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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/27907972/-tenofovir-alafenamide-fumarate-a-new-generation-of-tenofovir
#1
Svatava Snopková, Kateřina Havlíčková, Petr Husa
Antiretroviral therapy as a life-long treatment has to meet the criteria of maximum efficiency while maintaining the highest possible level of safety and tolerance. Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug with an excellent effect of virological suppression. However, some patients can over time develop clinically significant nephrotoxicity or bone loss. Tenofovir alafenamide fumarate (TAF) is a novel prodrug of tenofovir (TFV) that is more stable in human plasma and more efficiently penetrates into target cells than TFV...
September 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27894873/design-synthesis-and-anti-hiv-1-rt-evaluation-of-2-benzyl-4-chlorophenyl-amino-1-piperazin-1-yl-ethanone-derivatives
#2
Subhash Chander, Ping Wang, Penta Ashok, Liu-Meng Yang, Yong-Tang Zheng, Murugesan Sankaranarayanan
In this study, using molecular hybridization approach, fourteen novel 2-(benzyl(4-chlorophenyl)amino)-1-(piperazin-1-yl)ethanone derivatives (7a-n) were designed as inhibitor of HIV-1 RT. The binding affinity of the designed compounds with HIV-1 RT as well as their drug-likeness behavior was predicted using in-silico studies. All the designed compounds were synthesized, characterized and in-vitro evaluated for HIV-1 RT inhibitory activity, in which tested compounds displayed significant to weak potency against the selected target...
November 14, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27884636/an-in-vitro-and-in-vivo-study-of-peptide-functionalized-nanoparticles-for-brain-targeting-the-importance-of-selective-blood-brain-barrier-uptake
#3
Gerard H Bode, Gregory Coué, Christian Freese, Karin E Pickl, Maria Sanchez-Purrà, Berta Albaiges, Salvador Borrós, Ewoud C van Winden, Leto-Aikaterini Tziveleka, Zili Sideratou, Johan F Engbersen, Smriti Singh, Krystyna Albrecht, Jürgen Groll, Martin Möller, Andy J G Pötgens, Christoph Schmitz, Eleonore Fröhlich, Christian Grandfils, Frank M Sinner, C James Kirkpatrick, Harry W M Steinbusch, Hans-Georg Frank, Ronald E Unger, Pilar Martinez-Martinez
Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo...
November 21, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27873118/current-update-of-a-carboxymethylcellulose-peg-conjugate-platform-for-delivery-of-insoluble-cytotoxic-agents-to-tumors
#4
Yang Yang, Joseph Bteich, Shyh-Dar Li
Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, Cellax™ drug delivery platform was developed. Cellax™ is a polymer-based nanoparticle drug delivery system designed to solubilize hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved pharmacokinetic, safety, and efficacy profiles compared to native DTX (Taxotere®) and Nab-paclitaxel (Nab-PTX, Abraxane®) in multiple animal models...
November 21, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27847962/the-multi-target-effects-of-cni-1493-convergence-of-anti-amylodogenic-and-anti-inflammatory-properties-in-animal-models-of-alzheimer-s-disease
#5
Roman Sankowski, Arne Herring, Kathy Keyvani, Kathrin Frenzel, Jinyu Wu, Stephan Röskam, Carmen Noelker, Michael Bacher, Yousef Al-Abed
After several decades of Alzheimer's disease (AD) research and failed clinical trials, one can speculate that targeting a single pathway is not sufficient. However, a cocktail of novel therapeutics will constitute a challenging clinical trial. A more plausible approach will capitalize on a drug that has relevant and synergistic multiple-target effects in AD. We have previously demonstrated the efficacy of CNI-1493 in the CRND8 transgenic AD mouse model. Similar to many anti-inflammatory drugs that were tested in preclinical model of AD, it was speculated that the significant effect of CNI-1493 is due to its established anti-inflammatory properties in rodents and humans...
November 15, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27843368/an-evidence-based-review-of-certolizumab-pegol-in-the-treatment-of-active-psoriatic-arthritis-place-in-therapy
#6
REVIEW
María Laura Acosta-Felquer, Javier Rosa, Enrique R Soriano
Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of psoriatic arthritis (PsA) in Europe, the USA, and Latin American countries. CZP neutralizes TNF-α at its soluble and membrane portions. Due to the lack of Fc region, it does not induce complement or antibody-dependent cytotoxicity in vitro, unlike other TNFi. RAPID-PsA study, the only randomized clinical trial performed in PsA, is a Phase III clinical trial conducted in 409 PsA patients during 24 weeks...
2016: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/27836804/the-shape-effect-of-magnetic-mesoporous-silica-nanoparticles-on-endocytosis-biocompatibility-and-biodistribution
#7
Dan Shao, Meng-Meng Lu, Ya-Wei Zhao, Fan Zhang, Yong-Fei Tan, Xiao Zheng, Yue Pan, Xuan-Ang Xiao, Zheng Wang, Wen-Fei Dong, Jing Li, Li Chen
: Although the aspect ratio (AR) play a crucial role in determining biological effects of homogeneous nanomaterials, studies available concerning how the shape contributes to biological effect of heterogeneous nanomaterials is limited. To systematically clarify the shape influence on the endocytosis, biocompatibility and biodistribution of magnetic mesoporous silica nanoparticles (M-MSNPs), three FITC-labeled M-MSNPs with different aspect ratio (AR=1, 2, and 4) were specifically designed and constructed through altering the ratios of CTAB/TEOS in a modified so-gel method...
November 9, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27835915/unveiling-changes-in-the-landscape-of-patient-populations-in-cancer-early-drug-development
#8
REVIEW
Cinta Hierro, Analía Azaro, Guillem Argilés, Elena Elez, Patricia Gómez, Joan Carles, Jordi Rodon
The introduction of new Molecularly Targeted Agents (MTA) has changed the landscape in Early Drug Development (EDD) over the last two decades, leading to an improvement in clinical trial design. Previous Phase 1 (Ph1) studies with cytotoxics focused on safety objectives, only recruiting heavily pre-treated cancer patients, have been left behind. In this review, we will illustrate the slow although unstoppable change that has increasingly been observed in those populations candidate to participate in EDD trials with the advent of MTA...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833376/transarterial-chemoembolization-with-drug-eluting-beads-in-hepatocellular-carcinoma
#9
EDITORIAL
Hee Chul Nam, Bohyun Jang, Myeong Jun Song
Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads(®)) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor...
October 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27819247/generic-oncology-drugs-are-they-all-safe
#10
REVIEW
Y Tony Yang, Sumimasa Nagai, Brian K Chen, Zaina P Qureshi, Akida A Lebby, Samuel Kessler, Peter Georgantopoulos, Dennis W Raisch, Oliver Sartor, Terhi Hermanson, Robert C Kane, William J Hrushesky, Joshua J Riente, LeAnn B Norris, Laura R Bobolts, James O Armitage, Charles L Bennett
Although the availability of generic oncology drugs allows access to contemporary care and reduces costs, there is international variability in the safety of this class of drugs. In this Series paper, we review clinical, policy, safety, and regulatory considerations for generic oncology drugs focusing on the USA, Canada, the European Union (EU), Japan, China, and India. Safety information about generic formulations is reviewed from one agent in each class, for heavy metal drugs (cisplatin), targeted agents (imatinib), and cytotoxic agents (docetaxel)...
November 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27808117/evaluation-of-uttroside-b-a-saponin-from-solanum-nigrum-linn-as-a-promising-chemotherapeutic-agent-against-hepatocellular-carcinoma
#11
Lekshmi R Nath, Jaggaiah N Gorantla, Arun Kumar T Thulasidasan, Vinod Vijayakurup, Shabna Shah, Shabna Anwer, Sophia M Joseph, Jayesh Antony, Kollery Suresh Veena, Sankar Sundaram, Udaya K Marelli, Ravi S Lankalapalli, Ruby John Anto
We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27785801/regulatory-verification-on-safe-use-of-cytotoxic-drugs-in-veterinary-clinics-and-animal-hospitals
#12
V Fung, M Seneviratne
BACKGROUND: Veterinarians are increasingly being asked to provide chemotherapy for veterinary patients. However, chemotherapy agents have cytotoxic effects that can pose a health risk to workers from exposure. There are no published studies examining cytotoxic drug (CTD) contamination in veterinary practices in Australia. METHODS: CTD use at 13 veterinary clinics and animal hospitals across New South Wales (NSW) was verified for compliance with Work, Health and Safety (WHS) legislation on the effectiveness of exposure control measures...
November 2016: Australian Veterinary Journal
https://www.readbyqxmd.com/read/27773783/chitosan-oligosaccharide-biological-activities-and-potential-therapeutic-applications
#13
REVIEW
Chatchai Muanprasat, Varanuj Chatsudthipong
Chitosan oligosaccharide (COS) is an oligomer of β-(1➔4)-linked d-glucosamine. COS can be prepared from the deacetylation and hydrolysis of chitin, which is commonly found in the exoskeletons of arthropods and insects and the cell walls of fungi. COS is water soluble, non-cytotoxic, readily absorbed through the intestine and mainly excreted in the urine. Of particular importance, COS and its derivatives have been demonstrated to possess several biological activities including anti-inflammation, immunostimulation, anti-tumor, anti-obesity, anti-hypertension, anti-Alzheimer's disease, tissue regeneration promotion, drug and DNA delivery enhancement, anti-microbial, anti-oxidation and calcium-absorption enhancement...
October 20, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27771815/array-of-translational-systems-pharmacodynamic-models-of-anti-cancer-drugs
#14
REVIEW
Sihem Ait-Oudhia, Donald E Mager
Cancer is a complex disease that is characterized by an uncontrolled growth and spread of abnormal cells. Drug development in oncology is particularly challenging and is associated with one of the highest attrition rates of compounds despite substantial investments in resources. Pharmacokinetic and pharmacodynamic (PK/PD) modeling seeks to couple experimental data with mathematical models to provide key insights into factors controlling cytotoxic effects of chemotherapeutics and cancer progression. PK/PD modeling of anti-cancer compounds is equally challenging, partly based on the complexity of biological and pharmacological systems...
December 2016: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/27769413/discrimination-and-quantification-of-two-isomeric-antineoplastic-drugs-by-rapid-and-non-invasive-analytical-control-using-a-handheld-raman-spectrometer
#15
L M M Lê, A Tfayli, J Zhou, P Prognon, A Baillet-Guffroy, E Caudron
Raman spectroscopy is a rapid, non-destructive and non-invasive method that is a promising tool for real-time analytical control of drug concentrations. This study evaluated a handheld Raman device to discriminate and quantify two isomeric drugs used to treat cancer. Doxorubicin (DOXO) and epirubicin (EPIR) samples were analyzed at therapeutic concentrations from 0.1 to 2mg/mL (n=90) and 0.08-2mg/mL (n=90) by non-invasive measurements using a portable Raman spectrometer. The discrimination of these two molecules was demonstrated for all concentrations (n=180) by qualitative analysis using partial least square discriminant analysis (PLS-DA) with 100% classification accuracy, sensitivity and specificity and 0% error rate...
December 1, 2016: Talanta
https://www.readbyqxmd.com/read/27765369/eremophila-maculata-isolation-of-a-rare-naturally-occurring-lignan-glycoside-and-the-hepatoprotective-activity-of-the-leaf-extract
#16
Fadia S Youssef, Mohamed L Ashour, Mansour Sobeh, Hesham A El-Beshbishy, Abdel Nasser Singab, Michael Wink
BACKGROUND: The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant. PURPOSE: This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27765361/aralia-elata-var-mandshurica-rupr-maxim-j-wen-an-overview-of-pharmacological-studies
#17
Alexander N Shikov, Olga N Pozharitskaya, Valery G Makarov
PURPOSE: Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015. METHODS: The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27743771/anticandidal-synergistic-activity-of-green-tea-catechins-antimycotics-and-copper-sulphate-as-a-mean-of-combinational-drug-therapy-against-candidiasis
#18
J Anand, N Rai
The present investigation aims at evaluating synergistic herbal based composition of purified catechins with fluconazole, amphotericin B and copper sulphate against Candida albicans (MTCC 3017) and Candida glabrata (MTCC 3019). The catechins were isolated from green tea leaves of Assam, Himachal Pradesh and Uttarakhand regions of India. The synergistic activity of combinations against Candida species was assessed following microdilution checkerboard technique and time kill assay. The inhibitory action of most significant combination on treated Candida cells was assessed by scanning electron microscopy...
October 12, 2016: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/27704821/discovery-and-development-of-the-anti-human-immunodeficiency-virus-drug-emtricitabine-emtriva-ftc
#19
Dennis C Liotta, George R Painter
The HIV/AIDS epidemic, which was first reported on in 1981, progressed in just 10 years to a disease afflicting 10 million people worldwide including 1 million in the US. In 1987, AZT was approved for treating HIV/AIDS. Unfortunately, its clinical usefullness was severly limited by associated toxicities and the emergence of resistance. Three other drugs that were approved in the early 1990s suffered from similar liabilities. In 1990, the Liotta group at Emory University developed a highly diastereoselective synthesis of racemic 3'-thia-2',3'-dideoxycytidine and 3'-thia-2',3'-5-fluorodideoxycytidine and demonstrated that these compounds exhibited excellent anti-HIV activity with no apparent cytotoxicity...
October 5, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27700124/tenofovir-containing-thiolated-chitosan-core-shell-nanofibers-in-vitro-and-in-vivo-evaluations
#20
Jianing Meng, Vivek Agrahari, Miezan J Ezoulin, Chi Zhang, Sudhaunshu S Purohit, Agostino Molteni, Daniel Dim, Nathan A Oyler, Bi Botti C Youan
It is hypothesized that a thiolated chitosan (TCS) core/shell nanofiber (NF) can enhance the drug loading of tenofovir, a model low molecular weight and highly water soluble drug molecule, improve its mucoadhesivity, and in vivo safety. To test this hypothesis, PEO core with TCS shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analysised using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, and periodic acid colorimetric method, respectively...
October 4, 2016: Molecular Pharmaceutics
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