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https://www.readbyqxmd.com/read/28327131/transcriptome-analysis-of-pancreatic-cells-across-distant-species-highlights-novel-important-regulator-genes
#1
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
#2
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...
February 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28316026/zebrafish-as-a-model-to-evaluate-peptide-related-cancer-therapies
#3
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
https://www.readbyqxmd.com/read/28289406/antagonistic-activity-and-mode-of-action-of-phenazine-1-carboxylic-acid-produced-by-marine-bacterium-pseudomonas-aeruginosa-pa31x-against-vibrio-anguillarum-in-vitro-and-in-a-zebrafish-in-vivo-model
#4
Linlin Zhang, Xueying Tian, Shan Kuang, Ge Liu, Chengsheng Zhang, Chaomin Sun
Phenazine and its derivatives are very important secondary metabolites produced from Pseudomonas spp. and have exhibited broad-spectrum antifungal and antibacterial activities. However, till date, there are few reports about marine derived Pseudomonas and its production of phenazine metabolites. In this study, we isolated a marine Pseudomonas aeruginosa strain PA31x which produced natural product inhibiting the growth of Vibrio anguillarum C312, one of the most serious bacterial pathogens in marine aquaculture...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28278039/cardiovascular-toxicity-assessment-of-poly-ethylene-imine-based-cationic-polymers-on-zebrafish-model
#5
Qinglian Hu, Fengliang Guo, Fenghui Zhao, Guping Tang, Zhengwei Fu
Poly(ethylene imine)s (PEIs) have gained enormous attention in designing novel drug delivery systems for cancer treatment. High molecular weight of PEIs such as PEI 25 kD are promising for their drug carrying capacity. However, increased molecular weight is associated with toxicity. Currently, the toxicity evaluation of PEIs is mainly focused on the culture cell models, with very few studies investigating the risk assessment in vivo. Herein, the systemic evaluation of branched PEI 25 kD and PEI-CyD (PC) composed of low molecular PEI (Mw 600) and β-cyclodextrin (β-CyD) is performed in zebrafish model and endothelial cells...
March 6, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28277839/zebrafish-xenograft-models-of-cancer-and-metastasis-for-drug-discovery
#6
Hannah K Brown, Kristina Schiavone, Simon Tazzyman, Dominique Heymann, Timothy Ja Chico
Patients with metastatic cancer suffer the highest rate of cancer-related death, but existing animal models of metastasis have disadvantages that limit our ability to understand this process. The zebrafish is increasingly used for cancer modelling, particularly xenografting of human cancer cell lines, and drug discovery, and may provide novel scientific and therapeutic insights. However, this model system remains underexploited. Areas covered: The authors discuss the advantages and disadvantages of the zebrafish xenograft model for the study of cancer, metastasis and drug discovery...
March 1, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28270608/rab5-regulated-endocytosis-plays-a-crucial-role-in-apical-extrusion-of-transformed-cells
#7
Sayaka Saitoh, Takeshi Maruyama, Yuta Yako, Mihoko Kajita, Yoichiro Fujioka, Yusuke Ohba, Nobuhiro Kasai, Natsu Sugama, Shunsuke Kon, Susumu Ishikawa, Takashi Hayashi, Tomohiro Yamazaki, Masazumi Tada, Yasuyuki Fujita
Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28270026/manganese-and-cobalt-activate-zebrafish-ovarian-cancer-g-protein-coupled-receptor-1-but-not-gpr4
#8
Jun Negishi, Yuka Omori, Mami Shindo, Hayate Takanashi, Shiori Musha, Suminori Nagayama, Jun Hirayama, Hiroshi Nishina, Takashi Nakakura, Chihiro Mogi, Koichi Sato, Fumikazu Okajima, Yuta Mochimaru, Hideaki Tomura
Mammalian ovarian G-protein-coupled receptor 1 (OGR1) is activated by some metals in addition to extracellular protons and coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebrafish OGR1, zebrafish GPR4, and human GPR4 (zOGR1, zGPR4, and hGPR4, respectively) could sense the metals and activate the intracellular signaling pathways. On one hand, we found that only manganese and cobalt of the tested metals stimulated SRE-promoter activities in zOGR1-overexpressed HEK293T cells...
March 7, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28257660/induction-of-intrinsic-apoptosis-in-leukaemia-stem-cells-and-in-vivo-zebrafish-model-by-betulonic-acid-isolated-from-walsura-pinnata-hassk-meliaceae
#9
Kok Hoong Leong, Mohamad Azrul Mahdzir, Mohd Fadzli Md Din, Khalijah Awang, Yuka Tanaka, Kasem Kulkeaw, Tohru Ishitani, Daisuke Sugiyama
BACKGROUND: Leukaemia stem cells (LSC) have been associated with disease relapse and chemotherapy resistance. Betulonic acid (BA), a pentacyclic lupane-type triterpenoid, was reported to exhibit cytotoxicity toward various cancer cells and to be capable of inducing intrinsic apoptosis in solid tumours. However, the in vitro and in vivo apoptotic effects of BA against LSC remain unknown. HYPOTHESIS/PURPOSE: We aimed to determine whether BA isolated from bark of Walsura pinnata Hassk (Meliaceae) has pro-apoptotic effects on LSC in in vitro and in vivo models...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28230863/oncogenic-role-of-rab-escort-protein-1-through-egfr-and-stat3-pathway
#10
Un-Jung Yun, Jee Young Sung, Seog-Yun Park, Sang-Kyu Ye, Jaegal Shim, Jae-Seon Lee, Masahiko Hibi, Young-Ki Bae, Yong-Nyun Kim
Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28222105/stat3-cdc25a-dependent-cell-proliferation-promotes-embryonic-axis-extension-during-zebrafish-gastrulation
#11
Yinzi Liu, Diane S Sepich, Lilianna Solnica-Krezel
Cell proliferation has generally been considered dispensable for anteroposterior extension of embryonic axis during vertebrate gastrulation. Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome. Zebrafish Stat3 was proposed to govern convergence and extension gastrulation movements in part by promoting Wnt/Planar Cell Polarity (PCP) signaling, a conserved regulator of mediolaterally polarized cell behaviors...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28215799/comprehensive-understanding-of-pm2-5-on-gene-and-microrna-expression-patterns-in-zebrafish-danio-rerio-model
#12
Junchao Duan, Yang Yu, Yang Li, Li Jing, Man Yang, Ji Wang, Yanbo Li, Xianqing Zhou, Mark R Miller, Zhiwei Sun
PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process...
May 15, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#13
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28194644/ionizing-radiation-blocks-hair-cell-regeneration-in-zebrafish-lateral-line-neuromasts-by-preventing-wnt-signaling
#14
Rong Li, Guixiang Liao, Guo Yin, Baiyao Wang, Miaohong Yan, Xiaoshan Lin, Wenqing Zhang, Xiaohui Chen, Shasha Du, Yawei Yuan
Loss of hair cells occurs after radiotherapy, which is a major treatment modality for head and neck cancers. In the lateral line neuromasts of zebrafish, hair cells regenerate rapidly from supporting cells after damage from ototoxins. To investigate hair cell regeneration after radiation damage, zebrafish larvae were exposed to radiation, and hair cells were counted and cell proliferation was detected in neuromasts. After irradiation exposure, cell proliferation was inhibited in neuromasts and the number of supporting cells remained stable...
February 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28193911/eif3i-activity-is-critical-for-endothelial-cells-in-tumor-induced-angiogenesis-through-regulating-vegfr-and-erk-translation
#15
Yaguang Zhang, Ping Wang, Qian Zhang, Xiaomin Yao, Linjie Zhao, Yibin Liu, Xiaowei Liu, Rui Tao, Chuan Yu, Yuhao Li, Xiangrong Song, Shaohua Yao
Translational control is a critical step in the regulation of gene expression. Accumulating evidence shows that translational control of a subgroup of mRNAs tends to be selective. However, our understanding of the function of selective translational control in endothelial cells is still incomplete. We found that a key translational regulator, eIF3i, is highly expressed in endothelial cells during embryonic and tumor angiogenesis. Knockdown of eIF3i restrained cell proliferation and migration in endothelial cells...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28188179/new-insights-into-the-role-of-jmjd3-and-utx-in-axial-skeletal-formation-in-mice
#16
Chie Naruse, Shinwa Shibata, Masaru Tamura, Takayuki Kawaguchi, Kanae Abe, Kazushi Sugihara, Tomoaki Kato, Takumi Nishiuchi, Shigeharu Wakana, Masahito Ikawa, Masahide Asano
Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that Jmjd3 is essential for differentiation of various cell types, such as macrophages and epidermal cells in mice, whereas Utx is involved in cancer and developmental diseases in humans and mice as well as Hox regulation in zebrafish and nematodes. Here, we report that Jmjd3, but not Utx, is involved in axial skeletal formation in mice. A Jmjd3 mutant embryo (Jmjd3(Δ18/Δ18)), but not a catalytically inactive Utx truncation mutant (Utx(-/y)), showed anterior homeotic transformation...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183660/anticancer-activity-of-biologically-synthesized-silver-and-gold-nanoparticles-on-mouse-myoblast-cancer-cells-and-their-toxicity-against-embryonic-zebrafish
#17
Rajan Ramachandran, Chandran Krishnaraj, Allur Subramaniyan Sivakumar, Palaniappan Prasannakumar, V K Abhay Kumar, Kwan Seob Shim, Chul-Gyu Song, Soon-Il Yun
The aim of this study was to evaluate the anticancer activity of bioinspired silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mouse myoblast cancer cells (C2C12). Both AgNPs and AuNPs were biologically synthesized using Spinacia oleracea Linn., aqueous leaves extract. UV-Vis. spectrophotometer, high resolution-transmission electron microscopy (HR-TEM), field emission-scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) studies supported the successful synthesis of AgNPs and AuNPs...
April 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28181494/microenvironment-derived-factors-driving-metastatic-plasticity-in-melanoma
#18
Isabella S Kim, Silja Heilmann, Emily R Kansler, Yan Zhang, Milena Zimmer, Kajan Ratnakumar, Robert L Bowman, Theresa Simon-Vermot, Myles Fennell, Ralph Garippa, Liang Lu, William Lee, Travis Hollmann, Joao B Xavier, Richard M White
Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITF(LO) versus proliferative/MITF(HI) states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITF(HI)/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact a gene expression program of melanocyte differentiation...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28173755/melanoma-genome-evolution-across-species
#19
Emily R Kansler, Akanksha Verma, Erin M Langdon, Theresa Simon-Vermot, Alexandra Yin, William Lee, Marc Attiyeh, Olivier Elemento, Richard M White
BACKGROUND: Cancer genomes evolve in both space and time, which contributes to the genetic heterogeneity that underlies tumor progression and drug resistance. In human melanoma, identifying mechanistically important events in tumor evolution is hampered due to the high background mutation rate from ultraviolet (UV) light. Cross-species oncogenomics is a powerful tool for identifying these core events, in which transgenically well-defined animal models of cancer are compared to human cancers to identify key conserved alterations...
February 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28166211/divergent-effects-of-intrinsically-active-mek-variants-on-developmental-ras-signaling
#20
Yogesh Goyal, Granton A Jindal, José L Pelliccia, Kei Yamaya, Eyan Yeung, Alan S Futran, Rebecca D Burdine, Trudi Schüpbach, Stanislav Y Shvartsman
Germline mutations in Ras pathway components are associated with a large class of human developmental abnormalities, known as RASopathies, that are characterized by a range of structural and functional phenotypes, including cardiac defects and neurocognitive delays. Although it is generally believed that RASopathies are caused by altered levels of pathway activation, the signaling changes in developing tissues remain largely unknown. We used assays with spatiotemporal resolution in Drosophila melanogaster (fruit fly) and Danio rerio (zebrafish) to quantify signaling changes caused by mutations in MAP2K1 (encoding MEK), a core component of the Ras pathway that is mutated in both RASopathies and cancers in humans...
March 2017: Nature Genetics
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