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Cytotoxic drug safety

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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
#1
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 30min and >80% permeation in 45min. Superior cellular uptake potential (4.6 to 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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28322141/lessons-learned-from-gemcitabine-impact-of-therapeutic-carrier-systems-and-gemcitabine-s-drug-conjugates-on-cancer-therapy
#6
REVIEW
Sathish Dyawanapelly, Animesh Kumar, Manish K Chourasia
Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored...
2017: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/28316976/mutagenic-and-cytotoxicity-lqb-123-profile-safety-and-tripanocidal-effect-of-a-phenyl-t-butylnitrone-derivative
#7
Mauricio Peixoto Cupello, Francis Monique Saraiva, Pedro Ippolito, Andréia da Silva Fernandes, Rubem Figueiredo Sadoko Menna-Barreto, Debora de Sousa Dos Santos Costa, Jessica Isis Oliveira Paula, Paulo Roberto Ribeiro Costa, Natália Pereira Nogueira, Israel Felzenswalb, Ayres Guimarães Dias, Marcia Cristina Paes
The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50 = 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50 = 188...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28314699/safety-and-tolerability-of-idelalisib-lenalidomide-and-rituximab-in-relapsed-and-refractory-lymphoma-the-alliance-for-clinical-trials-in-oncology-a051201-and-a051202-phase-1-trials
#8
Sonali M Smith, Brandelyn N Pitcher, Sin-Ho Jung, Nancy L Bartlett, Nina Wagner-Johnston, Steven I Park, Kristy L Richards, Amanda F Cashen, Anthony Jaslowski, Scott E Smith, Bruce D Cheson, Eric Hsi, John P Leonard
BACKGROUND: A new generation of biological and targeted agents might potentially replace traditional cytotoxic agents in lymphoma. Lenalidomide plus rituximab was felt to be a safe and promising backbone based on available data. Idelalisib is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor that has promising activity as a monotherapy in refractory indolent lymphomas. The primary objective of these two trials was to determine the maximum tolerated dose of lenalidomide in combination with rituximab and idelalisib in relapsed follicular and mantle cell lymphoma...
March 14, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28301615/topical-approaches-to-improve-surgical-outcomes-and-wound-healing-a-review-of-efficacy-and-safety
#9
Kristin Totoraitis, Joel L Cohen, Adam Friedman
<p>Surgical procedures are an important piece of a dermatologist's daily practice. Therefore, the optimization of post-surgical wound healing is an area of utmost importance and interest. Although low risk, one notable barrier to proper wound healing is surgical site infection.</p> <p>In an attempt to mitigate this risk and improve surgical outcomes, multiple topical products continue to be used both pre- and postprocedure. Traditionally, this includes both topical antibiotics and antiseptics...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28293794/do-all-patients-in-the-phase-i-oncology-trials-need-to-be-hospitalized-domestic-but-outstanding-issues-for-globalization-of-drug-development-in-japan
#10
Akihiko Shimomura, Shunsuke Kondo, Noriko Kobayashi, Satoru Iwasa, Shigehisa Kitano, Kenji Tamura, Yutaka Fujiwara, Noboru Yamamoto
INTRODUCTION: Most trials investigating new drugs around the world, including phase I trials, are conducted in outpatient clinics. However, in Japan, regulatory authority requirements and traditional domestic guidelines often require hospitalization of phase I study participants. PATIENTS AND METHODS: Patients participating in single-agent phase I clinical trials at National Cancer Center Hospital between December 1996 and August 2014 were monitored. Toxicity requiring hospitalization is defined as toxicity that needs intensive treatment...
March 14, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28279788/containment-challenges-in-hpapi-manufacture-for-adc-generation
#11
REVIEW
Elizabeth Dunny, Imelda O'Connor, Jonathan Bones
Antibody-drug conjugates (ADCs) are emerging as an impactful class of therapeutics for the treatment of cancer because of their ability to harness the specificity of an antibody and the cytotoxic potential of the payload to target and destroy cancer cells. However, the potent nature of the cytotoxic payload creates associated manufacturing challenges for active pharmaceutical ingredient (API) manufacturers, because huge investment in containment technology is required to ensure the protection of operators and the environment...
March 6, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28276536/obinutuzumab-in-follicular-lymphoma
#12
N Martinez-Calle, R Figueroa-Mora, S Villar-Fernandez, M Marcos-Jubilar, C Panizo
The CD20 marker continues to be exploited as a therapeutic target for non-Hodgkin's lymphoma. Obinutuzumab is part of a new generation of anti-CD20 monoclonal antibodies, which are synthesized using molecular engineering technology, resulting in novel target epitopes and unprecedented optimization of antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Rituximab is the current gold standard for anti-CD20 therapy, yet despite outstanding results published over the past decade, many patients continue to relapse after anti-CD20 regimens...
December 2016: Drugs of Today
https://www.readbyqxmd.com/read/28276440/deconvolution-of-buparlisib-s-mechanism-of-action-defines-specific-pi3k-and-tubulin-inhibitors-for-therapeutic-intervention
#13
Thomas Bohnacker, Andrea E Prota, Florent Beaufils, John E Burke, Anna Melone, Alison J Inglis, Denise Rageot, Alexander M Sele, Vladimir Cmiljanovic, Natasa Cmiljanovic, Katja Bargsten, Amol Aher, Anna Akhmanova, J Fernando Díaz, Doriano Fabbro, Marketa Zvelebil, Roger L Williams, Michel O Steinmetz, Matthias P Wymann
BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target effect with microtubule polymerization. Here, we developed two chemical derivatives that differ from BKM120 by only one atom. We show that these minute changes separate the dual activity of BKM120 into discrete PI3K and tubulin inhibitors. Analysis of the compounds cellular growth arrest phenotypes and microtubule dynamics suggest that the antiproliferative activity of BKM120 is mainly due to microtubule-dependent cytotoxicity rather than through inhibition of PI3K...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28273638/antimalarial-activity-and-safety-assessment-of-flueggea-virosa-leaves-and-its-major-constituent-with-special-emphasis-on-their-mode-of-action
#14
Shiv Vardan Singh, Ashan Manhas, Yogesh Kumar, Sonali Mishra, Karuna Shanker, Feroz Khan, Kumkum Srivastava, Anirban Pal
A clinical emergency stands due to the appearance of drug resistant Plasmodium strains necessitate novel and effective antimalarial chemotypes, where plants seem as the prime option, especially after the discovery of quinine and artemisinin. The present study was aimed towards bioprospecting leaves of Flueggea virosa for its antimalarial efficacy and active principles. Crude hydro-ethanolic extract along with solvent derived fractions were tested in vitro against Plasmodium falciparum CQ sensitive (3D7) and resistant (K1) strains, where all the fractions exhibited potential activity (IC50 values <10μg/mL) against both the strains...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28270538/chemotherapy-drug-handling-in-first-opinion-small-animal-veterinary-practices-in-the-united-kingdom-results-of-a-questionnaire-survey
#15
E G Edery
To investigate how first opinion small animal veterinary surgeons in the UK handled chemotherapeutic agents, a questionnaire was distributed at the 2014 British Small Animal Veterinary Association congress and by internet. Chemotherapy was regularly offered by 70.4 per cent of the respondents. Gold standards defined according to available guidelines for safe handling of antineoplastic drugs were poorly followed by general practitioners with only 2 per cent of respondents complying with all of them. Dedicated facilities for preparation and administration of cytotoxic drugs were variably available among participants...
March 7, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28249824/a-new-construct-of-antibody-drug-conjugates-for-treatment-of-b-cell-non-hodgkin-s-lymphomas
#16
Libin Zhang, Yixin Fang, Jindřich Kopeček, Jiyuan Yang
The aim of this study was to develop a new class of antibody-drug conjugates (ADCs) with the potential to not only enhance treatment efficacy but also improve tolerability for patients with B-cell lymphomas. Classic ADCs consist of monoclonal antibodies (mAbs) linked to drugs or toxins. They selectively deliver toxic moieties to tumor cells. As such, they greatly improve the therapeutic index compared to traditional chemotherapeutic agents. However, the therapeutic efficacy and safety of ADCs are dependent on linker stability and payload toxicity...
February 26, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#17
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio A B Schutz, Joaquim Bellmunt, Guru Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAEs) have been described with immune checkpoint inhibitors (ICIs), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
February 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28242548/new-azole-derivatives-showing-antimicrobial-effects-and-their-mechanism-of-antifungal-activity-by-molecular-modeling-studies
#18
İnci Selin Doğan, Selma Saraç, Suat Sari, Didem Kart, Şebnem Eşsiz Gökhan, İmran Vural, Sevim Dalkara
Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28238155/safety-of-herbal-medicine-use-during-chemotherapy-in-patients-with-ovarian-cancer-a-bedside-to-bench-approach
#19
Eran Ben-Arye, Ofer Lavie, Noah Samuels, Hazem Khamaisie, Elad Schiff, Orit Gressel Raz, Jamal Mahajna
In this study, we explored herbal supplements used by patients during chemotherapy and test for herb-drug interactions and response of cancer cells to treatment. Patients with gynecological cancer referred to a complementary and integrative medicine (CIM) service were asked about their use of herbal medicine during chemotherapy. The leading five clinically relevant herbs selected for cytotoxicity analysis included the following: wheatgrass (Triticum aestivum), European mistletoe (Viscum album), ginger (Zingiber officinale), Ephedra (Ephedra campylopoda), and Oriental mistletoe (Viscum cruciatum)...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28225654/germicidal-efficacy-and-mammalian-skin-safety-of-222-nm-uv-light
#20
Manuela Buonanno, Brian Ponnaiya, David Welch, Milda Stanislauskas, Gerhard Randers-Pehrson, Lubomir Smilenov, Franklin D Lowy, David M Owens, David J Brenner
We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues...
February 22, 2017: Radiation Research
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