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https://www.readbyqxmd.com/read/29148232/disulfiram-combined-with-copper-inhibits-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma-through-the-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-pathways
#1
Yi Li, Li-Hui Wang, Hao-Tian Zhang, Ya-Ting Wang, Shuai Liu, Wen-Long Zhou, Xiang-Zhong Yuan, Tian-Yang Li, Chun-Fu Wu, Jing-Yu Yang
Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29137648/lesr-is-a-novel-upstream-regulator-that-controls-downstream-clp-expression-to-modulate-antibiotic-hsaf-biosynthesis-and-cell-aggregation-in-lysobacter-enzymogenes-oh11
#2
Huiyong Xu, Ruping Wang, Yangyang Zhao, Zheng Qing Fu, Guoliang Qian, Fengquan Liu
BACKGROUND: Heat-stable antifungal factor (HSAF) is a polycyclic tetramate macrolactam secondary metabolite that exhibits broad-spectrum inhibitory activities against filamentous fungal pathogens. The native yield of this chemical is low. It is also a great challenge to synthesize HSAF artificially, due to its complex structure. Understanding the regulatory mechanism underlying HSAF biosynthesis could provide genetic basis for engineering high HSAF-producing strain. The transcription factor Clp is a global regulator that controls bacterial pathogenicity and the expression of one hundred related genes in the phytopathogenic bacterium Xanthomonas campestris pv...
November 14, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29135106/evidence-for-the-efficacy-of-disulfiram-and-copper-combination-in-glioblastoma-multiforme-a-propos-of-a-case
#3
Petros N Karamanakos, Dimitrios T Trafalis, Dionysios J Papachristou, Eleftheria S Panteli, Maria Papavasilopoulou, Andreas Karatzas, Dimitrios Kardamakis, Georgios Nasioulas, Marios Marselos
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29130178/methods-to-study-quorum-sensing-dependent-virulence-and-movement-of-phytopathogens-in-planta
#4
Shulamit Manulis-Sasson, Laura Chalupowicz
Cell-to-cell communication mediated by the diffusible signal factor (DSF) is a common form of gene regulation and plays an important role in virulence of many plant pathogenic bacteria including Xanthomonas spp. Here we describe several approaches to study the involvement of DSF-dependent QS system of the plant pathogenic bacteria Xanthomonas campestris pv. pelargonii (Xhp) as an example of the Xanthomonas spp. The methods described include detection and measurement of DSF, movement in planta, colonization, and aggregate formation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29130167/ultra-performance-liquid-chromatography-mass-spectrometry-for-the-detection-and-quantification-of-diffusible-signal-factor-dsf-family-quorum-sensing-signals
#5
Lian Zhou, Shuang Sun, Wei Zhang, Ya-Wen He
Molecules of the diffusible signal factor (DSF) family represent a class of widely conserved quorum-sensing signals used by many Gram-negative bacterial pathogens. The measurement of DSF family signals is essential for understanding their biological roles, signaling pathway, and regulatory network. We are presenting here methods for extraction and purification of DSF family signals from culture supernatants, and further quantification of members of DSF family signals using an ultra-performance liquid chromatographic system (UPLC) coupled with an accurate time-of-flight mass spectrometry (TOF-MS) analysis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29128471/development-of-verbal-short-term-memory-and-working-memory-in-children-with-epilepsy-developmental-delay-and-impact-of-time-related-variables-a-cross-sectional-study
#6
Loretta van Iterson, Peter F de Jong
While short-term memory (STM) and working memory (WM) are understood as being crucial for learning, and children with epilepsy often experience learning difficulties, little is known about the age-related development of memory span tasks in children with epilepsy. Short-term memory and WM, operationalized as digit span forwards (DSF) or digit span backwards (DSB), respectively, were studied. Participants were 314 children with epilepsy and 327 typically developing children in ages between 5 and 15years and full scale intelligence quotient (FS-IQ)≥75...
November 8, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29082887/a-proposed-role-for-diffusible-signal-factors-in-the-biofilm-formation-and-morphological-transformation-of-helicobacter-pylori
#7
REVIEW
Pawel Krzyzek, Grazyna Gosciniak
Due to the increasing resistance of Helicobacter pylori to antibiotics, there is a growing need for new strategies for the effective eradication of this pathogen. The inhibition of quorum-sensing activity in most microorganisms leads to a decrease in virulence. A different reaction is observed in H. pylori, as interfering with the production of autoinducer-2 initiates biofilm formation and increases the survival of these bacteria. Therefore, it is believed that there is an alternative way to control the physiological changes of H...
October 30, 2017: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29077030/dietary-compound-resveratrol-is-a-pan-bet-bromodomain-inhibitor
#8
Luiz Antonio Dutra, David Heidenreich, Gabriel Dalio Bernardes da Silva, Chung Man Chin, Stefan Knapp, Jean Leandro Dos Santos
The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100 µM increased the melting temperature (∆Tm) of BET bromodomains by around 2...
October 27, 2017: Nutrients
https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#9
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29050650/glycaemic-response-after-intake-of-a-high-energy-high-protein-diabetes-specific-formula-in-older-malnourished-or-at-risk-of-malnutrition-type-2-diabetes-patients
#10
Hamid Laksir, Mirian Lansink, Sophie C Regueme, Johan de Vogel-van den Bosch, Andreas F H Pfeiffer, Isabelle Bourdel-Marchasson
BACKGROUND & AIMS: Several studies with diabetes-specific formulas (DSFs) for hyperglycaemic patients in need of nutritional support have been conducted in non-malnourished patients, mainly comparing products with varying macronutrient compositions. Here, the effect of a high energy, high protein DSF on postprandial responses was compared to a product with a similar macronutrient composition in malnourished or at risk of malnutrition patients with type 2 diabetes. METHODS: In this randomised, double-blind cross-over study, 20 patients were included...
October 6, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29029481/cell-cycle-specific-radiosensitisation-by-the-disulfiram-and-copper-complex
#11
Mathias Tesson, Giorgio Anselmi, Caitlin Bell, Robert Mairs
The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28990228/influence-of-outdoor-rearing-and-oleic-acid-supplementation-on-lipid-characteristics-of-muscle-and-adipose-tissues-from-obese-alentejano-pigs
#12
J M Martins, A Albuquerque, J A Neves, A B Freitas, R Charneca, J L Tirapicos
Data evaluating the effect of oleic-acid-enriched diets and outdoor rearing (with access to pasture) on the quality of Alentejano (AL) pork and fat are limited. The aim of this work was to study the effects of feeding low (LO) or high oleic acid (HO) diets to AL pigs reared in individual pens (IND) or outdoors (OUT) with access to pasture. Biceps femoris and dorsal subcutaneous fat (DSF) samples were collected to analyse chemical composition and lipids fatty acid (FA) profile. The expression of seven genes involved in lipogenesis, lipolysis and FA transport, as well as two transcription factors were also evaluated in the muscle...
October 8, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28986384/mass-spectrometry-for-fragment-screening
#13
REVIEW
Daniel Shiu-Hin Chan, Andrew J Whitehouse, Anthony G Coyne, Chris Abell
Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography...
October 6, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28957029/learning-simpler-language-models-with-the-differential-state-framework
#14
Alexander G Ororbia Ii, Tomas Mikolov, David Reitter
Learning useful information across long time lags is a critical and difficult problem for temporal neural models in tasks such as language modeling. Existing architectures that address the issue are often complex and costly to train. The differential state framework (DSF) is a simple and high-performing design that unifies previously introduced gated neural models. DSF models maintain longer-term memory by learning to interpolate between a fast-changing data-driven representation and a slowly changing, implicitly stable state...
September 28, 2017: Neural Computation
https://www.readbyqxmd.com/read/28950195/octa-arginine-modified-lipid-emulsions-as-a-potential-ocular-delivery-system-for-disulfiram-a-study-of-the-corneal-permeation-transcorneal-mechanism-and-anti-cataract-effect
#15
Chang Liu, Qi Lan, Wei He, Changlu Nie, Chunjuan Zhang, Tonghua Xu, Tongying Jiang, Siling Wang
The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8...
August 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28946828/retention-of-the-structure-and-function-of-heparan-sulfate-biomaterials-after-gamma-irradiation
#16
Raymond A A Smith, R J E Chua, Susan M Carnachan, Clarissa Ling Ling Tan, Ian M Sims, Simon F R Hinkley, Victor Nurcombe, Simon Cool
Heparan sulfate (HS) is a highly heterogeneous polysaccharide implicated in many important biological processes. Our previous work has demonstrated that a particular affinity-selected HS (referred to henceforth as 'HS3') is capable of enhancing the osteogenic effects of bone morphogenetic protein 2 (BMP2). Here, we gamma-irradiated HS with 26 kGy of ionizing radiation to determine how this affected the structure, composition and function. Initial structural studies were performed on a commercial preparation of HS as a proof-of-concept...
September 25, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28944755/the-intriguing-effect-of-delay-time-to-sentinel-lymph-node-biopsy-on-survival-a-propensity-score-matching-study-on-a-cohort-of-melanoma-patients
#17
Antonio Tejera-Vaquerizo, Miguel Angel Descalzo-Gallego, Victor Traves, Celia Requena, Isidro Bolumar, Angel Pla, Eduardo Nagore
BACKGROUND: Time between primary melanoma excision and sentinel lymph node biopsy (SLNB) has not been sufficiently studied as an independent predictor of survival in cutaneous melanoma. OBJECTIVES: We used propensity score matching to evaluate whether early SLNB (performed ≤40 days from excisional biopsy) is associated with higher mortality in patients with cutaneous melanoma. MATERIALS & METHODS: A retrospective cohort study at a tertiary melanoma referral centre...
September 23, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28944496/the-unidirectional-hypoxia-activated-prodrug-oct1002-inhibits-growth-and-vascular-development-in-castrate-resistant-prostate-tumors
#18
Heather Nesbitt, Jenny Worthington, Rachel J Errington, Laurence H Patterson, Paul J Smith, Stephanie R McKeown, Declan J McKenna
BACKGROUND: OCT1002 is a unidirectional hypoxia-activated prodrug (uHAP) OCT1002 that can target hypoxic tumor cells. Hypoxia is a common feature in prostate tumors and is known to drive disease progression and metastasis. It is, therefore, a rational therapeutic strategy to directly target hypoxic tumor cells in an attempt to improve treatment for this disease. Here we tested OCT1002 alone and in combination with standard-of-care agents in hypoxic models of castrate-resistant prostate cancer (CRPC)...
November 2017: Prostate
https://www.readbyqxmd.com/read/28895651/modulating-the-physical-and-electronical-properties-over-positional-isomerism-the-dispirofluorene-dihydroindacenodithiophene-dsf-idt-family
#19
Joëlle Rault-Berthelot, Jean-David Peltier, Cyril Poriel, Benoît Heinrich, Bertrand Donnio, Olivier Jeannin
We report the first studies on the intrinsic properties of a meta-substituted dihydroindacenodithienyl fragment and more generally the strong impact of positional isomerism on dihydroindacenodithiophene derivatives. The influence of the para and meta linkages has notably been highlighted not only on the electronic properties in solution (electrochemical properties, anodic polymerization, HOMO/LUMO energy levels, optical transitions, fluorescence spectra…) but also on the physical properties in the solid state (molecular organization, crystallinity and phase transitions)...
September 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28864067/a-novel-chemoradiation-targeting-stem-and-nonstem-pancreatic-cancer-cells-by-repurposing-disulfiram
#20
Juan Cong, Yangyang Wang, Xiao Zhang, Nan Zhang, Ling Liu, Klara Soukup, Theodoros Michelakos, Theodore Hong, Albert DeLeo, Lei Cai, Francesco Sabbatino, Soldano Ferrone, Hang Lee, Vera Levina, Bryan Fuchs, Kenneth Tanabe, Keith Lillemoe, Cristina Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year relative survival rate of 8% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs...
November 28, 2017: Cancer Letters
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