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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/29456473/adverse-events-of-trastuzumab-emtansine-t-dm1-in-the-treatment-of-her2-positive-breast-cancer-patients
#1
REVIEW
Lidia Kowalczyk, Rupert Bartsch, Christian F Singer, Alex Farr
The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29453543/toxic-and-beneficial-potential-of-silver-nanoparticles-the-two-sides-of-the-same-coin
#2
Lilian Rodrigues Rosa Souza, Veronica Santana da Silva, Leonardo Pereira Franchi, Tiago Alves Jorge de Souza
Nanotechnology has allowed great changes in chemical, biological and physical properties of metals when compared to their bulk counterparts. Within this context, silver nanoparticles (AgNPs) play a major role due to their unique properties, being widely used in daily products such as fabrics, washing machines, water filters, food and medicine. However, AgNPs can enter cells inducing a "Trojan-horse" type mechanism which potentially leads to cellular autophagy, apoptosis or necrosis. On the other hand, this cytotoxicity mechanism can be optimized to develop drug nanocarriers and anticancer therapies...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29450805/ph-responsive-cap-co-poly-methacrylic-acid-based-hydrogel-as-an-efficient-platform-for-controlled-gastrointestinal-delivery-fabrication-characterization-in-vitro-and-in-vivo-toxicity-evaluation
#3
Syed Ahmed Shah, Muhammad Sohail, Muhammad Usman Minhas, Nisar-Ur-Rehman, Shahzeb Khan, Zahid Hussain, Mudassir, Arshad Mahmood, Mubeen Kousar, Asif Mahmood
Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility...
February 15, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29445277/effects-of-silica-gentamicin-nanohybrids-on-osteogenic-differentiation-of-human-osteoblast-like-saos-2-cells
#4
Wei He, Dina A Mosselhy, Yudong Zheng, Qingling Feng, Xiaoning Li, Xing Yang, Lina Yue, Simo-Pekka Hannula
Introduction: In recent years, there has been an increasing interest in silica (SiO 2 ) nanoparticles (NPs) as drug delivery systems. This interest is mainly attributed to the ease of their surface functionalization for drug loading. In orthopedic applications, gentamicin-loaded SiO 2 NPs (nanohybrids) are frequently utilized for their prolonged antibacterial effects. Therefore, the possible adverse effects of SiO 2 -gentamicin nanohybrids on osteogenesis of bone-related cells should be thoroughly investigated to ensure safe applications...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29445145/canagliflozin-mediated-dual-inhibition-of-mitochondrial-glutamate-dehydrogenase-and-complex-i-an-off-target-adverse-effect
#5
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29435139/quantitative-high-throughput-phenotypic-screening-of-pediatric-cancer-cell-lines-identifies-multiple-opportunities-for-drug-repurposing
#6
Min Shen, Rosita Asawa, Ya-Qin Zhang, Elizabeth Cunningham, Hongmao Sun, Alexander Tropsha, William P Janzen, Eugene N Muratov, Stephen J Capuzzi, Sherif Farag, Ajit Jadhav, Julie Blatt, Anton Simeonov, Natalia J Martinez
Drug repurposing approaches have the potential advantage of facilitating rapid and cost-effective development of new therapies. Particularly, the repurposing of drugs with known safety profiles in children could bypass or streamline toxicity studies. We employed a phenotypic screening paradigm on a panel of well-characterized cell lines derived from pediatric solid tumors against a collection of ∼3,800 compounds spanning approved drugs and investigational agents. Specifically, we employed titration-based screening where compounds were tested at multiple concentrations for their effect on cell viability...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434728/chitosan-temperature-sensitive-gel-loaded-with-drug-microspheres-has-excellent-effectiveness-biocompatibility-and-safety-as-an-ophthalmic-drug-delivery-system
#7
Xiaoying Kong, Wenhua Xu, Cuiping Zhang, Wei Kong
In the present study, a temperature-sensitive gel composed of chitosan, carboxymethyl chitosan and glycerophosphate was prepared and loaded with chitosan microspheres encapsulating levofloxacin. The bioavailability of levofloxacin and the safety of this novel opthalmic drug delivery formulation were evaluated. Levofloxacin chitosan microspheres were prepared using the ionic gelation method, and the particle size and entrapment rate were determined. The morphology of the microspheres was observed by scanning electron microscopy...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432822/macromolecular-prodrugs-of-ribavirin-polymer-backbone-defines-blood-safety-drug-release-and-efficacy-of-anti-inflammatory-effects
#8
Kaja Zuwala, Camilla F Riber, Kaja Borup Løvschall, Anna H F Andersen, Lise Sørensen, Paulina Gajda, Martin Tolstrup, Alexander N Zelikin
Macromolecular (pro)drugs hold much promise as broad-spectrum antiviral agents as either microbicides or carriers for intracellular delivery of antiviral drugs. Intriguing opportunity exists in combining the two modes of antiviral activity in the same polymer structure such that the same polymer acts as a microbicide and also serves to deliver the conjugated drug (ribavirin) into the cells. We explore this opportunity in detail and focus on the polymer backbone as a decisive constituent of such formulations...
February 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29414105/discovery-of-ebselen-as-an-inhibitor-of-cryptosporidium-parvum-glucose-6-phosphate-isomerase-cpgpi-by-high-throughput-screening-of-existing-drugs
#9
Rana Eltahan, Fengguang Guo, Haili Zhang, Lixin Xiang, Guan Zhu
Cryptosporidium parvum is a water-borne and food-borne apicomplexan pathogen. It is one of the top four diarrheal-causing pathogens in children under the age of five in developing countries, and an opportunistic pathogen in immunocompromised individuals. Unlike other apicomplexans, C. parvum lacks Kreb's cycle and cytochrome-based respiration, thus relying mainly on glycolysis to produce ATP. In this study, we characterized the primary biochemical features of the C. parvum glucose-6-phosphate isomerase (CpGPI) and determined its Michaelis constant towards fructose-6-phosphate (Km = 0...
January 25, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29407369/immune-checkpoint-inhibitors-for-metastatic-bladder-cancer
#10
REVIEW
Francesco Massari, Vincenzo Di Nunno, Marta Cubelli, Matteo Santoni, Michelangelo Fiorentino, Rodolfo Montironi, Liang Cheng, Anto Lopez-Beltran, Nicola Battelli, Andrea Ardizzoni
Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy...
January 31, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29406793/development-and-evaluation-of-a-novel-microemulsion-of-dexamethasone-and-tobramycin-for-topical-ocular-administration
#11
Rinda Devi Bachu, Marina Stepanski, Rami M Alzhrani, Rose Jung, Sai H S Boddu
PURPOSE: The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections. METHODS: The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex®)...
February 6, 2018: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29401738/cytotoxicity-enhancement-in-breast-cancer-cells-with-carbonate-apatite-facilitated-intracellular-delivery-of-anti-cancer-drugs
#12
Tahereh Fatemian, Ezharul Hoque Chowdhury
Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved...
February 5, 2018: Toxics
https://www.readbyqxmd.com/read/29400987/dose-rounding-of-biologic-and-cytotoxic-anticancer-agents-a-position-statement-of-the-hematology-oncology-pharmacy-association
#13
Rebecca Fahrenbruch, Polly Kintzel, Anne Marie Bott, Steven Gilmore, Ryan Markham
PURPOSE: To present a position statement from the Hematology/Oncology Pharmacy Association (HOPA) that pertains to dose rounding of biologic and cytotoxic anticancer agents. METHODS: The HOPA Standards Committee organized a work group of oncology pharmacist specialists to examine the safety and value of dose rounding of biologic and cytotoxic anticancer agents. Primary literature that describes methods for dose rounding, with clinical or economic data, were analyzed...
February 5, 2018: Journal of Oncology Practice
https://www.readbyqxmd.com/read/29400697/randomized-controlled-trial-of-tnf-%C3%AE-antagonist-in-ctl-mediated-severe-cutaneous-adverse-reactions
#14
Chuang-Wei Wang, Lan-Yan Yang, Chun-Bing Chen, Hsin-Chun Ho, Shuen-Iu Hung, Chih-Hsun Yang, Chee-Jen Chang, Shih-Chi Su, Rosaline Chung-Yee Hui, See-Wen Chin, Li-Fang Huang, Yang Yu-Wei Lin, Wei-Yang Chang, Wen-Lang Fan, Chin-Yi Yang, Ji-Chen Ho, Ya-Ching Chang, Chun-Wei Lu, Wen-Hung Chung
BACKGROUND: Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial...
February 5, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29398301/human-and-mouse-artificial-chromosome-technologies-for-studies-of-pharmacokinetics-and-toxicokinetics
#15
REVIEW
Daisuke Satoh, Satoshi Abe, Kaoru Kobayashi, Yoshihiro Nakajima, Mitsuo Oshimura, Yasuhiro Kazuki
In the earliest stage of drug discovery/development, various cell-based models and animal models were used for the prediction of human pharmacokinetics and toxicokinetics. Unfortunately, drugs under development are often discontinued because their nonclinical results do not extrapolate to human clinical studies in relation to either safety or efficacy. Therefore, it is important to improve the time- and cost-effectiveness of drug development. This might be achieved by developing new technologies including pharmacokinetics and toxicokinetics models that use human and mouse artificial chromosome vectors (HACs/MACs)...
January 11, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29392969/metabolomics-reveals-the-depletion-of-intracellular-metabolites-in-hepg2-cells-after-treatment-with-gold-nanoparticles
#16
Jeremie Zander Lindeque, Alnari Matthyser, Shayne Mason, Roan Louw, Cornelius Johannes Francois Taute
Studies on the safety of gold nanoparticles (GNPs) are plentiful due to their successful application in drug delivery and treatment of diseases in trials. Cytotoxicity caused by GNPs has been studied on the physiological and biochemical level; yet, the effect of GNPs (particularly gold nano-spheres) on the metabolome of living organisms remains understudied. In this investigation, metabolomics was used to comprehensively study the metabolic alterations in HepG2 cells caused by GNPs; and to investigate the role of representative GNP coatings...
February 2, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29390506/efficacy-and-safety-of-nanoparticle-albumin-bound-paclitaxel-monotherapy-as-second-line-therapy-of-cytotoxic-anticancer-drugs-in-patients-with-advanced-non-small-cell-lung-cancer
#17
Masaki Anzai, Miwa Morikawa, Takehiro Okuno, Yukihiro Umeda, Yoshiki Demura, Tomoaki Sonoda, Makiko Yamaguchi, Kiyoshi Kanno, Kohei Shiozaki, Shingo Ameshima, Masaya Akai, Tamotsu Ishizuka
BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), which avoids toxicities associated with a vehicle used in solvent-based PTX, has already shown safety and efficacy in patients with non-small cell lung cancer (NSCLC). METHODS: A phase II study was performed to assess the safety and efficacy of nab-PTX monotherapy as second-line chemotherapy after cytotoxic anticancer drugs for previously treated advanced NSCLC. Thirty-two patients with advanced NSCLC who had previously undergone 1 regimen of cytotoxic anticancer drugs were enrolled...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29364441/cancer-immunology-and-melanoma-immunotherapy
#18
Rudinei Diogo Marques Linck, Rômulo Leopoldo de Paula Costa, Bernardo Garicochea
The stimulation of the immune system, in order to generate an attack against cancer cells, similarly to that which occurs in infectious disease, has long been matter of interest in oncology; however, only limited success has been achieved, with different treatment strategies tested in recent years. The development of new immune checkpoint inhibitors is currently changing this scenario, and immunotherapy is becoming a real choice among traditional cytotoxic treatments to fight cancer. Recent reports have shown efficacy and safety with the use of pembrolizumab, nivolumab, and ipilimumab for the treatment of different neoplasms, especially melanoma...
November 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29362482/arsenic-trioxide-promoting-etosis-in-acute-promyelocytic-leukemia-through-mtor-regulated-autophagy
#19
Tao Li, Ruishuang Ma, Yan Zhang, Hongdan Mo, Xiaoyan Yang, Shaoshan Hu, Lixiu Wang, Valerie A Novakovic, He Chen, Junjie Kou, Yayan Bi, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication...
January 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29350186/mri-tracing-non-invasive-tio2-based-nanoparticles-motivated-by-ultrasound-for-multi-mechanism-therapy-of-prostatic-cancer
#20
Pu Yuan, Dongkui Song
To reduce the side effects of chemotherapy and reach effective and safe therapy of prostate cancer, herein, a simple but multifunctional system TiO2:Gd@DOX/FA motivated by ultrasound was developed for MRI guided multi-mechanism therapy of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a nanocarrier with pH-responsive release of DOX. Doping of Gd could not only endow TiO2 the ability of magnetic resonance imaging (MRI), but also further improve sonodynamic ability of TiO2. The characterization revealed the as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high ROS production, T1-MRI contrast performance and excellent biocompatibility...
January 19, 2018: Nanotechnology
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