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https://www.readbyqxmd.com/read/28296148/dimp53-1-a-novel-small-molecule-dual-inhibitor-of-p53-mdm2-x-interactions-with-multifunctional-p53-dependent-anticancer-properties
#1
Joana Soares, Margarida Espadinha, Liliana Raimundo, Helena Ramos, Ana Sara Gomes, Sara Gomes, Joana B Loureiro, Alberto Inga, Flávio Reis, Célia Gomes, Maria M M Santos, Lucília Saraiva
The transcription factor p53 plays a crucial role in cancer development and dissemination, and thus p53-targeted therapies are amongst the most encouraging anticancer strategies. In human cancers with wild-type (wt) p53, its inactivation by interaction with murine double minute (MDM)2 and MDMX is a common event. Simultaneous inhibition of the p53 interaction with both MDMs is crucial to restore the tumor suppressor activity of p53. Here we describe the synthesis of the new tryptophanol-derived oxazoloisoindolinone DIMP53-1 and identify its activity as a dual inhibitor of the p53-MDM2/X interactions using a yeast-based assay...
March 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28260096/increased-%C3%AE-133p53-mrna-in-lung-carcinoma-corresponds-with-reduction-of-p21-expression
#2
Aikaterini Fragou, Georgios Tzimagiorgis, Christos Karageorgopoulos, Nikolaos Barbetakis, Axilleas Lazopoulos, Maria Papaioannou, Costas Haitoglou, Sofia Kouidou
Modification of p53 expression levels and its principle apoptosis and cell cycle regulatory partners, mouse double minute 2 homolog (MDM‑2) and p21, has been previously reported in various types of cancer. In the current study, the expression of Δ133p53 isoforms was investigated in lung carcinomas with respect to the expression of the aforementioned genes. The expression of p53 full‑length transcript and Δ133p53 isoforms α, β and γ transcripts, MDM‑2 and p21 transcripts were determined by reverse transcription‑quantitative polymerase chain reaction, in total RNA isolated from 17 lung carcinoma specimens and 17 corresponding adjacent non‑cancerous tissues...
February 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#3
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28159034/food-insecurity-and-health-status-in-deprived-populations-2014-a-multicentre-survey-in-seven-of-the-social-and-medical-healthcare-centres-casos-run-by-doctors-of-the-world-france
#4
S Laurence, E Durand, E Thomas, M Chappuis, J F Corty
OBJECTIVE: To document eating practices and socio-economic profiles of patients seen in the social and medical healthcare centres (CASOs in its French acronym) run by Doctors of the World (Médecins du Monde, MdM) in France and evaluate their nutritional and health status. STUDY DESIGN: The survey was carried out between April and May 2014 in seven CASOs in France. METHODS: All the patients attending MdM clinics were given a nutrition and health questionnaire...
February 2017: Public Health
https://www.readbyqxmd.com/read/28157969/second-order-few-mode-raman-amplifier-for-mode-division-multiplexed-optical-communication-systems
#5
Jiaxiong Li, Jiangbing Du, Lin Ma, Ming-Jun Li, Ke Xu, Zuyuan He
We experimentally demonstrate and investigate, for first time to our best knowledge, a second-order few-mode Raman amplifier for low noise distributed fiber amplification. The 1455 and 1360 nm pumps are both injected into the few-mode fiber (FMF) in the forms of two degenerate LP<sub>11</sub> modes in the backward direction. Within the band from 1542 to 1558 nm, maximum on-off gains of 4 dB are achieved for both LP<sub>01</sub> and LP<sub>11</sub> modes, and the differential modal gain (DMG) is less than 0...
January 23, 2017: Optics Express
https://www.readbyqxmd.com/read/28105750/development-of-a-peer-review-framework-for-cancer-multi-disciplinary-meetings
#6
Claire E Johnson, Neli Slavova-Azmanova, Christobel Saunders
BACKGROUND: There is no mechanism in place for monitoring or quality improvement of cancer multidisciplinary meetings (MDMs) in Australia. OBJECTIVE: To develop a peer review process for quality improvement of MDMs. METHODS: This project involved three phases: 1) development of a draft peer review framework, supporting documents and peer review process; 2) consultation with key stakeholders; 3) refinement of the framework, documents and processes following a pilot study with three MDMs...
January 20, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28068513/nrf2-dependent-induction-of-innate-host-defense-via-heme-oxygenase-1-inhibits-zika-virus-replication
#7
Hanxia Huang, Barry Falgout, Kazuyo Takeda, Kenneth M Yamada, Subhash Dhawan
We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retarding ZIKV replication...
March 2017: Virology
https://www.readbyqxmd.com/read/28049824/p53-pathway-is-involved-in-cell-competition-during-mouse-embryogenesis
#8
Guoxin Zhang, Yinyin Xie, Ying Zhou, Cong Xiang, Lai Chen, Chenxi Zhang, Xiaoshuang Hou, Jiong Chen, Hui Zong, Geng Liu
The function of tumor suppressor p53 has been under intense investigation. Acute stresses such as DNA damage are able to trigger a high level of p53 activity, leading to cell cycle arrest or apoptosis. In contrast, the cellular response of mild p53 activity induced by low-level stress in vivo remains largely unexplored. Murine double minute (MDM)2 and MDM4 are two major negative regulators of p53. Here, we used the strategy of haploinsufficiency of Mdm2 and Mdm4 to induce mild p53 activation in vivo and found that Mdm2(+/-)Mdm4(+/-) double-heterozygous mice exhibited normal embryogenesis...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28048335/su-g-tep3-13-the-role-of-nanoscale-energy-deposition-in-the-development-of-gold-nanoparticle-enhanced-radiotherapy
#9
C Kirkby, B Koger, N Suchowerska, D McKenzie
PURPOSE: Gold nanoparticles (GNPs) can enhance radiotherapy effects. The high photoelectric cross section of gold relative to tissue, particularly at lower energies, leads to localized dose enhancement. However in a clinical context, photon energies must also be sufficient to reach a target volume at a given depth. These properties must be balanced to optimize such a therapy. Given that nanoscale energy deposition patterns around GNPs play a role in determining biological outcomes, in this work we seek to establish their role in this optimization process...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27994863/guide-a-structured-pre-dialysis-programme-that-increases-the-use-of-home-dialysis
#10
Josanne S de Maar, Marjolein A J de Groot, Peter T Luik, Kwok Wai Mui, E Christiaan Hagen
BACKGROUND: Despite the many advantages it offers, the percentage of dialysis patients that receive home dialysis [peritoneal dialysis (PD) or home haemodialysis (HHD)] in the Netherlands has declined over the last decade. Pre-dialysis education could stimulate the use of home dialysis. This article presents the results of the pre-dialysis programme GUIDE, with regard to the following question: Does the implementation of a structured pre-dialysis programme with a home-focused approach increase the number of pre-dialysis patients that choose and receive home dialysis? METHODS: The GUIDE process starts when a patient has an eGFR of 15 mL/min/1...
December 2016: Clinical Kidney Journal
https://www.readbyqxmd.com/read/27994045/effects-of-activation-on-the-elastic-properties-of-intact-soleus-muscles-with-a-deletion-in-titin
#11
Jenna A Monroy, Krysta L Powers, Cinnamon M Pace, Theodore Uyeno, Kiisa C Nishikawa
Titin has long been known to contribute to muscle passive tension. Recently, it was also demonstrated that titin-based stiffness increases upon Ca(2+)-activation of wildtype mouse psoas myofibrils stretched beyond overlap of the thick and thin filaments. In addition, this increase in titin-based stiffness upon activation was impaired in single psoas myofibrils from mdm mice with a deletion in titin. Here, we investigate the effects of muscle activation on elastic properties of intact soleus muscles from wildtype and mdm mice to determine whether titin may contribute to active muscle stiffness...
December 19, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27959389/matrine%C3%A2-induced-apoptosis-in-hep3b-cells-via-the-inhibition-of-mdm2
#12
Ning Zhou, Jiequn Li, Ting Li, Guangshun Chen, Zhongqiang Zhang, Zhongzhou Si
Matrine, an alkaloid component derived from the Sophora root, can inhibit cancer cell proliferation and induce autophagy via p53 associated pathways. However, numerous tumor cells lack functional p53 and little is known about the effect of matrine on the p53‑deficient/mutant cancer cells. The present study aimed to assess anticancer effects of matrine in p53‑deficient human Hep3B hepatoma cells. The present results demonstrated that matrine caused Hep3B cell apoptosis by suppressing gene expression of minute double‑mutant (MDM)2...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27916740/development-of-europium-doped-core-shell-silica-cobalt-ferrite-functionalized-nanoparticles-for-magnetic-resonance-imaging
#13
Bhavesh D Kevadiya, Aditya N Bade, Christopher Woldstad, Benson J Edagwa, JoEllyn M McMillan, Balasrinivasa R Sajja, Michael D Boska, Howard E Gendelman
The size, shape and chemical composition of europium (Eu(3+)) cobalt ferrite (CFEu) nanoparticles were optimized for use as a "multimodal imaging nanoprobe" for combined fluorescence and magnetic resonance bioimaging. Doping Eu(3+) ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ∼7.2nm) were prepared by solvothermal techniques and encapsulated into poloxamer 407-coated mesoporous silica (Si-P407) to form superparamagnetic monodisperse Si-CFEu nanoparticles with a size of ∼140nm...
December 1, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27906000/the-antiviral-compound-bit225-inhibits-hiv-1-replication-in-myeloid-dendritic-cells
#14
Gabriela Khoury, Gary Ewart, Carolyn Luscombe, Michelle Miller, John Wilkinson
BACKGROUND: Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies...
February 8, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27902238/description-of-algoriphagus-iocasae-sp-nov-isolated-from-the-deep-sea-sediment-of-okinawa-trough
#15
Qing-Lei Sun, Li Sun
In this study, we reported the identification and species characterization of a novel Gram-staining-negative bacterium, strain S61T, isolated from the deep sea sediment in the Okinawa Trough. Growth of strain S61T occurred at 4-37 °C (optimum, 25 °C), pH 6.0-10.0 (optimum, 7.0), and with 0-8 % (w/v) NaCl (optimum, 2 %). Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain S61T belonged to the genus Algoriphagus. The closest phylogenetic neighbors of strain S61T were A. lutimaris S1-3T (98...
October 24, 2016: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/27828313/cost-effective-wavelength-reused-mdm-system-for-bidirectional-mobile-fronthaul
#16
Yuanxiang Chen, Juhao Li, Paikun Zhu, Huanfa Peng, Jinglong Zhu, Yu Tian, Zhongying Wu, Dawei Ge, Peng Zhou, Ke Liu, Yongchi Xu, Jingbiao Chen, Yongqi He, Zhangyuan Chen
In this paper, we propose a cost-effective wavelength-reused mode-division-multiplexing (MDM) system for high speed symmetrical bidirectional mobile fronthaul application. At the base band unit (BBU) pool, one of the spatial modes is used to transmit signal carrier while the others are used for downstream (DS) signal channels. At the remote radio unit (RRU) side, the signal carrier is split and reused as modulation carrier for all the upstream (US) signal channels after mode demultiplexing. Thanks to the low mode crosstalk characteristic of the mode multiplexer/demultiplexer (MUX/DEMUX) and few-mode fiber (FMF), the signal carrier and each signal channel can be effectively separated...
October 3, 2016: Optics Express
https://www.readbyqxmd.com/read/27810359/the-testis-specific-usp26-is-a-deubiquitinating-enzyme-of-the-ubiquitin-ligase-mdm2
#17
Shirly Lahav-Baratz, Yelena Kravtsova-Ivantsiv, Shay Golan, Aaron Ciechanover
Murine double minute-2 (Mdm2) is one of the E3-ligases of the androgen receptor besides being the major regulator of the p53 tumor suppressor. The testis-specific USP26 was demonstrated to regulate the androgen receptor. In the present study we examined possible association between the deubiquitinating enzyme - ubiquitin specific protease 26 (USP26), and the oncoprotein E3 ligase - (Mdm-2). We analyzed the half-life time of USP26 in HEK293 cells. In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract...
January 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27796344/antileukemic-scalarane-sesterterpenoids-and-meroditerpenoid-from-carteriospongia-phyllospongia-sp-induce-apoptosis-via-dual-inhibitory-effects-on-topoisomerase-ii-and-hsp90
#18
Kuei-Hung Lai, Yi-Chang Liu, Jui-Hsin Su, Mohamed El-Shazly, Chih-Fung Wu, Ying-Chi Du, Yu-Ming Hsu, Juan-Cheng Yang, Ming-Kai Weng, Chia-Hua Chou, Guan-Yu Chen, Yu-Cheng Chen, Mei-Chin Lu
Two new scalarane sesterterpenoids, 12β-(3'β-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12β-(3'β-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 μg/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase IIα expression...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27760375/p-cresyl-sulfate-affects-the-oxidative-burst-phagocytosis-process-and-antigen-presentation-of-monocyte-derived-macrophages
#19
M L V Azevedo, N B Bonan, G Dias, F Brehm, T M Steiner, W M Souza, A E M Stinghen, F C Barreto, Selene Elifio-Esposito, R Pecoits-Filho, A N Moreno-Amaral
Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×10(6) cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12...
November 30, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27688079/sarcomatoid-adrenal-carcinoma-case-report-with-contribution-to-pathogenesis
#20
Wolfgang Saeger, Werner Mohren, Matthias Behrend, Peter Iglauer, Waldemar Wilczak
A tumor in the adrenal region with two metastases in the liver was classified as poorly differentiated sarcoma on the base of extensive immunostainings (expression of vimentin, desmin, myogenin, and CD31, no expression of inhibin, melan A). Four years later in a second examination with molecular methods for a study of adrenal sarcomas, this diagnosis must be revised due to the lack of MDM-2 gene amplification and FKHR translocation which exclude sarcoma. Further immunostainings of many other parts of the tumor showed in one area more mature tumor tissue expressing synaptophysin, SF-1, and melan A...
September 29, 2016: Endocrine Pathology
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