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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/29233041/cardiotoxicity-evaluation-of-nine-alkaloids-from-rhizoma-coptis
#1
M Y Zhang, Y Y Yu, S F Wang, Q Zhang, H W Wu, J Y Wei, W Yang, S Y Li, H J Yang
PURPOSE: Alkaloids derived from Rhizoma Coptis (RC) has been widely applied to clinical treatments in China. However, the toxicity of RC and the alkaloids from RC remained controversial. The research is designed to clarify the cardiotoxic compounds found in RC. METHODS: In this study, the real-time cellular analysis cardio system and the high-content analysis were applied to monitor the function of cardiomyocytes (CMs) in the treatment of nine alkaloids in RC. Luciferase-coupled adenosine triphosphate (ATP) assay was used to detect cell viability...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#2
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29212781/analysis-of-drug-development-paradigms-for-immune-checkpoint-inhibitors
#3
Denis L Jardim, Debora de Melo Gagliato, Francis J Giles, Razelle Kurzrock
Immune checkpoint inhibitors have unique toxicities and response kinetics compared to cytotoxics and gene-targeted anti-cancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the US Food and Drug Administration (FDA) website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared to that found in later trials leading to regulatory approvals of the same agents...
December 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29209782/advances-in-immunotherapeutic-research-for-glioma-therapy
#4
REVIEW
Jeremy Tetsuo Miyauchi, Stella E Tsirka
Gliomas are primary malignancies of the brain. Tumors are staged based on malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma. Tumors are often diagnosed once patients become symptomatic, at which time the lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and difficult to treat. Most tumors are diagnosed de novo. The gold standard of therapy, implemented over a decade ago, consists of fractionated radiotherapy and temozolomide, but unfortunately, chemotherapeutic resistance arises...
December 5, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29208047/non-conventional-dosing-of-oral-anticancer-agents-in-oncology-and-malignant-haematology-a-systematic-review-protocol
#5
Faouzi Djebbari, Nicola Stoner, Verna Lavender
BACKGROUND: Recent advances in cancer therapeutics have resulted in significantly improved overall survival and progression-free survival for patients. Targeted oral systemic anticancer therapies (SACT) offer a range of treatment approaches that differ from traditional cytotoxic chemotherapy: non-cytotoxic oral SACT target malignant disease continuously, have less broad and more favourable safety profiles, which can improve patients' quality of life (QoL). Toxicities associated with daily oral SACT administration can, however, result in non-adherence and a reduced QoL...
December 6, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#6
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29193199/muc1-and-survivin-based-dna-vaccine-combining-immunoadjuvants-cpg-and-interleukin-2-in-a-bicistronic-expression-plasmid-generates-specific-immune-responses-and-anti-tumor-effects-in-a-murine-colorectal-carcinoma-model
#7
Chenlu Liu, Yu Xie, Bo Sun, Fei Geng, Fangfang Zhang, Qianqian Guo, Hui Wu, Bin Yu, Jiaxin Wu, Xianghui Yu, Wei Kong, Haihong Zhang
DNA vaccination is a promising cancer treatment due to its safety, but poor immunogenicity limits its application. However, immunoadjuvants, heterogeneous prime-boost strategies and combination with conventional treatments can be used to improve the anti-tumor immune effects. A CpG motif and interleukin 2 (IL-2) cytokine are often used as adjuvants. In this study, a DNA vaccine containing a CpG motif was constructed to evaluate its adjuvant effect. The results show that the cytotoxicity of the DNA vaccine was increased 5-fold, and survival life time was prolonged 2-fold by the CpG motif adjuvant...
November 28, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29184391/novel-production-method-of-innovative-antiangiogenic-and-antitumor-small-peptides-in-escherichia-coli
#8
Sarra Setrerrahmane, Jian Yu, Jingchao Hao, Heng Zheng, Hanmei Xu
Background: Developing innovative drugs with potent efficacy, specificity, and high safety remains an ongoing task in antitumor therapy development. In the last few years, peptide drugs have become attractive agents in cancer therapy. HM-3, mainly with antiangiogenic effect, and AP25, with an additional antiproliferative effect, are two peptides designed in our laboratory targeting αvβ3 and α5β1 integrins, respectively. The low molecular weight of the two peptides renders their recombinant expression very difficult, and the complicated structure of AP25 makes its chemical synthesis restricted, which presents a big challenge for its development...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29182718/a-3d-human-airway-model-enables-prediction-of-respiratory-toxicity-of-inhaled-drugs-in-vitro
#9
Kinga Balogh Sivars, Ulf Sivars, Ellinor Hornberg, Hui Zhang, Lena Brändén, Rosy Bonfante, Song Huang, Samuel Constant, Ian Robinson, Catherine J Betts, Per Åberg
Respiratory tract toxicity represents a significant cause of attrition of inhaled drug candidates targeting respiratory diseases. One of the key issues to allow early detection of respiratory toxicities is the lack of reliable and predictive in vitro systems. Here, the relevance and value of a physiologically relevant 3D human airway in vitro model (MucilAir™) were explored by repeated administration of a set of compounds with (n = 8) or without (n = 7) respiratory toxicity following inhalation in vivo...
November 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29181010/crystallizable-fragment-glycoengineering-for-therapeutic-antibodies-development
#10
REVIEW
Wei Li, Zhongyu Zhu, Weizao Chen, Yang Feng, Dimiter S Dimitrov
Monoclonal antibody (mAb)-based therapeutics are the fastest growing class of human pharmaceuticals. They are typically IgG1 molecules with N-glycans attached to the N297 residue on crystallizable fragment (Fc). Different Fc glycoforms impact their effector function, pharmacokinetics, stability, aggregation, safety, and immunogenicity. Fc glycoforms affect mAbs effector functions including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) by modulating the Fc-FcγRs and Fc-C1q interactions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29172458/transiently-thermoresponsive-acetal-polymers-for-safe-and-effective-administration-of-amphotericin-b-as-vaccine-adjuvant
#11
Simon Van Herck, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens, Xavier Saelens, Bruno G De Geest
The quest for new potent and safe adjuvants to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, Amphotericin B (AmpB) - an FDA-approved anti-fungal drug - has recently been discovered to possess TLR triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant...
November 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29163441/antifungal-and-anti-biofilm-activity-of-essential-oil-active-components-against-cryptococcus-neoformans-and-cryptococcus-laurentii
#12
Poonam Kumari, Rutusmita Mishra, Neha Arora, Apurva Chatrath, Rashmi Gangwar, Partha Roy, Ramasare Prasad
Cryptococcosis is an emerging and recalcitrant systemic infection occurring in immunocompromised patients. This invasive fungal infection is difficult to treat due to the ability of Cryptococcus neoformans and Cryptococcus laurentii to form biofilms resistant to standard antifungal treatment. The toxicity concern of these drugs has stimulated the search for natural therapeutic alternatives. Essential oil and their active components (EO-ACs) have shown to possess the variety of biological and pharmacological properties...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29148846/preparation-and-evaluation-of-curcumin-loaded-self-assembled-micelles
#13
Lu-Lu Wang, Dan-Dan He, Shu-Xia Wang, Yun-Hao Dai, Jian-Ming Ju, Cheng-Lei Zhao
Objective Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. Methods Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method...
November 17, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#14
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29136037/safety-pharmacokinetics-and-immunological-activities-of-multiple-intravenous-or-subcutaneous-doses-of-an-anti-hiv-monoclonal-antibody-vrc01-administered-to-hiv-uninfected-adults-results-of-a-phase-1-randomized-trial
#15
Kenneth H Mayer, Kelly E Seaton, Yunda Huang, Nicole Grunenberg, Abby Isaacs, Mary Allen, Julie E Ledgerwood, Ian Frank, Magdalena E Sobieszczyk, Lindsey R Baden, Benigno Rodriguez, Hong Van Tieu, Georgia D Tomaras, Aaron Deal, Derrick Goodman, Robert T Bailer, Guido Ferrari, Ryan Jensen, John Hural, Barney S Graham, John R Mascola, Lawrence Corey, David C Montefiori
BACKGROUND: VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. METHODS AND FINDINGS: HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29133762/rare-earth-nanoparticle-induced-cytotoxicity-on-spatial-cognition-memory-of-mouse-brain
#16
Cai-Hou Lin, Gui-Fen Liu, Jing Chen, Yan Chen, Ru-Hui Lin, Hong-Xing He, Jian-Ping Chen
BACKGROUND: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure...
November 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29131039/adverse-reactions-of-antibody-therapy-for-primary-cutaneous-lymphomas-rituximab-brentuximab-vedotin-alemtuzumab-and-mogamulizumab
#17
I Saulite, E Guenova, W Hoetzenecker
Treatment of advanced PCLs is limited and rarely reaches complete remission despite aggressive treatment modalities, such as polychemotherapy with various adverse effects. However, several monoclonal antibodies drug agents in patients with advanced primary cutaneous lymphomas demonstrate promising efficacy and manageable safety profiles. The monoclonal antibodies drug agents have favourable tolerability compared with multi-agent cytotoxic chemotherapy. However, adverse effects manifest with a broad clinical spectrum, hence the markers of targeted therapies are not limited to tumour cells but found on tumour cells and also on benign T and/or B cells...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29116801/effects-of-surface-charge-of-hyperbranched-polymers-on-cytotoxicity-dynamic-cellular-uptake-and-localization-hemotoxicity-and-pharmacokinetics-in-mice
#18
Liyu Chen, Joshua D Simpson, Adrian V Fuchs, Barbara E Rolfe, Kristofer J Thurecht
Nanoscaled polymeric materials are increasingly being investigated as pharmaceutical products, drug/gene delivery vectors, or health-monitoring devices. Surface charge is one of the dominant parameters that regulates nanomaterial behavior in vivo. In this paper, we demonstrated how control over chemical synthesis allowed manipulation of nanoparticle surface charge, which in turn greatly influenced the in vivo behavior. Three methacrylate/methacrylamide-based monomers were used to synthesize well-defined hyperbranched polymers (HBP) by reversible addition-fragmentation chain transfer (RAFT) polymerization...
November 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29111267/process-optimization-and-in-vivo-performance-of-docetaxel-loaded-phbv-tpgs-therapeutic-vesicles-a-synergistic-approach
#19
Harsh Vardhan, Pooja Mittal, Sandeep Kumar Reddy Adena, Mansi Upadhyay, Sarita Kumari Yadav, Brahmeshwar Mishra
This research was motivated due to substantial requirement of improved treatment for breast cancer which accounts for over 0.52 million deaths annually worldwide. Utilizing nanoparticles carrying active medicaments as targeted delivery carrier is emerging as a promising approach. For a drug to be clinically effective, it needs to be suitably protected in the biological fluid till it is delivered to the targeted site. Keeping above in mind, we prepared and optimized polymeric nanoparticles by polyhydroxybutyrate-co-hydroxyvalerate (PHBV) a biodegradable polymer utilizing modified emulsification solvent evaporation method...
October 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29109483/safety-of-nonporous-silica-nanoparticles-in-human-corneal-endothelial-cells
#20
Ja-Yeon Kim, Joo-Hee Park, Martha Kim, Hyejoong Jeong, Jinkee Hong, Roy S Chuck, Choul Yong Park
Nonporous silica nanoparticles (SiNPs) are promising drug carrier platforms for intraocular drug delivery. In this study, we investigated the safety of three different sizes of SiNPs (50, 100, and 150 nm) in a human corneal endothelial cell (HCEC) line, B4G12. The HCECs were exposed to different concentrations (0, 25, 50, and 100 µg/ml) of three sizes of SiNPs for up to 48 h. Cellular viability, autophagy, lactate dehydrogenase (LDH) assay, and mammalian target of rapamycin (mTOR) pathway activation were evaluated...
November 6, 2017: Scientific Reports
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