy Nguyen, Akanksha Verma, Rohan Bareja, Zhengming Chen, Theresa Scognamiglio, Olivier Elemento, Yariv Houvras
Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAF(V600E). Through the use of real-time in vivo imaging, we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAF(V600E). Adult zebrafish expressing BRAF(V600E) in thyrocytes developed invasive carcinoma...
March 28, 2017: ELife
https://www.readbyqxmd.com/read/28350247/the-transgenic-zebrafish-display-fluorescence-reflecting-the-expressional-dynamics-of-dihydrofolate-reductase
#15
Wen-Ni Chang, Wan-Yu Chi, Tseng-Ting Kao, Jen-Ning Tsai, Wangta Liu, Shih-Shin Liang, Chien-Chih Chiu, Bing-Hung Chen, Tzu-Fun Fu
Dihydrofolate reductase (DHFR) reduces folic acid and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate. DHFR is upregulated in rapidly proliferating cells and hence a favored target of antifolate drug against cancers, autoimmune diseases, and microbial infections. However, increased expression of dhfr contributed to the often emerging drug resistance and impeded the therapeutic efficacy of antifolate drugs. Therefore, comprehensive knowledge on the expressional control of dhfr becomes crucial...
March 28, 2017: Zebrafish
https://www.readbyqxmd.com/read/28350162/in-vivo-recognition-of-human-vascular-endothelial-growth-factor-by-molecularly-imprinted-polymers
#16
Alessandra Cecchini, Vittoria Raffa, Francesco Canfarotta, Giovanni Signore, Sergey Piletsky, Michael P MacDonald, Alfred Cuschieri
One of the mechanisms responsible for cancer-induced increased blood supply in malignant neoplasms is the overexpression of vascular endothelial growth factor (VEGF). Several antibodies for VEGF targeting have been produced for both imaging and therapy. Molecularly imprinted polymer nanoparticles, nanoMIPs, however, offer significant advantages over antibodies, in particular in relation to improved stability, speed of design, cost and control over functionalization. In the present study, the successful production of nanoMIPs against human VEGF is reported for the first time...
April 3, 2017: Nano Letters
https://www.readbyqxmd.com/read/28336914/inhibition-of-serum-and-glucocorticoid-regulated-kinase-1-as-novel-therapy-for-cardiac-arrhythmia-disorders
#17
Vassilios J Bezzerides, Aifeng Zhang, Ling Xiao, Bridget Simonson, Santosh A Khedkar, Shiro Baba, Filomena Ottaviano, Stacey Lynch, Katherine Hessler, Alan C Rigby, David Milan, Saumya Das, Anthony Rosenzweig
Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327131/transcriptome-analysis-of-pancreatic-cells-across-distant-species-highlights-novel-important-regulator-genes
#18
Estefania Tarifeño-Saldivia, Arnaud Lavergne, Alice Bernard, Keerthana Padamata, David Bergemann, Marianne L Voz, Isabelle Manfroid, Bernard Peers
BACKGROUND: Defining the transcriptome and the genetic pathways of pancreatic cells is of great interest for elucidating the molecular attributes of pancreas disorders such as diabetes and cancer. As the function of the different pancreatic cell types has been maintained during vertebrate evolution, the comparison of their transcriptomes across distant vertebrate species is a means to pinpoint genes under strong evolutionary constraints due to their crucial function, which have therefore preserved their selective expression in these pancreatic cell types...
March 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/28320616/high-content-screen-using-zebrafish-danio-rerio-embryos-identifies-a-novel-kinase-activator-and-inhibitor
#19
Werner J Geldenhuys, Sadie A Bergeron, Jackie E Mullins, Rowaa Aljammal, Briah L Gaasch, Wei-Chi Chen, June Yun, Lori A Hazlehurst
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28316026/zebrafish-as-a-model-to-evaluate-peptide-related-cancer-therapies
#20
REVIEW
Austin Y Shull, Chien-An A Hu, Yong Teng
Peptide-derived drug discovery has experienced a remarkable resurgence in the past decade since the failure of small-molecule modulators to effectively access the large binding surfaces of intracellular protein-protein interactions as well as "undruggable" residues of certain disease-driving proteins. However, the effectiveness of peptide-based cancer therapies is being questioned in light of declines in pharmaceutical R&D efficiency. As a model of whole organism, zebrafish provide a means to develop promising peptide and protein anticancer agents in an informative, cost-effective and time-efficient manner, which also allows for surveying mechanisms of drug action and optimization of drug delivery system...
March 18, 2017: Amino Acids
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