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https://www.readbyqxmd.com/read/28534941/two-natural-eudesmane-type-sesquiterpenes-from-laggera-alata-inhibit-angiogenesis-and-suppress-breast-cancer-cell-migration-through-vegf-and-angiopoietin-2-mediated-signaling-pathways
#1
Ning Liang, Yaolan Li, Hau Yin Chung
Eudesmane-type sesquiterpenes are natural sesquiterpenes with anti-inflammatory properties, but their anti-angiogenic activities are not known. The present study demonstrated that 5α-hydroxycostic acid and hydroxyisocostic acid, two eudesmane-type sesquiterpenes (ETSs), isolated from the herb Laggera alata, possessed anti-angiogenic effects. Under non-toxic dosage, ETSs suppressed VEGF‑induced proliferation in human umbilical vein endothelial cells (HUVECs) and vessel formation in zebrafish embryos. Moreover, ETSs inhibited VEGF-stimulated HUVEC migration, stress fibers and tube formation...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28526577/changes-in-tumor-cell-heterogeneity-after-chemotherapy-treatment-in-a-xenograft-model-of-glioblastoma
#2
Alessandra M Welker, Brian D Jaros, Min An, Christine E Beattie
Glioblastoma (GBM) is a highly aggressive brain cancer with limited treatments and poor patient survival. GBM tumors are heterogeneous containing a complex mixture of dividing cells, differentiated cells, and cancer stem cells. It is unclear, however, how these different cell populations contribute to tumor growth or whether they exhibit differential responses to chemotherapy. Here we set out to address these questions using a zebrafish xenograft transplant model (Welker et al., 2016). We found that a small population of differentiated vimentin-positive tumor cells, but a majority of Sox2-positive putative cancer stem cells, were dividing during tumor growth...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28525947/dianhydrogalactitol-a-potential-multitarget-agent-inhibits-glioblastoma-migration-invasion-and-angiogenesis
#3
Xia Jiang, Yinmei Huang, Xiaojie Wang, Qiaofang Liang, Yingjie Li, Fuji Li, Xuanhao Fu, Chonghuan Huang, Huagang Liu
The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28518096/invasive-behavior-of-human-breast-cancer-cells-in-embryonic-zebrafish
#4
Jiang Ren, Sijia Liu, Chao Cui, Peter Ten Dijke
In many cases, cancer patients do not die of a primary tumor, but rather because of metastasis. Although numerous rodent models are available for studying cancer metastasis in vivo, other efficient, reliable, low-cost models are needed to quickly access the potential effects of (epi)genetic changes or pharmacological compounds. As such, we illustrate and explain the feasibility of xenograft models using human breast cancer cells injected into zebrafish embryos to support this goal. Under the microscope, fluorescent proteins or chemically labeled human breast cancer cells are transplanted into transgenic zebrafish embryos, Tg (fli:EGFP), at the perivitelline space or duct of Cuvier (Doc) 48 h after fertilization...
April 25, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518092/isolation-of-the-side-population-in-myc-induced-t-cell-acute-lymphoblastic-leukemia-in-zebrafish
#5
Margaret M Pruitt, Wilfredo Marin, Michael R Waarts, Jill L O de Jong
Heterogeneous cell populations, from either healthy or malignant tissues, may contain a population of cells characterized by a differential ability to efflux the DNA-binding dye Hoechst 33342. This "side population" of cells can be identified using flow cytometric methods after the Hoechst 33342 dye is excited by an ultraviolet (UV) laser. The side population of many cell types contains stem- or progenitor-like cells. However, not all cell types have an identifiable side population. Danio rerio, zebrafish, have a robust in vivo model of T-cell acute lymphoblastic leukemia (T-ALL), but whether these zebrafish T-ALLs have a side population is unknown...
May 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28516954/histone-deacetylase-10-structure-and-molecular-function-as-a-polyamine-deacetylase
#6
Yang Hai, Stephen A Shinsky, Nicholas J Porter, David W Christianson
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish)...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512217/loss-of-the-homologous-recombination-gene-rad51-leads-to-fanconi-anemia-like-symptoms-in-zebrafish
#7
Jan Gregor Botthof, Ewa Bielczyk-Maczyńska, Lauren Ferreira, Ana Cvejic
RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28475330/discovery-and-characterization-of-r-s-n-3-cyanophenyl-n-6-tert-butoxycarbonylamino-3-4-dihydro-2-2-dimethyl-2h-1-benzopyran-4-yl-urea-a-new-histone-deacetylase-class-iii-inhibitor-exerting-antiproliferative-activity-against-cancer-cell-lines
#8
Michael Schnekenburger, Eric Goffin, Jin-Young Lee, Jun Young Jang, Aloran Mazumder, Seungwon Ji, Bernard Rogister, Nafila Bouider, Florence Lefranc, Walter Miklos, Véronique Mathieu, Pascal De Tullio, Kyu-Won Kim, Mario Dicato, Walter Berger, Byung Woo Han, Robert Kiss, Bernard Pirotte, Marc Diederich
A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. Based on computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea] which displays a potent antiproliferative activity on various glioma cell types, assessed by quantitative videomicroscopy, eventually triggering senescence...
May 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28465491/discovery-and-characterization-of-small-molecules-targeting-the-dna-binding-ets-domain-of-erg-in-prostate-cancer
#9
Miriam S Butler, Mani Roshan-Moniri, Michael Hsing, Desmond Lau, Ari Kim, Paul Yen, Marta Mroczek, Mannan Nouri, Scott Lien, Peter Axerio-Cilies, Kush Dalal, Clement Yau, Fariba Ghaidi, Yubin Guo, Takeshi Yamazaki, Sam Lawn, Martin E Gleave, Cheryl Y Gregory-Evans, Lawrence P McIntosh, Michael E Cox, Paul S Rennie, Artem Cherkasov
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450154/phenyl-butyrate-inhibits-pyruvate-dehydrogenase-kinase-1-and-contributes-to-its-anti-cancer-effect
#10
Wen Zhang, Shao-Lin Zhang, Xiaohui Hu, Kin Yip Tam
Phenyl butyrate (PB) has been proved to decrease pyruvate dehydrogenase (PDH) phosphorylation level and increase PDH activity by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) in fibroblast cells, PDH deficiency zebrafish and wild type mice. PB has also shown efficacy in many cancers and so far, all of its anti-tumor activity has been attributed to the histone deacetylase (HDAC) inhibition. As PDK1/PDH controls the critical switch between oxidative phosphorylation and glycolysis in cancer cells, PDK1 is a key target in tumor metabolism for anti-cancer treatment...
April 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28426725/dynamic-regulation-of-pin1-expression-and-function-during-zebrafish-development
#11
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
#12
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
#13
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
#14
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
#15
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...
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28411182/pegylation-rate-influences-peptide-based-nanoparticles-mediated-sirna-delivery-in-vitro-and-in-vivo
#16
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 12, 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
#17
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
#18
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-regulates-genes-associated-with-cardiovascular-disease-in-the-adult-zebrafish-heart-danio-rerio
#19
Logan Slade, Andrew Cowie, Chris J Martyniuk, 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 epidemiologic 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 cardiovascular system due to long-term, low-dose exposure over time...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28382676/natural-genomic-amplification-of-cholinesterase-genes-in-animals
#20
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
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