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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/28440698/therapeutic-peg-ceramide-nanomicelles-synergize-with-salinomycin-to-target-both-liver-cancer-cells-and-cancer-stem-cells
#1
Meiping Wang, Fangyuan Xie, Xikai Wen, Han Chen, Hai Zhang, Junjie Liu, He Zhang, Hao Zou, Yuan Yu, Yan Chen, Zhiguo Sun, Xinxia Wang, Guoqing Zhang, Chuan Yin, Duxin Sun, Jie Gao, Beige Jiang, Yanqiang Zhong, Ying Lu
AIM: Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. MATERIALS & METHODS: The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. RESULTS: SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells...
April 25, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28438386/catabolism-of-antibody-drug-conjugates-and-characterization-methods
#2
REVIEW
Mohammad Shadid, Stephen Bowlin, Jayaprakasam Bolleddula
Antibody drug conjugates (ADCs) are large molecule therapeutics in which a cytotoxic payload is conjugated to a monoclonal antibody (mAb) via a linker. The molecules are designed to selectively bind to target-expressing cells, thus delivering therapeutic agents directly to the tumor. Chemical and enzymatic stability prior to reaching the target is an important factor for ADCs since it impacts their safety, efficacy, and pharmacokinetics (PK). One of the main reasons for off-target effects of ADCs is premature release of cytotoxic agents, either in the blood stream or at non-specific sites...
April 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28429938/high-resolution-accurate-mass-mass-spectrometry-enables-in-depth-characterization-of-in-vivo-biotransformations-for-intact-antibody-drug-conjugates
#3
Jintang He, Dian Su, Carl K Ng, Luna Liu, Shang-Fan Yu, Thomas H Pillow, Geoffrey Del Rosario, Martine Darwish, Byoung-Chul Lee, Rachana Ohri, Hongxiang Zhou, Xueji Wang, Jiawei Lu, Surinder Kaur, Keyang Xu
Antibody-drug conjugates (ADCs) represent a promising class of therapeutics for the targeted delivery of highly potent cytotoxic drugs to tumor cells to improve bioactivity while minimizing side effects. ADCs are composed of both small and large molecules, and therefore have complex molecular structures. In vivo biotransformations may further increase the complexity of ADCs, representing a unique challenge for bioanalytical assays. Quadrupole time-of-flight mass spectrometry (Q-TOF MS) with electrospray ionization has been widely used for characterization of intact ADCs...
April 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28428751/identification-of-nf-%C3%AE%C2%BAb-as-determinant-of-posttraumatic-stress-disorder-and-its-inhibition-by-the-chinese-herbal-remedy-free-and-easy-wanderer
#4
Chunlan Hong, Anja Schüffler, Ulrich Kauhl, Jingming Cao, Ching-Fen Wu, Till Opatz, Eckhard Thines, Thomas Efferth
Posttraumatic stress disorder (PTSD) is a mental disorder developing after exposure to traumatic events. Although psychotherapy reveals some therapeutic effectiveness, clinically sustainable cure is still uncertain. Some Chinese herbal formulae are reported to work well clinically against mental diseases in Asian countries, but the safety and their mode of action are still unclear. In this study, we investigated the mechanisms of Chinese remedy free and easy wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining clinical data to search for mechanisms of PTSD with subsequent in vitro verification and bioinformatics techniques as follows: (1) by analyzing microarray-based transcriptome-wide mRNA expression profiling of PTSD patients; (2) by investigating the effect of FAEW and the antidepressant control drug fluoxetine on the transcription factor NF-κB using reporter cell assays and western blotting; (3) by performing molecular docking and literature data mining based on phytochemical constituents of FAEW...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424538/metal-complexes-in-cancer-therapy-an-update-from-drug-design-perspective
#5
REVIEW
Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman
In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28424323/dosing-three-drug-combinations-that-include-targeted-anti-cancer-agents-analysis-of-37-763-patients
#6
Mina Nikanjam, Sariah Liu, Jincheng Yang, Razelle Kurzrock
BACKGROUND: Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses for clinical trials of novel three-drug combinations is lacking. MATERIALS AND METHODS: Published phase I-III adult oncology clinical trials of three-drug combinations involving a targeted agent were identified by PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was calculated to compare the dose used in combination to the single agent recommended dose: (U...
April 19, 2017: Oncologist
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#7
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28420213/folate-decorated-nanomicelles-loaded-with-a-potent-curcumin-analogue-for-targeting-retinoblastoma
#8
Hashem Alsaab, Rami M Alzhrani, Prashant Kesharwani, Samaresh Sau, Sai Hs Boddu, Arun K Iyer
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers...
April 18, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28415455/heparin-modified-graphene-oxide-for-ph-sensitive-sustained-release-of-doxorubicin-hydrochloride
#9
Baomei Zhang, Xiaoye Yang, Yang Wang, Guangxi Zhai
A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28392690/hyaluronic-acid-nimesulide-conjugates-as-anticancer-drugs-against-cd44-overexpressing-ht-29-colorectal-cancer-in-vitro-and-in-vivo
#10
You-Sin Jian, Ching-Wen Chen, Chih-An Lin, Hsiu-Ping Yu, Hua-Yang Lin, Ming-Yuan Liao, Shu-Huan Wu, Yan-Fu Lin, Ping-Shan Lai
Carrier-mediated drug delivery systems are promising therapeutics for targeted delivery and improved efficacy and safety of potent cytotoxic drugs. Nimesulide is a multifactorial cyclooxygenase 2 nonsteroidal anti-inflammatory drug with analgesic, antipyretic and potent anticancer properties; however, the low solubility of nimesulide limits its applications. Drugs conjugated with hyaluronic acid (HA) are innovative carrier-mediated drug delivery systems characterized by CD44-mediated endocytosis of HA and intracellular drug release...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28391026/radiopharmaceuticals-in-the-elderly-cancer-patient-practical-considerations-with-a-focus-on-prostate-cancer-therapy-a-position-paper-from-the-international-society-of-geriatric-oncology-task-force
#11
John O Prior, Silke Gillessen, Manfred Wirth, William Dale, Matti Aapro, Wim J G Oyen
Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e...
April 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28387940/the-bial-10-2474-phase-1-study-a-drug-development-perspective-and-recommendations-for-future-first-in-human-trials
#12
REVIEW
Philip Chaikin
BIA 10-2474 (a fatty acid amide hydrolase inhibitor) was evaluated in a first-in-human phase 1 study in normal volunteers to assess safety/tolerability, pharmacokinetics, pharmacodynamics, and food effect. The dose-escalation process consisted of a single-ascending-dose phase (SAD) and multiple-ascending-dose phase (MAD). Prospective determination of the starting dose and maximal escalated dose was consistent with the usual clinical pharmacology principles for extrapolation of preclinical toxicology data to human equivalent doses...
April 7, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28376230/target-and-agent-prioritization-for-the-children-s-oncology-group-national-cancer-institute-pediatric-match-trial
#13
Carl E Allen, Theodore W Laetsch, Rajen Mody, Meredith S Irwin, Megan S Lim, Peter C Adamson, Nita L Seibel, D Williams Parsons, Y Jae Cho, Katherine Janeway
Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies...
May 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28375123/phytochemistry-brine-shrimp-lethality-and-mice-acute-oral-toxicity-studies-on-seed-extracts-of-vernonia-anthelmintica
#14
Subia Jamil, Rafeeq Alam Khan, Syeda Afroz, Shadab Ahmed
Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28350045/anti%C3%A2-wrinkle-effect-of-fermented-black-ginseng-on-human-fibroblasts
#15
Quynh Lien Pham, Hyun-Jun Jang, Kyu-Bong Kim
Fermented black ginseng (FBG) is processed by the repeated steaming and drying of fresh ginseng followed by fermentation with Saccharomyces cerevisiae. It is known to possess anti‑oxidative effects. Skin wrinkle formation is associated with oxidative stress and inflammatory reactions. The aim of this study was to determine whether FBG possesses anti‑wrinkle activity using human fibroblasts (HS68). According to the Korea Ministry of Food and Drug Safety (MFDS) guidelines for the evaluation of the efficacy of functional anti‑wrinkle cosmetics, we attempted to elucidate the effects of FBG on type I procollagen, matrix metalloproteinase (MMP)‑1, MMP‑2, MMP‑9 and tissue inhibitor of metalloproteinase‑2 (TIMP‑2)...
January 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28343014/natural-lipids-enriched-self-nano-emulsifying-systems-for-effective-co-delivery-of-tamoxifen-and-naringenin-systematic-approach-for-improved-breast-cancer-therapeutics
#16
Premjeet Singh Sandhu, Rajendra Kumar, Sarwar Beg, Sanyog Jain, Varun Kushwah, O P Katare, Bhupinder Singh
The nano-miceller drug delivery carriers of tamoxifen (TMX) having natural ingredients like polyunsaturated fatty acid (PUFA) with self-nano-emulsifying properties was developed with naringenin (NG) in a synergistic manner i.e. TMX-NG-SNEDDS. The optimized nano-formulation revealed complete drug release in 30 min and >80% permeation in 45 min. Superior cellular uptake potential (4.6-6.5-fold) of the TMX-NG-SNEDDS using Caco-2 cells while cytotoxicity study on MCF-7 cells indicated significant results (P<0...
March 23, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28335244/human-serum-albumin-nanoparticles-for-use-in-cancer-drug-delivery-process-optimization-and-in-vitro-characterization
#17
Nikita Lomis, Susan Westfall, Leila Farahdel, Meenakshi Malhotra, Dominique Shum-Tim, Satya Prakash
Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized...
June 15, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334507/comparative-study-of-cytotoxicity-and-genotoxicity-of-commercial-jeffamines%C3%A2-and-polyethylenimine-in-cho-k1-cells
#18
Leniher Castan, Cristiano José da Silva, Eduardo Ferreira Molina, Raquel Alves Dos Santos
Jeffamines(®) are a family of polymers containing primary amine groups attached to the extremities of polyether backbone which can be used as biomaterials. They have been used in combination with polyethylenimine (PEI) to improve biocompatibility in drug and gene delivery systems. Despite these facts, very few studies have been done on cytotoxicity and genotoxicity of pure Jeffamines(®) or compared with PEI. The present study aimed to evaluate and compare the cytotoxic and genotoxic effects of Jeffamines(®) and PEI in CHO-K1 cells...
March 23, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28327802/in-vitro-and-in-vivo-antileishmanial-activity-of-artemisia-annua-l-leaf-powder-and-its-potential-usefulness-in-the-treatment-of-uncomplicated-cutaneous-leishmaniasis-in-humans
#19
Luz Estella Mesa, Daniel Vasquez, Pierre Lutgen, Iván Darío Vélez, Adriana María Restrepo, Isabel Ortiz, Sara María Robledo
INTRODUCTION: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28325303/inhibition-of-egf-uptake-by-nephrotoxic-antisense-drugs-in%C3%A2-vitro-and-implications-for-preclinical-safety-profiling
#20
Annie Moisan, Marcel Gubler, Jitao David Zhang, Yann Tessier, Kamille Dumong Erichsen, Sabine Sewing, Régine Gérard, Blandine Avignon, Sylwia Huber, Fethallah Benmansour, Xing Chen, Roberto Villaseñor, Annamaria Braendli-Baiocco, Matthias Festag, Andreas Maunz, Thomas Singer, Franz Schuler, Adrian B Roth
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates...
March 17, 2017: Molecular Therapy. Nucleic Acids
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