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https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#1
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
February 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28205273/in-vitro-responses-to-known-in-vivo-genotoxic-agents-in-mouse-germ-cells
#2
Khaled Habas, Martin H Brinkworth, Diana Anderson
Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n-ethyl-n-nitrosourea (ENU), 6-mercaptopurine (6-MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration-dependent...
February 16, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28197307/synthesis-and-antitumor-activity-evaluation-of-a-novel-combi-nitrosourea-prodrug-bgcnu
#3
Yameng Wang, Ting Ren, Xinxin Lai, Guohui Sun, Lijiao Zhao, Na Zhang, Rugang Zhong
Chloroethylnitrosoureas (CENUs) are an important type of alkylating agent employed in the clinical treatment of cancer. However, the anticancer efficacy of CENUs is greatly decreased by a DNA repairing enzyme, O(6)-alkylguanine-DNA alkyltransferase (AGT), by preventing the formation of interstrand cross-links (ICLs). In this study, a combi-nitrosourea prodrug, namely, N-(2-chloroethyl)-N'-2-(O(6)-benzyl-9-guanine)ethyl-N-nitrosourea (BGCNU), which possesses an O(6)-benzylguanine (O(6)-BG) derivative and CENU pharmacophores simultaneously, was synthesized and evaluated for its ability to induce ICLs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28190923/diphenylarsinic-acid-exerts-promotion-effects-on-hepatobiliary-carcinogenesis-in-a-rat-medium-term-multiorgan-carcinogenicity-bioassay
#4
Naomi Ishii, Min Gi, Masaki Fujioka, Shotaro Yamano, Mai Okumura, Anna Kakehashi, Hideki Wanibuchi
We have previously demonstrated that diphenylarsinic acid (DPAA) promotes liver carcinogenesis in rats in a medium-term liver carcinogenicity bioassay. However, the effects of DPAA on other organs have not been determined. In the present study, the effects of DPAA on carcinogenesis were investigated using a rat multiorgan carcinogenicity bioassay. A total of 60 six-week-old male F344 rats were treated with the carcinogens diethylnitrosamine, N-butyl-N-(4-hydroxybutyl) nitrosamine, N-methyl-N-nitrosourea, N-bis (2-hydroxypropyl) nitrosamine, and 1,2-dimethylhydrazine dihydrochloride to initiate carcinogenesis in multiple organs...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#5
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan Edgerton, Ann D Thor, Pepper Schedin, Steven Anderson, Paul MacLean
Several epidemiological studies have associated metformin treatment with a reduction in breast cancer incidence in pre-diabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiological reports consistently link western-style high fat diets, which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28150874/the-caspase-3-p120-rasgap-stress-sensing-module-reduces-liver-cancer-incidence-but-does-not-affect-overall-survival-in-gamma-irradiated-and-carcinogen-treated-mice
#6
Güliz Vanli Jaccard, Christine Sempoux, Christian Widmann
Activation of oncogenes is the initial step in cellular transformation. Oncogenes favor aberrant proliferation and this initially also induces cellular stress. This oncogenic stress can act a safeguard mechanism against further transformation by inducing senescence or apoptosis. Yet, the few premalignant cells that tolerate and escape these senescent or apoptotic responses are those that will ultimately generate tumors. The caspase-3/p120 RasGAP module is a stress-sensing device that promotes survival under mild stress conditions...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28143714/chloroethylating-nitrosoureas-in-cancer-therapy-dna-damage-repair-and-cell-death-signaling
#7
REVIEW
Teodora Nikolova, Wynand P Roos, Oliver H Krämer, Herwig M Strik, Bernd Kaina
Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy...
January 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28137860/creatine-maintains-intestinal-homeostasis-and-protects-against-colitis
#8
Emre Turer, William McAlpine, Kuan-Wen Wang, Tianshi Lu, Xiaohong Li, Miao Tang, Xiaoming Zhan, Tao Wang, Xiaowei Zhan, Chun-Hui Bu, Anne R Murray, Bruce Beutler
Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS)...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28134622/mutations-in-tropomyosin-4-underlie-a-rare-form-of-human-macrothrombocytopenia
#9
Irina Pleines, Joanne Woods, Stephane Chappaz, Verity Kew, Nicola Foad, José Ballester-Beltrán, Katja Aurbach, Chiara Lincetto, Rachael M Lane, Galina Schevzov, Warren S Alexander, Douglas J Hilton, William J Astle, Kate Downes, Paquita Nurden, Sarah K Westbury, Andrew D Mumford, Samya G Obaji, Peter W Collins, Fabien Delerue, Lars M Ittner, Nicole S Bryce, Mira Holliday, Christine A Lucas, Edna C Hardeman, Willem H Ouwehand, Peter W Gunning, Ernest Turro, Marloes R Tijssen, Benjamin T Kile
Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Platelet number and volume are independent risk factors for heart attack and stroke. Here, we have identified 2 unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterized by low platelet count...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28123413/hsp70-cleavage-induced-photoreceptor-cell-death-caused-by-n-methyl-n-nitrosourea
#10
Yoshiki Koriyama, Ayako Furukawa
No abstract text is available yet for this article.
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28112267/visual-responses-of-photoreceptor-degenerated-rats-expressing-two-different-types-of-channelrhodopsin-genes
#11
Masatoshi Sato, Eriko Sugano, Kitako Tabata, Kei Sannohe, Yoshito Watanabe, Taku Ozaki, Makoto Tamai, Hiroshi Tomita
Optogenetic technologies are expected to be applicable for clinical use in restoring vision. However, the degree of recovered visual function is highly dependent on the function of the chosen optogenetic gene. To investigate the effect on visual function of dual expression of genes with different wavelength sensitivities, we transduced a modified Volvox-derived channelrhodopsin gene (mVChR1) via an adeno-associated virus vector into transgenic rats harbouring the ChR2 gene in retinal ganglion cells. These transgenic rats were given an intraperitoneal injection of N-methyl-N-nitrosourea to induce the degeneration of native photoreceptor cells prior to transduction of mVChR1...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28112220/the-natural-retinoprotectant-chrysophanol-attenuated-photoreceptor-cell-apoptosis-in-an-n-methyl-n-nitrosourea-induced-mouse-model-of-retinal-degenaration
#12
Fan-Li Lin, Cheng-Hui Lin, Jau-Der Ho, Jing-Lun Yen, Hung-Ming Chang, George C Y Chiou, Yu-Wen Cheng, George Hsiao
Retinitis pigmentosa (RP) is an inherited photoreceptor-degenerative disease, and neuronal degeneration in RP is exacerbated by glial activation. Cassia seed (Jue-ming-zi) is a traditional herbal medicine commonly used to treat ocular diseases in Asia. In this report, we investigated the retina-protective effect of chrysophanol, an active component of Cassia seed, in an N-methyl-N-nitrosourea (MNU)-induced mouse model of RP. We determined that chrysophanol inhibited the functional and morphological features of MNU-induced retinal degeneration using scotopic electroretinography (ERG), optical coherence tomography (OCT), and immunohistochemistry analysis of R/G opsin and rhodopsin...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28107677/sensitization-of-melanoma-cells-to-alkylating-agent-induced-dna-damage-and-cell-death-via-orchestrating-oxidative-stress-and-ikk%C3%AE-inhibition
#13
Anfernee Kai-Wing Tse, Ying-Jie Chen, Xiu-Qiong Fu, Tao Su, Ting Li, Hui Guo, Pei-Li Zhu, Hiu-Yee Kwan, Brian Chi-Yan Cheng, Hui-Hui Cao, Sally Kin-Wah Lee, Wang-Fun Fong, Zhi-Ling Yu
Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death...
January 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28091921/levels-of-mirna-and-hormones-in-thoracic-duct-lymph-in-rats-with-experimental-breast-cancer-induced-by-n-methyl-n-nitrosourea
#14
A P Lykov, A V Kabakov, O V Kazakov, N A Bondarenko, O V Poveshchenko, T V Raiter, A F Poveshchenko, D N Strunkin, V I Konenkov
We studied hormone levels in the thoracic duct lymph and expression of miRNA involved in the pathogenesis of breast cancer induced in rats by intramammary injection of N-methyl-Nnitrosourea. The correlations between miRNA expression and hormone levels depended on the type of treatment.
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28074112/isolation-and-characterization-of-antimutagenic-components-of-glycyrrhiza-aspera-against-n-methyl-n-nitrosourea
#15
Keiko Inami, Yusuke Mine, Jin Tatsuzaki, Chihiro Mori, Masataka Mochizuki
BACKGROUND: A powdered ethanolic extract of Glycyrrhiza aspera root exhibits antimutagenic activity against N-methyl-N-nitrosourea (MNU) based on the Ames assay with Salmonella typhimurium TA1535. The aim of this study was to identify the antimutagenic components of the powdered ethanolic extract of G. aspera root. RESULTS: The powdered ethanolic extract of G. aspera root was sequentially suspended in n-hexane, carbon tetrachloride, dichloromethane, ethyl acetate, and ethanol, and each solvent soluble fraction and the residue were assayed for antimutagenic activity against MNU in S...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28069436/streptozotocin-causes-neurotoxic-effect-in-cultured-cerebellar-granule-neurons
#16
Elisaveta E Genrikhs, Elena V Stelmashook, Sergey A Golyshev, Olga P Aleksandrova, Nickolay K Isaev
Streptozotocin (STZ) is a glucosamine-nitrosourea compound used for experimental simulation of sporadic Alzheimer's disease at intracerebroventricular administration in vivo. The studies of STZ influence on neurons of central nervous system performed on the primary cultures are practically absent. We have shown the application of STZ (1-5mM) in primary culture for 48h induced strong dose-dependent death in cultured cerebellar granule neurons. This toxic effect was decreased by pyruvate, insulin partially. Using the indicator Fluo-4 AM for measurements of intracellular calcium ions and tetramethylrhodamine ethyl ester (TMRE) for detection of changes of mitochondrial membrane potential in live cells we have shown that 5 h-exposure to STZ induced intensive increase of Fluo-4 and decrease TMRE fluorescence in neurons...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28057804/cell-cycle-progression-dictates-the-requirement-for-bcl2-in-natural-killer-cell-survival
#17
Charlotte Viant, Sophie Guia, Robert J Hennessy, Jai Rautela, Kim Pham, Claire Bernat, Wilford Goh, Yuhao Jiao, Rebecca Delconte, Michael Roger, Vanina Simon, Fernando Souza-Fonseca-Guimaraes, Stephanie Grabow, Gabrielle T Belz, Benjamin T Kile, Andreas Strasser, Daniel Gray, Phillip D Hodgkin, Bruce Beutler, Eric Vivier, Sophie Ugolini, Nicholas D Huntington
Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells...
February 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28049248/nestin-expression-in-the-adult-mouse-retina-with-pharmaceutically-induced-retinal-degeneration
#18
Chan Hee Moon, Heeyoon Cho, Yoon Kyung Kim, Tae Kwann Park
The present study investigated the temporal pattern and cellular localization of nestin in the adult mouse retina with pharmaceutically induced retinal degeneration using N-methyl-N-nitrosourea (MNU). After a single intraperitoneal injection of MNU in 8-week-old C57BL/6 mice, the animals were sacrificed at 1, 3, 5, 7, and 21 days (n = 6, in each stage). The eyes were examined by means of immunohistochemical tests using nestin, ionized calcium-binding adaptor molecule (Iba-1), CD11b, F4/80, and glial fibrillary acidic protein (GFAP)...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28040797/disease-subtype-independent-biomarkers-of-breast-cancer-chemoprevention-by-the-ayurvedic-medicine-phytochemical-withaferin-a
#19
Suman K Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Eun-Ryeong Hahm, Yongli Shuai, Ruchi Roy, Subrata K Pore, Krishna B Singh, Susan M Christner, Jan H Beumer, Nancy E Davidson, Shivendra V Singh
BACKGROUND: A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action. METHODS: Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group)...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28040063/pivotal-role-of-glutathione-depletion-in-enos-uncoupling-of-lps-treated-huvecs
#20
L Chen, E Liu, D Cao, S Li, C Xiao, M Xiong, Q Kou
The present study investigated the relationship between uncoupling of endothelial nitric oxide synthase (eNOS) and vascular endothelial cell (VEC) oxidative stress (OS) during sepsis and the role of eNOS glutathionylation in eNOS uncoupling of septic VECs. Human umbilical vein endothelial cells (HUVECs) cultured in vitro (EA.hy269 cell line) were incubated with Dulbecco's modified Eagle's medium (DMEM) (normal control group), lipopolysaccharide (LPS) (sepsis group), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (glutathionylation group), and LPS+ dithiothreitol (DTT) (deglutathionylation sepsis group)...
November 30, 2016: Cellular and Molecular Biology
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