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https://www.readbyqxmd.com/read/27929127/lipid-modified-g4-decoy-oligonucleotide-anchored-to-nanoparticles-delivery-and-bioactivity-in-pancreatic-cancer-cells
#1
S Cogoi, U Jakobsen, E B Pedersen, S Vogel, L E Xodo
KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919837/ex-vivo-itreg-differentiation-revisited-convenient-alternatives-to-existing-strategies
#2
Billur Akkaya, Amanda H Holstein, Christopher Isaac, Mitra P Maz, Deborah D Glass, Ethan M Shevach, Munir Akkaya
Ex-vivo differentiation of regulatory T cells (Tregs) from naïve CD4(+) T-cells has been widely used in immunological research. Isolation of a highly pure naïve T cell population is the key factor that determines the efficiency of subsequent Treg differentiation. Currently, this step relies mostly on FACS sorting, which is often costly, time consuming, and inconvenient. Alternatively, magnetic separation of T-cells can be performed; yet, available protocols fail to reach sort level purity and consequently result in low Treg differentiation efficiency...
December 2, 2016: Journal of Immunological Methods
https://www.readbyqxmd.com/read/27888145/critical-role-of-hnrnp-a1-in-activating-kras-transcription-in-pancreatic-cancer-cells-a-molecular-mechanism-involving-g4-dna
#3
REVIEW
Susanna Cogoi, Valentina Rapozzi, Sabina Cauci, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. Its crucial role in the tumourigenesis of pancreatic ductal adenocarcinoma (PDAC) has been widely demonstrated. As this deadly cancer does not sufficiently respond to conventional chemotherapies, it is important to increase our knowledge of pancreatic cancer biology, in particular how oncogenic KRAS is regulated. The promoter of KRAS contains a GA-element composed of runs of guanines that fold into a G4 structure. This unusual DNA conformation is recognized by several nuclear proteins, including MAZ and hnRNP A1...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27861158/myc-associated-zinc-finger-protein-promotes-the-invasion-and-metastasis-of-hepatocellular-carcinoma-by-inducing-epithelial-mesenchymal-transition
#4
Wei Luo, Xiaonian Zhu, Wei Liu, Yuan Ren, Chunhua Bei, Linyuan Qin, Xueyan Miao, Fen Tang, Guifang Tang, Shengkui Tan
MYC associated zinc finger protein (MAZ) plays a key role in regulation of gene expression and tumor development. Studies have shown that deregulated expression of MAZ is closely related to the progression of tumors such as glioblastoma, breast cancer, prostate cancer and liposarcoma. However, the role of MAZ in hepatocellular carcinoma (HCC) has not been fully elucidated. Here, we found that expression of MAZ was increased in HCC and correlated to the distant metastasis of HCC. Moreover, we found that MAZ had a relationship with zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), two important mesenchymal markers in epithelial-mesenchymal transition (EMT) that were over-expressed in HCC...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835937/fractional-laser-assisted-topical-delivery-leads-to-enhanced-accelerated-and-deeper-cutaneous-5-fluorouracil-uptake
#5
Emily Wenande, Uffe H Olesen, Mette M B Nielsen, Christian Janfelt, Steen Honoré Hansen, Rox Anderson, Merete Haedersdal
BACKGROUND: Topical 5-Fluorouracil (5-FU) exhibits suboptimal efficacy for non-melanoma skin cancer, attributed to insufficient intracutaneous penetration. This study investigates the impact of ablative fractional laser (AFXL) at different laser-channel depths on cutaneous 5-FU pharmacokinetics and biodistribution. METHODS: In vitro porcine skin underwent AFXL-exposure using a fractional 10,600nm CO2-laser, generating microscopic ablation zones (MAZ) reaching the dermoepidermal junction (MAZ-ED), superficial-(MAZ-DS), or mid-dermis(MAZ-DM)...
November 11, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27768596/elevated-expression-of-znf217-promotes-prostate-cancer-growth-by-restraining-ferroportin-conducted-iron-egress
#6
Xingkang Jiang, Changwen Zhang, Shiyong Qi, Shanqi Guo, Yue Chen, E Du, Hongtuan Zhang, Xiaoming Wang, Ranlu Liu, Baomin Qiao, Kuo Yang, Zhihong Zhang, Yong Xu
Although we and other studies indicated ZNF217 expression was increased in prostate cancer (PCa), the factors mediating its misregulated expression and their oncogenic activity remain largely unexplored. Recent evidence demonstrated that ferroportin (FPN) reduction lead to decreased iron export and increased intercellular iron that consequently aggravates the oncogenic effects of iron. In the present study, ZNF217 was identified as a transcriptional repressor that inhibits FPN expression. Increased of ZNF217 expression led to decreased FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth...
October 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27632283/iranian-johnsongrass-mosaic-virus-the-complete-genome-sequence-molecular-and-biological-characterization-and-comparison-of-coat-protein-gene-sequences
#7
Zohreh Moradi, Mohsen Mehrvar, Ehsan Nazifi, Mohammad Zakiaghl
Iranian johnsongrass mosaic virus (IJMV) is one of the most prevalent viruses causing maize mosaic disease in Iran. An IJMV isolate, Maz-Bah, was obtained from the maize showing mosaic symptoms in Mazandaran, north of Iran. The complete genomic sequence of Maz-Bah is 9544 nucleotides, excluding the poly(A) tail. It contains one single open reading frame of 9165 nucleotides and encodes a large polyprotein of 3054 amino acids, flanked by a 5'-untranslated region (UTR) of 143 nucleotides and a 3'-UTR of 236 nucleotides...
September 8, 2016: Virus Genes
https://www.readbyqxmd.com/read/27534615/gene-signatures-associated-with-adaptive-humoral-immunity-following-seasonal-influenza-a-h1n1-vaccination
#8
I G Ovsyannikova, H M Salk, R B Kennedy, I H Haralambieva, M T Zimmermann, D E Grill, A L Oberg, G A Poland
This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses...
December 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27391153/carboxyl-terminal-truncated-hbx-contributes-to-invasion-and-metastasis-via-deregulating-metastasis-suppressors-in-hepatocellular-carcinoma
#9
Weihua Li, Man Li, Dongjiang Liao, Xinpeng Lu, Xia Gu, Qianqian Zhang, Zhixiang Zhang, Hui Li
Hepatitis B virus (HBV) X protein (HBx), a trans-regulator, is frequently expressed in truncated form without carboxyl-terminus in hepatocellular carcinoma (HCC), but its functional mechanisms are not fully defined. In this report, we investigated frequency of this natural HBx mutant in HCCs and its functional significance. In 102 HBV-infected patients with HCC, C-terminal truncation of HBx, in contrast to full-length HBx, were more prevalent in tumors (70.6%) rather than adjacent non-tumorous tissues (29.4%) (p = 0...
July 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27386562/novel-multiple-sclerosis-susceptibility-loci-implicated-in-epigenetic-regulation
#10
Till F M Andlauer, Dorothea Buck, Gisela Antony, Antonios Bayas, Lukas Bechmann, Achim Berthele, Andrew Chan, Christiane Gasperi, Ralf Gold, Christiane Graetz, Jürgen Haas, Michael Hecker, Carmen Infante-Duarte, Matthias Knop, Tania Kümpfel, Volker Limmroth, Ralf A Linker, Verena Loleit, Felix Luessi, Sven G Meuth, Mark Mühlau, Sandra Nischwitz, Friedemann Paul, Michael Pütz, Tobias Ruck, Anke Salmen, Martin Stangel, Jan-Patrick Stellmann, Klarissa H Stürner, Björn Tackenberg, Florian Then Bergh, Hayrettin Tumani, Clemens Warnke, Frank Weber, Heinz Wiendl, Brigitte Wildemann, Uwe K Zettl, Ulf Ziemann, Frauke Zipp, Janine Arloth, Peter Weber, Milena Radivojkov-Blagojevic, Markus O Scheinhardt, Theresa Dankowski, Thomas Bettecken, Peter Lichtner, Darina Czamara, Tania Carrillo-Roa, Elisabeth B Binder, Klaus Berger, Lars Bertram, Andre Franke, Christian Gieger, Stefan Herms, Georg Homuth, Marcus Ising, Karl-Heinz Jöckel, Tim Kacprowski, Stefan Kloiber, Matthias Laudes, Wolfgang Lieb, Christina M Lill, Susanne Lucae, Thomas Meitinger, Susanne Moebus, Martina Müller-Nurasyid, Markus M Nöthen, Astrid Petersmann, Rajesh Rawal, Ulf Schminke, Konstantin Strauch, Henry Völzke, Melanie Waldenberger, Jürgen Wellmann, Eleonora Porcu, Antonella Mulas, Maristella Pitzalis, Carlo Sidore, Ilenia Zara, Francesco Cucca, Magdalena Zoledziewska, Andreas Ziegler, Bernhard Hemmer, Bertram Müller-Myhsok
We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation...
June 2016: Science Advances
https://www.readbyqxmd.com/read/27264947/laser-assisted-delivery-of-topical-methotrexate-in-vitro-investigations
#11
Elisabeth Hjardem Taudorf
Ablative fractional lasers (AFXL) are increasingly used to treat dermatological disorders and to facilitate laser-assisted topical drug delivery. In this thesis, laser-tissue interactions generated by stacked pulses with a miniaturized low-power 2,940 nm AFXL were characterized (study I). Knowledge of the correlation between laser parameters and tissue effects was used to deliver methotrexate (MTX) topically through microscopic ablation zones (MAZs) of precise dimensions. MTX is a well-known chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects, and topical delivery is thus of potential benefit...
June 2016: Danish Medical Journal
https://www.readbyqxmd.com/read/27194098/stakeholders-views-on-granting-prescribing-authority-to-pharmacists-in-nigeria-a-qualitative-study
#12
Asa Auta, Barry Strickland-Hodge, Julia Maz
Background In Nigeria, only medical doctors, dentists and some nurses in primary care facilities have the legal right to prescribe medicines to patients. Patients' access to prescription medicines can be seriously affected by the shortage of prescribers leading to longer waiting times in hospitals. Objective This research was carried out to investigate stakeholders' views on granting prescribing authority to pharmacists in Nigeria. Setting The study was conducted in Nigeria. Methods Qualitative, semi-structured interviews were conducted with 43 Nigerian stakeholders including policymakers, pharmacists, doctors and patient group representatives...
August 2016: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/27023055/corrigendum-maz-mediates-the-cross-talk-between-ct-1-and-notch1-signaling-during-gliogenesis
#13
Bin Liu, Anyun Ma, Feng Zhang, Yumeng Wang, Zengmin Li, Qingyu Li, Zhiheng Xu, Yufang Zheng
No abstract text is available yet for this article.
March 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26969559/challenges-to-clinical-pharmacy-practice-in-nigerian-hospitals-a-qualitative-exploration-of-stakeholders-views
#14
Asa Auta, Barry Strickland-Hodge, Julia Maz
RATIONALE, AIMS AND OBJECTIVES: In Nigeria, a shift from the traditional pharmacists' role of dispensing and compounding of medications began in the 1980s with the introduction of drug information services and unit dose-dispensing systems in some hospitals. More than three decades after this, clinical pharmacy practice is still underdeveloped. This study was conducted to explore stakeholders' views on the barriers to the development of clinical pharmacy practice in Nigerian hospitals...
October 2016: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/26902421/akt-phosphorylates-myc-associated-zinc-finger-protein-maz-releases-p-maz-from-the-p53-promoter-and-activates-p53-transcription
#15
Wei-Ping Lee, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Han-Chieh Lin, Shou-Dong Lee
The p53 protein is a cell cycle regulator. When the cell cycle progresses, p53 plays an important role in putting a brake on the G1 phase to prevent unwanted errors during cell division. Akt is a downstream kinase of receptor tyrosine kinase. Upon activation, Akt phorphorylates IKK that then phosphorylates IκB and releases NF-κB, leading to transcriptional activation of Dmp1. Dmp1 is a transcriptional activator of Arf. It has been known that oncogene activation stabilizes p53 through transcriptional activation of Arf, which then binds and inhibits Mdm2...
May 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/26867947/maz-mediates-the-cross-talk-between-ct-1-and-notch1-signaling-during-gliogenesis
#16
Bin Liu, Anyun Ma, Feng Zhang, Yumeng Wang, Zengmin Li, Qingyu Li, Zhiheng Xu, Yufang Zheng
Neurons and glia cells are differentiated from neural stem/progenitor cells (NSCs/NPCs) during brain development. Concomitant activation of JAK/STAT and NOTCH1 signaling is required for gliogenesis, a process to generate glia cells to ensure proper brain functions. NOTCH1 signaling is down-regulated during neurogenesis and up-regulated during gliogenesis. However, the underlying mechanism remains elusive. We report here that cardiotrophin-1 (CT-1) activates NOTCH1 signaling through the up-regulation of ADAM10, a rate-limiting factor of NOTCH1 signaling activation...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26859870/transcriptomics-modeling-of-the-late-gestation-fetal-pituitary-response-to-transient-hypoxia
#17
Charles E Wood, Eileen I Chang, Elaine M Richards, Maria Belen Rabaglino, Maureen Keller-Wood
BACKGROUND: The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia...
2016: PloS One
https://www.readbyqxmd.com/read/26846733/fractional-laser-assisted-drug-delivery-laser-channel-depth-influences-biodistribution-and-skin-deposition-of-methotrexate
#18
E H Taudorf, C M Lerche, A M Erlendsson, P A Philipsen, S H Hansen, C Janfelt, U Paasch, R R Anderson, M Haedersdal
BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM)...
July 2016: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/26713101/nucleic-acid-targeted-therapy-g4-oligonucleotides-downregulate-hras-in-bladder-cancer-cells-through-a-decoy-mechanism
#19
Giulia Miglietta, Alaa S Gouda, Susanna Cogoi, Erik B Pedersen, Luigi E Xodo
In a previous study we have demonstrated that two neighboring G-quadruplexes, hras-1 and hras-2, located immediately upstream of the major transcription start site of HRAS, bind MAZ, a nuclear factor that activates transcription (Cogoi, S.; et al. Nucl. Acid Res. 2014, 42, 8379). For the present study we have designed G4 oligonucleotides with anthraquinone insertions and locked nucleic acids (LNA) modifications mimicking quadruplex hras-1. Luciferase, qRT-PCR, and Western blot data demonstrate that these constructs efficiently down regulate HRAS in T24 bladder cancer cells...
December 10, 2015: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26656490/kras-promoter-oligonucleotide-with-decoy-activity-dimerizes-into-a-unique-topology-consisting-of-two-g-quadruplex-units
#20
Peter Podbevšek, Janez Plavec
Mutations of the KRAS proto-oncogene are associated with several tumor types, which is why it is being considered as a target for anti-cancer drug development. The human KRAS promoter contains a nuclease hypersensitive element (NHE), which can bind to nuclear proteins and is believed to form G-quadruplex structures. Previous studies showed that a 32-nt oligonucleotide (32R-3n) mimicking the KRAS NHE can reduce gene transcription by sequestering MAZ, a crucial transcription factor. Here we show that 32R-3n has to dimerize in order to fold into a G-quadruplex structure...
January 29, 2016: Nucleic Acids Research
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