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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#1
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28706579/conventional-vs-drug-eluting-beads-transarterial-chemoembolization-for-hepatocellular-carcinoma
#2
REVIEW
Jeong Eun Song, Do Young Kim
Transarterial chemoembolization (TACE) is the current standard of therapy for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE (cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drug-eluting beads (DEBs) have been imposed as novel drug-delivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE...
June 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28706279/elimination-of-undifferentiated-human-embryonic-stem-cells-by-cardiac-glycosides
#3
Yu-Tsen Lin, Cheng-Kai Wang, Shang-Chih Yang, Shu-Ching Hsu, Hsuan Lin, Fang-Pei Chang, Tzu-Chien Kuo, Chia-Ning Shen, Po-Ming Chiang, Michael Hsiao, Frank Leigh Lu, Jean Lu
An important safety concern in the use of human pluripotent stem cells (hPSCs) is tumorigenic risk, because these cells can form teratomas after an in vivo injection at ectopic sites. Several thousands of undifferentiated hPSCs are sufficient to induce teratomas in a mouse model. Thus, it is critical to remove all residue-undifferentiated hPSCs that have teratoma potential before the clinical application of hPSC-derived cells. In this study, our data demonstrated the cytotoxic effects of cardiac glycosides, such as digoxin, lanatoside C, bufalin, and proscillaridin A, in human embryonic stem cells (hESCs)...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705555/sonodynamic-therapy-based-on-combined-use-of-low-dose-administration-of-epirubicin-incorporating-drug-delivery-system-and-focused-ultrasound
#4
Masanori Maeda, Yoshihiro Muragaki, Jun Okamoto, Shin Yoshizawa, Nobutaka Abe, Hidekazu Nakamoto, Hiroshi Ishii, Kenichi Kawabata, Shinichiro Umemura, Nobuhiro Nishiyama, Kazunori Kataoka, Hiroshi Iseki
Sonodynamic therapy (SDT) is currently considered as one of the promising minimally invasive treatment options for solid cancers. SDT is based on the combined use of a sonosensitizer drug and high-intensity focused ultrasound (HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well known as effective sonosensitizers after interaction with focused ultrasound. Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed that comprises EPI through an acid-labile hydrazone bond...
July 10, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/28705043/mannosylated-liposomes-improve-therapeutic-effects-of-paclitaxel-in-colon-cancer-models
#5
Menghua Xiong, Qian Lei, Xinyu You, Tiantao Gao, Xuejiao Song, Yong Xia, Tinghong Ye, Lidan Zhang, Ningyu Wang, Luoting Yu
Mannose receptor (MR) is a highly effective endocytic receptor. It is closely related to tumor immune escape and metastasis. We found that MR was highly expressed in some colon cancer cell lines such as CT26 and HCT116 cells. Therefore MR might be a potential target in colon cancer therapy. In this study, we aimed to develop mannosylated liposomes containing anticancer drug paclitaxel (PTX) and investigate the potential effects on targeted therapy for colon cancer. Mannosylated liposomes were prepared by film dispersion method...
July 14, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28701038/micellear-gold-nanoparticle-as-delivery-vehicle-for-dual-tyrosine-kinase-inhibitor-zd6474-for-metastatic-breast-cancer-treatment
#6
Siddik Sarkar, Suraj Konar, Nagaprasad Puvvada, Shashi Rajput, Bn Prashanth Kumar, Raj R Rao, Amita Pathak, Paul B Fisher, Mahitosh Mandal
Therapeutic index of poorly water soluble drugs are often hampered due to poor pharmokinetics, reduced blood retention and lack of effective drug concentrations in the tumor region. In order to overcome these issues, drugs are often delivered using delivery vehicles to provide an enhanced therapeutic index. Gold nanoparticles synthesized in micellar networks of amphiphilic block copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific drug delivery owing to their low cytotoxicity and immunogenicity...
July 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28689093/immune-checkpoint-inhibitors-and-elderly-people-a%C3%A2-review
#7
REVIEW
Amaury Daste, Charlotte Domblides, Marine Gross-Goupil, Camille Chakiba, Amandine Quivy, Valérie Cochin, Erwan de Mones, Nicolas Larmonier, Pierre Soubeyran, Alain Ravaud
Immune checkpoint inhibitors, including targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte antigen 4 pathways, are a new type of cancer treatment. This approach of targeting the immune system has demonstrated dramatic efficacy for several cancers, and various drugs have been approved by health authorities and are used in clinical practice. Elderly patients (≥65 years) represent most of the cancers diagnosed and deaths by age group, with an increase expected over the next decade...
July 6, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28685299/conjugated-and-entrapped-hpma-pla-nano-polymeric-micelles-based-dual-delivery-of-first-line-anti-tb-drugs-improved-and-safe-drug-delivery-against-sensitive-and-resistant-mycobacterium-tuberculosis
#8
Seema Upadhyay, Iliyas Khan, Avinash Gothwal, Praveen K Pachouri, N Bhaskar, Umesh D Gupta, Devendra S Chauhan, Umesh Gupta
PURPOSE: First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. METHODS: HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and (1)H-NMR spectroscopy...
July 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28683185/design-and-construction-of-a-smart-targeting-drug-delivery-system-based-on-phototriggered-competition-of-host-guest-interaction
#9
Dan Zhao, Xiaoqing Yi, Gongdao Yuan, Renxi Zhuo, Feng Li
A smart targeting drug delivery nanocarrier is successfully constructed based on phototriggered competition of host-guest interaction. The targeting motif, i.e., biotin is first concealed by β-cyclodextrin (β-CD) via host-guest interaction. When the nanoparticles are exposed to UV light, the cleavage of photosensitive groups results in the exposure of adamantane (Ad) groups initially located in the interior of nanoassemblies, and β-CDs capped on biotin ligands can be replaced by Ad because of the higher binding constant between Ad and β-CD than that between biotin and β-CD...
July 6, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28662900/revisiting-the-use-of-spla2-sensitive-liposomes-in-cancer-therapy
#10
Houman Pourhassan, Gael Clergeaud, Anders E Hansen, Ragnhild G Østrem, Frederikke P Fliedner, Fredrik Melander, Ole L Nielsen, Ciara K O'Sullivan, Andreas Kjær, Thomas L Andresen
The first developed secretory phospholipase A2 (sPLA2) sensitive liposomal cisplatin formulation (LiPlaCis®) is currently undergoing clinical evaluation. In the present study we revisit and evaluate critical preclinical parameters important for the therapeutic potential and safety of platinum drugs, here oxaliplatin (L-OHP), formulated in sPLA2 sensitive liposomes. We show the mole percentage of negatively charged phospholipid needed to obtain enzyme-sensitivity for saturated systems is ≥25% for 16-carbon chain lipid membranes, and >40% for 18-chain lipid membranes, which was surprising as 25% is used clinically in LiPlaCis®...
June 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28658983/melphalan-hydrochloride-for-the-treatment-of-multiple-myeloma
#11
Fabrizio Esma, Marco Salvini, Rossella Troia, Mario Boccadoro, Alessandra Larocca, Chiara Pautasso
Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal failure, anemia, osteolytic bone lesions, and infections. Melphalan, a nitrogen mustard, is an alkylating agent synthesized in 1953, and it has been used in multiple myeloma therapy for fifty years. Although novel agents have been introduced in the past few decades improving prognosis of the disease, melphalan still maintains a crucial role in the treatment of MM acting both as cytotoxic agent through damage to DNA, and as immunostimulatory drug by inhibiting Interleukin-6, as well as interaction with dendritic cells, and immunogenic effects in tumor microenvironment...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28657910/a-palladium-ii-saccharinate-complex-of-terpyridine-exerts-higher-anticancer-potency-and-less-toxicity-than-cisplatin-in-a-mouse-allograft-model
#12
Yuksel Cetin, Zelal Adiguzel, Hivda U Polat, Tolga Akkoc, Arzu Tas, Buse Cevatemre, Gokalp Celik, Baris Carikci, Veysel T Yilmaz, Engin Ulukaya, Ceyda Acilan
The main aim of this study is to assess the safety and antitumor efficacy of a palladium(II) (Pd)-saccharinate complex with terpyridine. To characterize the Pd(II) complex in vitro, its cytotoxicity was evaluated using a water-soluble tetrazolium salt cell viability assay and the mechanism of cell death was assessed by DNA fragmentation/condensation and live cell imaging analyses. The antitumor efficacy and safety of the Pd(II) complex in-vivo were examined by analyzing reduction in tumor size, changes in body and organ weight, histopathological analysis of liver, kidney, and tumor sections, and biochemical analysis of serum in C57BL/6 mice...
June 27, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28652732/preparation-characterization-and-evaluation-of-amphotericin-b-loaded-mpeg-pcl-g-pei-micelles-for-local-treatment-of-oral-candida-albicans
#13
Li Zhou, Peipei Zhang, Zhuo Chen, Shaona Cai, Ting Jing, Huihui Fan, Fei Mo, Jiye Zhang, Rong Lin
Fatal Candida albicans infections in the mucosal system can occur in association with immune-compromised diseases and dysbacteriosis. Currently, amphotericin B (AmB) is considered to be the most effective antibiotic in the treatment of C. albicans infections, but its clinical application is limited by side effects and poor bioavailability. In order to use AmB in the local treatment of oral C. albicans infections, AmB/MPEG-PCL-g-PEI (monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone)-graft-polyethylenimine, MPP) micelles were prepared...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28643446/artemisinin-as-an-anticancer-drug-recent-advances-in-target-profiling-and-mechanisms-of-action
#14
REVIEW
Yin Kwan Wong, Chengchao Xu, Karunakaran A Kalesh, Yingke He, Qingsong Lin, W S Fred Wong, Han-Ming Shen, Jigang Wang
Artemisinin and its derivatives (collectively termed as artemisinins) are among the most important and effective antimalarial drugs, with proven safety and efficacy in clinical use. Beyond their antimalarial effects, artemisinins have also been shown to possess selective anticancer properties, demonstrating cytotoxic effects against a wide range of cancer types both in vitro and in vivo. These effects appear to be mediated by artemisinin-induced changes in multiple signaling pathways, interfering simultaneously with multiple hallmarks of cancer...
June 23, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#15
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28627385/advances-in-antibody-drug-conjugates-a-new-era-of-targeted-cancer-therapy
#16
REVIEW
Samaresh Sau, Hashem O Alsaab, Sushil Kumar Kashaw, Katyayani Tatiparti, Arun K Iyer
Antibody-drug conjugates (ADCs), a potent class of anticancer therapeutics, comprise a high-affinity antibody (Ab) and cytotoxic payload coupled via a suitable linker for selective tumor cell killing. In the initial phase of their development, two ADCs, Mylotarg(®), and Adcetris(®) were approved by the US Food and Drug Administration (FDA) for treating hematological cancer, but the real breakthrough came with the discovery of the breast cancer-targeting ADC, Kadcyla(®). With advances in bioengineering, linker chemistry, and potent cytotoxic payload, ADC technology has become a more powerful tool for targeted cancer therapy...
June 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28612260/utility-of-spherical-human-liver-microtissues-for-prediction-of-clinical-drug-induced-liver-injury
#17
William R Proctor, Alison J Foster, Jennifer Vogt, Claire Summers, Brian Middleton, Mark A Pilling, Daniel Shienson, Monika Kijanska, Simon Ströbel, Jens M Kelm, Paul Morgan, Simon Messner, Dominic Williams
Drug-induced liver injury (DILI) continues to be a major source of clinical attrition, precautionary warnings, and post-market withdrawal of drugs. Accordingly, there is a need for more predictive tools to assess hepatotoxicity risk in drug discovery. Three-dimensional (3D) spheroid hepatic cultures have emerged as promising tools to assess mechanisms of hepatotoxicity, as they demonstrate enhanced liver phenotype, metabolic activity, and stability in culture not attainable with conventional two-dimensional hepatic models...
June 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28608695/molecular-elucidation-of-biological-response-to-mesoporous-silica-nanoparticles-in-vitro-and-in-vivo
#18
Cheng-Chung Chou, Wei Chen, Yann Hung, Chung-Yuan Mou
Biomedical applications of mesoporous silica nanoparticles (MSNs) require efficient cellular uptake and low toxicity. The purpose of this study is to investigate the cellular uptake and toxicity of MSNs with different sizes and charges (50, 100, and 250 nm with a positive surface charge and 100 nm with a negative surface charge) exposed to human monocyte-derived macrophages, lung epithelium BEAS-2B cells, and mice using genome-wide gene expression analysis and cellular/animal-level end point tests. We found that MSNs can be taken up into cells through endocytosis in a charge- and size-dependent manner, with positively charged and larger MSNs being more easily taken up into the cells by recruiting more types of endocytotic pathways for more cellular uptake...
July 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28604124/test-systems-in-drug-discovery-for-hazard-identification-and-risk-assessment-of-human-drug-induced-liver-injury
#19
Richard J Weaver, Catherine Betts, Eric A G Blomme, Helga H J Gerets, Klaus Gjervig Jensen, Philip G Hewitt, Satu Juhila, Gilles Labbe, Michael J Liguori, Natalie Mesens, Monday O Ogese, Mikael Persson, Jan Snoeys, James L Stevens, Tracy Walker, B Kevin Park
The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered: The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities...
June 28, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28591563/evaluation-of-the-cytotoxicity-and-intestinal-absorption-of-a-self-emulsifying-drug-delivery-system-containing-sodium-taurocholate
#20
Hang Gao, Miao Wang, Dandan Sun, Shilin Sun, Cheng Sun, Jianguo Liu, Qingxiang Guan
Currently, many surfactants used in self-emulsifying drug delivery systems (SMEDDS) can cause gastrointestinal mucosal irritation and systemic toxicity. In the present study, SMEDDS were loaded with pueraria flavones, using sodium taurocholate to replace polyoxyl 40 dydrogenated castor oil (Cremophor® RH 40) as the surfactant (PF-SMEDDSNR) to reduce the toxicity of SMEDDS using Cremophor® RH 40 as the surfactant (PF-SMEDDSR). The absorption rate constants (Ka) and intestinal permeability coefficients (Peff) were measured...
August 30, 2017: European Journal of Pharmaceutical Sciences
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