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https://www.readbyqxmd.com/read/28340497/p450-inhibitor-ketoconazole-increased-the-intratumor-drug-levels-and-antitumor-activity-of-fenretinide-in-human-neuroblastoma-xenograft-models
#1
Lluis Lopez-Barcons, Barry J Maurer, Min H Kang, C Patrick Reynolds
We previously reported that concurrent ketoconazole, an oral anti-fungal agent and P450 enzyme inhibitor, increased plasma levels of the cytotoxic retinoid, fenretinide (4-HPR) in mice. We have now determined the effects of concurrent ketoconazole on 4-HPR cytotoxic dose-response in four neuroblastoma (NB) cell lines in vitro and on 4-HPR activity against two cell line-derived, subcutaneous NB xenografts (CDX) and three patient-derived NB xenografts (PDX). Cytotoxicity in vitro was assessed by DIMSCAN assay...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340489/mir-34a-3p-alters-proliferation-and-apoptosis-of-meningioma-cells-in-vitro-and-is-directly-targeting-smad4-frat1-and-bcl2
#2
Tamara V Werner, Martin Hart, Ruth Nickels, Yoo-Jin Kim, Michael D Menger, Rainer M Bohle, Andreas Keller, Nicole Ludwig, Eckart Meese
Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype.Following in silico prediction of potential targets of miR-34a-3p, SMAD4, FRAT1, and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3'UTRs...
March 23, 2017: Aging
https://www.readbyqxmd.com/read/28340478/different-dna-damage-response-of-cis-and-trans-isomers-of-commonly-used-uv-filter-after-the-exposure-on-adult-human-liver-stem-cells-and-human-lymphoblastoid-cells
#3
Anežka Sharma, Katarína Bányiová, Pavel Babica, Naouale El Yamani, Andrew Richard Collins, Pavel Čupr
2-ethylhexyl 4-methoxycinnamate (EHMC), used in many categories of personal care products (PCPs), is one of the most discussed ultraviolet filters because of its endocrine-disrupting effects. EHMC is unstable in sunlight and can be transformed from trans-EHMC to emergent cis-EHMC. Toxicological studies are focusing only on trans-EHMC; thus the toxicological data for cis-EHMC are missing. In this study, the in vitro genotoxic effects of trans- and cis-EHMC on adult human liver stem cells HL1-hT1 and human-derived lymphoblastoid cells TK-6 using a high-throughput comet assay were studied...
March 21, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#4
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28340427/identification-and-characterization-of-a-%C3%AE-defensin-gene-involved-in-the-immune-defense-response-of-channel-catfish-ictalurus-punctatus
#5
Jieyao Zhu, Hong Wang, Jun Wang, Xingli Wang, Shuang Peng, Yi Geng, Kaiyu Wang, Pin Ouyang, Zhiqiong Li, Xiaoli Huang, Defang Chen
Antimicrobial peptides are small peptides that play important roles in a host's innate immune response. As an important antimicrobial peptide, β-defensin widely distribute in mammals, insects and plants with broad-spectrum antimicrobial activity. In this study, the β-defensin gene of the channel catfish, Ictalurus punctatus, was cloned, sequenced, and subjected to a bioinformatic analysis. The β-defensin gene of the channel catfish contains three exons and two introns, and encodes a precursor peptide consisting of two domains: a signal peptide of 24 amino acid residues and a mature peptide of 43 amino acid residues...
March 21, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28340420/extended-anaerobic-conditions-in-the-biological-wastewater-treatment-higher-reduction-of-toxicity-compared-to-target-organic-micropollutants
#6
Johannes Völker, Tobias Vogt, Sandro Castronovo, Arne Wick, Thomas A Ternes, Adriano Joss, Jörg Oehlmann, Martin Wagner
Extended anaerobic conditions during biological wastewater treatment may enhance the biodegradation of micropollutants. To explore this, we combined iron-reducing or substrate-limited anaerobic conditions and aerobic pilot-scale reactors directly at a wastewater treatment plant. To investigate the detoxification by these processes, we applied two in vitro bioassays for baseline toxicity (Microtox) and reactive toxicity (AREc32) as well as in vivo bioassays with aquatic model species in two laboratory experiments (Desmodesmus subspicatus, Daphnia magna) and two on-site, flow-through experiments (Potamopyrgus antipodarum, Lumbriculus variegatus)...
March 14, 2017: Water Research
https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#7
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340410/development-of-fusogenic-glass-surfaces-that-impart-spatiotemporal-control-over-macrophage-fusion-direct-visualization-of-multinucleated-giant-cell-formation
#8
James J Faust, Wayne Christenson, Kyle Doudrick, Robert Ros, Tatiana P Ugarova
Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion...
March 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28340404/synthesis-in-vitro-antiproliferative-activity-and-kinase-profile-of-new-benzimidazole-and-benzotriazole-derivatives
#9
Konrad Chojnacki, Patrycja Wińska, Katarzyna Skierka, Monika Wielechowska, Maria Bretner
Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with Ki value in the range of 1...
March 16, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28340368/synthesis-molecular-docking-antimycobacterial-and-antimicrobial-evaluation-of-new-pyrrolo-3-2-c-pyridine-mannich-bases
#10
Gilish Jose, Tholappanavara H Suresha Kumara, Haliwana B V Sowmya, Dharmarajan Sriram, Tayur N Guru Row, Amar A Hosamani, Sunil S More, Bhavya Janardhan, B G Harish, Sandeep Telkar, Yalegara Siddappa Ravikumar
In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by (1)H NMR, (13)C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4](+2), H2O)...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340187/biofilm-adherence-and-hydrophobicity-as-virulence-factors-in-malassezia-furfur
#11
Letizia Angiolella, Claudia Leone, Florencia Rojas, Javier Mussin, María de Los Angeles Sosa, Gustavo Giusiano
Malassezia species are natural inhabitants of the healthy skin. However, under certain conditions, they may cause or exacerbate several skin diseases. The ability of this fungus to colonize or infect is determined by complex interactions between the fungal cell and its virulence factors. This study aims to evaluate "in vitro" the hydrophobicity levels, the adherence on a plastic surface and the biofilm formation of 16 clinical isolates of Malassezia furfur. Cellular surface hydrophobicity (CSH) levels were determined by two-phase system...
March 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#12
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28340154/irradiation-strongly-reduces-tumorigenesis-of-human-induced-pluripotent-stem-cells
#13
Shoki Inui, Kazumasa Minami, Emiko Ito, Hiromasa Imaizumi, Seiji Mori, Masahiko Koizumi, Satsuki Fukushima, Shigeru Miyagawa, Yoshiki Sawa, Nariaki Matsuura
Induced pluripotent stem (iPS) cells have demonstrated they can undergo self-renewal, attain pluripotency, and differentiate into various types of functional cells. In clinical transplantation of iPS cells, however, a major problem is the prevention of tumorigenesis. We speculated that tumor formation could be inhibited by means of irradiation. Since the main purpose of this study was to explore the prevention of tumor formation in human iPS (hiPS) cells, we tested the effects of irradiation on tumor-associated factors such as radiosensitivity, pluripotency and cell death in hiPS cells...
March 3, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28340100/glioblastoma-stem-cell-differentiation-into-endothelial-cells-evidenced-through-live-cell-imaging
#14
Xin Mei, Yin-Sheng Chen, Fu-Rong Chen, Shao-Yan Xi, Zhong-Ping Chen
Background.: Glioblastoma cell-initiated vascularization is an alternative angiogenesis called vasculogenic mimicry. However, current knowledge on the mechanism of de novo vessel formation from glioblastoma stem cells (GSCs) is limited. Methods.: Sixty-four glioblastoma samples from patients and 10 fluorescent glioma xenograft samples were examined by immunofluorescence staining for endothelial marker (CD34 and CD31) and glial cell marker (glial fibrillary acidic protein [GFAP]) expression...
March 8, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28340076/cisplatin-induced-renal-inflammation-is-ameliorated-by-cilastatin-nephroprotection
#15
Blanca Humanes, Sonia Camaño, Jose Manuel Lara, Venkatta Sabbisetti, María Ángeles González-Nicolás, Joseph V Bonventre, Alberto Tejedor, Alberto Lázaro
Background.: Cisplatin is a potent chemotherapeutic drug whose nephrotoxic effect is a major complication and a dose-limiting factor for antitumoral therapy. There is much evidence that inflammation contributes to the pathogenesis of cisplatin-induced nephrotoxicity. We found that cilastatin, a renal dehydropeptidase-I inhibitor, has protective effects in vitro and in vivo against cisplatin-induced renal damage by inhibiting apoptosis and oxidation. Here, we investigated the potential use of cilastatin to protect against cisplatin-induced kidney injury and inflammation in rats...
March 11, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28340071/variable-potassium-concentrations-which-is-right-and-which-is-wrong
#16
Talent Theparee, Robert C Benirschke, Hong-Kee Lee
Reverse pseudohyperkalemia is a term used to describe in vitro, falsely elevated potassium concentrations in plasma specimens that occur in association with extreme leukocytosis and are commonly associated with hematologic malignant neoplasms. Tumor lysis syndrome is an in vivo lysis of tumor cells that leads to elevated levels of potassium, uric acid, phosphate, and lactate dehydrogenase, as well as decreased calcium concentrations. Herein, we report a case of a 66-year-old Caucasian man with stage IV mantle-cell lymphoma who has elevated levels of potassium, uric acid, and phosphorus, as well as a white blood cell (WBC) count greater than 100,000 cells per mm3...
March 6, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28340065/the-next-three-decades-of-the-comet-assay-a-report-of-the-11th-international-comet-assay-workshop
#17
Gudrun Koppen, Amaya Azqueta, Bertrand Pourrut, Gunnar Brunborg, Andrew R Collins, Sabine A S Langie
The International Comet Assay Workshops are a series of scientific conferences dealing with practical and theoretical aspects of the Comet Assay (single-cell gel electrophoresis)-a simple method for detecting DNA strand breaks. The first paper describing such an assay was published over 30 years ago in 1984 by Swedish researchers O. Ostling and K. J. Johanson. Appropriately, the theme for the 2015 meeting was looking to the future: 'The Next 3 Decades of the Comet Assay'. The programme included 25 oral and 43 poster presentations depicting the latest advances in technical developments as well as applications of the comet assay in genotoxicity testing (in vitro and in vivo) and biomonitoring of both humans and the environment...
March 4, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28340056/neutrophil-derived-mitochondrial-dna-promotes-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-and-its-ligand-signalling-in-rheumatoid-arthritis
#18
Anne Contis, Stéphane Mitrovic, Julie Lavie, Isabelle Douchet, Estibaliz Lazaro, Marie-Elise Truchetet, Cyril Goizet, Cécile Contin-Bordes, Thierry Schaeverbeke, Patrick Blanco, Rodrigue Rossignol, Benjamin Faustin, Christophe Richez, Pierre Duffau
Objectives.: Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. Methods.: The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR...
March 13, 2017: Rheumatology
https://www.readbyqxmd.com/read/28339983/acr11-is-an-activator-of-plastid-type-glutamine-synthetase-gs2-in-arabidopsis-thaliana
#19
Takashi Osanai, Ayuko Kuwahara, Hitomi Otsuki, Kazuki Saito, Masami Yokota Hirai
Glutamine synthetase (GS) is an important enzyme for nitrogen assimilation, and GS2, encoded by GLN2, is the only plastid-type GS in Arabidopsis thaliana. A co-expression analysis suggested that the expression level of the gene encoding a uridylyltransferase-like protein, ACR11, is strongly correlated with GLN2 expression levels. Here we showed that the recombinant ACR11 protein increased GS2 activity in vitro by reducing the Km values of its substrate glutamine. A T-DNA insertion mutant of ACR11 exhibited a reduced GS activity under low nitrate conditions and reduced glutamine levels...
March 6, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28339937/uterine-artery-leptin-receptors-during-the-ovarian-cycle-and-pregnancy-regulate-angiogenesis-in-ovine-uterine-artery-endothelial-cells
#20
Vladimir E Vargas, Rosalina Villalon Landeros, Gladys E Lopez, Jing Zheng, Ronald R Magness
Leptin regulates body weight, reproductive functions, blood pressure, endothelial function, and fetoplacental angiogenesis. Compared to the luteal phase, the follicular phase and pregnancy are physiological states of elevated estrogen, angiogenesis, and uterine blood flow (UBF). Little is known concerning leptin and its receptors (OB-R) for regulating uterine artery (UA) angiogenesis. We : 1) Ex vivo expression of OB-R in UA endothelium (UAendo) and UA vascular smooth muscle (UAvsm) is elevated in pregnant vs...
March 1, 2017: Biology of Reproduction
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