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https://www.readbyqxmd.com/read/28819666/ph-responsive-prodrug-nanoparticles-based-on-a-sodium-alginate-derivative-for-selective-co-release-of-doxorubicin-and-curcumin-into-tumor-cells
#1
Cheng Gao, Fan Tang, Guiyi Gong, Jianxiang Zhang, Maggie P M Hoi, Simon M Y Lee, Ruibing Wang
In order to realize a combination of chemotherapy and selective drug release into tumor cells, novel pH-sensitive prodrugnanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for the selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells...
August 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28816367/the-in-vitro-and-in-vivo-antiangiogenic-effects-of-flavokawain-b
#2
Mariana C Rossette, Débora C Moraes, Erika K Sacramento, Marco Aurélio Romano-Silva, Juliana L Carvalho, Dawidson A Gomes, Hanna Caldas, Eitan Friedman, Luciana Bastos-Rodrigues, Luiz De Marco
Angiogenesis is implicated in the development of a variety of pathological processes, most commonly cancer. It is essential for tumor growth and metastasis, making it an important cancer therapeutic target. Naturally occurring substances have led to the discovery of anticancer agents. Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines. The antimetastatic potential of FKB has also been suggested...
August 17, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28805722/estrogen-repression-of-micrornas-is-associated-with-high-guanine-content-in-the-terminal-loop-sequences-of-their-precursors
#3
Amit Cohen, Mario Alberto Burgos-Aceves, Tamar Kahan, Yoav Smith
Widespread microRNA (miRNA) repression is a phenomenon observed in mammals after exposure to cigarette smoke and in many types of cancer. A comprehensive reduction in miRNA expression after treatment with the hormone estrogen has also previously been described. Here, we reveal a conserved association of miRNA downregulation after estrogen exposure in zebrafish, mouse, and human breast cancer cell line, with a high guanine content in the terminal loop sequences of their precursors, and offer a possible link between estrogen-related miRNA-adducts formation and carcinogenesis...
August 14, 2017: Biomedicines
https://www.readbyqxmd.com/read/28795798/a-two-photon-and-deep-red-emission-ratiometric-fluorescent-probe-with-a-large-emission-shift-and-signal-ratios-for-sulfur-dioxide-ultrafast-response-and-applications-in-living-cells-brain-tissues-and-zebrafishes
#4
Yanyan Ma, Yonghe Tang, Yuping Zhao, Shiying Gao, Weiying Lin
Sulfur dioxide (SO2) is a dangerous environmental pollutant. Excessive intake of it may cause some respiratory diseases and even lung cancer. The development of effective methods for detecting of SO2 is of great importance for environment and physiology. Herein, we have designed and synthesized a novel two-photon (TP) and deep-red emission ratiometric fluo-rescent probe (CP) for detecting of SO2. Notably, the novel probe CP exhibited ultrafast response to SO2 in less than 5 sec-onds, and displayed a great emission shift (195 nm) and a large emission signal ratio variation (enhancement from 0...
August 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28795750/supramolecular-alleviation-of-cardiotoxicity-of-a-small-molecule-kinase-inhibitor
#5
Xue Yang, Qiaoxian Huang, David Bardelang, Chunming Wang, Simon M Y Lee, Ruibing Wang
Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO by a synthetic receptor cucurbit[7]uril (CB[7]) alleviated the inherent cardiotoxicity of SO, as demonstrated in an in vivo zebrafish model. Moreover, the anti-cancer activity of SO was well preserved, upon its encapsulation by CB[7], as demonstrated by both in vitro and in vivo cancer/angiogenesis models...
August 10, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28792859/elucidating-the-role-of-plexin-d1-in-body-fat-distribution-and-susceptibility-to-metabolic-disease-using-a-zebrafish-model-system
#6
James E N Minchin, John F Rawls
Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution of lipid deposited within adipose tissue (AT) - so called body fat distribution (BFD) - is a strong risk factor for NCDs. BFD is highly heritable; however, the genetic basis of BFD is almost entirely unknown. Genome-wide association studies have identified several loci associated with BFD, including at Plexin D1 (PLXND1) - a gene known to modulate angiogenesis...
July 27, 2017: Adipocyte
https://www.readbyqxmd.com/read/28791769/fluorescent-polymer-nanoparticles-for-cell-barcoding-in-vitro-and-in-vivo
#7
Bohdan Andreiuk, Andreas Reisch, Marion Lindecker, Gautier Follain, Nadine Peyriéras, Jacky G Goetz, Andrey S Klymchenko
Fluorescent polymer nanoparticles for long-term labeling and tracking of living cells with any desired color code are developed. They are built from biodegradable poly(lactic-co-glycolic acid) polymer loaded with cyanine dyes (DiO, DiI, and DiD) with the help of bulky fluorinated counterions, which minimize aggregation-caused quenching. At the single particle level, these particles are ≈20-fold brighter than quantum dots of similar color. Due to their identical 40 nm size and surface properties, these nanoparticles are endocytosed equally well by living cells...
August 9, 2017: Small
https://www.readbyqxmd.com/read/28790117/in-vivo-validation-of-papss1-3-phosphoadenosine-5-phosphosulfate-synthase-1-as-a-cisplatin-sensitizing-therapeutic-target
#8
Ada W Y Leung, Chansey J Veinotte, Nicole Melong, Min Hee Oh, Kent T J Chen, Katey Enfield, Ian Backstrom, Corinna Warburton, Donald T Yapp, Jason N Berman, Marcel B Bally, William W Lockwood
INTRODUCTION: Our previous screening efforts found that inhibition of PAPSS1 increases the potency of DNA damaging agents in non-small cell lung cancer (NSCLC) cell lines. Here, we explored the clinical relevance of PAPSS1 and further investigated it as a therapeutic target in pre-clinical model systems. METHODS: PAPSS1 expression and cisplatin IC50 values were assessed in 52 lung adenocarcinoma (LAC) cell lines. Effects of PAPSS1 inhibition on A549 cisplatin sensitivity under hypoxic and starvation conditions, in 3D spheroids, as well as in zebrafish and mouse xenografts, were evaluated...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28777795/regulation-of-gli-ciliary-localization-and-hedgehog-signaling-by-the-py-nls-karyopherin-%C3%AE-2-nuclear-import-system
#9
Yuhong Han, Yue Xiong, Xuanming Shi, Jiang Wu, Yun Zhao, Jin Jiang
Hedgehog (Hh) signaling in vertebrates depends on primary cilia. Upon stimulation, Hh pathway components, including Gli transcription factors, accumulate at primary cilia to transduce the Hh signal, but the mechanisms underlying their ciliary targeting remains largely unknown. Here, we show that the PY-type nuclear localization signal (PY-NLS)/karyopherinβ2 (Kapβ2) nuclear import system regulates Gli ciliary localization and Hh pathway activation. Mutating the PY-NLS in Gli or knockdown of Kapβ2 diminished Gli ciliary localization...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28774621/zebrafish-embryo-toxicity-of-15-chlorinated-brominated-and-iodinated-disinfection-by-products
#10
David Hanigan, Lisa Truong, Michael Simonich, Robert Tanguay, Paul Westerhoff
Disinfection to protect human health occurs at drinking water and wastewater facilities through application of non-selective oxidants including chlorine. Oxidants also transform organic material and form disinfection by-products (DBPs), many of which are halogenated and cyto- and genotoxic. Only a handful of assays have been used to compare DBP toxicity, and researchers are unsure which DBP(s) drive the increased cancer risk associated with drinking chlorinated water. The most extensive data set employs an in vitro model cell, Chinese hamster ovary cells...
August 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28774574/fluoro-and-pentafluorothio-analogs-of-the-antitumoral-curcuminoid-ef24-with-superior-antiangiogenic-and-vascular-disruptive-effects
#11
Florian Schmitt, Madeleine Gold, Gerrit Begemann, Ion Andronache, Bernhard Biersack, Rainer Schobert
A series of 14 analogs of the curcuminoid EF24, (3E,5E)-3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone, bearing fluorine or pentafluorothio substituents, were prepared and tested for antiproliferative, vascular-disruptive, and antiangiogenic activity, as well as for their influence on other cancer-relevant targets. They proved antiproliferative against eight cancer cell lines with IC50 values in the low single-digit micromolar to triple-digit nanomolar range. Like EF24, the hexafluoro 3c and 3d and bis(pentafluorothio) 4f derivatives arrested HT-29 colon carcinoma cells in G2/M phase of the cell cycle, yet inhibited angiogenesis, e...
July 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28760346/a-defect-in-the-mitochondrial-protein-mpv17-underlies-the-transparent-casper-zebrafish
#12
Gianluca D'Agati, Rosanna Beltre, Anna Sessa, Alexa Burger, Yi Zhou, Christian Mosimann, Richard M White
The casper strain of zebrafish is widely used in studies ranging from cancer to neuroscience. casper offers the advantage of relative transparency throughout adulthood, making it particularly useful for in vivo imaging by epifluorescence, confocal, and light sheet microscopy. casper was developed by selective breeding of two previously described recessive pigment mutants: 1) nacre, which harbors an inactivating mutation of the mitfa gene, rendering the fish devoid of pigmented melanocytes; and 2) roy orbison, a mutant with so-far unidentified genetic cause that lacks reflective iridophores...
July 28, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28758266/a-ph-sensitive-macromolecular-prodrug-as-tlr7-8-targeting-immune-response-modifier
#13
Stefan Aichhorn, Anne Linhardt, Angela Halfmann, Markus Nadlinger, Stefanie Kirchberger, Manuela Stadler, Barbara Dillinger, Martin Distel, Alexander Dohnal, Ian Teasdale, Wolfgang Schoefberger
The chemical synthesis and biological activity of novel functionalized imidazoquinoline derivatives to generate Toll-like receptor 7/8 specific prodrugs are presented. In vivo activity of ImQs to induce inflammation was confirmed in zebrafish larvae. After covalent ligation to fully biodegradable polyphosphazenes, the macromolecular prodrugs were designed to undergo intracellular pH-sensitive release of ImQs to induce inflammation through binding to endosomal TLR7/8. We showed ImQ dissociation from prodrugs at a pH 5 pointing towards endosomal prodrug degradability...
July 30, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28753586/development-of-zebrafish-medulloblastoma-like-pnet-model-by-talen-mediated-somatic-gene-inactivation
#14
Jaegal Shim, Jung-Hwa Choi, Moon-Hak Park, Hyena Kim, Jong Hwan Kim, Seon-Young Kim, Dongwan Hong, Sunshin Kim, Ji Eun Lee, Cheol-Hee Kim, Jeong-Soo Lee, Young-Ki Bae
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53e7/e7 mutant zebrafish...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28753575/glioblastoma-and-glioblastoma-stem-cells-are-dependent-on-functional-mth1
#15
Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target...
July 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743793/animal-models-of-men-1
#16
Hermine Mohr, Natalia S Pellegata
Animal models of cancer have been instrumental in advancing our understanding of the biology of tumor initiation and progression, in studying gene function, and in performing preclinical studies aimed at testing novel therapies. Several animal models of the MEN1 syndrome have been generated in different organisms by introducing loss-of-function mutations in the orthologues of the human MEN1 gene. In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and rats. These model systems with their specific advantages and limitations have contributed to elucidate the function of Menin in tumorigenesis, which turned out to be remarkably conserved from flies to mammals, as well as the biology of the disease...
July 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28742327/amphiphilic-peptide-nanorods-based-on-oligo-phenylalanine-as-a-biocompatible-drug-carrier
#17
Su Jeong Song, Seulgi Lee, Kyoung-Seok Ryu, Joon Sig Choi
Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH3F8 (Arg-His3-Phe8), as a drug-delivery carrier. Arginine is an essential amino acid in typical cell-penetration peptides, and histidine induces endo- and lysosomal escape because of its proton sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for stable self-assembly and drug encapsulation...
August 11, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28718799/zebrafish-as-a-model-organism-for-the-development-of-drugs-for-skin-cancer
#18
REVIEW
Fatemeh Bootorabi, Hamed Manouchehri, Reza Changizi, Harlan Barker, Elisabetta Palazzo, Annalisa Saltari, Mataleena Parikka, Carlo Pincelli, Ashok Aspatwar
Skin cancer, which includes melanoma and squamous cell carcinoma, represents the most common type of cutaneous malignancy worldwide, and its incidence is expected to rise in the near future. This condition derives from acquired genetic dysregulation of signaling pathways involved in the proliferation and apoptosis of skin cells. The development of animal models has allowed a better understanding of these pathomechanisms, with the possibility of carrying out toxicological screening and drug development. In particular, the zebrafish (Danio rerio) has been established as one of the most important model organisms for cancer research...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718729/the-novel-autophagy-inhibitor-elaiophylin-exerts-antitumor-activity-against-multiple-myeloma-with-mutant-tp53-in-part-through-endoplasmic-reticulum-stress-induced-apoptosis
#19
Gaoxiang Wang, Pan Zhou, Xing Chen, Lei Zhao, Jiaqi Tan, Yang Yang, Yong Fang, Jianfeng Zhou
Elaiophylin is a natural compound and a novel and potent inhibitor of late stage autophagy with outstanding antitumor activity in human ovarian cancer cells. However, the possible biologic effects and functional linkage between elaiophylin and multiple myeloma (MM) have not been explored. This study aimed to assess the effect of elaiophylin on MM cells with mutant TP53 and the possible molecular mechanism. The results suggested that elaiophylin exerted anti-myeloma activity by inducing apoptosis and proliferation arrest...
July 18, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28710811/insights-from-zebrafish-on-human-pigment-cell-disease-and-treatment
#20
REVIEW
Cynthia D Cooper
Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans...
July 14, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
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