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Cytotoxic drug safety

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
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
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
Julian Mackay-Wiggan, Ali Jabbari, Nhan Nguyen, Jane E Cerise, Charlotte Clark, Grace Ulerio, Megan Furniss, Roger Vaughan, Angela M Christiano, Raphael Clynes
BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS...
September 22, 2016: JCI Insight
P Mahesh Kumar, Animesh Ghosh
Silver sulfadiazine has been frequently used as an antibacterial agent for topical treatment of partial thickness burn wounds. In this study, we present the preparation of silver sulfadiazine microsponges by w/o/w emulsion solvent evaporation method. Formulation variables were optimized by using 3(2) factorial design. The optimized microsponges were characterized by FTIR, DSC, PXRD, particle size analysis, SEM analysis and mercury intrusion porosimetry studies. Viscosity, texture analysis and ex vivo drug deposition study of optimized microsponge loaded gel were also evaluated...
September 30, 2016: European Journal of Pharmaceutical Sciences
Carolin Sellmann, Achim Doerner, Christine Knuehl, Nicolas Rasche, Vanita Sood, Simon Krah, Laura Rhiel, Annika Messemer, John Wesolowski, Mark Schuette, Stefan Becker, Lars Toleikis, Harald Kolmar, Bjoern Hock
Bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs), have already demonstrated benefits for the treatment of cancer in several clinical studies, showing improved drug selectivity and efficacy. In particular, simultaneous targeting of prominent cancer antigens, such as EGF receptor (EGFR) and c-MET, by bsAbs has raised increasing interest for potentially circumventing receptor crosstalk and c-MET mediated acquired resistance during anti-EGFR monotherapy. In this study, we combined the selectivity of EGFR x c-MET bsAbs with the potency of cytotoxic agents via bispecific antibody-toxin conjugation...
September 30, 2016: Journal of Biological Chemistry
Patricia Losada-Pérez, Mehran Khorshid, Frank Uwe Renner
Despite the environmentally friendly reputation of ionic liquids (ILs), their safety has been recently questioned given their potential as cytotoxic agents. The fundamental mechanisms underlying the interactions between ILs and cells are less studied and by far not completely understood. Biomimetic films are here important biophysical model systems to elucidate fundamental aspects and mechanisms relevant for a large range of biological interaction ranging from signaling to drug reception or toxicity. Here we use dissipative quartz crystal microbalance QCM-D to examine the effect of aqueous imidazolium-based ionic liquid mixtures on solid-supported biomimetic membranes...
2016: PloS One
Lawrence J Thomas, Laura Vitale, Thomas O'Neill, Ree Y Dolnick, Paul K Wallace, Hans Minderman, Lauren E Gergel, Eric M Forsberg, James M Boyer, James R Storey, Catherine D Pilsmaker, Russell A Hammond, Jenifer Widger, Karuna Sundarapandiyan, Andrea Crocker, Henry C Marsh, Tibor Keler
T cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues thus representing a promising target for antibody-mediated therapy. To this end we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1...
September 26, 2016: Molecular Cancer Therapeutics
Cassilda Cunha-Reis, Alexandra Machado, Luísa Barreiros, Francisca Araújo, Rute Nunes, Vítor Seabra, Domingos Ferreira, Marcela A Segundo, Bruno Sarmento, José das Neves
Combining two or more antiretroviral drugs in one medical product is an interesting but challenging strategy for developing topical anti-HIV microbicides. We developed a new vaginal delivery system comprising the incorporation of nanoparticles (NPs) into a polymeric film base - NPs-in-film - and tested its ability to deliver tenofovir (TFV) and efavirenz (EFV). EFV-loaded poly(lactic-co-glycolic acid) NPs were incorporated alongside free TFV into fast dissolving films during film manufacturing. The delivery system was characterized for physicochemical properties, as well as genital distribution, local and systemic 24h pharmacokinetics (PK), and safety upon intravaginal administration to mice...
September 21, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
N Houédé, G Locker, C Lucas, H Soto Parra, U Basso, D Spaeth, R Tambaro, L Basterretxea, F Morelli, C Theodore, L Lusuardi, N Lainez, A Guillot, G Tonini, J Bielle, X Garcia Del Muro
BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded...
2016: BMC Cancer
Jung-Min Lee, Cody J Peer, Minshu Yu, Lauren Amable, Nicolas Gordon, Christina M Annunziata, Nicole Houston, Andrew K L Goey, Tristan M Sissung, Bernard Parker, Lori Minasian, Victoria Chiou, Robert F Murphy, Brigitte C Widemann, William D Figg, Elise C Kohn
PURPOSE: Our preclinical studies showed the PARP inhibitor, olaparib prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic/pharmacodynamic (PK/PD) effects, safety and activity of the combination. PATIENTS AND METHODS: Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200mg bid, days1-7) in a 3+3 dose escalation with carboplatin AUC4 or 5 q21 days, up to eight cycles, followed by olaparib maintenance...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Young-Min Han, Jong-Min Park, Jing X Kang, Ji-Young Cha, Ho-Jae Lee, Migeyong Jeong, Eun-Jin Go, Ki Baik Hahm
Non-steroidal anti-inflammatory drugs (NSAIDs) damage the gastrointestinal (GI) epithelial cell membranes by inducing several signals through lipid raft organization after membrane incorporation, whereas ω-3 polyunsaturated fatty acids (PUFAs) relieve inflammation, reduce oxidative stress, and provide cytoprotection, consequent to lipid raft disorganization. Therefore, we hypothesized that ω-3 PUFAs can protect the GI from NSAID-induced damages by initiating the gatekeeper action of cell membranes, subsequent to anti-inflammatory and anti-oxidative actions...
2016: Scientific Reports
Yue Qiu, Qianwen Yu, Kairong Shi, Mengmeng Zhang, Xianyang Zhou, Yuting Yang, Yayuan Liu, Jiajing Tang, Xuhui Wang, Qin He
Cell-penetrating peptides (CPPs) are widely used in the development of various drug delivery systems because of their ability of penetrating plasma membrane. However, the safety of their application remains largely unknown. In this study, we found that the incubation of two main kinds of CPPs with human normal liver cells could cause the occurrence of apoptosis and necrosis, then the detailed apoptosis-related protein were detected out. To discover the specific way which leads to these results, several methods were used in this study...
September 19, 2016: Amino Acids
Stefan Hartmann, Jennifer R Grandis
INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and the majority of patients present with advanced stage disease. Chemotherapy is an important component of head and neck cancer treatment regimens and has shown beneficial effects in locally advanced and recurrent/metastatic stages of disease. Approximately 25% of HNSCC patients are aged 70 and older, often associated with co-morbid medical conditions. Most clinical trials exclude patients of advanced chronological age such that valid information about the efficacy and safety of drugs and treatment regimens in elderly patients is not available...
October 2016: Expert Opinion on Pharmacotherapy
Yu Liu, Jia Yang, Xin Wang, Ju Liu, Zhaobo Wang, Hongsheng Liu, Lijiang Chen
In this study, a controlled drug release system based on redox-responsive nanomicelles for drug delivery was described. The system was constructed by linking poly (acryic acid) (PAA) with D-α-tocopherol succinate (VES) via a disulfide bond linker (ss). This amphiphilic polymer (PAAssVES) was synthesized by coupling reaction and its chemical structure was confirmed by FT-IR and (1)HNMR analyses. PAAssVES was found to self-assemble into nanomicelles with diameter of about 130 nm, and a critical micelle concentration of about 6...
December 2016: Journal of Biomaterials Science. Polymer Edition
Soheil Tavakolpour, Seyed Moayed Alavian, Shahnaz Sali
BACKGROUND: Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease's progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. OBJECTIVES: In this study, we focused on treating CHB infection via the manipulation of T cells' responses to identify possible approaches to cure CHB...
June 2016: Hepatitis Monthly
Delyan P Ivanov, Abdal-Jabbar Al-Rubai, Anna M Grabowska, Margaret K Pratten
Chemotherapy-induced neurotoxicity can reduce the quality of life of patients by affecting their intelligence, senses and mobility. Ten percent of safety-related late-stage clinical failures are due to neurological side effects. Animal models are poor in predicting human neurotoxicity due to interspecies differences and most in vitro assays cannot distinguish neurotoxicity from general cytotoxicity for chemotherapeutics. We developed in vitro assays capable of quantifying the paediatric neurotoxic potential for cytotoxic drugs...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Eugene R Bleecker, J Mark FitzGerald, Pascal Chanez, Alberto Papi, Steven F Weinstein, Peter Barker, Stephanie Sproule, Geoffrey Gilmartin, Magnus Aurivillius, Viktoria Werkström, Mitchell Goldman
BACKGROUND: Eosinophilia is associated with worsening asthma severity and decreased lung function, with increased exacerbation frequency. We assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, for patients with severe, uncontrolled asthma with eosinophilia. METHODS: We did a randomised, double-blind, parallel-group, placebo-controlled phase 3 study at 374 sites in 17 countries...
September 2, 2016: Lancet
Jun Deng, Changyou Gao
The unique features of nanomaterials have led to their rapid development in the biomedical field. In particular, functionalized nanoparticles (NPs) are extensively used in the delivery of drugs and genes, bio-imaging and diagnosis. Hence, the interaction between NPs and cells is one of the most important issues towards understanding the true nature of the NP-mediated biological effects. Moreover, the intracellular safety concern of the NPs as a result of intracellular NP degradation remains to be clarified in detail...
October 14, 2016: Nanotechnology
Xiaowei Tai, Yang Wang, Li Zhang, Yuting Yang, Kairong Shi, Shaobo Ruan, Yayuan Liu, Huile Gao, Zhirong Zhang, Qin He
Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect...
October 2, 2016: Journal of Drug Targeting
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