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https://www.readbyqxmd.com/read/27915005/development-and-characterisation-of-disulfiram-loaded-plga-nanoparticles-for-the-treatment-of-non-small-cell-lung-cancer
#1
Mohammad Najlah, Zahima Ahmed, Mohammed Iqbal, Zhipeng Wang, Patrica Tawari, Weiguang Wang, Christopher McConville
Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4 minutes) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model...
November 30, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27895076/mesothelial-cells-create-a-novel-tissue-niche-that-facilitates-gastric-cancer-invasion
#2
Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells...
November 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#3
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27882330/aldh2-inhibition-potentiates-high-glucose-stress-induced-injury-in-cultured-cardiomyocytes
#4
Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Suresh Selvaraj Palaniyandi
Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27831632/disulfiram-as-a-candidate-nf-%C3%AE%C2%BAb-and-proteasome-inhibitor-prevents-endometriotic-implant-growing-in-a-rat-model-of-endometriosis
#5
O Celik, A Ersahin, M Acet, N Celik, Y Baykus, R Deniz, E Ozerol, I Ozerol
OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27813538/the-use-of-differential-scanning-fluorimetry-in-the-rational-design-of-plastic-antibodies-for-protein-targets
#6
Jon Ashley, Yunus Shukor, Ibtisam E Tothill
The development of molecularly imprinted polymer nanoparticles (MIP-NPs), which specifically bind biomolecules, is of great interest in the area of biosensors, sample purification, therapeutic agents and biotechnology. Polymerisation techniques such as precipitation polymerisation, solid phase synthesis and core shell surface imprinting have allowed for significant improvements to be made in developing MIP-NPs which specifically recognise proteins. However, the development of MIP-NPs for protein templates (targets) still require lengthy optimisation and characterisation using different ratios of monomers in order to control their size, binding affinity and specificity...
November 14, 2016: Analyst
https://www.readbyqxmd.com/read/27803460/an-ophthalmic-formulation-of-disulfiram-nanoparticles-prolongs-drug-residence-time-in-lens
#7
Noriaki Nagai, Yu Mano, Yoshimasa Ito
Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27796875/molecular-and-spectroscopic-characterization-of-aspergillus-flavipes-and-pseudomonas-putida-l-methionine-%C3%AE-lyase-in-vitro
#8
Ashraf S A El-Sayed, Laura E Ruff, Salah E Abdel Ghany, Gul Shad Ali, Sadik Esener
Pseudomonas putida L-methionine γ-lyase (PpMGL) has been recognized as an efficient anticancer agent, however, its antigenicity and stability remain as critical challenges for its clinical use. From our studies, Aspergillus flavipes L-methionine γ-lyase (AfMGL) displayed more affordable biochemical properties than PpMGL. Thus, the objective of this work was to comparatively assess the functional properties of AfMGL and PpMGL via stability of their internal aldimine linkage, tautomerism of pyridoxal 5'-phosphate (PLP) and structural stability responsive to physicochemical factors...
October 29, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27794454/characterization-of-aminoacyl-trna-synthetase-stability-and-substrate-interaction-by-differential-scanning-fluorimetry
#9
REVIEW
Jamie A Abbott, Nathan M Livingston, Shawn B Egri, Ethan Guth, Christopher S Francklyn
Differential scanning fluorimetry (DSF) is a fluorescence-based assay to evaluate protein stability by determining protein melting temperatures. Here, we describe the application of DSF to investigate aminoacyl-tRNA synthetase (AARS) stability and interaction with ligands. Employing three bacterial AARS enzymes as model systems, methods are presented here for the use of DSF to measure the apparent temperatures at which AARSs undergo melting transitions, and the effect of AARS substrates and inhibitors. One important observation is that the extent of temperature stability realized by an AARS in response to a particular bound ligand cannot be predicted a priori...
October 26, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27789147/utilizing-direct-skin-feeding-assays-for-development-of-vaccines-that-interrupt-malaria-transmission-a-systematic-review-of-methods-and-case-study
#10
REVIEW
Elizabeth B Brickley, Mamadou Coulibaly, Erin E Gabriel, Sara A Healy, Jen C C Hume, Issaka Sagara, Sekou F Traore, Ogobara Doumbo, Patrick E Duffy
Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations...
October 24, 2016: Vaccine
https://www.readbyqxmd.com/read/27765525/the-clinical-and-economic-impact-of-the-use-of-diabetes-specific-enteral-formula-on-icu-patients-with-type-2-diabetes
#11
Yin-Yi Han, Sheng-Ru Lai, Jamie S Partridge, Michael Y Wang, Suela Sulo, Fang-Wei Tsao, Refaat A Hegazi
BACKGROUND & AIMS: Patients admitted to intensive care units (ICUs) often need enteral nutrition (EN) support. For patients with type 2 diabetes (T2D), standard EN formulas may not provide ideal nutrients. The purpose was to investigate whether use of a diabetes-specific formula (DSF) could provide clinical and health economic benefits (compared to standard formulas) in critically ill patients with T2D. METHODS: This study was a retrospective analysis of medical records and expenditure data covering a 5-year period (2009-2013) from the hospitalization database of the National Taiwan University Hospital...
October 6, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27739422/decrease-in-ph-destabilizes-individual-vault-nanocages-by-weakening-the-inter-protein-lateral-interaction
#12
Aida Llauró, Pablo Guerra, Ravi Kant, Brian Bothner, Núria Verdaguer, Pedro J de Pablo
Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results performed with bulk techniques or at non-physiological conditions have suggested pH as a parameter to control vault dynamics. Here we use Atomic Force Microscopy (AFM) to monitor the structural evolution of individual vault particles while changing the pH in real time...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725388/design-of-novel-ophthalmic-formulation-containing-drug-nanoparticles-and-its-usefulness-as-anti-glaucoma-drugs
#13
Noriaki Nagai
 The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/27703465/using-the-disease-state-fingerprint-tool-for-differential-diagnosis-of-frontotemporal-dementia-and-alzheimer-s-disease
#14
Miguel Ángel Muñoz-Ruiz, Anette Hall, Jussi Mattila, Juha Koikkalainen, Sanna-Kaisa Herukka, Minna Husso, Tuomo Hänninen, Ritva Vanninen, Yawu Liu, Merja Hallikainen, Jyrki Lötjönen, Anne M Remes, Irina Alafuzoff, Hilkka Soininen, Päivi Hartikainen
BACKGROUND: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. AIMS: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). METHODS: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases...
May 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27684731/gata3-rs3824662-gene-polymorphism-as-possible-risk-factor-in-a-cohort-of-egyptian-patients-with-pediatric-acute-lymphoblastic-leukemia-and-its-prognostic-impact
#15
Youssef M Mosaad, Rasha Elashery, Ahmad Darwish, Omar A Sharaf Eldein, Tarek Barakat, Samy Marouf, Noha T Abou El-Khier, Laila F Youssef, Iman M Fawzy
To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = ...
August 9, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27684652/diffusible-signal-factor-dependent-quorum-sensing-in-pathogenic-bacteria-and-its-exploitation-for-disease-control
#16
REVIEW
J M Dow
Cell-to-cell signals of the diffusible signal factor (DSF) family are cis-2-unsaturated fatty acids of differing chain length and branching pattern. DSF signalling has been described in diverse bacteria to include plant and human pathogens where it acts to regulate functions such as biofilm formation, antibiotic tolerance and the production of virulence factors. DSF family signals can also participate in interspecies signalling with other bacteria and interkingdom signalling such as with the yeast Candida albicans...
September 29, 2016: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/27661293/examining-the-construct-validity-of-the-mmpi-2-rf-interpersonal-functioning-scales-using-the-computerized-adaptive-test-of-personality-disorder-as-a-comparative-framework
#17
Annabel O Franz, Tiffany M Harrop, David M McCord
This study aimed to examine the construct validity of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) interpersonal functioning scales (Ben-Porath & Tellegen, 2008/2011 ) using as a criterion measure the Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF; Simms et al., 2011 ). Participants were college students (n = 98) recruited through the university subject pool. A series of a priori hypotheses were developed for each of the 6 interpersonal functioning scales of the MMPI-2-RF, expressed as predicted correlations with construct-relevant CAT-PD-SF scales...
September 23, 2016: Journal of Personality Assessment
https://www.readbyqxmd.com/read/27602492/anti-hepatocellular-carcinoma-properties-of-the-anti-alcoholism-drug-disulfiram-discovered-to-enzymatically-inhibit-the-ampk-related-kinase-snark-in-vitro
#18
Kaku Goto, Naoya Kato, Raymond T Chung
We recently described that the anti-apoptotic AMPK-related kinase, SNARK, promotes transforming growth factor (TGF)-β signaling in hepatocellular carcinoma (HCC) cells, as a potentially new therapeutic target. Here we explored FDA-approved drugs inhibiting the enzymatic activity of SNARK, using an in vitro luminescence kinase assay system. Interestingly, the long-used anti-alcoholism drug disulfiram (DSF), also known as Antabuse, emerged as the top hit. Enzymatic kinetics analyses revealed that DSF inhibited SNARK kinase activity in a noncompetitive manner to ATP or phosphosubstrates...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27595587/xanthomonas-campestris-fabh-is-required-for-branched-chain-fatty-acid-and-dsf-family-quorum-sensing-signal-biosynthesis
#19
Yong-Hong Yu, Zhe Hu, Hui-Juan Dong, Jin-Cheng Ma, Hai-Hong Wang
Xanthomonas campestris pv. campestris (Xcc), a Gram-negative phytopathogenic bacterium, causes black rot disease of cruciferous vegetables. Although Xcc has a complex fatty acid profile comprised of straight-chain fatty acids and branched-chain fatty acids (BCFAs), and encodes a complete set of genes required for fatty acid synthesis, there is still little known about the mechanism of BCFA synthesis. We reported that expression of Xcc fabH restores the growth of Ralstonia solanacearum fabH mutant, and this allows the R...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27542268/targeting-aldh1a1-by-disulfiram-copper-complex-inhibits-non-small-cell-lung-cancer-recurrence-driven-by-aldh-positive-cancer-stem-cells
#20
Xinwei Liu, Lihui Wang, Wei Cui, Xiangzhong Yuan, Lulu Lin, Qi Cao, Nannan Wang, Yi Li, Wei Guo, Xun Zhang, Chunfu Wu, Jingyu Yang
The existence of cancer stem cells (CSCs) in non-small cell lung cancer (NSCLC) has profound implications for cancer therapy. In this study, a disulfiram/copper (DSF/Cu) complex was evaluated in vitro and in vivo for its efficacy to inhibit CSCs, which drive recurrence of NSCLC. First, we investigated whether DSF/Cu could inhibit ALDH-positive NSCLC stem cells in vitro and tumors derived from sorted ALDH-positive CSCs in vivo. DSF/Cu (0.5/1 μmol/l) significantly inhibited the expression of stem cell transcription factors (Sox2, Oct-4 and Nanog) and reduced the capacities of NSCLC stem cells for self-renewal, proliferation and invasion in vitro...
August 16, 2016: Oncotarget
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