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Cytotoxic drug safety

Kalpana Javvaji, Gousia Begum, Shruti S Deshpande, Rohit Kumar Rana, Sunil Misra
Calcium carbonate (CaCO3) based materials as feasible pH sensitive drug carriers which can actively dissolve in acidic microenvironment of cancer cells, are finding increasing importance. This has drawn our interest in the development of a bio-inspired polypeptide- mediated method to design calcium carbonate microspheres loaded with tetracycline (CaCO3-TC) with an aim to explore its safe application in cancer therapeutics. Its therapeutic application in cancer patients essentially demands its safety information on the normal cells...
June 20, 2018: Chemical Research in Toxicology
Ammar Almaaytah, Mohammed T Qaoud, Ahmad Abualhaijaa, Qosay Al-Balas, Karem H Alzoubi
Introduction: As the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents. Aim: The hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile...
2018: Infection and Drug Resistance
Waqas Muhammad Usman, Tin Chanh Pham, Yuk Yan Kwok, Luyen Tien Vu, Victor Ma, Boya Peng, Yuen San Chan, Likun Wei, Siew Mei Chin, Ajijur Azad, Alex Bai-Liang He, Anskar Y H Leung, Mengsu Yang, Ng Shyh-Chang, William C Cho, Jiahai Shi, Minh T N Le
Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA...
June 15, 2018: Nature Communications
Nurul Akma Hanan, Hock Ing Chiu, Muggundha Raoov Ramachandran, Wai Hau Tung, Nur Nadhirah Mohamad Zain, Noorfatimah Yahaya, Vuanghao Lim
In the field of medicine, nanomaterials, especially those derived using the green method, offer promise as anti-cancer agents and drug carriers. However, the biosafety of metallic nanoparticles used as anti-cancer agents remains a concern. The goal of this systematic review was to compare the cytotoxicity of different plant-mediated syntheses of metallic nanoparticles based on their potency, therapeutic index, and cancer cell type susceptibility in the hopes of identifying the most promising anti-cancer agents...
June 11, 2018: International Journal of Molecular Sciences
G Milano, F Innocenti, B Lacarelle, J Ciccolini
There is a rising evidence that the proverbial statement "No pain, No gain" first coined at the light of pioneering clinical experiences with canonical chemotherapy still holds true in the era of modern treatments of cancer. This close relationship between the occurrence of specific drug-related toxicity and treatment outcome has been confirmed since then with a large variety of treatments, ranging from cytotoxics, hormonotherapy, targeted therapy and much interestingly even with the latest immune checkpoint inhibitors...
July 2018: Critical Reviews in Oncology/hematology
Klaudia T Warzecha, Matthias Bartneck, Diana Möckel, Lia Appold, Can Ergen, Wáel Al Rawashdeh, Felix Gremse, Patricia M Niemietz, Willi Jahnen-Dechent, Christian Trautwein, Fabian Kiessling, Twan Lammers, Frank Tacke
Poly n -butylcyanoacrylate (PBCA)-based hard-shell microbubbles (MB) have manifold biomedical applications, including targeted drug delivery or contrast agents for ultrasound (US)-based liver imaging. MB and their fragments accumulate in phagocytes, especially in the liver, but it is unclear if MB affect the function of these immune cells. We herein show that human primary monocytes internalize different PBCA-MB by phagocytosis, which transiently inhibits monocyte migration in vertical chemotaxis assays and renders monocytes susceptible to cytotoxic effects of MB during US-guided destruction...
May 2018: Advanced Biosystems
Paul Ametsbichler, Antje Böhlandt, Dennis Nowak, Rudolf Schierl
INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a new promising treatment for patients with peritoneal carcinomatosis. It is supposed to provide a higher local drug concentration and deeper penetrate into the tumor tissue compared to systemic chemotherapy or hyperthermic intraperitoneal chemotherapy perfusion (HIPEC). Due to the application of cytotoxic drug aerosols within the operating room (OR), concern has been raised regarding the occupational exposure risk of the involved OR staff...
May 22, 2018: European Journal of Surgical Oncology
Charlotte Egeland, Lene Baeksgaard, Helle Hjorth Johannesen, Johan Löfgren, Christina Caroline Plaschke, Lars Bo Svendsen, Julie Gehl, Michael Patrick Achiam
Background and study aims:  Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug's cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer. Patients and methods:  In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin...
June 2018: Endoscopy International Open
Neil E McCarthy, Matthias Eberl
Human γδ T-cells include some of the most common "antigen-specific" cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes...
2018: Frontiers in Immunology
S Ndaw, O Hanser, V Kenepekian, M Vidal, M Melczer, A Remy, A Robert, N Bakrin
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced over the last decade for the treatment of peritoneal carcinomatosis. In this procedure, heated cytotoxic drugs are administered directly into the abdominal cavity, ensuring cancer cells to be exposed while reducing systemic toxicity. More recently, pressurized intraperitoneal aerosol chemotherapy (PIPAC), where the chemotherapeutic drug is injected into the peritoneal cavity as an aerosol under pressure, has been proposed to patients in palliative situation, as a new approach...
May 28, 2018: Toxicology Letters
Marta Swatko-Ossor, Katarzyna Klimek, Anna Belcarz, Anna Kaczor Agnieszka, Monika Pitucha, Grazyna Ginalska
As a continuation of previous tests concerning new N-substituted 3-amino-4-phenyl-5-oxo-pyrazolinecarboxamide derivatives (R3, R4 and R8) of notable antibacterial activity, their antitubercular potential against different mycobacterial strains was estimated. Tests performed on virulent (reference and clinical) strains of Mycobacterium bovis and Mycobacterium tuberculosis revealed the highest therapeutic potential of R8 derivative: MIC within the range 7.8-15.6 μg/ml and TI (therapeutic index) within the range 46...
May 23, 2018: European Journal of Pharmaceutical Sciences
Éanna Forde, Ghady Shafiy, Deirdre Fitzgerald-Hughes, Adam A Strömstedt, Marc Devocelle
Antimicrobial peptides (AMPs) are promising broad-spectrum antibiotic candidates in the wake of multi-drug resistant pathogens. Their clinical use still requires a solution based on lead optimisation and/or formulation to overcome certain limitations, such as unwanted cytotoxicity. A prodrug approach could overcome this safety barrier and can be achieved through reversible reduction or neutralisation of the AMPs' net cationic charge. By prodrug activation through pathogen associated enzymes, this approach could increase the therapeutic index of membrane active peptides...
May 24, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
Emily E Bosco, R James Christie, Rosa Carrasco, Darrin Sabol, Jiping Zha, Karma DaCosta, Lee Brown, Maureen Kennedy, John Meekin, Sandrina Phipps, Joanne Ayriss, Qun Du, Binyam Bezabeh, Partha Chowdhury, Shannon Breen, Cui Chen, Molly Reed, MaryJane Hinrichs, Haihong Zhong, Zhan Xiao, Rakesh Dixit, Ronald Herbst, David A Tice
Despite recent advances in treatment, breast cancer remains the second-most common cause of cancer death among American women. A greater understanding of the molecular characteristics of breast tumors could ultimately lead to improved tumor-targeted treatment options, particularly for subsets of breast cancer patients with unmet needs. Using an unbiased genomics approach to uncover membrane-localized tumor-associated antigens (TAAs), we have identified glial cell line derived neurotrophic factor (GDNF) family receptor α 1 (GFRA1) as a breast cancer TAA...
May 1, 2018: Oncotarget
Jian Chen, Wenjuan Li, Ke Cui, Kaiyuan Ji, Shuxiang Xu, Yang Xu
Cancer chemotherapeutic agents such as doxorubicin are DNA damage inducers that also kill normal cells, making them highly toxic to cancer patients. To improve the efficacy and safety of chemotherapy, it is important to develop new chemotherapeutic agents that selectively kill cancer cells. Here we demonstrate that artemisitene (ATT), a natural derivative of the antimalarial drug artemisinin, selectively induces DNA double-stranded breaks (DSBs) and apoptosis in various human cancer cells by suppressing the expression of topoisomerases in human cancer cells...
May 24, 2018: Oncogene
Jeffrey Baron, Eunice S Wang
Gemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths seen in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML...
May 22, 2018: Expert Review of Clinical Pharmacology
Tatiana Zanela da Silva Marques, Ralph Santos-Oliveira, Luciana Betzler de Oliveira de Siqueira, Verônica da Silva Cardoso, Zaida Maria Faria de Freitas, Rita de Cássia da Silva Ascenção Barros, Ana Lúcia Vazquez Villa, Mariana Sato de Souza de Bustamante Monteiro, Elisabete Pereira Dos Santos, Eduardo Ricci-Junior
Background: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo. Methods: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis...
2018: International Journal of Nanomedicine
Valeri V Mossine, Deborah L Chance, James K Waters, Thomas P Mawhinney
Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1...
May 21, 2018: Antimicrobial Agents and Chemotherapy
Gabriela Wyszogrodzka, Przemysław Dorożyński, Barbara Gil, Wieslaw J Roth, Maciej Strzempek, Bartosz Marszałek, Władysław P Węglarz, Elżbieta Menaszek, Weronika Strzempek, Piotr Kulinowski
PURPOSE: The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety. METHODS: Fe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction...
May 18, 2018: Pharmaceutical Research
Michael G Lancina, Juan Wang, Geoffrey S Williamson, Hu Yang
In this work, we report synthesis and characterization of DenTimol, a dendrimer-based polymeric timolol analog as glaucoma medication. A timolol precursor (S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine (OTM) was reacted with the heterobifunctional amine polyethylene glycol acetic acid (Amine-PEG-Acetic Acid, Mn=2000 g/mol) via the ring opening reaction of epoxide by an amine to form OTM-PEG conjugate. OTM-PEG was then coupled to ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimer G3 to generate DenTimol using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) coupling reaction...
May 16, 2018: Molecular Pharmaceutics
Josefina Marin, María Laura Acosta Felquer, Enrique R Soriano
Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204...
2018: Open Access Rheumatology: Research and Reviews
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