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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/28238155/safety-of-herbal-medicine-use-during-chemotherapy-in-patients-with-ovarian-cancer-a-bedside-to-bench-approach
#1
Eran Ben-Arye, Ofer Lavie, Noah Samuels, Hazem Khamaisie, Elad Schiff, Orit Gressel Raz, Jamal Mahajna
In this study, we explored herbal supplements used by patients during chemotherapy and test for herb-drug interactions and response of cancer cells to treatment. Patients with gynecological cancer referred to a complementary and integrative medicine (CIM) service were asked about their use of herbal medicine during chemotherapy. The leading five clinically relevant herbs selected for cytotoxicity analysis included the following: wheatgrass (Triticum aestivum), European mistletoe (Viscum album), ginger (Zingiber officinale), Ephedra (Ephedra campylopoda), and Oriental mistletoe (Viscum cruciatum)...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28225654/germicidal-efficacy-and-mammalian-skin-safety-of-222-nm-uv-light
#2
Manuela Buonanno, Brian Ponnaiya, David Welch, Milda Stanislauskas, Gerhard Randers-Pehrson, Lubomir Smilenov, Franklin D Lowy, David M Owens, David J Brenner
We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues...
February 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28224367/novel-treatment-with-intraperitoneal-moc31pe-immunotoxin-in-colorectal-peritoneal-metastasis-results-from-the-immunopeca-phase-1-trial
#3
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/28223423/modulating-therapeutic-activity-and-toxicity-of-pyrrolobenzodiazepine-antibody-drug-conjugates-with-self-immolative-disulfide-linkers
#4
Thomas H Pillow, Melissa Schutten, Shang-Fan Yu, Rachana Ohri, Jack Sadowsky, Kirsten Achilles Poon, Willy Solis, Fiona Zhong, Geoffrey Del Rosario, Mary Ann T Go, Jeffery Lau, Sharon Yee, Jintang He, Luna Liu, Carl Ng, Keyang Xu, Douglas D Leipold, Amrita V Kamath, Donglu Zhang, Luke Masterson, Stephen J Gregson, Philip W Howard, Fan Fang, Jinhua Chen, Janet Gunzner-Toste, Katherine K Kozak, Susan Spencer, Paul Polakis, Andrew G Polson, John A Flygare, Jagath R Junutula
A novel disulfide linker was designed to enable a direct connection between cytotoxic pyrrolobenzodiazepine (PBD) drugs and the cysteine on a targeting antibody for use in antibody-drug conjugates (ADCs). ADCs composed of a cysteine-engineered antibody were armed with a PBD using a self-immolative disulfide linker. Both the chemical linker and the antibody site were optimized for this new bioconjugation strategy to provide a highly stable and efficacious ADC. This novel disulfide ADC was compared to a conjugate containing the same PBD drug, but attached to the antibody via a peptide linker...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28216150/novel-biodegradable-poly-gamma-glutamic-acid-amphotericin-b-complexes-show-promise-as-improved-amphotericin-b-formulations
#5
T Dinh, Q Zia, S Zubair, P Stapleton, R Singh, M Owais, S Somavarapu
Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues or high production costs. AmB complexes based on poly(gamma-glutamic acid) (PGGA) have been prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone®) and liposomal AmB (AmBisome®). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a theoretical drug loading (up to 76...
February 16, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#6
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
February 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28212490/vitamin-e-succinate-grafted-chitosan-oligosaccharide-rgd-conjugated-tpgs-mixed-micelles-loaded-with-paclitaxel-for-u87mg-tumor-therapy
#7
Yanzuo Chen, Shu Feng, Wenchao Liu, Zeting Yuan, Peihao Yin, Feng Gao
The poor therapeutic efficacy of hydrophobic chemotherapeutic drugs is an intrinsic limitation to successful chemotherapy. In the present study, a multitask delivery system based on arginine-glycine-aspartic acid peptide (RGD) decorated vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/RGD-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS-RGD) mixed micelles (VeC/T-RGD MM) was first prepared for targeted delivery of a hydrophobic anticancer drug, paclitaxel (PTX), to improve the efficacy of U87MG tumor therapy...
February 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28185800/inhaled-sildenafil-as-an-alternative-to-oral-sildenafil-in-the-treatment-of-pulmonary-arterial-hypertension-pah
#8
Jahidur Rashid, Brijeshkumar Patel, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH...
February 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28177682/reversal-of-p-glycoprotein-medicated-multidrug-resistance-and-pharmacokinetics-study-in-rats-by-wyx-5
#9
Yuzhu Wang, Jian Cui, Yuxuan Dai, Yuxiang Wu, Wenlong Huang, Hai Qian, Liang Ge
Multidrug resistance (MDR) is one of the major obstacles confronted in cancer chemotherapy, which mainly due to the overexpression of P-glycoprotein (P-gp). Co-administration of anticancer drugs and P-gp inhibitors is a promising approach to overcome MDR. WYX-5, a novel P-gp inhibitor, shows a notable reversal effect with low cytotoxicity in vitro. In this paper, the reversal mechanism and safety of the MDR modulator WYX-5 were explored in vitro, and evaluated for its pharmacokinetics and effects on Adriamycin (ADM) metabolism <i>in vivo</i>...
December 22, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28167742/structural-and-preclinical-studies-of-computationally-designed-non-nucleoside-reverse-transcriptase-inhibitors-for-treating-hiv-infection
#10
Shalley N Kudalkar, Jagadish Beloor, Albert H Chan, Won-Gil Lee, William L Jorgensen, Priti Kumar, Karen S Anderson
The clinical benefits of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles and heightened antiviral activity. We used computational and structure-guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are members of a class of catechol diethers...
February 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28167221/toxicological-evaluation-of-5-methoxy-2-aminoindane-meai-binge-mitigating-agent-in-development
#11
Jakob A Shimshoni, Ilan Winkler, Nir Edery, Ezekiel Golan, René van Wettum, David Nutt
5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28165804/improved-oral-absorption-and-anti-lung-cancer-activity-of-paclitaxel-loaded-mixed-micelles
#12
Jian Hou, E Sun, Zhen-Hai Zhang, Jing Wang, Lei Yang, Li Cui, Zhong-Cheng Ke, Xiao-Bin Tan, Xiao-Bin Jia, Huixia Lv
The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28163965/ethnobotanical-survey-and-toxicity-evaluation-of-medicinal-plants-used-for-fungal-remedy-in-the-southern-highlands-of-tanzania
#13
Mourice Victor Nyangabo Mbunde, Ester Innocent, Faith Mabiki, Pher G Andersson
BACKGROUND/AIM: Some of the antifungal drugs used in the current treatments regime are responding to antimicrobial resistance. In rural areas of Southern Tanzania, indigenous people use antifungal drugs alone or together with medicinal plants to curb the effects of antibiotic resistance. This study documented ethnobotanical information of medicinal plants used for managing fungal infections in the Southern Highlands of Tanzania and further assess their safety. MATERIALS AND METHODS: Ethnobotanical survey was conducted in Makete and Mufindi districts between July 2014 and December 2015 using semi-structured questionnaires followed by two focus group discussions to verify respondents' information...
January 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28150359/potential-role-of-tracing-stem-cell-transplantation-and-effects-on-the-immune-cell-function-of-ferumoxytol-combining-with-heparin-and-protamine-in-vivo-in-vitro
#14
Jingyuan Zhao, Xin Guan, Yang Liu, Hua Piao, Rutao Liu, Xiang Zhou, Bo Sun, Yue Du, Jing Liu
Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P) and ferumoxytol (F)(HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs...
February 2, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28147308/mono-functionalized-glycosylated-platinum-iv-complexes-possessed-both-ph-and-redox-dual-responsive-properties-exhibited-enhanced-safety-and-preferentially-accumulated-in-cancer-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#15
Jing Ma, Xiande Yang, Wenpei Hao, Zhonglv Huang, Xin Wang, Peng George Wang
A serious of carbohydrate-conjugated platinum(IV) complexes in the form Pt(L2)(A2)(OH)R based on the clinical drug cisplatin and oxaliplatin were designed, synthesized and evaluated as antitumor agents in vitro and in vivo. The conjugates possessing both pH and redox dual-responsive properties exhibited more potent cytotoxicity in seven different human cancer cell lines and lower toxicity to the normal 3T3 cells than cisplatin, oxaliplatin and even the reported bis-functionalized glycosylated platinum(IV) complexes indicating the enhanced safety of the sugar conjugates...
January 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28138910/spray-dried-thiolated-chitosan-coated-sodium-alginate-multilayer-microparticles-for-vaginal-hiv-microbicide-delivery
#16
Jianing Meng, Vivek Agrahari, Miezan J Ezoulin, Sudhaunshu S Purohit, Tao Zhang, Agostino Molteni, Daniel Dim, Nathan A Oyler, Bi-Botti C Youan
It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state (31)P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively...
January 30, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28124617/in-vitro-and-in-vivo-evaluation-of-dmso-and-azone-as-penetration-enhancers-for-cutaneous-application-of-celecoxib
#17
Thassia D Arc Senna, Hilton Antonio Mata Dos Santos, Daniel Mabundu Kibwila, Alvaro Costa Leitão, Alexandre Dos Santos Pyrrho, Marcelo De Pádula, Elaine Cruz Rosas, Tatiana Almeida Pádua, Marilisa Guimarães Lara, Maria Bernadete Riemma Pierre
BACKGROUND: Celecoxib (CXB) has been explored as an anti-inflammatory or chemopreventive drug for topical treatment of skin diseases and cancer. OBJECTIVE: The main aim of this work was to investigate the potential of dimethylsufoxide (DMSO) and Azone (AZ) as penetration enhancers (P.Es) for topical delivery of CXB. METHOD: The in vitro studies, drug release, skin permeability and potential cytotoxicity/genotoxicity were carried out with formulations containing or not DMSO or AZ (5% and 10%)...
January 25, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28114249/inhibitors-of-cytotoxic-t-lymphocyte-antigen-4-and-programmed-death-1-programmed-death-1-ligand-for-metastatic-melanoma-dual-versus-monotherapy-summary-of-advances-and-future-directions-for-studying-these-drugs
#18
Kimberly Loo, Adil I Daud
Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28110818/cystatin-c-peptidomimetic-derivative-with-antimicrobial-properties-as-a-potential-compound-against-wound-infections
#19
Michał Pikuła, Maria Smużyńska, Adam Krzystyniak, Maciej Zieliński, Paulina Langa, Milena Deptuła, Adriana Schumacher, Jakub Łata, Mirosława Cichorek, Anders Grubb, Piotr Trzonkowski, Franciszek Kasprzykowski, Sylwia Rodziewicz-Motowidło
A peptidomimetic called A20 (Cystapep 1) structurally based upon the N-terminal fragment of human cystatin C is known to have strong antibacterial properties. A20 is characterized by high activity against several bacterial strains often isolated from infected wounds, including methicillin-resistant S. aureus (MRSA). In this work we wanted to explore the therapeutic potential of A20 in the treatment of wound infections. We examined, cytotoxicity, allergenicity and impact of A20 on the proliferation and viability of human keratinocytes...
January 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28099878/screening-verification-and-analysis-of-biomarkers-for-drug-induced-cardiac-toxicity-in-vitro-based-on-rtca-coupled-with-pcr-array-technology
#20
Lu Zhang, Meng-Xi Xu, Qing-Sheng Yin, Cai-Ying Zhu, Xue-Lian Cheng, Yi-Ran Ren, Peng-Wei Zhuang, Yan-Jun Zhang
Cardiotoxicity is one of the most serious side effects of new drugs. Early detection of the drug induced cardiotoxicity based on the biomarkers provides an important preventative strategy for detecting potential cardiotoxicity of candidate drugs. In this study, we aim to identify the predictive genomics biomarkers for drug-induced cardiac toxicity based on the RTCA coupled with PCR Array technology in primary cells. Three prototypical cardiotoxic compounds (doxorubicin, isoproterenol, ouabain) with different mechanisms were firstly real-time monitored to diagnose the cytotoxicity by using the RTCA, while the functional alterations of cardiomyocytes were also monitored by analyzing the beating frequency of cardiomyocytes...
February 15, 2017: Toxicology Letters
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