Novel 3,4-Dihydroisocoumarins Inhibit Human P-gp and BCRP in Multidrug Resistant Tumors and Demonstrate Substrate Inhibition of Yeast Pdr5

In this study, the three natural compounds 6-methoxymellein (3), angelicoin B (4) and ellagic acid as well as nine novel 3,4-dihydroisocoumarins (Figure 1) were analyzed regarding their cytotoxicity in cancer cells and inhibition of the endogenously expressed human ABC transporters P-gp, BCRP, and MRP1 and of the yeast transporter Pdr5. For further insights into the mechanism of action, Pdr5 ATPase and substrate transport assays were performed. These results were complemented with molecular docking studies that indicate that differences in the inhibitory power of the investigated 3,4-dihydroisocoumarins with respect to P-gp-mediated transport result from differences in the compounds’ binding affinities to P-gp. FIGURE 1 Figure 1. Structures of natural and synthetic 3,4-dihydroisocoumarins. Materials and Methods Chemicals and Reagents A549 and HCT-15 cells were purchased from the German Collection of Microorganisms and Cell Cultures (Braunschweig, Germany) and H69AR cells from the American Type Culture Collection (Manassas, VA, United States). Dr. Erasmus Schneider (Wadsworth Center, New York State Department of Health, Albany, NY, United States) kindly provided the MCF-7/MX cells. Cell culture media and supplements were purchased from Thermo Fisher Scientific (Waltham, MA, United States). Yeast extract, peptone, and D-glucose were purchased from Carl Roth (Karlsruhe, Germany). Hoechst 33342, rhodamine 6G (R6G) and adenosine 5′-triphosphate (ATP)...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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This study aims to reflect on the process of adoption of the preprints publication model, briefly delimiting its history and current use by the national and the international scientific community. Departing from the literature and a consultation of preprint repositories, this reflection intends to highlight the main challenges that preprint implementation will face in the Nursing area, along with its specificities. While considering its benefits for scientific dissemination, this study points out the difficulties that may arise from the implementation of mostly north-American science models in a peripheral country such as ...
Source: Revista da Escola de Enfermagem da USP - Category: Nursing Source Type: research
This article gives an overview of the current results of PET with radiolabelled amino acids in therapy monitoring of standard therapy as well as various innovative approaches in the treatment of patients with cerebral gliomas.Expert opinion: Amino acid PET has proven to be helpful in therapy monitoring of gliomas, the costs are low in relation to the costs of therapy and the clinical benefit, and a widespread clinical use is highly desirable. PMID: 31829748 [PubMed - as supplied by publisher]
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Authors: Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR Abstract Introduction: Leukodystrophies constitute heterogenous group of rare heritable disorders primarily affecting the white matter of central nervous system. These conditions are often under-appreciated among physicians. The first clinical manifestations of leukodystrophies are often nonspecific and can occur in different ages from neonatal to late adulthood periods. The diagnosis is, therefore, challenging in most cases.Area covered: Herein, the authors discuss different aspects of leukodystrophies. The authors used...
Source: Expert Review of Neurotherapeutics - Category: Neurology Tags: Expert Rev Neurother Source Type: research
Conclusions: In patients discontinuing natalizumab, fingolimod has a favorable benefit–risk profile over 48 months. These findings also suggest using a short washout following natalizumab discontinuation, consistent with guidelines and current clinical practice in Germany.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 13 December 2019Source: Brain, Behavior, and ImmunityAuthor(s): N.B. Teixeira, M.B. Sant'Anna, A.C. Giardini, L.P. Araujo, L.A. Fonseca, A.S. Basso, Y. Cury, G. PicoloAbstractMultiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG35-55-induced EAE, an animal mod...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research
Ceribell Inc., the company that set out to simplify bedside electroencephalogram (EEG) monitoring with its Ceribell Rapid Response EEG and took home the 2019 Medical Design Excellence Awards Best-in-Show award, has just launched Clarity, a new 24/7 bedside EEG monitoring and alerting technology. The company made the announcement at the American Epileptology Society Annual Meeting. Ceribell Rapid Response EEG was designed to ease EEG setup and triage for patients with suspicion of seizure, and application does not require an EEG technician. In addition to winning the MDEA Best in Show, the system was also recognized with a ...
Source: MDDI - Category: Medical Devices Authors: Tags: Software Source Type: news
Among women with metastatic breast cancer, use of an investigational oral form of paclitaxel yielded a higher overall response rate than the IV form, but administration was unique and time-consuming.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Hematology-Oncology News Source Type: news
Publication date: Available online 12 December 2019Source: The LancetAuthor(s): Jack Cuzick, Ivana Sestak, John F Forbes, Mitch Dowsett, Simon Cawthorn, Robert E Mansel, Sibylle Loibl, Bernardo Bonanni, D Gareth Evans, Anthony Howell, IBIS-II investigatorsSummaryBackgroundTwo large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo...
Source: The Lancet - Category: General Medicine Source Type: research
Publication date: Available online 12 December 2019Source: Journal of the Formosan Medical AssociationAuthor(s): Chien-Lin Chen, Wei-Chuan Chang, Ching-Sheng Hsu
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
ConclusionsThis study provides initial perspectives on measles preparedness among Idaho CAHs, despite limited generalizability. Future studies should explore whether self-reported preparedness measures reflect the ability of the CAHs to control measles spread when cases present for care.
Source: American Journal of Infection Control - Category: Infectious Diseases Source Type: research
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