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https://www.readbyqxmd.com/read/28227912/a-hybrid-discrete-continuous-model-of-in-vitro-spheroid-tumor-growth-and-drug-response
#1
Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giorgos Tzedakis, Evangelos Liapis, Eleftheria Tzamali, Giannis Zacharakis, Vangelis Sakkalis, Giannis Zacharakis, Vangelis Sakkalis, Evangelos Liapis, Giorgos Tzedakis, Eleftheria Tzamali
Anti-cancer therapy efficacy in solid tumors mainly depends on drug transportation through the vasculature system and the extracellular matrix, on diffusion gradients and clonal heterogeneity within the tumor mass, as well as on the responses of the individual tumor cells to drugs and their interactions with each other and their local microenvironment. In this work, we develop a mathematical predictive model for tumor growth and drug response based on 3D spheroids experiments that possess several in vivo features of tumors and are considered better for drug screening...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226332/responsible-safe-and-effective-prescription-of-opioids-for-chronic-non-cancer-pain-american-society-of-interventional-pain-physicians-asipp-guidelines
#2
Laxmaiah Manchikanti, Adam M Kaye, Nebojsa Nick Knezevic, Heath McAnally, Konstantin Slavin, Andrea M Trescot, Susan Blank, Vidyasagar Pampati, Salahadin Abdi, Jay S Grider, Alan D Kaye, Kavita N Manchikanti, Harold Cordner, Christopher G Gharibo, Michael E Harned, Sheri L Albers, Sairam Atluri, Steve M Aydin, Sanjay Bakshi, Robert L Barkin, Ramsin M Benyamin, Mark V Boswell, Ricardo M Buenaventura, Aaron K Calodney, David L Cedeno, Sukdeb Datta, Timothy R Deer, Bert Fellows, Vincent Galan, Vahid Grami, Hans Hansen, Standiford Helm Ii, Rafael Justiz, Dhanalakshmi Koyyalagunta, Yogesh Malla, Annu Navani, Kent H Nouri, Ramarao Pasupuleti, Nalini Sehgal, Sanford M Silverman, Thomas T Simopoulos, Vijay Singh, Daneshvari R Solanki, Peter S Staats, Ricardo Vallejo, Bradley W Wargo, Arthur Watanabe, Joshua A Hirsch
BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl...
February 2017: Pain Physician
https://www.readbyqxmd.com/read/28226245/subconjunctival-injectable-dendrimer-dexamethasone-gel-for-the-treatment-of-corneal-inflammation
#3
Uri Soiberman, Siva P Kambhampati, Tony Wu, Manoj K Mishra, Yumin Oh, Rishi Sharma, Jiangxia Wang, Abdul Elah Al Towerki, Samuel Yiu, Walter J Stark, Rangaramanujam M Kannan
Corneal inflammation is often encountered as a key pathological event in many corneal diseases. Current treatments involve topical corticosteroids which require frequent instillations due to rapid tear turnover, causing side-effects such as corneal toxicity and elevated intraocular pressure (IOP). Hence, new interventions that can reduce side effects, dosing frequency, and increase patient compliance can be highly beneficial. In this study, we explore a subconjunctival injectable gel based on G4-PAMAM dendrimer and hyaluronic acid, cross-linked using thiol-ene click chemistry, incorporated with dendrimer dexamethasone (D-Dex) conjugates as a potential strategy for sustained delivery and enhanced bioavailability of corticosteroids...
February 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#4
Young-Eun Cho, Eun-Ju Im, Pyong-Gon Moon, Esteban Mezey, Byoung-Joon Song, Moon-Chang Baek
Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury...
2017: PloS One
https://www.readbyqxmd.com/read/28225252/luminescent-re-i-carbonyl-complexes-as-trackable-photocorms-for-co-delivery-to-cellular-targets
#5
Indranil Chakraborty, Jorge Jimenez, W M C Sameera, Masako Kato, Pradip K Mascharak
A family of Re(I) carbonyl complexes of general formula [ReX(CO)3(phen)](0/1+) (where X = Cl(-), CF3SO3(-), MeCN, PPh3, and methylimidazole) derived from 1,10-phenanthroline (phen) exhibits variable emission characteristics depending on the presence of the sixth ancillary ligand/group (X). All complexes but with X = MeCN exhibit moderate CO release upon irradiation with low-power UV light and are indefinitely stable in anaerobic/aerobic environment in solution as well as in solid state when kept under dark condition...
February 22, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#6
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28225057/intracellular-drug-bioavailability-a-new-predictor-of-system-dependent-drug-disposition
#7
André Mateus, Andrea Treyer, Christine Wegler, Maria Karlgren, Pär Matsson, Per Artursson
Intracellular drug exposure is influenced by cell- and tissue-dependent expression of drug-transporting proteins and metabolizing enzymes. Here, we introduce the concept of intracellular bioavailability (Fic) as the fraction of extracellular drug available to bind intracellular targets, and we assess how Fic is affected by cellular drug disposition processes. We first investigated the impact of two essential drug transporters separately, one influx transporter (OATP1B1; SLCO1B1) and one efflux transporter (P-gp; ABCB1), in cells overexpressing these proteins...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224957/-medicines-and-elderly-patients-abuse-dependency-or-attraction
#8
Pascal Menecier, Laure Menecier-Ossia
Psychotropic medicines represent, after alcohol, the second class of substances most susceptible to abuse by elderly people. It can be particularly difficult for caregivers to understand such behaviour as these are prescription-only medicines. This misuse is partly a result of older people tending to trivialise and overrate pharmaceutical drugs, ignoring the potential of non-medicinal methods and psychotherapeutic treatments. The boundaries between prescribed use, overuse, self-medication, excessive use, dependency or addiction to prescription drugs are blurred in older people...
January 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28224619/fl-asparaginase-mediated-downregulation-of-c-myc-promotes-1-25-oh-2-d3-induced-myeloid-differentiation-in-acute-myeloid-leukemia-cells
#9
Ju Han Song, Eunchong Park, Myun Soo Kim, Kyung-Min Cho, Su-Ho Park, Arim Lee, Jiseon Song, Hyeoung-Joon Kim, Jeong-Tae Koh, Tae Sung Kim
Treatment of acute myeloid leukemia (AML) largely depends on chemotherapy, but current regimens have been unsatisfactory for long-term remission. Although differentiation induction therapy utilizing 1,25(OH)2 D3 (VD3) has shown great promise for the improvement of AML treatment efficacy, severe side effects caused by its supraphysiological dose limit its clinical application. Here we investigated the combinatorial effect of l-asparaginase (ASNase)-mediated amino acid depletion and the latent alternation of VD3 activity on the induction of myeloid differentiation...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224386/%C3%AE-bisabolol-inhibits-aspergillus-fumigatus-af239-growth-via-affecting-microsomal-%C3%A2-24-sterol-methyltransferase-as-a-crucial-enzyme-in-ergosterol-biosynthesis-pathway
#10
Zahra Jahanshiri, Masoomeh Shams-Ghahfarokhi, Farnoush Asghari-Paskiabi, Reza Saghiri, Mehdi Razzaghi-Abyaneh
Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28224367/novel-treatment-with-intraperitoneal-moc31pe-immunotoxin-in-colorectal-peritoneal-metastasis-results-from-the-immunopeca-phase-1-trial
#11
Ida S Frøysnes, Yvonne Andersson, Stein G Larsen, Ben Davidson, Janne-Merete Torset Øien, Kari Hauge Olsen, Karl-Erik Giercksky, Lars Julsrud, Øystein Fodstad, Svein Dueland, Kjersti Flatmark
BACKGROUND: MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC...
February 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28224246/comparison-of-veterinary-drug-residue-results-in-animal-tissues-by-ultrahigh-performance-liquid-chromatography-coupled-to-triple-quadrupole-or-quadrupole-time-of-flight-tandem-mass-spectrometry-after-different-sample-preparation-methods-including-use-of-a-commercial
#12
Tarun Anumol, Steven J Lehotay, Joan Stevens, Jerry Zweigenbaum
Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and for other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as many analytes as possible, with higher priority given to the drugs of most concern, in an efficient and robust manner. The U.S. Department of Agriculture has implemented a multiclass, multi-residue method based on sample preparation using dispersive solid phase extraction (d-SPE) for cleanup and ultrahigh-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ) for analysis of >120 drugs at regulatory levels of concern in animal tissues...
February 21, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28224194/mycoepoxydiene-suppresses-hela-cell-growth-by-inhibiting-glycolysis-and-the-pentose-phosphate-pathway
#13
Kehua Jin, Li Li, Xihuan Sun, Qingyan Xu, Siyang Song, Yuemao Shen, Xianming Deng
Upregulation of glycolysis and the pentose phosphate pathway (PPP) is a major characteristic of the metabolic reprogramming of cancer and provides cancer cells with energy and vital metabolites to support their rapid proliferation. Targeting glycolysis and the PPP has emerged as a promising antitumor therapeutic strategy. Marine natural products are attractive sources for anticancer therapeutics, as evidenced by the antitumor drug Yondelis. Mycoepoxydiene (MED) is a natural product isolated from a marine fungus that has shown promising inhibitory efficacy against HeLa cells in vitro...
February 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28224082/clinical-characteristics-of-adult-patients-with-inborn-errors-of-metabolism-in-spain-a-review-of-500-cases-from-university-hospitals
#14
J Pérez-López, L Ceberio-Hualde, J S García-Morillo, J M Grau-Junyent, A Hermida Ameijeiras, M López-Rodríguez, J C Milisenda, M Moltó Abad, M Morales-Conejo, J J Nava Mateos
Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28223860/polymeric-films-as-a-promising-carrier-for-bioadhesive-drug-delivery-development-characterization-and-optimization
#15
Pallavi Bassi, Gurpreet Kaur
Bioadhesive films using tamarind seed polysaccharide were prepared for the treatment of candida vaginitis using nystatin as the model drug. Films were prepared by solvent casting method. A 3(2) factorial design was employed to study the effect of independent variables (polymer and plasticizer concentration) on a range of dependent variables namely mechanical, swelling, interfacial, and bioadhesive properties through response surface methodological approach, using Design Expert® software. Formulation composition that provided the most desired and optimized results was selected using desirability approach...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28223856/uncertainties-around-incretin-based-therapies-a-literature-review
#16
REVIEW
Bader Al Tulaihi, Samia Alhabib
Background: Diabetes mellitus is a chronic debilitating and non-communicable disease. It has several long-term outcomes that are associated with various end organ damage, mainly the heart, blood vessels, eyes, nerves, and kidneys. There are different modalities of treatment of diabetes. The recent incretin-based therapies provided an innovative class of drugs including GLP-1 receptor agonists and DPP-4 inhibitors. This review aims to summarize the available evidence of their effectiveness. Method: This is a narrative review...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28223526/hypermutation-signature-reveals-a-slippage-and-realignment-model-of-translesion-synthesis-by-rev3-polymerase-in-cisplatin-treated-yeast
#17
Romulo Segovia, Yaoqing Shen, Scott A Lujan, Steven J M Jones, Peter C Stirling
Gene-gene or gene-drug interactions are typically quantified using fitness as a readout because the data are continuous and easily measured in high throughput. However, to what extent fitness captures the range of other phenotypes that show synergistic effects is usually unknown. Using Saccharomyces cerevisiae and focusing on a matrix of DNA repair mutants and genotoxic drugs, we quantify 76 gene-drug interactions based on both mutation rate and fitness and find that these parameters are not connected. Independent of fitness defects, we identified six cases of synthetic hypermutation, where the combined effect of the drug and mutant on mutation rate was greater than predicted...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223499/two-metal-versus-one-metal-mechanisms-of-lysine-adenylylation-by-atp-dependent-and-nad-dependent-polynucleotide-ligases
#18
Mihaela-Carmen Unciuleac, Yehuda Goldgur, Stewart Shuman
Polynucleotide ligases comprise a ubiquitous superfamily of nucleic acid repair enzymes that join 3'-OH and 5'-PO4 DNA or RNA ends. Ligases react with ATP or NAD(+) and a divalent cation cofactor to form a covalent enzyme-(lysine-Nζ)-adenylate intermediate. Here, we report crystal structures of the founding members of the ATP-dependent RNA ligase family (T4 RNA ligase 1; Rnl1) and the NAD(+)-dependent DNA ligase family (Escherichia coli LigA), captured as their respective Michaelis complexes, which illuminate distinctive catalytic mechanisms of the lysine adenylylation reaction...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223427/calcium-dependent-enhancement-by-extracellular-acidity-of-the-cytotoxicity-of-mitochondrial-inhibitors-against-melanoma
#19
Fumihito Noguchi, Shigeki Inui, Clare Fedele, Mark Shackleton, Satoshi Itami
Extracellular acidity is a hallmark of cancers and is independent of hypoxia. Since acidity potentiates malignant phenotypes, therapeutic strategies that enhance the targeting of oncogenic mechanisms in an acidic microenvironment should be effective. We report here that drugs which abrogate mitochondrial respiration show enhanced cytotoxicity against melanoma cells in a normoxic but acidic extracellular pH, independent from P53 mutations, BRAF (V600E) mutations and/or resistance against BRAF inhibitors. Conversely, the cytotoxicity against melanoma cells of mitochondrial inhibitors is impaired by a neutral or alkaline extracellular pH and in vivo systemic alkalinization with NaHCO3 enhanced subcutaneous tumor growth and lung metastasis of B16F10 cells in mice treated with the mitochondrial inhibitor phenformin...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223414/the-flavonoid-cyanidin-blocks-binding-of-the-cytokine-interleukin-17a-to-the-il-17ra-subunit-to-alleviate-inflammation-in-vivo
#20
Caini Liu, Liang Zhu, Koichi Fukuda, Suidong Ouyang, Xing Chen, Chenhui Wang, Cun-Jin Zhang, Bradley Martin, Chunfang Gu, Luke Qin, Suguna Rachakonda, Mark Aronica, Jun Qin, Xiaoxia Li
Cyanidin, a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, including asthma, diabetes, atherosclerosis, and cancer, through its anti-inflammatory effects. We investigated the molecular basis of cyanidin action. Through a structure-based search for small molecules that inhibit signaling by the proinflammatory cytokine interleukin-17A (IL-17A), we found that cyanidin specifically recognizes an IL-17A binding site in the IL-17A receptor subunit (IL-17RA) and inhibits the IL-17A/IL-17RA interaction...
February 21, 2017: Science Signaling
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