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zebrafish cancer

Katarzyna Modzelewska, Elena F Boer, Timothy L Mosbruger, Daniel Picard, Daniela Anderson, Rodney R Miles, Mitchell Kroll, William Oslund, Theodore J Pysher, Joshua D Schiffman, Randy Jensen, Cicely A Jette, Annie Huang, Rodney A Stewart
Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway...
October 25, 2016: Cell Reports
Jakarwan Yostawonkul, Suvimol Surassmo, Tawin Iempridee, Wittaya Pimtong, Kunat Suktham, Warayuth Sajomsang, Pattarapond Gonil, Uracha Rungsardthong Ruktanonchai
A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200-400nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE>90%)...
September 29, 2016: Colloids and Surfaces. B, Biointerfaces
Lloyd Hamilton, Katy R Astell, Gergana Velikova, Dirk Sieger
Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number of microglia, which promote tumor growth and surrounding tissue invasion. However, it is unclear how microglia and glioma cells physically interact and if there are differences, depending on glioma cell type. Hence, we have developed a novel live imaging assay to study microglia-glioma interactions in vivo in the zebrafish brain. We transplanted well-established human glioblastoma cell lines, U87 and U251, into transgenic zebrafish lines with labelled macrophages/microglia...
October 25, 2016: Zebrafish
Xiaofeng Wu, Lihong Li, Wen Shi, Qiuyu Gong, Huimin Ma
Fluorescence imaging of tyrosinase (a cancer biomarker) in living organisms is of great importance for biological studies. However, selective detection of tyrosinase remains a great challenge because current fluorescent probes that contain the 4-hydroxyphenyl moiety show similar fluorescence responses to both tyrosinase and some reactive oxygen species (ROS), thereby suffering from ROS interference. Herein, a new tyrosinase-recognition 3-hydroxybenzyloxy moiety, which exhibits distinct fluorescence responses for tyrosinase and ROS, is proposed...
October 24, 2016: Angewandte Chemie
Junji Itou, Sunao Tanaka, Wenzhao Li, Atsuo Iida, Atsuko Sehara-Fujisawa, Fumiaki Sato, Masakazu Toi
During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1...
October 20, 2016: Biochimica et Biophysica Acta
Xunian Zhou, Grace Gar-Lee Yue, Minghua Liu, Zhili Zuo, Julia Kin-Ming Lee, Mingyue Li, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid isolated from the plant Isodon eriocalyx var. laxiflora, has emerged as a promising anticancer agent. The effects of EriB on angiogenesis were explored in the present study. Here we demonstrated that the subintestinal vein formation was significantly inhibited by EriB treatment (10, 15 μM) in zebrafish embryos, which was resulted from the alteration of various angiogenic genes as shown in transcriptome profiling. In human umbilical vein endothelial cells, EriB treatment (50, 100 nM) could significantly block vascular endothelial growth factors (VEGF)-induced cell proliferation, tube formation, cell migration and cell invasion...
October 14, 2016: Oncotarget
Su Jung Hwang, Hyeung-Geun Park, Yohan Park, Hyo-Jong Lee
Previously, we reported that α-quaternary chiral lactam derivatives have broad spectrum anticancer activity. However, the underlying molecular mechanisms and its relevance are largely unknown. In the present study, we report progress on α-quaternary chiral lactam analogues that address this, focusing on the novel analogue YH-304 as a candidate to broadly target human cancer cells. The effect of YH-304 on cell transformation was assessed by clonogenic assay in non-small cell lung cancer cells (NSCLCs) A549 and 226B...
October 11, 2016: International Journal of Oncology
Adrian G Murphy, Rory Casey, Aoife Maguire, Miriam Tosetto, Clare T Butler, Emer Conroy, Alison L Reynolds, Kieran Sheahan, Diarmuid O'Donoghue, William M Gallagher, David Fennelly, Breandán N Kennedy, Jacintha O'Sullivan
Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75 g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p < 0...
October 14, 2016: Scientific Reports
Wai-Lun Kwong, Kar-Yee Lam, Chun-Nam Lok, Yau-Tsz Lai, Pui-Yan Lee, Chi-Ming Che
A macrocyclic ruthenium(III) complex [Ru(III) (N2 O2 )Cl2 ]Cl (Ru-1) is reported as an inhibitor of angiogenesis and an anti-tumor compound. The complex is relatively non-cytotoxic towards endothelial and cancer cell lines in vitro, but specifically inhibited the processes of angiogenic endothelial cell tube formation and cancer cell invasion. Moreover, compared with known anti-cancer ruthenium complexes, Ru-1 is distinct in that it suppressed the expression of vascular endothelial growth factor receptor-2 (VEGFR2), and the associated downstream signaling that is crucial to tumor angiogenesis...
October 17, 2016: Angewandte Chemie
Gianfranco Matrone, John J Mullins, Carl S Tucker, Martin A Denvir
CDK9 is a known regulator of cellular transcription, growth and proliferation. Small molecule inhibitors are currently being developed and assessed in clinical trials as anti-cancer drugs. The zebrafish embryo provides an ideal model to explore the effects of CDK9 inhibition in-vivo. This has not been adequately explored previously at the level of a whole organism. We have compared and contrasted the effects of pharmacological and molecular inhibition of CDK9 on somatic growth, apoptosis and cellular proliferation in zebrafish larvae between 0 to 120 hours post fertilisation (hpf) using flavopiridol, a selective CDK9 antagonist, and CDK9-targeting morpholino...
October 7, 2016: Cell Cycle
Robert Gerlai, Tanya L Poshusta, Mindy Rampersad, Yohaan Fernandes, Tammy M Greenwood, Margot A Cousin, Eric W Klee, Karl J Clark
The zebrafish enjoys several advantages over other model organisms. It is small, easy to maintain, prolific, and numerous genetic tools are available for it. For example, forward genetic screens have allowed investigators to identify important genes potentially involved in a variety of functions from embryogenesis to cancer. However, despite its sophisticated behavioral repertoire, behavioral methods have rarely been utilized in forward genetic screens. Here, we employ a two-tiered strategy, a proof of concept study, to explore the feasibility of behavioral screens...
October 5, 2016: Behavior Genetics
Martin Hagedorn, Géraldine Siegfried, Katarzyna B Hooks, Abdel-Majid Khatib
Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer...
September 26, 2016: Oncotarget
Jinhong Liu, Zifei Zhu, Jia Tang, Qinghua Lin, Li Chen, Jianbo Sun
A total of 16 targeted NO-releasing betulinic acid (BA) derivatives were designed and synthesized as potential anticancer agents. Most IC50 values were under 1.0 μM in vitro test against HepG2 and B16. The result suggested that derivatives of BA with α,β-unsaturated ketone skeleton possessed significant cytotoxic activities than the others, among which derivatives with three carbons in diol linker (15b and 15c) exhibited the highest anti-cancer activity. NO-releasing amount detection of partial target compounds suggested that NO-releasing amount of this series of BA derivatives positively correlates with their cytotoxic activities...
September 26, 2016: Anti-cancer Agents in Medicinal Chemistry
Sheng-Hui Chiu, Gangaraju Gedda, Wubshet Mekonnen Girma, Jem-Kun Chen, Yong-Chien Ling, Anil V Ghule, Keng-Liang Ou, Jia-Yaw Chang
: Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging...
September 20, 2016: Acta Biomaterialia
Marina Venero Galanternik, Mark E Lush, Tatjana Piotrowski
Collective cell migration is an essential process during embryonic development and diseases such as cancer, and still much remains to be learned about how cell intrinsic and environmental cues are coordinated to guide cells to their targets. The migration-dependent development of the zebrafish sensory lateral line proves to be an excellent model to study how proteoglycans control collective cell migration in a vertebrate. Proteoglycans are extracellular matrix glycoproteins essential for the control of several signaling pathways including Wnt/β-catenin, Fgf, BMP and Hh...
September 15, 2016: Developmental Biology
(no author information available yet)
No abstract text is available yet for this article.
September 2016: Anticancer Research
Chad Jansen, Jaya Sahni, Sayuri Suzuki, F David Horgen, Reinhold Penner, Andrea Fleig
TRPM7 is a member of the Transient-Receptor-Potential Melastatin ion channel family. TRPM7 is a unique fusion protein of an ion channel and an α-kinase. Although mammalian TRPM7 is well characterized biophysically and its pivotal role in cancer, ischemia and cardiovascular disease is becoming increasingly evident, the study of TRPM7 in mouse models has been hampered by embryonic lethality of transgenic ablations. In zebrafish, functional loss of TRPM7 (drTRPM7) manifests itself in an array of non-lethal physiological malfunctions...
2016: Scientific Reports
Augustine T Nkembo, Elizabeth Ntantie, Olufisayo O Salako, Felix Amissah, Rosemary A Poku, Lekan M Latinwo, Nazarius S Lamango
Angiogenesis is essential for solid tumor growth, therapeutic resistance and metastasis, the latest accounting for 90% of cancer deaths. Although angiogenesis is essential for the malignant transformations in solid tumors and therefore is an attractive target, few drugs are available that block tumor angiogenesis. The focus has been to block signaling by receptor tyrosine kinases (RTKs), such as for vascular endothelial growth factor (VEGF), whose activation abrogate apoptosis and promote angiogenesis. The polyisoprenylated cysteinyl amide inhibitors (PCAIs) were designed to modulate aberrant polyisoprenylated small G-proteins such as mutant Ras whose constitutive activation promotes RTKs signaling...
September 8, 2016: Oncotarget
S R Punganuru, R Samala, K S Srivenugopal
In this paper a simple and efficient method for the unsymmetrical terphenyls via sequential one-pot Suzuki coupling reactions using Pd(OAc)2 without isolation of the intermediate is described. The prepared terphenyls were found to possess potent anticancer properties against a panel of cancer cells which includes A549, HeLa, MCF7, DU145, HT29 and BxPC-3. Structural similarity with combretastatin A4, these terphenyls disrupted the tubulin polymerization in vitro and destabilized the microtubules in cells. Flow cytometry studies indicated growth arrest of cells in the G2/M phase of the cell cycle corresponding to antimitotic action...
September 14, 2016: Drug Research
Xiang Tu, YuanPing Deng, Jing Chen, Quan Hu, ChengShi He, James B Jordan, Sen Zhong
ETHNOPHARMACOLOGICAL RELEVANCE: Few studies have explored the anti-angiogenic effects of TCM - even more so, as it applies to cancer treatment research. Heat-clearing and detoxicating TCM is the most frequently used category in the treatment of cancerous tumors, but lacks sufficient validation studies. AIM OF THE STUDY: The present research (in our series of studies) aims to explore the anti-angiogenic effects of TCM; so we begin with heat-clearing and detoxicating TCM...
September 8, 2016: Journal of Ethnopharmacology
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