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https://www.readbyqxmd.com/read/28088004/a-catechin-nanoformulation-inhibits-wm266-melanoma-cell-proliferation-migration-and-associated-neo-angiogenesis
#1
Nicoletta di Leo, Matteo Battaglini, Liron Berger, Martina Giannaccini, Luciana Dente, Silke Hampel, Orazio Vittorio, Giuseppe Cirillo, Vittoria Raffa
We validated the anticancer potential of a nanoformulation made by (+)-catechin, gelatin and carbon nanotubes in terms of inhibition of cancer cell proliferation, migration and associated neo-angiogenesis. Gelatin was selected to stabilize the catechin without compromising its anti-oxidant potential and the carbon nanotubes were used to increase its intracellular bioavailability. The anticancer potential of the resulting nanohybrid was validated on an aggressive melanoma cell line, in vitro and in zebrafish xenotransplants...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28087763/circadian-kinetics-of-cell-cycle-progression-in-adult-neurogenic-niches-of-a-diurnal-vertebrate
#2
Veronica Akle, Alexander J Stankiewicz, Vasili Kharchenko, Lili Yu, Peter V Kharchenko, Irina V Zhdanova
: The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal life-style. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in five of the sixteen neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus and cerebellum...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28075592/total-syntheses-and-biological-activities-of-vinylamycin-analogs
#3
Jinghan Wang, Beijia Kuang, Xiaoqian Guo, Jianwei Liu, Yahui Ding, Jiangnan Li, Shende Jiang, Ying Liu, Fang Bai, Luyuan Li, Quan Zhang, Xiao-Yu Zhu, Bo Xia, Chun-Qi Li, Liang Wang, Guang Yang, Yue Chen
Natural depsipeptide vinylamycin was reported to be an antibiotic previously. Herein, we report vinylamycin to be active against K562 leukemia cells (IC50 = 4.86 μM), and be unstable in plasma (t1/2 = 0.54 h). A total of 24 vinylamycin analogs with modification of the OH group and chiral centers were generated via a combinatorial approach. The lead compound 1a was subsequently characterized as having: no anti-microbial activity, significantly higher plasma stability (t1/2 = 14.3 h), improved activity against K562 leukemia cells (IC50 = 0...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28061458/oncometabolite-succinate-promotes-angiogenesis-by-upregulating-vegf-expression-through-gpr91-mediated-stat3-and-erk-activation
#4
Xianmin Mu, Ting Zhao, Che Xu, Wei Shi, Biao Geng, Jiajia Shen, Chen Zhang, Jinshun Pan, Jing Yang, Shi Hu, Yuanfang Lv, Hao Wen, Qiang You
Altered cellular metabolism is now generally acknowledged as a hallmark of cancer cells, the resultant abnormal oncometabolites cause both metabolic and nonmetabolic dysregulation and potential transformation to malignancy. A subset of cancers have been found to be associated with mutations in succinate dehydrogenase genes which result in the accumulation of succinate. However, the function of succinate in tumorigenesis remains unclear. In the present study, we aim to investigate the role of oncometabolite succinate in tumor angiogenesis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061455/enhancement-of-the-bioavailability-of-a-novel-anticancer-compound-acetyltanshinone-iia-by-encapsulation-within-mpeg-plga-nanoparticles-a-study-of-formulation-optimization-toxicity-and-pharmacokinetics
#5
Qi Wang, Na Wei, Xiaofeng Liu, Alex Chang, Kathy Qian Luo
The Poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (mPEG-PLGA) nanoparticles carrying acetyltanshinone IIA (ATA), a novel anti-breast cancer agent, were prepared by ultrasonic emulsion method to enhance the bioavailability and reduce the toxicity. Systematic optimization of encapsulation process was achieved using an orthogonal design. Drug efficacy analysis showed that ATA nanoparticles were as effective as free ATA against estrogen receptor positive breast cancer cells, but much less toxic towards human endothelial cells...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#6
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28055019/rep1-inhibits-foxo3-mediated-apoptosis-to-promote-cancer-cell-survival
#7
Kwon-Ho Song, Seon Rang Woo, Joon-Yong Chung, Hyo-Jung Lee, Se Jin Oh, Soon-Oh Hong, Jaegal Shim, Yong Nyun Kim, Seung Bae Rho, Seung-Mo Hong, Hanbyoul Cho, Masahiko Hibi, Dong-Jun Bae, Sang-Yeob Kim, Min Gyu Kim, Tae Woo Kim, Young-Ki Bae
Rab escort protein 1 (REP1) is a component of Rab geranyl-geranyl transferase 2 complex. Mutations in REP1 cause a disease called choroideremia (CHM), which is an X-linked eye disease. Although it is postulated that REP1 has functions in cell survival or death of various tissues in addition to the eye, how REP1 functions in normal and cancer cells remains to be elucidated. Here, we demonstrated that REP1 is required for the survival of intestinal cells in addition to eyes or a variety of cells in zebrafish, and also has important roles in tumorigenesis...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28049852/in-vivo-severity-ranking-of-ras-pathway-mutations-associated-with-developmental-disorders
#8
Granton A Jindal, Yogesh Goyal, Kei Yamaya, Alan S Futran, Iason Kountouridis, Courtney A Balgobin, Trudi Schüpbach, Rebecca D Burdine, Stanislav Y Shvartsman
Germ-line mutations in components of the Ras/MAPK pathway result in developmental disorders called RASopathies, affecting about 1/1,000 human births. Rapid advances in genome sequencing make it possible to identify multiple disease-related mutations, but there is currently no systematic framework for translating this information into patient-specific predictions of disease progression. As a first step toward addressing this issue, we developed a quantitative, inexpensive, and rapid framework that relies on the early zebrafish embryo to assess mutational effects on a common scale...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28035003/a-quininib-analogue-and-cysteinyl-leukotreine-receptor-antagonist-inhibits-vegf-independent-angiogenesis-and-exerts-an-additive-anti-angiogenic-response-with-bevacizumab
#9
Clare T Butler, Alison L Reynolds, Miriam Tosetto, Eugene T Dillon, Patrick Guiry, Gerard Cagney, Jacintha O'Sullivan, Breand Aacuten N Kennedy
Excess blood vessel growth contributes to the pathology of metastatic cancers and age-related retinopathies. Despite development of improved treatments, these conditions are associated with high economic costs and drug resistance. Bevacizumab (Avastin®), a monoclonal antibody against vascular endothelial growth factor (VEGF) is used clinically to treat certain types of metastatic cancers. Unfortunately, many patients do not respond or inevitably become resistant to bevacizumab, highlighting the need for more effective anti-angiogenic drugs with novel mechanisms of action...
December 29, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28008157/the-tumor-associated-yb-1-protein-new-player-in-the-circadian-control-of-cell-proliferation
#10
Cristina Pagano, Orsola di Martino, Gennaro Ruggiero, Andrea Maria Guarino, Nathalie Mueller, Rima Siauciunaite, Markus Reischl, Nicholas Simon Foulkes, Daniela Vallone, Viola Calabrò
Correct spatial and temporal control of cell proliferation is of fundamental importance for tissue homeostasis. Its deregulation has been associated with several pathological conditions. In common with almost every aspect of plant and animal biology, cell proliferation is dominated by day-night rhythms generated by the circadian clock. However, our understanding of the crosstalk between the core clock and cell cycle control mechanisms remains incomplete. In this study, using zebrafish as a vertebrate model system, we show that the nuclear localization of the Y-box binding protein 1 (YB-1), a regulator of cyclin expression and a hallmark of certain cancers, is robustly regulated by the circadian clock...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/28005909/neural-crest-migration-and-survival-are-susceptible-to-morpholino-induced-artifacts
#11
Elena F Boer, Cicely A Jette, Rodney A Stewart
The neural crest (NC) is a stem cell-like embryonic population that is essential for generating and patterning the vertebrate body, including the craniofacial skeleton and peripheral nervous system. Defects in NC development underlie many birth defects and contribute to formation of some of the most malignant cancers in humans, such as melanoma and neuroblastoma. For these reasons, significant research efforts have been expended to identify genes that control NC development, as it is expected to lead to a deeper understanding of the genetic mechanisms controlling vertebrate development and identify new treatments for NC-derived diseases and cancers...
2016: PloS One
https://www.readbyqxmd.com/read/27996046/rare-disruptive-mutations-in-ciliary-function-genes-contribute-to-testicular-cancer-susceptibility
#12
Kevin Litchfield, Max Levy, Darshna Dudakia, Paula Proszek, Claire Shipley, Sander Basten, Elizabeth Rapley, D Timothy Bishop, Alison Reid, Robert Huddart, Peter Broderick, David Gonzalez de Castro, Simon O'Connor, Rachel H Giles, Richard S Houlston, Clare Turnbull
Testicular germ cell tumour (TGCT) is the most common cancer in young men. Here we sought to identify risk factors for TGCT by performing whole-exome sequencing on 328 TGCT cases from 153 families, 634 sporadic TGCT cases and 1,644 controls. We search for genes that are recurrently affected by rare variants (minor allele frequency <0.01) with potentially damaging effects and evidence of segregation in families. A total of 8.7% of TGCT families carry rare disruptive mutations in the cilia-microtubule genes (CMG) as compared with 0...
December 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27995293/comparative-analysis-of-transcriptional-profile-changes-in-larval-zebrafish-exposed-to-zinc-oxide-nanoparticles-and-zinc-sulfate
#13
Ryeo-Ok Kim, Jin Soo Choi, Byoung-Chul Kim, Woo-Keun Kim
Many studies of the toxic effects of zinc oxide nanoparticles (ZnO NPs) in aquatic organisms have been performed because of increasing ZnO NP use. However, the toxicological pathways are not understood. In this study, ZnO NPs were found to be more toxic than ZnSO4 to zebrafish larvae, but ZnO NP toxicity did not involve transcript alterations. Biological processes affected by ZnO NPs and ZnSO4 were investigated by performing ingenuity pathway analysis on differently expressed genes in larvae exposed to sub-lethal ZnO NP and ZnSO4 concentrations...
December 19, 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27988227/methods-for-the-analysis-of-early-oogenesis-in-zebrafish
#14
Yaniv M Elkouby, Mary C Mullins
Oocyte differentiation is a highly dynamic and intricate developmental process whose mechanistic understanding advances female reproduction, fertility, and ovarian cancer biology. Despite the many attributes of the zebrafish model, it has yet to be fully exploited for the investigation of early oocyte differentiation and ovarian development. This is partly because the properties of the adult zebrafish ovary make it technically challenging to access early stage oocytes. As a result, characterization of these stages has been lacking and tools for their analysis have been insufficient...
December 14, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27965040/hemodynamic-shear-stress-stimulates-migration-and-extravasation-of-tumor-cells-by-elevating-cellular-oxidative-level
#15
Shijun Ma, Afu Fu, Geraldine Giap Ying Chiew, Kathy Qian Luo
Cancer cells are shed into the blood stream and are exposed to hemodynamic shear stress during metastasis. It has been shown that shear stress can destroy circulating tumor cells (CTCs) both in vitro and in vivo. However, it remains unclear whether shear stress can modulate the properties and functions of tumor cells in a manner that might help CTCs to exit circulation. In this study, we established a microfluidic circulatory system to apply physiological fluid shear stress on breast cancer cells and demonstrated that an arterial level of shear stress significantly enhanced tumor cell migration in transwell and wound healing assays, and enhanced extravasation in a transendothelial assay...
December 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27936296/antiangiogenic-and-toxic-effects-of-genistein-usnic-acid-and-their-copper-complexes-in-zebrafish-embryos-at-different-developmental-stages
#16
Heidrun Draut, Tobias Rehm, Gerrit Begemann, Rainer Schobert
Angiogenesis plays a major role in the normal embryonic development and in diseases such as cancer. Drugs that control angiogenesis are an alternative way to tackle this disease. The polyphenols usnic acid 3, genistein 5, and daidzein 6 were tested for antiangiogenic and unwanted effects in zebrafish embryos whose blood vessel system resembles that of mammals. The established tyrosine kinase inhibitors axitinib 1 and tyrphostin AG490 2 were included for comparison. All compounds except 6 caused distinct antiangiogenic effects such as a concentration-dependent reduction of intersegmental vessels, dorsal longitudinal anastomotic vessels, subintestinal veins and secondary sprouts...
December 9, 2016: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/27933602/fish-tales-the-use-of-zebrafish-xenograft-human-cancer-cell-models
#17
REVIEW
Yvette Drabsch, B Ewa Snaar-Jagalska, Peter Ten Dijke
Advances in scientific techniques have provided researchers with exceptional new opportunities to identify and monitor changes between different cancer types, during different stages of progression, between individual tumor cells and in the surrounding stroma. The wealth of information that can be obtained from new scientific techniques places additional requirements on the conventional cancer models. New models that could be used to rapidly access the (potential) functional importance of newly identified (epi)genetic and proteomic changes and test the efficacy on emerging (combinatorial) therapies are desperately required...
December 9, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27924582/modeling-rasopathies-with-genetically-modified-mouse-models
#18
Isabel Hernández-Porras, Carmen Guerra
The RAS/MAPK signaling pathway plays key roles in development, cell survival and proliferation, as well as in cancer pathogenesis. Molecular genetic studies have identified a group of developmental syndromes, the RASopathies, caused by germ line mutations in this pathway. The syndromes included within this classification are neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NS-ML, formerly known as LEOPARD syndrome), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Legius syndrome (LS, NF1-like syndrome), capillary malformation-arteriovenous malformation syndrome (CM-AVM), and hereditary gingival fibromatosis (HGF) type 1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924011/roles-for-aprin-pds5b-in-homologous-recombination-and-in-ovarian-cancer-prediction
#19
Anthony M Couturier, Hubert Fleury, Anne-Marie Patenaude, Victoria L Bentley, Amélie Rodrigue, Yan Coulombe, Joshi Niraj, Joris Pauty, Jason N Berman, Graham Dellaire, Javier M Di Noia, Anne-Marie Mes-Masson, Jean-Yves Masson
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites. We find that APRIN interacts directly with RAD51, PALB2 and BRCA2. APRIN stimulates RAD51-mediated DNA strand invasion. APRIN also binds DNA with an affinity for D-loop structures and single-strand (ss) DNA. APRIN is a new homologous recombination (HR) mediator as it counteracts the RPA inhibitory effect on RAD51 loading to ssDNA...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923599/the-role-of-the-atm-chk-p53-pathway-in-mediating-dna-damage-in-hand-foot-syndrome-induced-by-pld
#20
Jie Yang, Long Qiao, Zhen Zeng, Junnai Wang, Tao Zhu, Juncheng Wei, Mingfu Wu, Shuangmei Ye, Xiaoyuan Huang, Ding Ma, Ronghua Liu, Qinglei Gao
Pegylated liposomal doxorubicin (PLD) has been approved to treat patients with various types of cancers because it rarely caused side effects, such as cardiotoxicity, in comparison to doxorubicin, but it frequently results in hand-foot syndrome (HFS). This may affect the quality of life and require a reduction in the PLD dose. The pathophysiology of HFS was not well understood. This study was aimed at exploring the mechanism of HFS induced by PLD. We compared the effects of different doses of PLD on the proliferation inhibition and apoptosis in vitro in HaCaT cells and analyzed the skin changes and skin cell DNA damage in vivo using a zebrafish model...
January 4, 2017: Toxicology Letters
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