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Cytotoxic drug safety

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https://www.readbyqxmd.com/read/28819666/ph-responsive-prodrug-nanoparticles-based-on-a-sodium-alginate-derivative-for-selective-co-release-of-doxorubicin-and-curcumin-into-tumor-cells
#1
Cheng Gao, Fan Tang, Guiyi Gong, Jianxiang Zhang, Maggie P M Hoi, Simon M Y Lee, Ruibing Wang
In order to realize a combination of chemotherapy and selective drug release into tumor cells, novel pH-sensitive prodrugnanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for the selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells...
August 18, 2017: Nanoscale
https://www.readbyqxmd.com/read/28817445/the-safety-of-pembrolizumab-in-metastatic-melanoma-and-rheumatoid-arthritis
#2
Akshjot Puri, Jade Homsi
Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies...
August 16, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28808387/new-apigenin-glycoside-polyphenolic-constituents-anti-inflammatory-and-hepatoprotective-activities-of-gaillardia-grandiflora-and-gaillardia-pulchella-aerial-parts
#3
Fatma A Moharram, Rabab Abd El Moneim El Dib, Mohamed S Marzouk, Siham M El-Shenawy, Haitham A Ibrahim
BACKGROUND: Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. AIM OF THE STUDY: Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808293/targeting-apolipoprotein-e-amyloid-%C3%AE-binding-by-peptoid-cpo_a%C3%AE-17-21%C3%A2-p-ameliorates-alzheimer-s-disease-related-pathology-and-cognitive-decline
#4
Shan Liu, Shinae Park, Grant Allington, Frances Prelli, Yanjie Sun, Mitchell Martá-Ariza, Henrieta Scholtzova, Goutam Biswas, Bernard Brown, Philip B Verghese, Pankaj D Mehta, Yong-Uk Kwon, Thomas Wisniewski
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807243/is-hyperthermic-intraperitoneal-chemotherapy-hipec-safe-for-healthcare-workers
#5
REVIEW
Simon Rodier, Guillaume Saint-Lorant, Jean-Marc Guilloit, Agnès Palix, Fabienne Divanon, François Sichel, Raphaël Delépée
BACKGROUND: During hyperthermic intraperitoneal chemotherapy (HIPEC), caregivers are exposed by different routes to cytotoxic drugs. This review proposes an overview of the safety of HIPEC by assessing existing data on protection procedures, biological and non-biological samples. Based on these data, relevant good practices, eventual irrelevant overprotection procedures and missing data to implement adapted protections are highlighted. MATERIALS AND METHODS: Data were extracted from a systematic review of literature from 1980 till 2016: number and type of surgical procedure, healthcare professionals present, protective equipment, samples, pre-analytical method and analytical method...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28803932/the-thiopurine-nucleoside-analogue-6-methylmercaptopurine-riboside-6mmpr-effectively-blocks-zika-virus-replication
#6
Otavio Valério de Carvalho, Daniele Mendes Félix, Leila Rodrigues de Mendonça, Catarina Maria Cataldi Sabino de Araújo, Rafael Freitas de Oliveira Franca, Marli Tenório Cordeiro, Abelardo Silva Júnior, Lindomar José Pena
Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of the disease caused by the virus. The ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here, we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analog derived from the prodrug azathioprine (AZA), against the epidemic ZIKV strain circulating in Brazil...
August 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28799187/safety-evaluation-of-combination-carboplatin-and-toceranib-phosphate-palladia-in-tumour-bearing-dogs-a-phase-i-dose-finding-study
#7
R M Wouda, S E Hocker, M L Higginbotham
Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low-dose metronomic and/or anti-angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose-finding clinical trial assumed an open-label 3 + 3 cohort design. Client-owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled...
August 10, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28777969/method-validation-and-nanoparticle-characterization-assays-for-an-innovative-amphothericin-b-formulation-to-reach-increased-stability-and-safety-in-infectious-diseases
#8
Maraine Catarina Tadini, Ana Maria de Freitas Pinheiro, Daniel Blascke Carrão, Ana Luiza Scarano Aguillera Forte, Sofia Nikolaou, Anderson R M de Oliveira, Andresa Aparecida Berretta, Franciane Marquele-Oliveira
Drug Delivery Systems (DDS) of known drugs are prominent candidates towards new and more-effective treatments of various infectious diseases as they may increase drug bioavailability, control drug delivery and target the site of action. In this sense, the encapsulation of Amphotericin B (AmB) in Nanostructured Lipid Carriers (NLCs) designed with pH-sensible phospholipids to target infectious tissues was proposed and suitable analytical methods were validated, as well as, proper nanoparticle characterization were conducted...
July 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28777439/combining-cytotoxicity-assessment-and-xenopus-laevis-phenotypic-abnormality-assay-as-a-predictor-of-nanomaterial-safety
#9
Karamallah Al-Yousuf, Carl A Webster, Grant N Wheeler, Francesca Baldelli Bombelli, Victoria Sherwood
The African clawed frog, Xenopus laevis, has been used as an efficient pre-clinical screening tool to predict drug safety during the early stages of the drug discovery process. X. laevis is a relatively inexpensive model that can be used in whole organism high-throughput assays whilst maintaining a high degree of homology to the higher vertebrate models often used in scientific research. Despite an ever-increasing volume of biomedical nanoparticles (NPs) in development, their unique physico-chemical properties challenge the use of standard toxicology assays...
August 4, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28773087/improved-gene-transfer-with-functionalized-hollow-mesoporous-silica-nanoparticles-of-reduced-cytotoxicity
#10
Zhengwen Zhan, Xiaoxu Zhang, Jiayuan Huang, Ying Huang, Zhengwei Huang, Xin Pan, Guilan Quan, Hu Liu, Lili Wang, And Chuanbin Wu
Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene delivery carriers. However, 25 kD PEI could significantly reduce the safety of the modified MSNs although it is efficient for intracellular delivery of nucleic acids. In addition, limited drug loading remains a challenge for conventional MSNs drug carriers...
June 30, 2017: Materials
https://www.readbyqxmd.com/read/28763145/phase-ii-study-of-s-1-plus-leucovorin-in-patients-with-metastatic-colorectal-cancer-regimen-of-1-week-on-1-week-off
#11
Jin Li, Ruihua Xu, Jianming Xu, Tadamichi Denda, Koji Ikejiri, Lin Shen, Yasushi Toh, Ken Shimada, Takeshi Kato, Kenji Sakai, Manabu Yamamoto, Hideyuki Mishima, Jinwan Wang, Hideo Baba
A phase II study of S-1 plus leucovorin (LV) given in a 4-week schedule (2 weeks administration followed by 2 weeks rest) for patients with untreated metastatic colorectal cancer (mCRC) showed the combination was effective, but grade 3 toxicities (diarrhea, stomatitis, anorexia) occurred at a relatively high rate. In this phase II study, we evaluated the efficacy and safety of a 2-week schedule of S-1 plus LV. Patients with mCRC received oral S-1 (40-60 mg) and LV (25 mg) twice daily for 1 week, followed by 1 week rest...
August 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28758827/lymphoproliferative-disorders-in-patients-with-rheumatoid-arthritis-in-the-era-of-widespread-use-of-methotrexate-a-review-of-the-literature-and-current-perspective
#12
Masayoshi Harigai
Lymphoproliferative disorders (LPD) in patients receiving methotrexate (MTX) have gained strong attention. In this article, I reviewed the basic and clinical findings of this issue. Patients with RA possess a high risk of lymphoma, but epidemiological evidence showing an association between the use of MTX and lymphoma is still limited. Rapid regression of LPD after stopping MTX in patients with RA strongly suggests that there is a causative relationship. Genetic predisposition, accumulated inflammation, impaired generation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes, effects of MTX on the regulation of EBV genes, and low hypermethylation of apoptosis-related genes are relevant to the development of LPD and rapid regression after cessation of MTX...
July 31, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28757155/antibody-drug-conjugates-for-treatment-of-breast-cancer-novel-targets-and-diverse-approaches-in-adc-design
#13
REVIEW
Pamela A Trail, Gene M Dubowchik, Timothy Lowinger
Breast cancer is a heterogeneous group of malignancies with a spectrum of molecular subtypes, pathologies and outcomes that together comprise the most common non-cutaneous cancer in women. Currently, over 80% of breast cancer patients are diagnosed at relatively early stages of disease where there are encouraging data on outcomes and long term survival. However, there is currently no curative option for those patients with metastatic disease and there is a substantial medical need to identify effective and safe treatment options for these patients...
July 27, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28756917/promising-antileishmanial-effectiveness-of-doxorubicin-and-doxil-against-leishmania-major-an-in%C3%A2-vitro-assay
#14
Azar Shokri, Javad Akhtari, Masoud Keighobadi, Mahdi Fakhar, Saeed Hosseini Teshnizi, Saeed Emami, Sajede Sadjjadian
OBJECTIVE: To evaluate the effect of doxorubicin and its pegylated liposomal formulation (Doxil, Caelyx) on in vitro susceptibility of promastigote and amastigote stages of Leishmania major. METHODS: Throughout in vitro assays the IC50 was calculated in the promastigotes and amastigotes forms in J774 macrophage cell line. Also as cytotoxicity in J774 cell line macrophages. RESULTS: Doxorubicin and Doxil showed the same activity against promastigote form with IC50 values of 10...
June 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28750895/genotoxic-evaluation-of-poly-anhydride-nanoparticles-in-the-gastrointestinal-tract-of-mice
#15
T Iglesias, J M Irache, M Butinar, B Turk, A López de Cerain, A Azqueta
Gantrez(®) AN 119-based NPs have been developed as oral drug carriers due to their strong bioadhesive interaction with components of the gastrointestinal mucosa and to their adaptable surface. The use of mannosamine to coat Gantrez(®) AN 119-based NPs results in a high mucus-permeable carrier, able to reach the gastrointestinal epithelium. Although their efficacy to transport a therapeutic agent has been demonstrated, their safety has not yet been thoroughly studied. They have proved to be non-cytotoxic, non-genotoxic and non-mutagenic in vitro; however, the in vivo toxicity profile has not yet been determined...
July 24, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28747001/novel-thiosemicarbazide-derivatives-with-4-nitrophenyl-group-as-multi-target-drugs-%C3%AE-glucosidase-inhibitors-with-antibacterial-and-antiproliferative-activity
#16
Maciej Wos, Małgorzata Miazga-Karska, Agnieszka A Kaczor, Katarzyna Klimek, Zbigniew Karczmarzyk, Dorota Kowalczuk, Waldemar Wysocki, Grazyna Ginalska, Zofia Urbanczyk-Lipkowska, Maja Morawiak, Monika Pitucha
A series of thiosemicarbazides with 4-nitrophenyl group was obtained in the reaction of carboxylic acid hydrazides with isothiocyanates. All compounds were checked for their antibacterial and antiproliferative activity. Our results have shown that derivatives 6-8 possessed antibacterial activity against S. aureus, S. epidermidis, S. mutans and S. sanguinis, moderate cytotoxicity and good therapeutic safety in vitro. Additionally, compounds 1 and 4 significantly inhibited A549, HepG2 and MCF-7 cell division...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28744161/emerging-combination-therapies-for-the-management-of-multiple-myeloma-the-role-of-elotuzumab
#17
REVIEW
Wei-Chih Chen, Abraham S Kanate, Michael Craig, William P Petros, Lori A Hazlehurst
Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28739504/improved-metabolic-stability-and-therapeutic-efficacy-of-a-novel-molecular-gemcitabine-phospholipid-complex
#18
Chander Parkash Dora, Varun Kushwah, Sameer S Katiyar, Pradeep Kumar, Viness Pillay, Sarasija Suresh, Sanyog Jain
The aim of the present research is to increase lipid solubility, metabolic stability and therapeutic efficacy of water soluble gemcitabine (GEM) via phospholipid complex (PC) formation. A novel phospholipid complex of GEM was successfully prepared and optimized. Physical interaction of GEM with phospholipid was evaluated by DSC, FT-IR, (1)H NMR, (31)P-NMR and P-XRD. SEM images of GEM-PC showed rough structure and TEM images of diluted aqueous dispersion of GEM-PC showed micellar structure. In silico study also revealed the significant interaction between drug and phospholipid...
July 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28737125/taxanes-in-combination-with-platinum-derivatives-for-the-treatment-of-ovarian-cancer%C3%A2-during-pregnancy-a-literature-review%C3%A2
#19
Xiaoling Zheng, Yao Zhu, Yunchun Zhao, Shisen Feng, Caihong Zheng
Ovarian cancer is one of the most common types of solid carcinoma diagnosed during pregnancy. Taxane plus a platinum derivative is a combination therapy that is predominantly used in the treatment of ovarian cancer in non-pregnant women. Pregnancy adds various complexities to a course of treatment. In pregnant patients diagnosed with cancer during the first trimester, the risks of fetal malformations and fetal loss increase following the administration of cytotoxic drugs, and this is higher with multi-agent vs...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28733879/anticancer-activity-of-salicin-and-fenofibrate
#20
Marwa Sabaa, Hassan M ELFayoumi, Shimaa Elshazly, Mahmoud Youns, Waleed Barakat
Cancer refers to a disorder of cell proliferation that leads to tumor production. Cancer is usually treated by surgery, chemotherapeutic drugs, and radiation. Despite the presence of many anticancer drugs, cancer is still an uncontrolled disease and is a major cause of death worldwide. In addition, most anticancer drugs have severe side effects that can limit their use in some patients. This study aims to investigate the possible anticancer activity of two clinically used drugs: a natural antioxidant agent (salicin) and an antihyperlipidemic agent (fenofibrate) against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (Panc-1)...
July 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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